CA3050693A1 - Oral care composition and use and method for the prevention and control of plaque formation, bad breath, gingivitis, periodontal diseases and/or dental caries - Google Patents

Abstract

A use and a method for oral care composition comprising sodium chloride free sea water, a silver ions solution and optionally a pharmaceutically acceptable carrier or excipient (preferably free of chlorine ions). A method and a use for cleaning of teeth, treating or reducing dental enamel erosion, reducing bacterially-generated biofilm and plaque, gingivitis, inhibiting tooth decay and formation of cavities, and/or reducing dentinal hypersensitivity.

Description

ORAL CARE COMPOSITION AND USE AND METHOD FOR THE PREVENTION
AND CONTROL OF PLAQUE FORMATION, BAD BREATH, GINGIVITIS, PERIODONTAL DISEASES AND/OR DENTAL CARIES
Technical field [0001] The invention relates to a new oral care composition for the prevention and control of plaque formation, bad breath, gingivitis, periodontal disease and/or dental caries. Also, the invention relates to a use of said oral care composition and to a method comprising a step involving said oral care composition.
Background of the invention

[0002] It is known that the oral cavity, one of the most densely populated sites of the human body with microbial flora, promotes the establishment of distinct microbial communities: dental plaque, subgingival plaque and tongue coating. Over 500 microbial species have been isolated from the oral cavity, many of which are recognized as pathogens.

[0003] Self performed mechanical home-care methods (brushing, flossing) contribute to the maintenance of oral hygiene and prevention of oral infections. However, these procedures require time, motivation and manual dexterity. Also, bacteria are often left behind, especially in hard-to-reach areas, such as posterior teeth and marginal gingiva.

[0004] Pathogenic microorganisms are implicated in the initiation and progression of at least oral conditions selected from the group consisting of plaque, halitosis, gingivitis, periodontis and dental caries.

[0005] A variety of oral care compositions have been commercialized with different microcidal agents. However, they are providing more or less satisfactory results, but also side effects.
Plague

[0006] Dental plaque is a host associated biofilm known as soft deposit adhering on surfaces of teeth and is considered to be the primary cause of bad breath, gingivitis, periodontitis and dental caries. Therefore, control and reduction of dental plaque are essential to a sound oral hygiene and global health.

[0007] More than 500 different types of microorganisms have been found in well-developed human dental plaque. Some may be important in the pathogenesis of the oral disease, and others may not. If not controlled, the normal metabolic activity of these plaque organisms can produce various acids, such as acetic, butyric and lactic acids, which may react with calcium of dental enamel resulting in decalcifications, and initiation and progression of dental caries. Other microbial by-products may attack soft gum tissue leading to gingivitis and later on periodontitis.

[0008] The prevention and control of dental plaque remain lingering issues of high importance to oral and general health, with a significant social and financial impact on modern societies.
Halitosis

[0009] Oral malodor (Halitosis), commonly known as "bad breath" is a condition that affects up to 50 % of the global population. In addition to breath odour, individuals may have unpleasant taste, described as bitter, dry, fecal, metallic, hot or pasty. Two of the most frequent causes of bad breath are:
- Tongue coating, and - Tonsillolith.
Tongue coating

[0010] Tongue coating is a bacterial whitish or yellowish plaque formed on the surface of the posterior part of the tongue. It is composed of epithelial cells peeled off the oral mucosa, salivary proteins and food protein remains, which serve as food subtract to present bacterial flora, and especially anaerobic proteolytic bacteria. As a result of bacterial metabolism unpleasant smell is produced, which is nothing but bad breath itself.

[0011] Tongue coating is basically formed with a decrease of salivary flow or an epithelial desquamation above physiological limits, or even both conditions.
There are several causes for increasing cell desquamation including oral respiration or snoring, use of orthodontic appliances, the habit of biting lips and cheeks, frequent ingestion of alcoholic beverages, or even the use of mouthwashes containing alcohol.
Tonsillolith

[0012] Tonsillolith is a "little paste" that is formed into invaginations existing in the tonsils - tonsil crypts. Its content is similar to tongue coating and is formed by the same mechanism of epithelial desquamation and reduction of salivary flow.

[0013] It is generally recognized that bad odour, associated with the tongue coating and with tonsillolith, is due to the presence of Gram-negative anaerobic bacteria within the tongue coating and tonsillolith. These bacteria actively degrade, and the debris left in the mouth result in the production of sulfur-containing amino-acids, methionine and cysteine, and generate pungent compounds collectively known as volatile sulfur compounds (VSC). Hydrogen sulfide (H-S-H), methyl mercaptan (CH3-S-H) and dimethyl sulfide (CH3-S-CH3), are the principal odour components generated.

[0014] These substances, especially methyl mercaptan, have an unpleasant odour, even in a very low concentration, and thus exhalation is perceived as bad breath.

[0015] It is also recognized that VSC can produce biological effects, such as altering the epithelial barrier within the oral cavity, resulting in bleeding and painful inflammation of oral tissue. For example, methyl mercaptan enables the penetration of bacterial toxins into the underling connecting tissue through the increased permeability of oral mucosa.
This volatile compound can alter enzymatic and immunologic activities, delay wound healing and influence gene activity through the alteration cell shape and cytoskeleton pattern.

[0016] An important factor is that, among bacteria present in the tongue coating and tonsillolith, there are bacteria that may cause oral and systemic diseases.
Therefore, removal and control of the tongue coating and tonsillolith are important in preventing oral diseases, as well as systemic diseases, such as gastritis and pneumonia.

[0017] In addition to the Gram-negative anaerobic bacteria many individuals who complain about bad breath and bad taste, have substantial amounts of yeast.
Among them Candida albicans is the species most often responsible for infection in the oral cavity and may cause a variety of disorders including gingival bleeding and denture stomatitis.
Gingivitis

[0018] Gums are pinkish brownish colored soft tissue holding the tooth in bone sockets by adhering them firmly throughout periodontal ligaments to periosteum. Gums are basically called gingiva and the inflammatory diseases are called gingivitis in general.
Gingivitis is comprised of different forms of gingival diseases. These diseases manifest clinical signs of inflammation and are classified into two main groups:
non-plaque induced, and plaque-induced.
Non-plaque induced gingivitis

[0019] Gingival conditions not induced by plaque are common and can help explain the many different forms of periodontal diseases (Holmstrup, "Non-Plaque-Induced Gingival Lesions" Ann Periodontal, vol. 4, No.1, December 1999, pp. 20-28).

[0020] The causes of non-plaque induced gingival disease include, bacterial, viral and fungal infections, genetic disorders, mucocutaneous diseases (e.g., Lichen planus), traumatic tooth brushing and allergic reaction to drugs.
Plaque-induced gingivitis

[0021] Plaque induced gingivitis is defining as gingival inflammation, which is confined to the gingival margin. It is associated with dental plaque and no other local contributing factors. Gram-positive and Gram-negative bacteria produce many metabolites that induce gingival inflammation. The clinical features of this condition include redness, swelling and bleeding on probing. Plaque induced gingivitis is one of the most frequent periodontal diseases, affecting more than 90 % of the population, regardless of age, sex or race.
Periodontitis

[0022] Periodontitis is defined as an inflammation of the gingiva extending into the supporting structure of teeth. The disease is characterized by loss of teeth attachment, due to destruction of the periodontal ligaments and loss of the adjacent supporting bone.
There is a relative agreement among specialized scientists that at least seven to eight organisms are fairly certain to be involved in various types of periodontal diseases. These are: Actinomyces viscosus, A. gin givalis, Aggregatibacter actimomycetemcomitans, Porphyromonas gin givalis, Tannerella forsythia, Prevotella intermedia, Cam pylobacter rectus and Spirochetes. Those, and probably other, not yet identified organisms, are considered to be important in gingivitis development, in progression from gingivitis to periodontitis, as well as in the advancing lesion of both chronic and aggressive periodontitis.
Dental caries

[0023] Dental cavities are generally considered to be caused by microorganisms such as Lactobacillus and Streptococcus mutans which adhere to the surface of the teeth, especially in pits and crevices, and form dental plaque.

[0024] Glucans produced from sucrose by the S. mutans glucosyltransferases (GTF) have been indicated as the primary factor in the adherence of the bacteria to tooth surfaces. Dietary sucrose is believed to be the principal material utilized by the S. mutans in plaque, resulting in lactic acid production and subsequent enamel decalcification.
Attempts to reduce and control dental plaque have been made by inhibiting the ability of S. mutans to colonize. However, possibility due to the vitality of S. mutans when routinely contacted with food carbohydrate, it has been shown to be very difficult to inhibit its growth and thereby promote oral hygiene, without undesirable anti-microbial side effects.
Prior art

[0025] A variety of available oral care products comprise ingredients selected from one or more anti-bacterial agents, buffering agents, humectants, surfactants, thickeners, breath fresheners, agents that interfere with or prevent bacterial attachment, flavoring, flagrance, coloring, whitening agent, calcium sources, phosphate sources, potassium salt, anionic polymers, and others.

[0026] In U.S. Patent 4,022,880 to Vinson et al., a compound providing zinc ions as an anticalculus agent is mixed with an antibacterial agent effective to retard the growth of the plaque bacteria.

[0027] Also, a wide variety of antibacterial agents was described in the art with the zinc compounds including cationic materials, such as guanides and quaternary ammonium compounds, as well as noncationic compounds, such as halogenated salicylanilides and halogenated hydroxydiphenyl ethers. Also, a noncationic antibacterial antiplaque halogenated hydroxydiphenyl ether-triclosan was disclosed in combination with zinc citrate trihydrate in European Patent Publication 161,899 (Saxton et al.) and in European patent Publication 271,332 (Davis et al.).

[0028] A mouthwash containing triclosan in a carrier system, containing a solubilizing agent, such as propylene glycol, is also disclosed.

[0029] Also, cationic antibacterial agents, such as chlorhexidine, benzalkonium chloride and cetylpyridinium chloride have been the subject of investigation as antibacterial and anti plaque agents. However, they appear to be generally non-effective when used with anionic materials. Noncationic antibacterial materials, on the other hand, can be compatible with anionic components in oral composition. US Patent 5,401,496 (Fitzig et al.: March 28, 1995) discloses a preparation comprising a synthetic oil of a caprylic/capric triglyceride mixture. US Patent 5,738,840 (Richter; April 14, 1998) discloses an aqueous composition comprising chloride dioxide and a metal chloride salt.

[0030] In a study of microbicidal activity of silver sulfadiazine 657 different types of bacteria from 22 different bacterial species were exposed. All strains were inhibited by levels which can easily be obtained topically. Strains resistant to sulfadiazine or multiple antibiotics were sensitive to silver sulfadiazine ("Carr, Howard S., Wlodkowski, Theodore J., and Rosenkranz, Herbert S., November 1973; Silver sulfadiazine: In Vitro Antibacterial Activity. Antimicrobial Agents and Chemotherapy, 4(5), 585- 587.

[0031] Also, various rinse preparations are known for treating halitosis. US
Patent 6,132,701 (Perez et al.: October 17, 2000) discloses a method for reducing halitosis that includes an aqueous solution of calcium hydroxide for rinsing the oral cavity.
In general, known anti-halitosis mouthwashes may not remove the often bitter or pasty taste that causes distress to the individual, suggesting that they leave microorganisms in numbers large enough to generate by-products that continue to affect the taste perceptions of the affected people.

[0032] Salt water rinses are generally considered as excellent short-term treatment of wounds in the mouth or after teeth extraction, sore throat or gum sores. US
Patent 4581226A describes a sea water solution that may be used to irrigate eye and nasal mucosa, pharyngeal mucosa, external auditory meatus, tissue lining the cavity of the mouth and vaginal tissue. Thus, when used for irrigation, the solution may be applied as a nose spray, an ear and eyewash, a mouth wash and also a douche.

[0033] Also, QuintonTM Marine Plasma can be used in place of saline solution in root canal washings and in cases of periodontal osteoporosis; US 4581226A (DiIon R.) has discussed that sea water has exhibited bacteriostatic properties; and US
Patent 6,071,500 (Thislet, June 6, 2000) discloses a breath cleansing spray that includes xylitol as a sweetener and calcium hydroxide to raise the pH of the saliva. QuintonTM
Marine Plasma (QMP), is sea water derived from regions of intense (vortex) reproduction of plankton in the Atlantic Ocean. QMP is enriched with various mineral compounds, trace elements, and biologically active substances. However, the specific mechanisms underlying the beneficial effects of the QMP on living organisms remain unclear.

[0034] It has been recognized, since ancient times, that salt is not only a natural disinfectant, but it also removes swelling from tissue and promotes wound healing. Salt also promotes isotonic effect which means it contains the same salts and minerals our body produces preventing destruction of cells migrating into the area trying to repair the wound.

[0035] Recently, a new generation of mouthwash has been produced (Pekovic et aL, "Comparative Study Of Antimicrobial Toxicity And Physicochemical Properties Of The New Generation Mouthwash OralNetTM' With Common Mouthwashes", EC Microbiology, Vol. 2, Issue 3, November 2015, pp. 317-327) that contains ultra-pure sea water and colloidal silver as active ingredients. However, it has been shown that ultra pure see water and colloidal silver have reacted physico-chemically, resulting in turbidity and precipitation, to thereby negatively affect the properties and efficiency of such a mouthwash.

[0036] Therefore, there is a strong need for an oral care composition avoiding drawbacks of existing oral care compositions.

[0037] Also, there is a strong need for use of an anti-microbial oral care composition, preferably a mouthwash composition, containing microbicidal agents with a broad-spectrum activity, as a supplement to mechanical home-care procedures. Such agents should not have properties to induce a microbial resistance, nor to have any side effects on oral tissue, cells or teeth.

[0038] Also, there is a strong need for a new oral care composition, preferably a mouthwash composition, defining a mile stone in modern dentistry by controlling and preventing dental plaque formation and consequent oral diseases conditions.

[0039] Also, there is a strong need for a new oral care composition, preferably a mouthwash composition, allowing to reduce dental plaque and promoting oral hygiene by reducing dental caries and gingivitis.

[0040] Also, there is a strong need for a new oral care composition, such as a mouthwash composition, for the prevention and control of plaque formation and consequent microbial involvement in the etiology of bad breath, gingivitis, periodontal disease and dental caries, without drawbacks of existing oral care compositions.

[0041] Also, there is a strong need for a method for the prevention and control of plaque formation and consequent microbial involvement in the etiology of bad breath, gingivitis, periodontal disease and dental caries, said method comprising a step involving the contact of a new oral care composition, such as a new mouthwash composition, which does not present drawbacks of existing oral care compositions.

[0042] Also, with the high incidence of oral diseases, increasing cost of dental services and development of antibiotic resistance, there is a global need for protection of oral health through safe and effective alternative treatments.

[0043] The Applicant has now surprisingly discovered a new oral care composition allowing to overcome, at least in part, above mentioned drawbacks and to meet with the above-mentioned needs.

[0044] According to a preferred aspect, the Applicant has surprisingly discovered a new oral care composition, more preferably a new mouthwash, allowing to overcome the above-mentioned drawbacks, and allowing to meet the above-mentioned needs. Of course, the new oral care composition may be under any form, and preferably under the form of a mouthwash.

[0045] Also, the Applicant has now surprisingly discovered a new use and a new method involving the above-mentioned new oral care composition, said use and method allowing at least in part to overcome, and preferably allowing to overcome, the above-mentioned drawbacks and to meet with the above-mentioned needs.
Summary of the invention

[0046] An embodiment of the present invention relates to an oral care composition comprising, but not limited to, two active ingredients:
sodium chloride-free sea water, preferably ultra pure sodium chloride-free sea water, and a silver ion solution.

[0047] Another embodiment of the present invention relates to the oral care composition defined hereinabove, optionally further comprising a pharmaceutically acceptable carrier or excipient, said pharmaceutically acceptable carrier or excipient being free of chloride ions.

[0048] Silver ion solution may be prepared according to any techniques well known in the art. Preferably, the silver ion solution may be prepared by electrolysis procedure of pure silver (99.9%) in deionized water using a low voltage DC power source (9 to 30 VDC). When electric current passes through the silver electrodes, some silver atoms, at the interface with the deionized water, lose an electron and change the atom into an ion.
Whereas metallic silver is not water soluble, silver ions are water soluble producing an ionic silver solution in deionising water which is free of any other ions of physic-chemical substances.

[0049] The Applicant has surprisingly discovered that it is possible to avoid this color change, by removing sodium chloride from sea water. Any technics well known in the art can be used. Preferably, sodium chloride can be removed by standard inversed-osmosis procedure. Following inversed osmosis removal of the sodium chloride from the sea water, the contact with ionic silver solution has not generated any detectable color change of the mixture.

[0050] Another embodiment of the present invention allows to at least reduce or allows to overcome, several of the drawbacks of existing oral care composition, concerning the reduction and elimination of harmful microorganisms within the oral cavity.

[0051] Also, another embodiment of the present invention encompasses an oral care composition, a use and a method to clean and disinfect an oral cavity and provide improved methods of promoting oral health and/or systemic health by reducing potential for oral diseases and systemic infection via the oral cavity.

[0052] Also, another embodiment of the present invention provides an oral care composition and a method allowing to reduce and/or prevent the formation of plaque and the etiology of halitosis, gingivitis, periodontitis and dental caries.

[0053] Also, another embodiment of the present invention relates to an oral care composition whose primary active microbicidal ingredients comprise sodium chloride-free sea water, preferably ultra pure sodium chloride-free sea water, and a silver ions solution.

[0054] Also, another embodiment of the present invention relates to an oral care composition whose primary active microbicidal ingredients comprise sodium chloride-free sea water, preferably ultra pure sodium chloride-free sea water, a silver ions solution, and optionally a pharmaceutically acceptable carrier or excipient, said pharmaceutically acceptable carrier or excipient being free of chloride ions.

[0055] Also, another embodiment of the present invention relates to a new oral care composition that is capable of elimination of oral pathogenic bacteria on contact.

[0056] Also, another embodiment of the present invention relates to a method comprising a step of directly contacting an oral care composition according to the invention with the oral cavity, e.g. washing the teeth and oral cavity, optionally in conjunction with brushing of teeth to reduce plaque formation.

[0057] Also, another embodiment of the present invention relates to a oral care composition, use and/or method described herein that can be used for the prevention and treatment of halitosis, gingival inflammation or bleeding, and/or periodontal disease and/or dental caries, as well as to reduce the pain associated with oral disease.

[0058] Also, another embodiment of the present invention relates to an oral care composition effective in the treatment of mixed bacterial infections that is a combination of anaerobes and aerobes consisting of Bacteroides sp., Fusobacterium sp. and Peptostreptococcus sp., as well as yeast species such as C. albicans.

[0059] Also, another embodiment of the present invention provides oral care composition containing sea water from which sodium chloride has been removed and a silver ions solution, which act in synergy against oral disease and dental caries etiologic agents.

[0060] Also, another embodiment of the present invention provides oral care composition containing sea water from which sodium chloride has been removed, a silver ions solution, and optionally a pharmaceutically acceptable carrier or excipient, said pharmaceutically acceptable carrier or excipient being free of chloride ions, which act in synergy against oral disease and dental caries etiologic agents.

[0061] Without being bound to the theory, the Applicant believes that silver ion particles block dentine and openings of dentinal tubuli as a physical barrier and kill accumulated bacteria by ions damaging cell membrane and blocking of respiratory enzyme of pathogens.

[0062] Also, another embodiment of the invention relates to a synergetic killing of oral pathogens with silver ions solution and sodium-chloride free sea water. Also, said sodium chloride-free sea water further contributes by its osmolality, based on a rich content of minerals and metals, and presence of natural antibiotics.

[0063] Also, another embodiment of the invention relates to a synergetic killing of oral pathogens with silver ions solution, sodium-chloride free sea water, and optionally a pharmaceutically acceptable carrier or excipient, said pharmaceutically acceptable carrier or excipient being free of chloride ions. Also, said sodium chloride-free sea water further contributes by its osmolality, based on a rich content of minerals and metals, and presence of natural antibiotics.

[0064] Also, antimicrobial synergy between sodium chloride-free sea water and silver ions solution may result in generation of additional microbicidal ingredients such as silver diamide fluoride (SDF) (Ag+ (NH3)2 F-) and possibly many others. SDF is known in prevention and stopping dental decay. The Applicant believes that this synergy may produce positive results in patients that had not found relief from halitosis, plaque accumulation, gingivitis, periodontitis and dental caries.

[0065] According to another embodiment of the invention, the oral care composition can be used for control of total salivary microbial load by continuous maintaining pH
around 7.5.

[0066] According to another embodiment of the invention, the oral care composition, use and/or method described herein can be used to prevent and treat fungal infection, caused by C. alb/cans.

[0067] Another embodiment of the invention relates to the oral care composition defined above, with a reduction and/or none of the side effects found in topical uses of both sea water and colloidal silver solution.

[0068] Another embodiment of the invention relates to the oral care composition optionally further comprising additional ingredients, e.g., selected from but not limited to one or more of water, surfactants, solvent, vitamins, minerals, polymers, enzymes, humectants, thickeners, additional antimicrobial agents, additional preservatives, flavorings, colorings and/or combination thereof.

[0069] The description and specific examples illustrate various embodiments of the invention.

- Recitation of multiple embodiments having stated features that are not intended to exclude other oral compositions having additional features or different combinations of the stated features. Furthermore, the recitation of one or more preferred embodiments does not imply that other embodiments are not useful and are not intended to exclude other embodiments from the scope of the invention.
- Specific examples are provided only for illustrative purposes of how to make, use and practice the compositions and methods of this invention.
- The active ingredients of present invention can be delivered in the form of any oral care formulations, for example mouthwash, toothpaste, powder, cream, strip, gum, or any other formulation known in the art. The oral care compositions of present invention preferably are in the form of a mouthwash and disinfectant of toothbrushes and dentures.
- The term "dentifrice" as used through the description denotes a paste, gel, lozenge, gum or liquid formulation. The dentifrice may be in any desired form, such as deep stripped, surface stripped, multilayered having a gel surround the paste, or any compositions thereof.
- The expressions "pharmaceutically acceptable carrier or excipient", as used through this description, represents any safe and effective materials for use herein. Said "pharmaceutically acceptable carrier or excipient" is free of chloride ions. Optionally, such materials may include, for example, thickening agents, humectants, ionic active ingredients, buffering agents, anticalculus agents, abrasive polishing materials, peroxide sources, alkali metal bicarbonate, salts, surfactants, titanium dioxide, coloring agents, flavor sweetening agents, antimicrobial agents, herbal agents, desensitizing agents, stain reducing agents, and mixtures thereof.
- The expression free of chloride ions means that the concentration of chloride ions is lesser than 5 ppm, preferably lesser than 3 ppm, and more preferably lesser than 1 ppm.

- As used herein the words "preferred" and "preferably" are not limiting and only refer to the embodiment of the invention that affords certain further benefits, under certain circumstances.
The word "include", and its variant is intended to be non-limiting, such that recitation of items in a list is not to the exclusions of other like items that may, also be useful in the materials, compositions, and methods of this invention.
In a similar manner, the description of certain advantages or disadvantages of known materials and methods is not intended to limit the scope of the invention.
- As used herein the term "about" indicates a possible variation of up to 5 `)/0 in the value.
Unless stated otherwise, all percentages of composition components given in this specification are by weight based on a total weight of the composition.
The composition and formulation that are provided herein are described and claimed with reference to their ingredients, as is usual in the art. As would be evident to one skilled in the art, the ingredients may in some instances react with one another, so that the true composition of the active ingredients of the final composition may not correspond exactly to the ingredients listed. Thus, it should be understood that the invention extends to the product of the combination and interaction of the listed ingredients.
- As indicated throughout the following description, ranges are used as shorthand for describing each and every value that is within the range. Any value within the range can be selected as the terminus of the range.
The examples and other embodiments described herein are indicative and not intended to be limiting in describing the full scope and methods of this invention.
Detailed description of the invention

[0070] Another embodiment of the present invention relates to an oral care composition comprising:
(i) sodium chloride-free sea water; and (ii) a silver ions solution.

[0071] Another embodiment of the present invention relates to the oral care composition defined hereinabove, wherein with respect to the total weight of the oral care composition, said cornposition cornprises:
up to 30.00 wt.-% of the sodium chloride-free sea water; and up to 70.00 wt.-% of the silver ions solution, said silver ions solution containing in an aqueous medium from 5 ppm to 20 ppm of silver ions.

[0072] Another embodiment of the present invention relates to the oral care composition defined hereinabove, wherein with respect to the total weight of the oral care cornposition, said cornposition cornprises:
up to 32.00 wt.-% of the sodium chloride-free sea water; and up to 68.00 wt.-% of the silver ions solution, said silver ions solution containing in an aqueous medium from 5 ppm to 20 ppm of silver ions, preferably from 10ppm to 15ppm of silver ions.

[0073] Another embodiment of the present invention relates to the oral care composition defined hereinabove, wherein with respect to the total weight of the oral care cornposition, said cornposition comprises:
up to 32.00 wt.-% of the sodium chloride-free sea water; and up to 68.00 wt.-% of the silver ions solution, said silver ions solution containing in an aqueous medium from 5 ppm to 20 ppm of silver ions, preferably from 10ppm to 15ppm of silver ions.

[0074] Another embodiment of the present invention relates to the oral care composition defined hereinabove, wherein the aqueous medium of the silver ions solution is free of chloride ions. Preferably, the aqueous medium is distilled water, deionized water, demineralized water or a mixture thereof, more preferably deionized water. Much more preferably, the amount of chloride ions is lesser than 5 ppm, or lesser than 3 ppm.

[0075] Another embodiment of the present invention relates to the oral care composition defined hereinabove, further comprising a pharmaceutically acceptable carrier or excipient, said pharmaceutically acceptable carrier or excipient being free of chloride ions.

[0076] Another embodiment of the present invention relates to the oral care composition defined hereinabove, wherein the pharmaceutically acceptable carrier or excipient may represent up to 75 wt.- /0 of the total weight of the oral care composition.

[0077] Another embodiment of the present invention relates to an oral care composition consisting of:
(I) sodium chloride-free sea water; and (ii) a silver ions solution.

[0078] Another embodiment of the present invention relates to the oral care composition defined hereinabove, consisting of:
(i) up to 30.00 wt.-% of the sodium chloride-free sea water;
(ii) up to 70.00 wt.-% of the silver ions solution; and (iii) from 0 to 75.00 wt.% of the pharmaceutically acceptable carrier or excipient.

[0079] Another embodiment of the present invention relates to the oral care composition defined hereinabove, wherein the sodium chloride-free sea water is obtained from a synthetic sea water according to ASTM D1141-98, 2013.

[0080] Another embodiment of the present invention relates to the oral composition defined hereinabove, wherein the sodium chloride-free sea water is an ultra pure sodium chloride-free sea water obtained by inverse osmosis procedure.

[0081] Another embodiment of the present invention relates to the oral care composition defined hereinabove, wherein said ultra pure sodium chloride-free sea water is obtained by mechanical withdrawal of the sodium chloride from sea water. In this regard, any processes and/or devices well known to persons skilled in the art can be used for the mechanical withdrawal of sodium chloride from sea water.

[0082] Another embodiment of the present invention relates to the oral care composition defined hereinabove, wherein the ultra pure sodium chloride-free sea water contains less than 5 ppm of sodium chloride.

[0083] Another embodiment of the present invention relates to the oral care composition defined hereinabove, wherein the silver ions solution is an aqueous solution of at least one generator of silver ions comprising water, preferably distilled water, deionized water or demineralized water, more preferably deionized water.

[0084] Another embodiment of the present invention relates to the oral care composition defined hereinabove, further comprising at least one additional ingredient selected from the group consisting of surfactants, solvent, vitamins, minerals, polymers, enzymes, humectants, thickeners, additional antimicrobial agents, additional preservatives, flavorings, colorings and mixtures thereof. Preferably, said at least one additional ingredient is free of chloride ions.

[0085] Another embodiment of the present invention relates to the oral care composition further comprising at least one additional ingredient selected from the group consisting of flavorings agents, colorings agents and mixtures thereof.

[0086] Another embodiment of the present invention relates to the oral care composition defined hereinabove, wherein the pharmaceutically acceptable carrier or excipient comprises distilled water, deionized water, demineralized water or mixtures thereof, preferably is deionized water.

[0087] Another embodiment of the present invention relates to the oral care composition defined hereinabove, wherein the pharmaceutically acceptable carrier or excipient represents from 68 wt.-% to 75 wt.-% of the total weight of the oral care composition.

[0088] Another embodiment of the present invention relates to the oral care composition defined hereinabove, wherein 30.00 wt.-% of the sodium chloride-free sea water and 70 wt.-% of the silver ions solution represents about 100 wt.-% of the total weight of the oral care composition.

[0089] Another embodiment of the present invention relates to the oral care composition defined hereinabove, wherein the silver ions solution represents from 110 wt.-% to 125 wt.-% of the total weight of the sodium chloride-free sea water.

[0090] Another embodiment of the present invention relates to the oral care composition defined hereinabove, further comprising at least one additive selected from the group consisting of flavoring agents and coloring agents. Preferably, said at least one additive is free of chloride ions.

[0091] Another embodiment of the present invention relates to the oral care composition defined hereinabove, wherein the flavoring agent is selected from the group consisting of menthol, zinc citrate, zinc chloride, tutti-frutti, methyl salicylate, Eucalyptus oil, spearmint oil and peppermint oil.

[0092] Another embodiment of the present invention relates to the oral care composition defined hereinabove, wherein the flavoring agent is menthol, and wherein said menthol represents from 0.017 wt.-% to 0.021 wt.-% of the total weight of the oral care composition.

[0093] Another embodiment of the present invention relates to the oral care composition defined hereinabove, wherein the coloring agent is Fast Green (USP-C.I.
42053).

[0094] Another embodiment of the present invention relates to the oral care composition defined hereinabove, wherein the Fat Green represents from 0.001 wt.-% to 0.005 wt.-% of the total weight of the oral care composition.

[0095] Another embodiment of the present invention relates to the oral care composition defined hereinabove, further comprising at least one microbicidal ingredients selected from the group consisting of, delmopinol, triclosan, Sanguinaria Canadensis, propolis, Aloe vera, sage (salvia officinaffis), lemon (Citrus limon), pine (Pinus sylvetris), echinacea (Echinacea purpurea and agustifolia), rathany (Krameria trianda) and cheeseweed mallow (Melva parviflora L.).

[0096] Another embodiment of the present invention relates to the oral care composition defined hereinabove, further comprising a source of fluoride ions, and wherein the silver ion precursor is silver diamine fluoride (SDF).

[0097] According to another embodiment of the invention, the oral care composition may include mouthwashes, mouthrinses, dentifrices, dental gels, lozenges, beads, gums, oral stripes, mints, liquid toothpaste, sprays, paint-on gels, lip-balms, whitening strips, breathe strips, oral chews, and combinations thereof.

[0098] According to another embodiment of the invention, the oral care composition can be used for example for plaque prevention and control of bad odour formation, prevention and control of gingivitis, periodontitis and dental caries.

[0099] Another embodiment of the present invention relates to the oral care composition which is a mouthwash composition comprising with respect to the total weight of the oral care composition:
Ingredients Concentration* (wt.-%) Sodium chloride-free sea water 30.0 Solution of silver ions in deionized water (15 ppm 69.98 Ag+) Flavoring agent (Mint -CAS NO. 2216-51-5) 0.019 Coloring agent (Fast Green C.I. 42053) 0.001

[0100] Another embodiment of the present invention relates to a use of the oral care composition defined hereinabove, for cleaning of teeth, treating or reducing dental enamel erosion, reducing bacterially-generated biofilm and plaque, gingivitis, inhibiting tooth decay and formation of cavities, and/or reducing dentinal hypersensitivity.

[0101] Another embodiment of the present invention relates to a method for cleaning of the teeth, treating or reducing dental enamel erosion, reducing bacterially-generated biofilm and plaque, gingivitis, inhibiting tooth decay and formation of cavities, and/or reducing dentinal hypersensitivity, said method comprising a step of contacting the oral care composition defined hereinabove, with teeth.

[0102] Another embodiment of the present invention relates to a use of the oral care composition defined hereinabove, as a vehicle for the addition of bactericide antibiotics and for the treatment of inflamed tissue.
Sea water

[0103] On average, according to another embodiment of the invention, sea water has a salinity of about 3.5% (35 g/L, or 599 mM), which is a specific gravity of about 1.025.
This means that every kilogram (roughly one liter by volume) of sea water has approximately 35 grams (1.2 oz) of dissolved salts (predominantly sodium (Na+
) and chloride (Cl-) ions). Average density at the surface is 1.025 g/ml. Sea water is denser than both fresh water and pure water (density 1.0 g/ml at 4 C) because the dissolved salts increase the mass by a larger proportion than the volume. Sea water pH
is limited to a range between 7.5 and 8.4. Total molar composition of unaltered sea water (i.e.
before removal of chloride ions), has the following values:
(Salinity = 35 g/1) H20 53.6 Cl- 0.546 Na + 0.469 Mg2+ 0.0528 S02- 0.0282 Ca2+ 0.0103 K+ 0.0102 Ct* 0.00206 Br- 0.000844 _ Bt** 0.000416 Sr + 0.000091 F- 0.000068 *ct = Carbon total **Bt =Boron total

[0104] Unaltered sea water is known to possess bactericidal activity against a variety of terrestrial organisms.

[0105] The sea water flora is mostly composed of Gram-negative bacteria suggesting that it disfavors growth of Gram-positive organisms. However, the Gram-positive bacteria are typically pathogens responsible for one-third of all bacterial infections in humans and are capable of causing serious and sometime fatal infections in newborn infants. Many oral flora pathogens belong to the Gram-positive group of microorganisms such as Staphylococcus and Streptococcus genera, Actinomyces viscosus, A. naestundi, and others.

[0106] Within recent years emphasis has been placed upon the mechanism of the observed bactericidal activity of unaltered sea water. Without being bound to the theory, the mechanism appears to be selected from the group consisting of:
a) physico-chemical, and b) biological.
Sodium chloride-free sea water

[0107] According to the present invention, a sodium chloride-free sea water is a sea water where the concentration of sodium chloride is lesser than 5 ppm, preferably lesser than 3 ppm, and more preferably lesser than 2 ppm.

[0108] Preferably, the sodium chloride-free sea water may be obtained from a synthetic sea water according to ASTM D1141-98, 2013, or an ultra pure sodium chloride-free sea water obtained by inverse osmosis procedure or by any mechanical any processes and/or devices well known to persons skilled in the art for the mechanical withdrawal of sodium chloride from sea water.
Ionic silver solution

[0109] Prior to 1938, colloidal silver was used by physicians as a mainstream antibiotic treatment and was considered quite "high-tech." The March 1978 issue of Science Digest, in an article, "Our Mightiest Germ Fighter by Jim Powell, pp.1-3, reported:
"Thanks to eye-opening research, silver is emerging as a wonder of modern medicine. It is well known that an antibiotic kills perhaps a half-dozen different disease organisms, but silver kills some 650.

[0110] . Current FDA approved silver-based products include:
- Silver topical ointments for burns, - Slow replaces silver wound dressing, - Colloidal silver water purification, - Silver fabric surgical gowns and drape, and - Silver sutures.

[0111] Colloidal silver is also currently used by NASA and the World Health Organization as drinking water disinfectant (http:/rationalwiki.org/wiki/colloidal-silver).

[0112] The production of silver-based products has evolved over last decades resulting in modern technologies that allow the manufacturing of ionic silver, which is recognized as more efficient in microbial destruction, as compared to colloidal silver.

[0113] According to another embodiment of the invention, the silver ions solution is a suspension of microscopic particles of silver usually in water that has gained, in recent years, the reputation of powerful broad-spectrum contact antibiotic, and preventive against various infections. Many brands of silver-based products are available on the market. The highest grade is produced by the electro-colloidal / non-chemical method where the silver ions have been dispersed in water within and bound by an electric current. Advantageously, the super-fine silver ions may be suspended for a very long period of time in deionized water at concentration of 5 ppm to 20 ppm, preferably 5 ppm to 15 ppm, 10 ppm to 15 ppm or 10 ppm to 20 ppm.

[0114] Silver ions are pure metallic ions with a positive electric charge.
Silver ions and most silver compounds have an oligodynamic effect and are toxic for bacteria, algae and fungi in vitro. It is considered that silver ions interfere with the bacteria in at least three ways:
- The most frequent description of the mechanism of microbial destruction is the damage of microbial membrane by silver ions (Ag+) which are considered to irreversibly damage cell membrane, as well as key enzyme respiratory systems;

Binding to the amino acids and nucleic acids of cells, and blocking the metabolism of the bacteria;
There is a general consideration that the presence of silver ions near a bacterium, fungus or any other single-celled pathogen, disables its oxygen metabolism enzyme, its chemical lung, so to say. Rapidly, the pathogen suffocates and dies, and is cleared out of the body by the immune, lymphatic and elimination systems.

[0115] Silver, used as a topical antiseptic, is incorporated by bacteria and it kills them.
Thus, dead bacteria may be the source of silver ions which may continue to perpetuate the killing of other microbes.

[0116] Unlike pharmaceutical antibiotics, which destroy beneficial enzymes, colloidal silver ions leave these tissue-cell enzymes intact, as they are radically different from the enzymes of primitive single-celled life. Thus, silver ions are considered absolutely safe for humans, reptiles, plants and all multi-celled living organisms.

[0117] It is known that "super-germs" are resistant to most modern antibiotics.
Contrarily, it is believed that single-celled germs cannot mutate into silver-resistant forms, as happens with conventional antibiotics. Therefore, it is considered that no tolerance to silver ions would develop through mutation. Inside the body, silver ions apparently do not form toxic compounds or react with anything other than germs.

[0118] One possible precursor of silver ion is silver diamine fluoride (SDF). The SDF
is postulated to prevent or arrest carries by three mechanisms:
The first of these is through the action of silver ions, damaging microbial cell membrane, The second mechanism is based on the reaction of silver ions with bacterial amino acids and nucleic acids, which prevent bacterial metabolism and kills them, The third mechanism is based on silver ion with enamel structure precipitations resulting in formation of a protective layer of insoluble acid resistant silver apatite on the surface of dentine.

[0119] Recent studies show that SDF is more effective than fluoride varnish in prevention and arrest of dental caries (Rosenblatt et al., "Silver Diamine Fluoride: A
Caries 'Silver-Fluoride Bullet-, J. Dent. Res., 88(2), pp.116-125).
Pharmaceutically acceptable carrier or excipient

[0120] According to another embodiment of the invention, the pharmaceutically acceptable carrier or excipient may be a liquid, semi-solid or solid. A
liquid, as used herein can be a fluid or as in other embodiments, a high viscosity liquid such that flow is imperceptible under ambient conditions. A liquid can be a thixotropic liquid.
A semi-solid can be a gel, a colloid, or a gum. In other embodiments, the carrier or excipient may be substantially non-aqueous.

[0121] As a non-limiting example, in the case the oral care composition is a mouthwash, the pharmaceutically acceptable carrier or excipient may be water.

[0122] According to another embodiment of the invention, the specific composition of the pharmaceutically acceptable carrier or excipient preferably depends on the intended use of the composition. Non-limiting examples of pharmaceutically acceptable carrier or excipient may include ultra pure distilled or deionized water.

[0123] According to another embodiment of the invention, the oral care composition may further comprise additives. Non-limiting examples of such additives may comprise at least one of negative fluor ions, preservative agents, flavoring agents, sweeteners, anticalculus agents, pH adjusters, thickening agents, surfactants, colorants, chelating agents and eventually any other additives well known in the art of oral care composition.

[0124] According to another embodiment of the invention, the pharmaceutically acceptable carrier or excipient in the present invention may also comprise thickeners, gelling agents or combination thereof. Thickeners or gelling agents useful herein may include inorganic, natural or synthetic thickeners or gelling agents. Examples of thickeners and gelling agents include inorganic thickening silicas such as: an amorphous silica, for example Zeodent 165; Irish moss, iota-carrageenan, gum tragacanth or polyvinyl pyrrolidone. In certain embodiments, the pharmaceutically acceptable carrier or 'excipient may comprise a polishing agent, such as silica, a calcined alumina, sodium bicarbonate, calcium carbonate, dicalcium phosphate or calcium pyrophosphate.
Negative fluor ion (Fluoride)

[0125]
Fluoride (F¨) is negative ion of the element fluorine. Fluoride interacts with hydroxyapatite in order to form a stronger compound that is less susceptible to acid attack on teeth. Precursors of fluoride ions, or fluoride-providing components are known as anti caries agents.

[0126] According to another embodiment of the invention, the oral care composition may further include one or more fluoride precursors. In addition to sea water, a wide variety of ion-yielding material can be employed as soluble fluoride precursors in the present oral care compositions. Preferably, representative ion fluoride precursors include, but are not limited to, stannous fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicae, amine fluoride, ammonium fluoride, and combination thereof.

[0127] Where the oral care composition contains calcium salts, the fluoride salts are preferably salts wherein the fluoride is covalently bound to another atom, e.g., as in sodium monofluorophosphate, rather than merely ionically bound, e.g., sodium fluoride.
The preservative agents

[0128] According to another embodiment of the invention, the preservative agents are usually comprised by substances added to oral hygiene and personal hygiene products, cosmetics and perfumes, having as primary purpose to preserve them from damage and/or deterioration caused by microorganisms during manufacture and storage, as well as to protect consumers from inadvertent contamination during use of the product.
Flavoring agents

[0129] According to another embodiment, the flavoring agents are those known in the art, such as natural and artificial flavoring agents. They provide the oral care composition with a pleasant flavor and consequently to the breath of the mouthwash user.
Good flavoring agents not only enhances product acceptability, but also attracts consumers to buy it again. Also, flavoring agents provide a sensation of taste on the tongue and also a key signal which, when perceived by the brain, becomes closely linked to product characteristics and performance to influence the perceptions of the consumer.

[0130] According to another embodiment of the invention, the flavoring agents may be chosen from synthetic flavors oils or flavoring aromatics, and/or oils, oleo resins and extracts derived from plants, leaves, flowers, fruits and so forth, and combination thereof.
Preferably, commonly used flavoring agents include, but are not limited to, mints such as peppermint, artificial vanilla, cinnamon derivatives and various fruit flavors, whether employed individually or in admixture. More preferably, flavoring agent in the oral care composition according to the present invention is, but not limited to, mint at a concentration of 0.01 % to 0.05 "Yo by weight of the total weight.
Sweeteners

[0131] According to another embodiment of the invention, sweeteners may include water-soluble sweetening agents i.e. monosaccharides, disaccharides and polysaccharides, such as xylose, ribose, glucose (dextrose), mannose, galatose, fructose (levulose), sucrose or maltose.
Anticalculus agents

[0132] According to another embodiment of the invention, anticalculus agent (tartar control) agent) may include, without limitation, phosphates and polyphosphates. As non-limiting examples, phosphate may encompass orally acceptable mono and polyphosphates, for example P16 phosphates, monomeric phosphates such as monobasic, dibasic or tribasic phosphate, dimeric phosphates such as pyrophosphates, and multimeric phosphates, e.g. sodium hexametaphosphate.

[0133] In particular other non-limiting examples, phosphate may be selected from the group consisting of alkali dibasic phosphate and alkali pyrophosphate salts selected from the group consisting of dibasic sodium phosphate, dibasic potassium phosphate, dicalcium phosphate dehydrate, calcium pyrophosphate, tetrasodium pyrophosphate, sodium tripolyphosphate and mixture of any of the two or more of these.

[0134] In other embodiments, the anticalculus agents may also include polyaminopropanesulfonic acid, hexamethaphosphate salts, zinc citrate trihydrate, polypeptides, polyolefin sulfonatem polyolefin phosphates, diphosuphionates.

[0135] According to another embodiment of the invention, the anticalculus agent may also comprise phosphate salts. In particular embodiments, these salts may be alkali phosphate salts, i.e., salts of alkali metal hydroxides or alkali earth hydroxides, for example, sodium, potassium or calcium salts which are abundant in sea water.
pH/pH adjuster/buffer

[0136] According to another embodiment of the invention, the oral care composition may have a pH generally in the range of from 7 to 8. Preferably, the pH is about 7.5 and may be characterized as being isotonic.

[0137] According to another embodiment of the invention, the pH can be controlled with a pH adjuster. Non-limiting examples of possible pH adjuster may be an acid or a base. Preferably, a pH adjuster may be an acid such as citric acid or benzoic acid, or a base such as sodium hydroxide or a buffer such as sodium citrate, benzoate, carbonate or bicarbonate, disodium hydrogen phosphate, sodium dihydrogen phosphate, etc.
Thickening agent

[0138] According to another embodiment of the invention, the oral care composition may comprise at least one thickening agent. According to another embodiment of the invention, thickening agents may be any thickening agent well known in the art of oral care compositions. As a non-limiting example, when the oral care composition is a dentifrice, the at least one thickening agent provides required rheological properties, so that the dentifrice can be stored in dispensing container over a period of time and thereafter reliably dispensed there from by the user. It should have the adequate viscosity not only to be dispensed but also to exhibit an acceptable consistency within the mouth during tooth brushing.

[0139] According to another embodiment of the invention, when the oral care composition is selected from the group consisting of toothpaste, creams and gels typically contain a natural or synthetic thickener or gelling agent in proportion of 0.1 wt.-% to 10 wt.-% with respect to the total weight of the oral care composition.

[0140] According to another embodiment of the invention, the thickening agents may include modified cellulose, such as carboxymethyl cellulose (CMC), and other polysaccharide or gum components.

[0141] According to another embodiment of the invention, a polysaccharide thickening agent may consist consists of at least one xanthan gum which is present in an amount of from 0.1 to 1.5 wt.-% based on the total weight of the composition.
Optionally, minor amounts of additional thickeners may also be present, for example carrageenan gum, tragacanth, starch, polyvinylpirollidone, hydroxyethypropyl cellulose, hydroxybutyl, ethyl cellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, sodium CMC
and colloidal silica.
Surfactants

[0142] According to another embodiment of the invention, the oral care composition may contain any type of surfactant well known in the art of oral care composition, preferably anionic surfactants, such as for example:
- Higher alkyl sulfates, such as sodium lauryl sulfate, _ Higher alkyl ether sulfates, e.g., of formula CH3(CH2)mCH2 (OCH2CH2)30S03X, wherein m is 6-16, e.g., 10, n is 1-6, e.g., 2,3 or 4, and X is Na or K, for example sodium laureth-2 sulfate (CH3(CH2)10CH2(OCH2CH2)20S03Na), - Higher alkyl aryl sulfonate such as sodium benzene sulfonate (sodium lauryl benzene sulfonate), - Higher alkyl sulfoacetates, such as sodium laudryl sulfoacetate (dodecyl sodium sulfoacetate), higher fatty acids esters of 1,2-dihydroxy propane sulfonate, sulfocolaurate (N-2-ethyl laurate potassium sulfoacetamide) and sodium lauryl sarcosinate, Water-soluble salt of higher fatty acid monosulfates, such as the sodium salt of the monosulfated monoglyceride of hydrogenated coconut oil fatty acids, such as sodium N-methyl N-cocoyl taurate, sodium cocomonoglyceride sulfate.
Colorant

[0143] According to another embodiment of the invention, the oral care composition may comprise at least one colorant.

[0144] The at least one colorant may be any colorant known in the art of food and oral hygiene products. The group of ingredients with colorant action includes, but is not limited to all colorant, for food or oral hygiene products, available on the market.
Preferably different ingredients with colorant action may be used to provide product with a gamma of color options. More preferably, the group of ingredients with colorant action is present in an amount from about 0.0001 wt.- /0 to about 1wt.- /0 of the total weight of the oral care composition, much more preferably about 0.0001 wt.-%.

[0145] According to another embodiment of the invention, the at least one colorant may be Fast Green at concentration of 0.001 % to 0.005 `)/0 by weight of the total weight of the oral care composition.
Chelating [0046] According to another embodiment of the invention, the oral care composition may also include one or more chelating agents able to complex calcium found in the cell walls of the bacteria, binding of this calcium weakens the bacterial cell wall and facilitates bacterial lysis.
Water [0147] According to another embodiment of the invention, water may be preferably deionized and free of organic impurities. More preferably, water commonly makes up the balance of the oral care composition and includes, e.g., 40 wt.-% to 75 wt.-%
by weight of the total weight of the oral care composition. Much more preferably, amount of water may include the free water which is added plus that amount which is introduced with other materials such sea water, ionic silver solution, water, or any components of the oral care composition according to the invention.

Other optional ingredients [0148] According to another embodiment of the invention, oral care composition may contain a variety of known ingredients including, but not limited to, whitening agents, preservative silicones, chlorophyll compounds and/or ammoniated materials, such as urea, diammonium phosphate adhesives, sudsing agents, flooring agents, additional antiplaque agents and abrasive agents. Those ingredients, when present, are incorporated in the proportion which do not substantially adversely affect the properties and characteristics desired. Also, other optional components are further described in U.S.
Pat. No. 5,004,597, to Majeti; U.S. Pat. No. 3,959,458, to Agricola et at. and U.S. Pat.
No. 3,937,807, to Haefele.
[0149] The embodiments described herein will be further understood by reference to the following non-limiting examples:
Examples of preferred compositions [0150] As mentioned above, the oral care composition of the present invention may be applied to a variety of oral care products. Here are some examples of preferred formulations showing concentration of ingredients:
1. Mouthwash Ingredients Concentration wt.-%
Sodium-chloride free sea water 30.0 Silver ions solution (15ppm Ag+ in 69.98 deionized water) Mint (CAS N 2216-51-5) 0.019 Colorant (Fast Green C.I. 42053) 0.001 2. Oral care composition for disinfection of toothbrushes and dentures Ingredients Concentration wt.-%
Sodium-chloride free sea water 28.0 Silver ions solution (15ppm Ag+ in 71.98 deionized water) Mint (CAS N 2216-51-5) 0.019 Colorant (Fast Green C.I. 42053) 0.001 [0151] Table 1. EVALUATION OF EFFICACY OF THE MOUTHWASH ON PLAQUE
- INVOLVED BACTERIA
[0152] A. Experimental treatment with the content of mouthwash Microbs Initial suspension Contact time, in minutes: (% of reduction) *TCM/ml 0.5 1 2 S. mills 1.3x 105 52.1 92.5 99.9 S. oralis 1.3x 105 60.8 91.0 99.9 S. mitor 1.3x 105 63.5 94.3 99.9 S. sanguis 1.3x 105 59.9 93.7 99.9 *TMC= total microbial count [0153] B. Control treatment with PBS*
Microbs Initial suspension Contact time, in minutes: (% of reduction) **TCM/ml 0.5 1 2 S. mitts 1.3 x 105 0.8 0.9 0.9 S. oralis 1.3x 105 0.6 0.6 0.7 S. mitor 1.3x 105 0.9 1.1 1.0 S. sanguis 1.3x 105 0.4 0.5 0.6 *PBS = Phosphate buffered solution **TMC= Total microbial count [0154] Table 2. EVALUATION OF EFFICACY OF THE MOUTHWASH ON
BACTERIA INVOLVED IN THE ETIOLOGY OF HALITOSIS
[0155] A. Experimental treatment with the content of mouthwash Microbs Initial suspension Contact time, in minutes: (% of *TCM/ml reduction) 0.5 1 2 Porphyromonas gin givalis 1.3 x 105 59.6 91.1 99.9 Prevotella intermedia 1.3x 105 66.1 94.6 99.9 Fusobacterium nucleatum 1.3 x 105 54.7 92.8 99.9 Treponema dent/cola 1.3 x 105 57.0 93.9 99.9 *TMC= total microbial count [0156] B. Control treatment with PBS*
Microbs Initial suspension Contact time, in minutes: (% of **TCM/ml reduction) 0.5 1 2 P. gingivalis 1.3 x 105 0.2 0.3 0.5 P. intermedia 1.3 x 105 0.2 0.3 0.4 F. nucleatum 1.3 x 105 0.1 0.2 0.5 T. dent/cola 1.3 x 105 0.3 0.3 0.5 *PBS = Phosphate buffered solution **TMC= Total microbial count [0157] Table 3. EVALUATION OF EFFICACY OF THE MOUTHWASH ON
BACTERIA INVOLVED IN THE ETIOLOGY OF GINGIVITIS
[0158] A. Experimental treatment with the content of mouthwash Microbs Initial suspension Contact time, in minutes: (% of reduction) *TCM/ml 0.5 1 2 Actinomyces viscosus 1.3 x 105 49.5 89.0 99.9 A. gingival 1.3x 105 51.6 91.6 99.9 P. rectus 1.3x 105 52.8 90.3 99.9 *TMC= total microbial count [0159] B. Control treatment with PBS**
Microbs Initial suspension Contact time, in minutes: (% of *TC Mimi reduction) 0.5 1 2 Actinomyces viscosus 1.3 x 105 0.1 0.2 0.3 A. gingival 1.3x 105 0.1 0.3 0.3 P. rectus 1.3x 105 0.2 0.2 0.3 *TMC= total microbial count **PBS = Phosphate buffered solution [0160] Table 4. EVALUATION OF EFFICACY OF THE MOUTHWASH ON
BACTERIA INVOLVED IN THE ETIOLOGY OF PERIODONTITIS
[0161] A. Experimental treatment with the content of mouthwash Microbs Initial suspension Contact time, in minutes:
*TC Mimi (% of reduction) 0.5 1 2 Aggregatibacter 1.3 x 105 56.3 92.9 99.9 actinomicetemcomitans Porfiromonas gin givalis 1.3 x 105 58.7 94.1 99.9 Compilobacter rectus 1.3 x 105 58.5 93.8 99.9 *TMC= total microbial count [0162] B. Control treatment with PBS*
Microbs Initial suspension Contact time, in minutes:
**TCM/ml (% of reduction) 0.5 1 2 Aggregatibacter 1.3 x 105 0.1 0.2 0.3 actinomicetemcomitans Porfiromonas gingivalis 1.3 x 105 0.1 0.2 0.2 Compilobacter rectus 1.3x 105 0.2 0.2 0.2 * PBS = Phosphate buffered solution **TMC= Total microbial count [0163] Table 5. EVALUATION OF EFFICACY OF THE MOUTHWASH ON
BACTERIA INVOLVED IN THE ETIOLOGY OF DENTAL CARIES
[0164] A. Experimental treatment with the content of mouthwash Microbs Initial suspension Contact time, in minutes: (% of reduction) *TCM/ml 0.5 1 2 Streptococcus mutans 1.3 x 105 61.6 94.0 99.9 Lactobacilus 1.3x 105 65.3 96.2 99.9 *TMC= total microbial count [0165] B. Control treatment with PBS*
Microbs Initial suspension Contact time, in minutes: (% of reduction) **TCM/m I 0.5 1 2 S. mutans 1.3x 105 0.1 0.1 0.2 Lactobacilus 1.3 x 105 0.1 0.1 0.2 * PBS = Phosphate buffered solution **TMC= Total microbial count [0166] Table 6. EVALUATION OF EFFICACY OF THE MOUTHWASH ON
BACTERIAL SPECIES AND C. ALBICANS THAT ARE INVOLVED IN MIXED
ORAL INFECTIONS
[0167] A. Experimental treatment with the content of mouthwash Microbs Initial suspension Contact time, in minutes: (% of reduction) *TC Mimi 0.5 1 2 Bacteroides gingivalis 1.3 x 105 59.6 91.8 99.9 Fusobacterium 1.3 x 105 54.1 93.4 99.9 Peptosteptococcus 1.3 x 105 60.2 95.0 99.9 C. albicans 1.3 x 105 58.3 90.3 99.9 *TMC= total microbial count [0168] B. Control treatment with PBS*
Microbs Initial suspension Contact time, in minutes: (% of reduction) **TCM/ml 0.5 1 2 B. gin givalis 1.3 x 105 0.2 0.2 0.3 Fusobacterium 1.3 x 105 0.1 0.2 0.4 Peptosteptococcus 1.3 x 105 0.1 0.2 0.3 C. albicans 1.3x 105 0.2 0.3 0.3 *PBS = Phosphate buffered solution **TMC= Total microbial count [0169] Table 7. EVALUATION OF EFFICACY OF THE SYNERGETIC EFFECT OF
THE ACTIVE INGREDIENTS OF MOUTHWASH ON ORAL DISEASES
INVOLVED IN BACTERIA
[0170] A. Experimental treatment with the Sodium chloride-free sea water Microbs Initial suspension Contact time, in minutes: (% of reduction) *TC M/m I 0.5 1 2 A. viscosus 1.3 x 105 40.8 80.5 90.8 C. albicans 1.3x 105 51.0 82.1 93.1 B. gingivalis 1.3x 105 50.2 84.3 94.9 F. nucleatum 1.3 x 105 48.6 83.5 96.1 S. mutans 1.3x 105 47.3 80.9 91.3 *TMC= total microbial count [0171] B. Experimental treatment with ionic silver solution Microbs Initial suspension Contact time, in minutes: (% of reduction) *TCM/ml 0.5 1 2 A. viscosus 1.3 x 105 42.6 83.9 93.6 C. albicans 1.3x 105 53.0 84.7 95.0 B. gingivalis 1.3x 105 52.3 86.8 98.2 F. nucleatum 1.3 x 105 50.7 85.2 99.9 S. mutans 1.3x 105 49.5 81.9 94.7 *TMC= total microbial count [0172] C. Experimental treatment with the whole content of mouthwash Microbs Initial suspension Contact time, in minutes: (% of reduction) *TC Mimi , 0.5 1 2 A. viscosus 1.3 x 105 49.9 89.8 99.9 C. albicans 1.3x 105 58.3 ' 40.3 99.9 B. gingivalis 1.3x 105 . 59.6 . 91.8 99.9 F. nucleatum 1.3 x 105 - 54.1 93.4 99.9 S. mutans 1.3x 105 - 52.1 - 92.5 99.9 *TMC= total microbial count [0173] D. Control treatment with PBS*
Microbs Initial suspension Contact time, in minutes: (% of reduction) **TC Mimi 0.5 1 2 A. viscosus 1.3x 105 0.2 0.2 0.2 C. albicans 1.3x 105 0.1 0.2 0.3 B. gingivalis 1.3x 105 0.1 0.2 0.3 F. nucleatum 1.3 x 105 0.2 0.3 0.3 S. mutans 1.3x 105 0.2 0.2 0.3 *PBS = Phosphate buffered solution **TMC= Total microbial count [0174] Table 8. COMPARATIVE EVALUATION OF TURNIDITY OF ORALNETTm MOUTHWASH AND THE MOUTHWASH BASED ON PRESENT
INVENTION
Mouthwash Turbidity in NTU* during time after manufacturing lh 1 day 2 days 5 days OralNetTM 12 16 18 18 Present invention mouthwash 4 4 4 4 *NTU = Nephelometric turbidity unit Microbicidal efficacy of the present invention [0175] A new generation of mouthwash, called "OralNet", is commercially available on the market in the province of Quebec, Canada. According to the technical specifications, OralNet is based on ultrapure Arctic Ocean water supplemented with colloidal silver. The study reports the microbicidal efficacy against salivary flora of healthy individuals, toxicity, endogenous pH and physicochemical content of OralNet as evaluated in comparison with 7 over-the-counter (OTC) mouthwashes (Pekovic et al., "Comparative Study Of Antimicrobial Toxicity And Physicochemical Properties Of The New Generation Mouthwash 'OralNetTM' With Common Mouthwashes", EC Microbiology, Vol. 2, Issue 3, November 2015, pp. 317-327). The obtained results show that OralNet displayed the highest microbicidal activities in vitro exceeding 99.9 % after 30 seconds of contact with test organisms and the lowest toxicity in vitro (3.69 %), as compared to the standard mouthwashes studied. In addition, OralNet has well balance endogenous pH
(7.5), as well as a simple chemical structure composed of two natural active ingredients.
[0176] However, it was noticed that sodium-chloride from sea water reacted with colloidal silver solution, resulting in a substantial change of the color and increased turbidity level.
[0177] According to a preferred embodiment of the invention, the Applicant has surprisingly discovered that by the use of sodium chloride-free water, silver ion solution and deionized water for preparing the oral care composition according to the invention, the change of color and increase of turbidity has been avoided. Also, the microbicidal activity of each ingredient, as well as the synergetic microbial effect of both active ingredients, has been significantly increased, as illustrated in the above Tables 1 ¨ 8.
Antimicrobial Preservation Effectiveness Test [0178] The Antimicrobial Preservation Effectiveness test is used to determine the antimicrobial preservation effectiveness of the water-based product compositions by means of a double challenge test. Products compositions are developed to withstand microbial challenges introduced by normal consumer use. The test is run on aged samples (13 weeks, 40 C). The test used two pools of microorganisms:
bacteria/yeast and mold. The product is challenged at 1% level at day 0 and at day 7.
Reduction of the inoculum is monitored over a 28-day period. The following are the accepted criteria for the mouthwash formulas.
-Bacteria and yeast must show a 99.9 % reduction (3 logs) of the inoculum as determined by plate count at day 7 following each inoculation. No increase after 7 days of the second inoculation and for the remainder of the test within normal variation data;
-Mold must show a 90 % reduction (1 log) of the inoculum as determined by the plate count on day 14 following the second inoculation (day 21). No increase from day 14 to day 21 of the second inoculation of the test within normal variation of the data;
[0179] The content of the present invention is in compliance with the requirement of antimicrobial preservation effectiveness test.
[0180]
Equivalent changes, modifications and variations of specific embodiments, materials, compositions and methods may be made within the scope of the present invention, with substantially similar results.
[0181] Many modifications and variations are possible and would be apparent to a person skilled in the light of art of present invention. It is therefore to be understood that the invention can be practiced otherwise than as specifically described herein and still will be within the spirit and scope of the appended claims.

Claims (26)

Claims

1. An oral care composition comprising:
(i) sodium chloride-free sea water; and (ii) a silver ions solution.

2. The oral care composition according to claim 1, wherein with respect to the total weight of the oral care composition, said composition comprises:
up to 30.00 wt.-% of the sodium chloride-free sea water; and up to 70.00 wt.-% of the silver ions solution, said silver ions solution containing in an aqueous medium from 5 ppm to 20 ppm of silver ions.

3. The oral care composition according to claim 2, wherein the silver ions solution contains from 10 ppm to 15 ppm of silver ions.

4. The oral care composition according to claim 1, wherein with respect to the total weight of the oral care composition, said composition comprises:
up to 30.22 wt.-% of the sodium chloride-free sea water;
up to 69.78 wt.-% of the silver ions solution, said silver ions solution containing in an aqueous medium from 10 ppm to 15 ppm of silver ions.

5. The oral care composition according to any one of claims 1 to 4, wherein the sodium chloride-free sea water is obtained from a synthetic sea water according to ASTM D1141-98, 2013.

6. The oral care composition according to any one of claims 1 to 5, wherein the sodium chloride-free sea water is an ultra pure sodium chloride-free the sodium chloride-free sea water is an ultra pure sodium chloride-free sea water.

7. The oral care composition according to claim 6, wherein said ultra pure sodium chloride-free sea water is obtained by mechanical withdrawal of the sodium chloride from sea water.

8. The oral care composition according to claim 6 or 7, wherein the ultra pure sodium chloride-free sea water contains less 5 ppm of sodium chloride.

9. The oral care composition according to any one of claims 1 to 8, wherein the silver ions solution is an aqueous solution of Ag+ in a pharmaceutically acceptable aqueous medium that is free of chloride ions.

10. The oral care composition according to claim 9, wherein the water of the pharmaceutically acceptable aqueous medium of the silver ions solution is selected from the group consisting of distilled water, deionized water, demineralized water and mixtures thereof.

11. The oral care composition according to any one of claims 1 to 10, further comprising a pharmaceutically acceptable carrier or excipient, and wherein the pharmaceutically acceptable carrier or excipient is free of chloride ions.

12. The oral care composition according to claim 11, wherein the pharmaceutically acceptable carrier or excipient is selected from the group consisting of distilled water, deionized water, demineralized water and mixtures thereof.

13. The oral care composition according to claim 11 or 12, wherein the pharmaceutically acceptable carrier or excipient represents up to 75 wt.-% of the total weight of the oral care composition.

14. The oral care composition according to any one of claims 1 to 10, wherein the wt.-% of the sodium chloride-free sea water and the silver ions solution represents about 100 wt.-% of the total weight of the oral care composition.

15. The oral care composition according to any one of claims 1 to 13, further comprising at least one additional ingredient selected from the group consisting of surfactants, solvent, vitamins, minerals, polymers, enzymes, humectants, thickeners, additional antimicrobial agents, additional preservatives, flavorings, coloring and mixtures thereof.

16. The oral care composition according to any one of claims 1 to 13, further comprising at least one additional ingredient selected from the group consisting of flavorings agents, colorings agents and mixtures thereof.

17. The oral care composition according to claim 16, wherein the flavoring agent is selected from the group consisting of menthol, zinc citrate, zinc chloride, tutti-frutti, methyl salicylate, Eucalyptus oil, spearmint oil and peppermint oil.

18. The oral care composition according to claim 17, wherein the flavoring agent is menthol, and wherein said menthol represents from 0.019 wt-% to 0.05 wt.-% of the total weight of the oral care composition.

19. The oral care composition according to any one of claims 15 to 18, wherein the coloring agent is Fast Green.

20. The oral care composition according to claim 19, wherein the Fat Green represents from 0.001 wt.-% to 0.005 wt.-% of the total weight of the oral care composition.

21. The oral care composition according to any one of claims 1 to 14 and 16 to 21, further comprising at least one microbicidal ingredients selected from the group consisting of delmopinol, bicarbonate, triclosan, Sanguinaria Canadensis, propolis, Aloe vera, sage (salvia officinallis), lemon (Citrus limon), pine (Pinus sylvetris), echinacea (Echinacea purpurea and agustifolia), rathany (Krameria trianda) and cheeseweed mallow (MaIva paiviflora L.).

22. The oral care according to any one of claims 1 to 13 and 15 to 21, further comprising a source of fluoride ion and wherein the silver ion solution is obtained from silver diamine fluoride (SDF).

23. An oral care composition which is defining a mouthwash composition and comprising with respect to the total volume of the oral care composition:

24. Use of an oral care composition as defined in any one of claims 1 to 23, for cleaning of teeth, treating or reducing dental enamel erosion, reducing bacterially-generated biofilm and plaque, gingivitis, inhibiting tooth decay and formation of cavities, and/or reducing dentinal hypersensitivity.

25. Method for cleaning of the teeth, treating or reducing dental enamel erosion, reducing bacterially-generated biofilm and plaque, gingivitis, inhibiting tooth decay and formation of cavities, and/or reducing dentinal hypersensitivity, said method comprising a step of contacting an oral care composition as defined in any one of claims 1 to 23 with teeth.

26. Use of an oral care composition as defined in any one of claims 1 to 23, as a vehicle for the addition of bactericides antibiotics and for the treatment of inflamed tissue.