• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    ''ORAL COMPOSITIONS COMPRISING A ZINC COMPOUND AND AN ANTIMICROBIAL AGENT''. The present invention relates to oral compositions and methods of using them. Oral compositions comprise a first component comprising at least one Eh-enhancing compound and a pharmaceutically acceptable carrier, and a second component comprising at least one zinc compound, an antimicrobial agent and a pharmaceutically acceptable carrier.
    公开号:BR112013003081B1
    申请号:R112013003081-0
    申请日:2011-08-05
    公开日:2022-02-01
    发明作者:Marvin Cohen；Susanne Cohen；Bob Flynn
    申请人:The Research Foundation For The State University Of New York；
    IPC主号:
    专利说明:

    CROSS-REFERENCE TO RELATED PATENT APPLICATIONS
    [0001] This patent application claims the benefit of Provisional Application US 61/371,695, filed August 7, 2010 and Provisional Application US 61/371,696, filed August 7, 2010. The disclosure of each of the identified patent applications in this paragraph is hereby incorporated by reference in its entirety. FIELD
    [0002] The present disclosure relates generally to oral compositions, oral care systems and methods of using the same. More particularly, the present disclosure pertains to oral compositions comprising at least one Eh-enhancing compound and at least one zinc compound, and methods of using the same. In a particular embodiment, cetylpyridinium chloride (CPC), C21H38NCl, is also included in the oral composition. BACKGROUND
    [0003] This section provides background information related to the present disclosure that is not necessarily prior art.
    [0004] The hard and soft tissues of the mouth are covered with microbial populations that include bacteria having different metabolic capabilities where microbial populations can include Gram-positive bacteria and Gram-negative bacteria. In general, aerobic Gram-positive bacteria readily catabolize carbohydrates to produce acids that attack the hard tissues of the oral cavity, and which over time can result in the formation of dental carious lesions (cavities). In contrast, Gram-negative anaerobic bacteria metabolize various amino acids included in salivary peptides and proteins to form the end products that easily favor the formation of bad breath and gingivitis-periodontitis. This process of degradation of peptides, proteins and amino acids by bacteria in the mouth is referred to as oral bacterial putrefaction. The mixture of malodorous compounds produced by Gram-negative anaerobic bacteria during putrefactive degradation of proteins, peptides, and amino acids includes hydrogen sulfide, methyl mercaptan, and dimethyl sulfide (formed from the sulfur-containing amino acids cysteine, cystine, and methionine); indole and skatole (formed during tryptophan metabolism); cadaverine and putrescine (produced from lysine and ornithine); and butyrate and valerate (produced from the metabolism of other amino acids). The production of these malodorous compounds in the oral cavity results in a condition commonly referred to as bad breath.
    [0005] Hydrogen sulfide, methyl mercaptan, butyrate and propionate are putrefaction end products that also have cell and tissue altering non-inflammatory roles in the periodontitis process. Hydrogen sulfide and methyl mercaptan are compounds particularly effective in facilitating toxin and other penetrability of the oral epithelium through large molecular weight compounds produced by Gram-negative anaerobic bacteria, and leading to the inflammation and tissue degradation characteristics of gingivitis and periodontitis. Gingivitis is a condition where the gums become red, swollen and bleeding. If left untreated, gingivitis can develop into periodontitis, a condition characterized by destruction of the periodontium, including loss of epithelial attachment, periodontal membrane and ligament destruction, and loss of gingiva and alveolar bone. Severe periodontitis resulting in deep periodontal pockets can ultimately result in tooth loss.
    [0006] Previous studies have largely focused on the use of germicidal agents to treat gingivitis-periodontitis and bad breath. These studies did not recognize that gingivitis-periodontitis and bad breath arise from a common process, namely oral bacterial putrefaction; and also that this putrefaction can be inhibited by decreasing the ability of oral bacteria to simultaneously reduce the oxidation-reduction potential (Eh) of the oral cavity and at the same time elevating existing Eh to where oral environmental Eh is not conducive to oral putrefaction. and production of oral disease.
    [0007] U.S. Patent 6,929,790 to Kleinberg et al., which is a continuation patent application to the U.S. 6,423,300 which is a divisional patent application of the U.S. 6,409,992, reports an oral composition comprising a zinc compound and at least one Eh-enhancing compound.
    [0008] U.S. Patent 6,723,305 to DePierro et al. reports an oral composition comprising a compound of zinc and CPC. SUMMARY
    [0009] This section provides a general summary of the disclosure, and is not an inclusive disclosure of its full scope or all of its features.
    [0010] Generally, an oral composition is provided here. The oral composition is able to inhibit the formation of sulfur-containing compounds, reducing bad breath and gingivitis, reducing the formation of dental caries, inhibiting the formation of plaque and reducing the formation of plaque and tartar (calculus). Furthermore, an oral care system comprising an oral composition described herein is also provided.
    [0011] In one embodiment, an oral composition is provided comprising: a first component comprising at least one Eh-enhancing compound and a pharmaceutically acceptable carrier, and a second component comprising at least one zinc compound, cetylpyridinium chloride (CPC) and a pharmaceutically acceptable carrier.
    [0012] In a particular embodiment, the first and second components are stored separately.
    [0013] In some embodiments, the oral composition further comprises xylitol and/or other oral health ingredients.
    [0014] In yet another embodiment, a method is provided for reducing bad breath, treating or alleviating dental disease, reducing plaque, and reducing canker sores. The methods comprise releasing the oral composition into an oral cavity in a subject. The subject may be a human or non-human animal.
    [0015] Other areas of applicability will become evident from the description provided here. The description and specific examples in this summary are intended for illustrative purposes only and are not intended to limit the scope of the present disclosure. BRIEF DESCRIPTION OF THE DRAWINGS
    [0016] The figures described here are for illustrative purposes only of the selected embodiments and not all possible implementations, and are not intended to limit the scope of the present disclosure.
    [0017] Figure 1 is a graphical representation of volatile sulfur compounds (VSCs) in parts-per-billion (ppb) units as measured by a Halimeter, where subjects were tested with distilled water. The vertical axis is VSCs in ppb and the horizontal axis is time in minutes.
    [0018] Figure 2 is the same as Figure 1, except that the subjects were tested with Listerine®.
    [0019] Figure 3 is the same as Figure 1, except that the subjects were tested with SmartMouth®.
    [0020] Figure 4 is the same as Figure 1, except that subjects were tested with SmartMouth Advanced Clinical Formula (ACF) (SmartMouthACF™). DETAILED DESCRIPTION
    [0021] Exemplary embodiments will now be described more fully with reference to the accompanying drawings.
    [0022] In one embodiment, an oral composition is provided which is formed by contacting, such as mixing, a first component and a second component described herein. The term "oral composition" is intended to include various modalities of compositions that are useful for all aspects of oral hygiene including, but not limited to, preventing and/or treating oral disease, maintaining oral health, reducing or eliminating bad breath ( bad breath), whiten teeth, prevent gum decay and/or prevent tooth decay. More particularly, the oral composition facilitates preventing oral bacteria from reducing the oxidation-reduction potential (Eh) of an oral cavity and, at the same time, facilitates increasing the existing oxidation-reduction potential to a level where an oral environment is created that it is not conducive to oral putrefaction and production of oral disease. Further, the oral composition can be used to inhibit the formation of sulfur-containing anions, reduce gingivitis, reduce dental caries formation, reduce canker sores, inhibit plaque formation, and/or reduce plaque and tartar (calculus) formation.
    [0023] The first component comprises at least one Eh-enhancing compound. An Eh-enhancing compound, as defined herein, is a compound capable of raising the Eh of the oral cavity directly or indirectly. Non-limiting examples of Eh-enhancing compound include oxidation-reducing buffers; hydrogen peroxide; an oxyhalogen compound, such as sodium chlorite and sodium bromite; and commercially possible combinations thereof. Additional examples of the Eh-enhancing compound include fermentable sugars such as glucose, galactose, glutose, fructose, maltose, lactose and sucrose. Fermentable sugars, when metabolized by oral bacteria and in particular oral streptococci, in the presence of oxygen, can produce, inter alia, hydrogen peroxide.
    [0024] In one embodiment, the concentration of the Eh-enhancing compound in the first component can range from about 0.01% (100 ppm) to about 3.0% (30,000 ppm), particularly about 0.04% (400 ppm) to about 1.2% (12,000 ppm), and more particularly about 0.06% (600 ppm) to about 0.6% (6,000 ppm). In particular embodiments, the concentration of the Eh-enhancing compound is about 0.01% (100 ppm) or about 0.02% (200 ppm) or about 0.03% (300 ppm) or about 0.03% (300 ppm). 04% (400 ppm) or about 0.05% (500 ppm) or about 0.06% (600 ppm) or about 0.07% (700 ppm) or about 0.08% (800 ppm) or about 0.09% (900 ppm) or about 0.1% (1000 ppm) or about 0.2% (2000 ppm) or about 0.3% (3000 ppm) or about 0.4 % (4000 ppm) or about 0.5% (5000 ppm) or about 0.6% (6000 ppm) or about 0.7% (7000 ppm) or about 0.8% (8000 ppm) or about 0.9% (9000 ppm) or about 1.0% (10,000 ppm) by weight of the first component.
    [0025] Additionally, the concentration of the Eh-enhancing compound in the oral composition can range from about 0.005% (50 ppm) to about 1.5% (15,000 ppm), particularly about 0.02% (200 ppm) to about 0.6% (6,000 ppm), and more particularly about 0.03% (300 ppm) to about 0.3% (3,000 ppm) by weight of the oral composition.
    [0026] In some embodiments, a chlorine-containing compound may be added to the first component. In a particular embodiment, a chlorine-containing compound may be added to the first component when the Eh-enhancing compound is hydrogen peroxide or a fermentable sugar in an amount sufficient to inhibit the catalase(s) in the oral cavity from breaking down. in) hydrogen peroxide or fermentable sugar. The chlorine-containing compound may be able to inhibit catalase activity in the oral cavity. Suitable chlorine-containing compounds in the various oral compositions include alkali metal chloride salts and alkaline earth metal chloride salts, such as, for example, NaCl and CaCl 2 .
    [0027] In one embodiment, the concentration of the chlorine-containing compound in the first component ranges from about 0.5% (500 ppm) to about 2.5% (2500 ppm) by weight of the first component, particularly from about 0 .7% (700 ppm) to about 2.3% (2300 ppm), and even more particularly from about 1.0% (1000 ppm) to about 2.0% (2000 ppm) by weight of the first component. In particular embodiments, the concentration of the chlorine-containing compound is about 1.0% (1000 ppm) or about 1.2% (1200 ppm) or about 1.4% (1400 ppm) or about 1.6% (1600 ppm) or about 1.8% (1800 ppm) or about 2.0% (2000 ppm) by weight of the first component.
    [0028] Additionally, the concentration of the chlorine-containing compound in the oral composition can range from about 0.25% (250 ppm) to about 1.25% (1250 ppm) by weight of the oral composition, particularly from about 0. 35% (350 ppm) to about 1.15% (1150 ppm), and even more particularly from about 0.5% (500 ppm) to about 1.0% (1000 ppm) by weight of the oral composition .
    [0029] The second component comprises at least one zinc compound. The zinc compound can be any compound capable of providing freely available zinc ions. Without being bound by theory, it is believed that freely available zinc ions are able to inhibit a decrease in Eh in the oral cavity. Unbound zinc ions provide freely available zinc ions, and therefore have a greater reaction with Eh-lowering enzymes within the oral cavity than bound zinc ions. Specifically, these freely available zinc ions can inhibit the breakdown by oral bacteria of cysteine or cystine from saliva, mucosal tissues, and/or food. As a result, oral bacteria are prevented from decreasing the Eh existing within the oral cavity.
    [0030] Non-limiting examples of zinc compounds suitable for use include any soluble zinc salt capable of providing freely available zinc ions when dissolved in water. For example, zinc chloride, zinc acetate, zinc lactate, zinc salicylate, zinc sulfate, zinc nitrate, and any possible combination thereof can be used. In a particular embodiment, the zinc compound comprises zinc chloride. In another embodiment, the second component may comprise zinc chloride and an additional zinc compound. In other alternative embodiments, the zinc compound may comprise at least one of zinc acetate; zinc lactate; zinc salicylate; zinc sulfate; zinc nitrate; and/or any possible combination thereof.
    [0031] In one embodiment, the zinc ion concentration in the second component can range from about 0.02% (200 ppm) to about 1.0% (10000 ppm), more particularly about 0.04% ( 400 ppm) to about 0.7% (7000 ppm) by weight of the second component. In particular embodiments, the zinc ion concentration is about 0.04% (400 ppm) or about 0.05% (500 ppm) or about 0.06% (600 ppm) or about 0.07% (700 ppm) or about 0.08% (800 ppm) or about 0.09% (900 ppm) or about 0.1% (1000 ppm) or about 0.2% (2000 ppm) or about 0.3% (3000 ppm) or about 0.4% (4000 ppm) or about 0.5% (5000 ppm) or about 0.6% (6000 ppm) or about 0.7% ( 7000 ppm) by weight of the second component.
    [0032] Additionally, the concentration of zinc ion in the oral composition can range from about 0.01% (100 ppm) to about 0.5% (5000 ppm), particularly from about 0.02% (200 ppm ) to about 0.35% (3500 ppm) by weight of the oral composition.
    [0033] In another embodiment, the second component may also include CPC which has, among other things, antigingivitis and/or antiplaque effects. CPC is a cationic surfactant that has strong bactericidal and fungal resistivity effects. In particular, CPC is a quaternary ammonium salt which generally conforms to the formula C21H38NCl. CPC can act primarily as an antimicrobial agent by penetrating the cell membrane, which causes leakage of components into the cell, disruption of bacterial metabolism, inhibition of cell growth, and ultimately cell death.
    [0034] To be considered therapeutically effective as an anti-gingivitis/anti-plaque product, the active ingredient must demonstrate that it is statistically substantially equivalent to the standard formulation and statistically superior to the negative control as assessed by reasonable statistical analysis (see, Fed. Reg. Vol. 68, No. 103, which is hereby incorporated by reference in its entirety, see particularly pp. 3224041 and pp. 32247-48).
    [0035] In one embodiment, the concentration of CPC in the second component can range from about 0.02% (200 ppm) to about 0.6% (6000 ppm), more particularly from about 0.09% (900 ppm). ppm) to about 0.2% (2000 ppm) by weight of the second component. In particular embodiments, the concentration of CPC is about 0.09% (900 ppm) or about 0.1% (1000 ppm) or about 0.2% (2000 ppm) by weight of the second component.
    [0036] Additionally, the concentration of CPC in the oral composition can range from about 0.01% (100 ppm) to about 0.3% (3000 ppm), particularly from about 0.045% (450 ppm) to about of 0.1% (1000 ppm) by weight of the oral composition. For example, in some embodiments, the concentration of CPC is about 0.05% (500 ppm) or about 0.06% (600 ppm) or about 0.07% (700 ppm) or about 0.08 % (800 ppm) or about 0.09% (900 ppm) or about 0.1% (1000 ppm) by weight of the oral composition.
    [0037] In one embodiment, the second component comprises about 0.02% (200 ppm) by weight to about 1.0% (10,000 ppm) by weight of zinc ion and about 0.02% (200 ppm ) by weight to about 0.6% (6,000 ppm) by weight of CPC.
    [0038] In a particular embodiment, the second component comprises about 0.04% (400 ppm) by weight to about 0.7% (7000 ppm) by weight of zinc ion and about 0.09% (900 ppm) by weight to about 0.2% (2000 ppm) by weight of CPC.
    [0039] It is contemplated herein that any of the Eh-enhancing compounds listed above may be used in combination with any of the zinc compounds listed above. For example, any of the Eh-enhancing compounds listed above can be used in the first component, while any of the zinc compounds listed above can be used in the second component. There may be trace amounts of each in each component. For example, an oral composition is provided comprising:- a first component comprising at least one Eh-enhancing compound selected from the group consisting of an oxidation-reducing buffer; hydrogen peroxide; an oxyhalogen compound, such as sodium chlorite and sodium bromite; and combinations thereof; and wherein the first component optionally contains at least one chlorine-containing compound selected from the group consisting of an alkali metal chloride salt and an alkaline earth metal chloride salt, such as NaCl and CaCl 2 ; and - a second component comprising at least one zinc compound selected from the group consisting of zinc chloride; zinc acetate; zinc lactate; zinc salicylate; zinc sulfate; zinc nitrate; and combinations thereof; and optionally CPC.
    [0040] In one embodiment, the oral composition comprises a first component comprising hydrogen peroxide and optionally sodium chloride and optionally CPC; and a second component comprising zinc chloride and optionally CPC.
    [0041] In one embodiment, the oral composition comprises a first component comprising a fermentable sugar and optionally sodium chloride and optional CPC, and a second component comprising zinc chloride and optionally CPC.
    [0042] In one embodiment, the oral composition comprises a first component comprising sodium chlorite and optionally sodium chloride and optionally CPC; and a second component comprising zinc chloride and optionally CPC.
    [0043] In one embodiment, the oral composition comprises: about 0.01% by weight to about 3.0% by weight of an Eh-enhancing compound; about 0.02% by weight to about 1.0% by weight zinc ion; about 0.02% by weight to about 0.6% by weight of CPC; and at least one pharmaceutically acceptable carrier.
    [0044] In one embodiment, the oral composition comprises from about 0.5% by weight to about 2.5% by weight of the chlorine-containing compound, and wherein the second component comprises from about 0.02% by weight to about from 1.0% by weight of zinc ion and about 0.02% by weight to about 0.6% by weight of CPC.
    [0045] In a particular embodiment, the oral composition is prepared by mixing a first component comprising the Eh-enhancing compound and a pharmaceutically acceptable carrier and a second component comprising the zinc compound, CPC and a pharmaceutically acceptable carrier.
    [0046] In various embodiments, the oral composition may also include additional components such as, for example, at least one of essential oils, a desensitizing agent; a bleaching agent; an antimicrobial agent; an antibiotic and/or antifungal agent; an antiviral agent; an anti-cavity agent; an antiplaque agent; an anti-tartar agent; an antioxidant; an anti-inflammatory; a deodorant; a polishing agent; a detergent; a film forming agent; a mineralizer or remineralizer; an agent to reduce or alleviate dry mouth; a coloring agent; a humectant; a sweetener; and/or condiments.
    [0047] For example, in one embodiment an oral composition according to the invention may comprise: a first component comprising at least one Eh-enhancing compound; a second component comprising at least one zinc compound; a third component selected from the group consisting of essential oils; a bleaching agent; cetylpyridinium chloride; an antimicrobial agent; an antifungal agent; an antiviral agent; an antioxidant agent; an anti-cavity agent; an antiplaque agent; a desensitizing agent; and an agent for relieving or reducing dry mouth; and a pharmaceutically acceptable carrier.
    [0048] In a particular embodiment, the first component comprises sodium chlorite or hydrogen peroxide; the second component comprises a zinc compound selected from the group consisting of zinc chloride, zinc acetate, zinc salicylate, zinc sulfate, and zinc nitrate; and the third component is selected from the group consisting of essential oils; a bleaching agent; or cetylpyridinium chloride.
    [0049] In one embodiment, the oral composition further comprises essential oils. For example, essential oils may comprise eucalyptol, menthol, methyl salicylate, and thymol.
    [0050] In one embodiment, the oral composition further comprises a desensitizing agent. Desensitizing agents suitable for use in the oral composition include, for example, benzocaine, potassium nitrate; potassium fluoride; strontium chloride; potassium chloride; potassium citrate; iron oxalate; sodium nitrate; lithium nitrate; magnesium nitrate; calcium nitrate; calcium hydroxide; dibasic calcium phosphate; strontium acetate; sodium monofluorophosphate; bisabolol; a local or systemic analgesic agent such as NSAIDS, aspirin, acetaminophen and/or codeine; and combinations thereof.
    [0051] In one embodiment, the oral composition further comprises a bleaching agent. Bleaching agents suitable for use in the oral composition include, for example, peroxides, pH raising agents, sodium hypochlorite and salts thereof, and combinations thereof. For example, urea peroxide or carbamide peroxide, hydrogen peroxide, sodium bicarbonate, and combinations thereof.
    [0052] In one embodiment, the oral composition further comprises an antimicrobial agent. Antimicrobial agents suitable for use in the oral composition include, for example, chlorhexidine, an aerobic Gram-positive antibacterial agent, a Gram-negative antibacterial agent, bromochloroprene, 1,6-bis(p-chlorophenyldiguanide) hexane, and water-soluble salts. thereof, such as digluconate, diacetate, dilactate, dichlorohydrate; 1,6-di(2-ethylhexyldiguanido)hexane and 1,6-di(2-ethylhexyldiguanido)hexetidine, and water-soluble salts thereof; 1,6-di(2-benzyldiguanido)hexane, 1,6-di(2-benzyldiguanido)hexamidine, p-chlorophenyldiguanido, N-(4-chlorobenzyl)-N5-(2,4-dichlorobenzyl)oliguanido, and soluble salts in water thereof such as biguanide; betanaptol, chlorothymol, thymol, anethole, eucalyptol, carvacrol, menthol, phenol, amylphenol, hexylphenol, heptylphenol, octylphenol, hexylresorcinol, hexachlorophene [2,2-methylene bis(3,4,6-trichlorophenol)], 1,1'- hexamethylene bis(5-)p-chlorophenyl)biguanido), methyl salicylate, and salts thereof; quaternary ammonium salt compounds such as morpholinium tetradecyl sulfate. laurylpyridinium chloride, myristylpyridinium chloride, cetylpyridinium fluoride, cetylpyridinium chloride, cetylpyridinium bromide, cetylpyridinium iodide, stearylpyridinium chloride, dodecyltrimethylammonium chloride, tetradecyltrimethylammonium chloride, hexadecyltrimethylammonium bromide, C12-C16 benzyldimethylammonium chloride (chloride benzethonium), phenoxy ethyl dodecyl dimethylammonium bromide (domiphene bromide), triclobisonium chloride, benzoic acid, sodium benzoate, potassium benzoate, boric acid, tyrothricin, gramicidin, triclosan, mutanase, dextranase, tin fluoride and combinations thereof .
    [0053] In one embodiment, the oral composition further comprises other antimicrobials such as antibiotic agents and/or antifungal agents. Suitable antibiotic and/or antifungal agents for use in the oral composition include, for example, amoxicillin, amoxicillin-clavulanate, clindamycin, doxycycline, metronidazole, metronidazole-spiramycin, and combinations thereof.
    [0054] In one embodiment, the oral composition further comprises an antiviral agent. Antiviral agents suitable for use in the oral composition include, for example, abacavir, acyclovir, acyclovir, adefovir dipivoxil, amantadine, amprenavir, ampligen, arbidol, atazanavir, atripla, boceprevir, cidofovir, combivir, darunavir, delavirdine, didanosine, docosanol, edoxudine , efavirenz, emtricitabine, enfuvirtide, entecavir, entry inhibitors, fanciclovir, a fixed-dose combination (antiretroviral), fomivirsen, fosamprenavir, foscarnet, fosfonet, a fusion inhibitor, ganciclovir, ibacitabine, immunovir, idoxuridine, imiquimod, indinavir, inosine , integrase inhibitor, interferon type III, interferon type II, interferon type I, interferon, lamivudine, lopinavir, loviride, maraviroc, morozidine, metisazone, nelfinavir, nevirapine, nexavir, nucleoside analogues (analog reverse transcriptase inhibitors) nucleoside), oseltamivir, peginterferon alfa-2a, pegylated interferon alfa, penciclovir, peramivir, pleconaryl, podofilox, podophyllotoxin, i protease inhibitor, pyramidine, raltegravir, a reverse transcriptase inhibitor, ribavirin, rimantadine, ritonavir, saquinavir, stavudine, a synergistic (antiretroviral) enhancer, tea tree oil, tenofovir, tenofovir disoproxil, tipranavir, trifluridine, trizivir, tromantadine, truvada, valaciclovir, valganciclovir, vicriviroc, vidarabine, viramidine, zalcitabine, zanamivir, and zidovudine.
    [0055] In one embodiment, the oral composition further comprises an anti-cavity agent. Suitable anti-cavity agents for use in the oral composition include, for example, fluoride, sodium fluoride, sodium monofluorophosphate, nicomethanol fluorhydrate, tin fluoride, ammonium fluoride, potassium fluoride, aluminum fluoride, calcium fluoride, cuprous fluoride, barium fluoride; organic fluorides such as long chain amine fluoride, fluorophosphates, aluminum difluorophosphate, sodium fluorozirconate, potassium fluorozirconate, tin fluorozirconate, sodium silicofluoride, fluorinated sodium calcium pyrophosphate, green tea, spirulina algae, and combinations thereof .
    [0056] In one embodiment, the oral composition further comprises an antiplaque agent. Suitable antiplaque agents for use in the oral composition include, for example, an alcohol such as ethanol, triclosan, sanguinarine, hexetidine, zinc citrate, a fluoride, sodium lauryl sulfate, zinc phosphate, zinc acetate, zinc aspartate, zinc acetylmethionate, zinc citrate trihydrate, zinc tannate, zinc gluconate, zinc lactobionate, zinc maltobionate, hydrolyzed zinc collagen, zinc pyrrolidone carboxylic acid, zinc tribromo-salicylanphiide, zinc caprylate, zinc octoate, zinc laurate, zinc myristate, zinc stearate, zinc oleate, zinc carbonate, zinc borate, zinc silicate, zinc sulfide, zinc sulfate, zinc oxide, zinc phenol sulfonate, zinc stannate, zinc dl-lactate, trihydrate, tannic acid, citric acid, acetic acid, lactic acid, sodium trihydrogen pyrophosphate, disodium dihydrogen pyrophosphate, trisodium hydrogen pyrophosphate, mono- hi trisodium hydrogen pyrophosphate hydrate, trisodium hydrogen pyrophosphate nonahydrate, tetrasodium pyrophosphate, tetrasodium pyrophosphate decahydrate, potassium trihydrogen pyrophosphate, dipotassium dihydrogen pyrophosphate, pyrophosphate tripotassium hydrogen pyrophosphate, tetrapotassium pyrophosphate, diammonium dihydrogen pyrophosphate, triammonium hydrogen pyrophosphate, triammonium hydrogen pyrophosphate monohydrate, calcium dihydrogen pyrophosphate, calcium pyrophosphate, tetraaluminum pyrophosphate , and combinations thereof.
    [0057] In one embodiment, the oral composition further comprises an anti-calculus/anti-calculus agent. Suitable anti-calculus/anti-calculus agents for use in the oral composition include, for example, pyrophosphate, a zinc salt, and combinations thereof.
    [0058] In one embodiment, the oral composition further comprises an antioxidant. Antioxidants suitable for use in the oral composition include, for example, vitamins, such as vitamin A, C, or E; polyphenols; tocopherols; ethylenediaminetetraacetic acid; butylated hydroxytoluene (BHT); and propyl gallate.
    [0059] In one embodiment, the oral composition further comprises an anti-inflammatory agent. Suitable anti-inflammatory agents for the gingiva include, but are not limited to, beta-glycerretinic acid, enoxolone, salicylic acid, azulene, ginkgo biloba, amamelis, corticosteroids, NSAIDs, and salts thereof.
    [0060] In one embodiment, the oral composition further comprises an agent for reducing and/or alleviating dry mouth. Suitable agents for reducing and/or alleviating dry mouth include, but are not limited to, lactoferrin, lysozyme, lactoperoxidase, immunoglobulins, colostrum extract, glucose oxidase, amylase, amyloglucosidase, glucoxidase, papain, peptizime, aloe vera, a flavoring component identical to natural that can make your mouth water and combinations thereof.
    [0061] In one embodiment, the oral composition further comprises a deodorant. Deodorants suitable for use in the oral composition include, for example, chlorhexidine, hydrogen peroxide, vitamin B, vitamin C, sodium bicarbonate, an herb, and combinations thereof.
    [0062] In one embodiment, the oral composition further comprises a polishing agent. Polishing agents suitable for use in the oral composition include, for example, calcium carbonate, dicalcium phosphate dihydrate, aluminum hydroxide, dental-type silicas, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium, anhydrous calcium phosphate, dicalcium phosphate, tribasic calcium phosphate, sodium phosphate, potassium phosphate, calcium pyrophosphate, insoluble sodium metaphosphate, disodium orthophosphate, dibasic sodium phosphate, magnesium hydroxide, magnesium carbonate, magnesium silicate, magnesium trisilicate, trimagnesium phosphate, monomagnesium phosphate, magnesium oxide, stannic oxide, zinc oxide, bentonite, pumice flour, α-alumina trihydrate, alumina, aluminum silicate, zirconium silicate , hydroxyapatite, cross-linked urea-formaldehyde resin, cross-linked melamine-formaldehyde resin, polymethacrylate, polymethylmethacrylate, polystyrene, polyethylene powder, silica gel, silica gel des hydrate, sodium glycerophosphate, sodium trimetaphosphate, organic phosphates, and combinations thereof.
    [0063] In one embodiment, the oral composition further comprises a detergent. Detergents suitable for use in the oral composition include, for example, sodium lauryl sulfate, sodium lauryl sarcosinate, sodium methyl cocoyl taurate, polysorbates, sorbitan derivatives and combinations thereof.
    [0064] In one embodiment, the oral composition further comprises a film-forming agent. Suitable film forming agents to protect against tobacco tar and other tannins include, but are not limited to, polyethylene glycol (PEG), petrolatum, paraffin oil, dimethicone, magnesium stearate and stearic acid.
    [0065] In one embodiment, the oral composition further comprises a mineralizer or remineralizers. Suitable dental enamel mineralizers or remineralizers include, but are not limited to, calcium in any form of the mineral and organic salts of apatite and hydroxyapatite.
    [0066] In one embodiment, the oral composition further comprises a coloring agent. Suitable coloring agents include, but are not limited to, red, blue and green food coloring such as FD and C type dyes and lakes, e.g. D&C blue #1, D&C blue #4, D&C brown #1, D&C green #5 to #8, D&C orange #4 to #11, D&C yellow #2 to #11, D&C red #6 to #40, FD&C blue #1, FD&C blue #2,, FD&C blue #4, FD&C red #3, FD&C red #4, FD&C red #33, FD&C red #40, FD&C yellow #5, FD&C yellow #6, FD&C yellow #10, FD&C orange #4, FD&C green #3, carmine, and fruit and vegetable.
    [0067] In one embodiment, the oral composition further comprises a humectant. Humectants suitable for use in the oral composition include, but are not limited to, glycerin, propylene glycol, hydrogenated glucose syrup, polyethylene glycol-14 (PEG-14), polyethylene glycol-18 (PEG-18), polyethylene glycol-55 ( PEG-55), polyethylene glycol-100 (PEG-100), polyethylene glycol-135 (PEG-135), polyethylene glycol-180 (PEG-180), polyethylene glycol-200 (PEG-4), polyethylene glycol-240 ( PEG-240), polyethylene glycol-300 (PEG-6), polyethylene glycol-400 (PEG-8), polyethylene glycol-450 (PEG-9), polyethylene glycol-500 (PEG-10), polyethylene glycol-600 ( PEG-12), polyethylene glycol-1540 (PEG-32), polyethylene glycol-2000 (PEG-40 or PEG-2M), polyethylene glycol-3000 (PEG-60), polyethylene glycol-4000 (PEG-75), polyethylene glycol-6000 (PEG-150), polyethylene glycol-9000 (PEG-9M or PEG-200), polyethylene glycol-20,000 (PEG-20M or PEG-350), polyethylene glycol-600,000 (PEG-14M), propylene glycol ( PG), glycerol (glycerin), erythritol, xylitol, sorbitol, mannitol, lactitol, starch hydrolysates hydrogenated.
    [0068] In one embodiment, the oral composition further comprises a sweetener that improves the taste of the oral composition and freshens the breath. Sweeteners suitable for use in the oral composition include, for example, xylitol, sodium saccharin, menthol, eucalyptus, sorbitol, mannitol, saccharin, aspartame, acesulfame potassium (acesulfame K), stevia, peppermint oil, spearmint oil, and combinations thereof.
    [0069] In one embodiment, the oral composition further comprises a flavoring. Suitable seasonings include, but are not limited to, menthol, eucalyptol, peppermint oil, spearmint oil, fennel oil, benzaldehyde, bitter almond oil, camphor, cedar leaf oil, cinnamic aldehyde, cinnamon, citronella oil, clove oil, heliotropin, lavender oil, phenyl salicylate, pine oil, pine needle oil, rosemary oil, sassafras oil, thyme oil, thymol, wintergreen, lemon oil, orange oil, vanillin, carvone, anethole, irone, iris, caraway, coriander, pepper, eugenol, nutmeg, and other generally safe (GRAS) flavoring oils by the Federal Drug and Food Administration (FDA).
    [0070] Each of the first and second components further comprises one or more pharmaceutically acceptable carriers. Pharmaceutically acceptable carriers for use in oral compositions and systems are well known in the art. Non-limiting examples of suitable pharmaceutically acceptable carriers include glycerin, water, saline, dextrose, sucrose, glycerol, polyethylene glycol, ethanol, sorbitol, mannitol, xylitol, and combinations thereof.
    [0071] In one embodiment, the oral composition further contains any combination of the above-described components. One such modality is targeted at any combination of the desensitizing agents; bleaching agents; antimicrobial agents; antibiotic and/or antifungal agents; antiviral agents; anti-cavity agents; antiplaque agents; anti-tartar agents; antioxidants; anti-inflammatories; an agent to reduce or alleviate dry mouth; a deodorant; a polishing agent; a detergent; a film forming agent; a mineralizer or remineralizer; a coloring agent; a humectant; a sweetener; and/or condiments described above.
    [0072] In one embodiment, an oral composition is provided wherein a first component comprises at least one Eh-enhancing compound; a second component comprises at least one zinc compound; and at least one additional (third) component selected from the group consisting of essential oils; a bleaching agent, cetylpyridinium chloride or other antimicrobial agent, an antifungal agent, and an antiviral agent; an antioxidant agent; an anti-cavity agent; an antiplaque agent; a desensitizing agent and an agent for relieving or reducing dry mouth; and a pharmaceutically acceptable carrier.
    [0073] In one embodiment, an oral composition is provided wherein a first component comprises sodium chlorite or hydrogen peroxide; a second component comprises a zinc compound selected from the group consisting of zinc chloride, zinc acetate, zinc lactate, zinc salicylate, zinc sulfate, and zinc nitrate; and at least one other component (optionally part of the second component) comprising essential oils; a bleaching agent; or cetylpyridinium chloride.
    [0074] In one embodiment, an oral composition is provided wherein a first component comprises at least one Eh-enhancing compound and a pharmaceutically acceptable carrier, and a second component comprises at least one zinc compound, cetylpyridinium chloride (CPC) and a pharmaceutically acceptable carrier. In a particular embodiment, the first and second components are separately stored.
    [0075] An effective amount of such combinations is determined by the particular components used in the oral composition. Furthermore, the oral composition is not limited to the agents and components described above, but may include various other agents and components.
    [0076] The pH of the oral composition of the present invention is dependent on the particular Eh-enhancing compound and the particular zinc compound combination used. For example, when the Eh-enhancing compound is hydrogen peroxide, the pH of the oral composition ranges from about 3.0 to about 6.0. In one embodiment, the pH ranges from about 3.5 to about 5.0, and more suitably, from about 4.2 to about 4.8. An acidic pH ensures the availability of freely available zinc ions. This is because zinc ions, above a pH of about 6.0, combine with hydroxide ions in the solution to form poorly soluble zinc hydroxide, thus making freely available zinc ions less available.
    [0077] On the other hand, when the Eh-enhancing compound is an oxyhalogen compound, such as sodium chlorite, a pH between about 2.0 to about 6.5 is unsuitable for the stability of the chlorite. of sodium during storage. At an acidic pH, unstable and less desirable chlorine dioxide is produced. The pH of the first composition during storage needs to be between about 7.0 and about 8.5 where sodium chlorite is very stable. The instability of zinc ions at a pH of 6.0 and above, and the instability of chlorite at a pH of about 6.0 and below, can make it advantageous at times to keep the first and second compositions separate in two compartments or a two-phase system until ready to use.
    [0078] In one embodiment, an oral composition is provided comprising a first component comprising about 0.04% by weight to about 1.2% by weight of sodium chlorite and the pH of the first component ranges from about 7, 0 to about 8.5, and a second component comprising about 0.04% by weight to about 0.7% by weight zinc ion and about 0.09% by weight to about 0.2% by weight of CPC and the pH of the second component ranges from about 3.0 to about 6.0.
    [0079] In one embodiment, the first and second components are separately or substantially stored away from contact with each other, and may be brought into contact, such as mixing with each other, by users prior to use. The components can be contacted for about 10 seconds to about 30 minutes before use. In a particular embodiment, the first and second components are contacted within about 10 minutes of use, and more particularly, within about 5 minutes of use.
    [0080] Once a first and second component, as described here, are brought into contact with each other, some of the zinc compound dissociates into freely available zinc ions.
    [0081] In one embodiment, an oral composition is provided comprising: about 0.005% by weight to about 1.5% by weight of an Eh-enhancing compound; about 0.01% by weight to about 0.5% by weight zinc ion; about 0.01% by weight to about 0.3% by weight of CPC; and at least one pharmaceutically acceptable carrier, wherein the oral composition is prepared by mixing a first component comprising the Eh enhancing compound and a pharmaceutically acceptable carrier and a second component comprising a zinc compound, CPC and a pharmaceutically acceptable carrier.
    [0082] In another embodiment of the invention, an oral composition described herein may contain xylitol. The inclusion of xylitol can be used to facilitate lessening of periodontal disease and plaque adhesion within the oral cavity. Bacteria in the oral cavity release toxins that break down tissues, thus facilitating the growth of infections. Specifically, bacteria help in creating plaque along the gum line. Over time, continued exposure to plaque can lead to periodontal disease. Furthermore, dextrans in the oral cavity have been shown to accelerate the aggregation of bacteria, as the adhesion of plaque to the teeth is increased. Xylitol facilitates the reduction of dextrans formation in the oral cavity. As such, plaque adhesion is reduced which leads to a reduction in periodontal disease.
    [0083] Furthermore, using xylitol has shown a reduction in the decomposition of new teeth, along with retention and even reversal of existing tooth decay. Specifically, xylitol suppresses at least some of the most harmful strains of oral bacteria, so the use of xylitol can provide a long-term change in the bacterial communities present in the oral cavity. In addition, xylitol has the ability to enhance the mineralization of enamel on teeth and can be used to effectively treat small stains of decay on teeth. Additionally, xylitol can stimulate the flow of saliva and help keep salivary minerals in a useful form. As such, xylitol can be used to increase saliva production for people who suffer from dry mouth due to illness, aging, or drug side effects.
    [0084] In one embodiment, xylitol is mixed with a small amount of titanium tetrafluoride to provide an enhanced effect that further reduces plaque adhesion in the oral cavity.
    [0085] In addition, the xylitol-containing oral composition may also be useful for reducing bacteria that can cause ear, nose, and/or throat infections. Furthermore, the oral composition containing xylitol may also be useful in reversing bone loss, decreasing insulin resistance, decreasing hypertension that may be associated with diabetes, and/or correcting hormonal imbalances.
    [0086] Typically, the amount of xylitol in the oral composition will depend on the type of oral composition and the desired function of the xylitol. For example, when the oral composition is a mouthwash, the composition may include an amount of xylitol from about 0.1% by weight to about 15% by weight of the total oral composition. In another embodiment, when the oral composition is a confectionery or chewing gum, the oral composition may include an amount of xylitol from about 0.1% by weight to about 50% by weight. Xylitol can be included in the first or second composition. In an alternative embodiment, the xylitol is stored separately from the first and second compositions.
    [0087] The oral composition optionally contains xylitol and/or other components as described herein. In one embodiment, the further formed oral composition includes a concentration of xylitol ranging from about 0.1% to about 50% by weight of the composition. In a particular embodiment, the concentration of xylitol ranges from about 0.1% to about 50% by weight of the oral composition.
    [0088] The oral compositions of the present disclosure can be provided in a variety of oral vehicles suitable for administration to human and/or non-human animals. For example, oral compositions can be in the form of a solid, liquid, spray, gel, foam, syrup, or powder. Additionally, the oral composition can be delivered orally by means of a dental care product, a food product, a tablet, capsule, an instant-cast formulation, a candy, a lozenge, a chewing gum, a confectionery, a paste of teeth, mouth rinse, breath spray and/or a mint.
    [0089] In one embodiment, the oral composition of the invention may comprise a first component and a second component, as described herein, which are separately stored, for example, in separate containers or a container having separate compartments for each component. As used herein, the phrase "stored separately" refers to substantially preventing a first component and a second component from contacting each other to the desired point of use. For example, a first and second component may be contained in separate containers to substantially prevent premature contact. The term "substantially" prevent is intended to encompass both preventing 100% physical contact of the components with each other to the desired point of use and where the components may come into inconsequential chemical contact. Any known container or device for storing the components can be used separately for immediate development. For example, a syringe-like barrel may be used where the components are kept separate until the plunger is activated, a bottle, a tube, a capsule, or any equivalent thereof.
    [0090] Alternatively, in another embodiment, the oral composition may be a solution where one of the first or second components is encapsulated (or any equivalent of a capsule). For example, the first component may be a solution and the second component may be present in the solution in an encapsulated form.
    [0091] In another embodiment, the oral composition may be a tablet, confectionery or a chewing gum where the first and second components are substantially prevented from contacting each other until placed in a contactor, for example, by the user. Additional examples include a biphasic tablet or capsule that can be used wherein the first component and the second component are substantially prevented from mixing or contacting each other.
    [0092] In another embodiment, the oral composition can be delivered to non-human animals in the form of a pet mouthwash or can be rinse, toothpaste, pet spray, pet care, pet food, pet food and/or a chew toy.
    [0093] Furthermore, delivery vehicles for the oral composition are not limited to the vehicles disclosed above, but may also include any other acceptable oral delivery mechanism.
    [0094] In another embodiment, an oral care system is provided which forms an oral composition as described in more detail below. The oral care system facilitates preventing oral bacteria from reducing an oxidation-reduction potential (Eh) of the oral cavity and at the same time facilitates increasing the existing oxidation-reduction potential to a level, at which an oral environment is created. which is not conducive to oral putrefaction and production of oral disease.
    [0095] In one embodiment, an oral care system comprising a first component and a second component, as described herein, is provided. In a particular embodiment, the first and second components are separately stored, or substantially prevented from contacting each other, in the oral care system.
    [0096] In other embodiments, methods of using the oral care systems and oral compositions of the invention are provided.
    [0097] The methods described herein involve releasing an oral composition, in accordance with the present invention, into a subject's oral cavity. In particular embodiments, prior to releasing the oral composition into the oral cavity, the first component and the second component are mixed as described above.
    [0098] In one embodiment, a method is provided for inhibiting the formation of sulfur-containing compounds in the oral cavity and preventing reduction of the oxidation-reduction potential of the oral cavity by releasing into the oral cavity the oral composition comprising an effective amount of sulfur ions. zinc, an Eh-enhancing compound, and cetylpyridinium chloride. As defined herein, sulfur-containing compounds include, for example, sulfide, hydrogen sulfide, and methyl mercaptan. In a particular embodiment, an effective amount is sufficient to inhibit the formation of sulfur-containing compounds and/or prevent a reduction in the oxidation-reduction potential of the oral cavity. For example, an effective amount of zinc ion in a toothpaste or mouthwash can range from about 0.01% to about 0.5% by weight and, in a particular embodiment, from about 0.02% to about 0.02% by weight. of 0.35% by weight of the oral composition.
    [0099] In one embodiment, a method is also provided for reducing bad breath by releasing into the oral cavity the oral composition containing effective amounts of zinc ion, an Eh-enhancing compound and cetylpyridinium chloride. Yet, a reduction or alleviation of bad breath (bad breath), conversely, can mean providing fresh or clean breath. Bad breath, in some circumstances, can be quantified using an organoleptic (smell) test. Alternatively, bad breath can be quantified using a Halimeter which measures sulfur gases from bad breath in parts per billion (ppb).
    [0100] In one embodiment, the method is effective to reduce bad breath for at least 2 hours to about 12 hours. For example, the oral composition and method of using an oral composition described herein can reduce bad breath for at least 2 hours, preferably 3 hours, preferably 4 hours, preferably 5 hours, preferably 6 hours, preferably 7 hours, preferably 8 hours, preferably 9 hours, preferably 10 hours, preferably 11 hours, preferably 12 hours. In some modalities, the method is effective in reducing bad breath for more than 12 hours or at least 12 hours.
    [0101] In one embodiment, there is also provided a method of preventing or alleviating dental disease comprising releasing into the oral cavity effective amounts of zinc ion, an Eh-enhancing compound and cetylpyridinium chloride, wherein dental diseases include, for example , gingivitis, periodontitis, and tooth decay. Without being bound by theory, an effective amount of zinc ion, an Eh-enhancing compound and/or cetylpyridinium chloride is believed to be an amount sufficient to raise the oxidation-reduction potential of the oral cavity to normal levels. This can prevent or reduce tooth decay, gingivitis or periodontitis. For example, an effective amount of an oral composition is an amount sufficient to reduce or prevent the formation of malodorous compounds such as hydrogen sulfide and the growth of harmful Gram-negative anaerobic bacteria that can cause gingivitis and periodontitis.
    [0102] In one embodiment, a method is provided for decreasing plaque adhesion, and/or treating periodontal disease within the oral cavity, gingivitis, periodontitis, and/or reducing tooth decay by releasing an effective amount of the composition into the oral cavity. oral.
    [0103] In one embodiment, a method is provided for desensitizing dentin by releasing an effective amount of the oral composition into the oral cavity. In another embodiment, the oral composition to be delivered additionally contains at least one desensitizing agent, such as, but not limited to, the desensitizing agents listed above.
    [0104] In one embodiment, a method is provided for whitening teeth by releasing an effective amount of the oral composition into the oral cavity. In another embodiment, the oral composition to be delivered additionally contains at least one bleaching agent, such as, but not limited to, the bleaching agents listed above.
    [0105] In one embodiment, a method is provided for providing an antimicrobial benefit to a subject by delivering an effective amount of the oral composition to the oral cavity. In another embodiment, the oral composition to be delivered additionally contains at least one antimicrobial agent, such as, but not limited to, the antimicrobial agents listed above.
    [0106] In one embodiment, a method is provided for providing an antibiotic benefit to a subject by delivering the oral composition to the oral cavity. In another embodiment, the oral composition to be delivered additionally contains at least one antibiotic agent, such as, but not limited to, the antibiotic and/or antifungal agents listed above.
    [0107] In one embodiment, a method is provided for reducing or preventing cavities in a subject by releasing the oral composition into the oral cavity. In another embodiment, the oral composition to be delivered additionally contains at least one anti-cavity agent, such as, but not limited to, the anti-cavity agents listed above.
    [0108] In one embodiment, a method is provided for reducing plaque in a subject by releasing the oral composition into the oral cavity. In another embodiment, the oral composition to be delivered additionally contains at least one antiplaque agent, such as, but not limited to, the antiplaque agents listed above.
    [0109] In one embodiment, a method is provided for reducing tartar/calculus by releasing the oral composition into the oral cavity. In another embodiment, the oral composition to be delivered additionally contains at least one anti-calculus (anti-calculus) agent, such as, but not limited to, the anti-calculus/anti-calculus agents listed above.
    [0110] In one embodiment, a method is provided for deodorizing a subject's oral cavity by releasing the oral composition into the oral cavity. In another embodiment, the oral composition to be delivered additionally contains at least one deodorizing agent, such as, but not limited to, the deodorizing agents listed above.
    [0111] In one embodiment, a method for polishing teeth by releasing the oral composition into the oral cavity is also provided. In another embodiment, the oral composition to be delivered additionally contains at least one polishing agent, such as, but not limited to, the polishing agents listed above.
    [0112] In one embodiment, a method is provided for reducing or preventing gingivitis by releasing the oral composition into the oral cavity. The oral composition may contain any additional antigingivitis agent and/or any additional ingredient listed herein.
    [0113] In one embodiment, a method is provided for treating, alleviating or preventing or reducing the occurrence of canker sores by releasing the oral composition into the oral cavity.
    [0114] In one embodiment, the oral composition may be administered from one to five times per day. In one embodiment, the oral composition can be administered three times a day, preferably twice a day, or even once a day.
    [0115] In another embodiment of the invention, the compositions disclosed herein may be administered to non-human animals, such as pets. For example, any of the oral composition modalities can be delivered to the oral cavity of a non-human animal. In addition, either method can be used with non-human animals, where the subject is a non-human animal. Examples include domestic animals such as dogs and cats; and livestock/farm animals such as horses, cows and pigs; or for health purposes with exotic wildlife such as animals in zoos or their natural environments.
    [0116] It has been discovered by the present inventors that CPC remains in the oral cavity for long periods after use which can be useful in maintaining a healthy oral cavity for longer periods of time between treatments. The addition of CPC to the oral composition demonstrates a definite, additional effectiveness.
    [0117] It was further discovered by the inventors of the present invention that coercive activity exists between CPC and the Eh-enhancing compound and the zinc compound. For example, coercive activity exists between CPC, sodium chlorite and a zinc compound. The oral composition with CPC has an enhanced beneficial effect (i.e., more than additive) for the subject compared to the oral composition without CPC. For example, statistical analysis demonstrates that the oral composition containing CPC has an enhanced effect to reduce bad breath, and has an enhanced antigingivitis, antiplaque and antitartar (calculus) effect compared to the oral composition without CPC. See Figures 3 and 4.
    [0118] The present disclosure also provides an article of manufacture comprising a packaging material and one or more of the oral compositions described herein contained within the packaging material. The packaging material used to contain the oral compositions may comprise glass, plastic, metal or any other suitably inert material. For example, a dentifrice containing the oral composition may be contained in a collapsible tube, such as aluminum, or plastic, or a squeeze tube, pump, or pressurized dispenser to measure the contents, or in a tear-able sachet. In addition, the packaging material may be capable of holding the zinc compound and the Eh-enhancing compound separately so that they can be mixed prior to use of the oral composition. In addition, any of the above-described optional components or combinations thereof may be premixed with either the first and second components, or cetylpyridinium chloride. Alternatively, any of the above-described optional components or combinations thereof may be stored separately from the first and second components. As such, the optional compound, zinc compound, Eh-enhancing compound, and cetylpyridinium chloride are all mixed together prior to use of the oral composition.
    [0119] Separate compositions may optionally be co-packaged, for example, in a single container or in a plurality of containers. For example, separate containers for the zinc compound and the Eh-enhancing compound used. Separate containers may also be presented separately to a consumer and independently, for use according to the methods described here.EXAMPLE
    [0120] Oral compositions in accordance with the present revelation are formulated for various evaluations. For all Formulations (1-12), the pH range of Solution 1 is from about 7.0 to about 7.65; and the pH range of Solution 2 is from about 4.2 to about 4.8.





    EXAMPLE 13 - CYSTEINE CHALLENGE TESTING.
    [0121] Cysteine challenge testing is an in vivo methodology designed to: (1) stimulate a significant production of VSCs in the mouth, simulating a condition of severe halitosis; and (2) assess the degree to which a test product/ingredient can prevent the formation of these VSCs, thus preventing bad breath. In such testing, a subject rinses with a specified amount of a cysteine-containing solution. Cysteine is an amino acid that acts as a food source, and is readily metabolized by anaerobic Gram-negative bacteria. The by-product of this bacterial metabolism is hydrogen sulfide, the most prevalent rapidly forming component of VSCs. Under normal circumstances in the presence of cysteine, Gram-negative anaerobes will generate dramatically high levels of VSCs. Such increases in VSCs ("peaks") are evaluated before and after administering a test rinse ("test rinse") to determine that the short and long period of the test rinse affects VSC production.
    [0122] The first step in the cysteine challenge test is to measure the subject's baseline pre-test VSC level in ppb with a Halimeter. Prior to rinsing with any test rinse, a subject rinses with a cysteine solution for 25 seconds, gargles for 5 seconds (for a total of 30 seconds), and the VSC level is again measured in ppb ("pre-peak peak"). test"). After any cysteine rinse, the VSC level gradually returns to a minimum value ("baseline value") as the cysteine is depleted. This usually takes about twenty minutes. Any post-rinse cysteine measurement that falls to 350 ppb or below is considered a baseline value (based on statistical analysis of the present study). Once at baseline value after the very first cysteine rinse, the test subject is administered the test rinse and VSC measurements are taken again. The subject rinses with a cysteine solution numerous times in the remaining test period to determine whether or not a spike occurs ("post-test spike") at each testing point, typically at 20 to 180 minute intervals over a total period. of 540 minutes.
    [0123] The presence or absence of post-test spikes indicate whether or not a test rinse inhibits the ability of Gram-negative anaerobes to metabolize cysteine and produce VSCs, and if so, whether such inhibition continues over time. . If the first cysteine rinse administered after the test rinse results in a post-test peak ("first post-test peak") that is about the same level as the concurrent pre-test peak, the rinse is established test does not inhibit anaerobic cysteine metabolism or production of VSCs. Conversely, when the first cysteine challenge administered after the test rinse results in no post-test peak, the test rinse is established to inhibit the ability of anaerobes to metabolize cysteine and produce VSCs. The continued presence or absence of post-test spikes with additional cysteine challenges determines whether or not a test rinse has a long-term effect on such anaerobes and their VSC production.
    [0124] Cysteine test challenge results (clinically generated bad breath) are also correlated with organoleptic test results (naturally occurring bad breath) with respect to prevention of bad breath through test rinse.
    [0125] Specifically, cysteine challenge testing was used to measure the effectiveness of four mouthwashes: a placebo (distilled water), a commercially available mouthwash (Listerine®), another commercially available mouthwash (SmartMouth®), and SmartMouth ACF™. The correlation between cysteine challenge testing of all test rinses and organoleptic testing in corresponding, previously published, double-blind clinical studies ("prior studies") was then evaluated.
    [0126] Distilled water, as the control in this study, does not contain any ingredient that would affect Gram-negative anaerobes or their ability to metabolize amino acids. This would explain why double-blind clinical studies using organoleptic testing have shown that a distilled water control does not provide fresh breath/prevent bad breath for longer than an hour.
    [0127] Five adult subjects participate in a screening visit. During the screening visit, the candidate signs an Informed Consent Form, is asked pertinent medical questions, signs a non-disclosure agreement (NDA), and completes a demographic form.
    [0128] A candidate accepted into the study after passing the inclusion/exclusion criteria checklist, which follows a dental screening that is administered by a licensed dentist. Written instructions are given to the subject listing certain dietary and oral hygiene restrictions to be followed in preparation for the test. Two weeks prior to testing and during the testing period, the subject has to refrain from using any oral hygiene product with the exception of standard toothpaste (Colgate®) and flossing. On the morning of the test visits, the subject does not brush or use any oral hygiene products and does not drink.
    [0129] The Halimeter is recalibrated before each test run, adjusted to 0.0 ppb and checked for stability. The Halimeter is adjusted to read 0.0 ppb when needed. An oral suspended sample (air) is taken by placing the tip of a straw attached to the Halimeter in the posterior third of the mouth, one centimeter above the tongue, with the lips slightly apart. The straw is not touched by the subject's lips, teeth, or tongue. The subject is taught to breathe as needed through the nose and not to blow through a straw. The maximum peak reading is recorded.
    [0130] At each testing visit, the subject's initial pre-test VSC level (in ppb) is established by taking three successive Halimeter readings.
    [0131] Subject rinses with 5 mL of a 6 mM solution of Cysteine for 25 seconds, gargles for 5 seconds (for a total of 30 seconds), and expectorates. The next reading is taken immediately. Four more readings are taken at five-minute intervals (20 minutes total).
    [0132] Subject rinses vigorously with 10 ml of a single unit of test material or 5 ml each of two unit test material (mouthwash or control) for 30 seconds, gargle for 15 seconds (to a total of 45 seconds) and sputum. Neither the subject nor the tester knows which test rinse is being administered. After 10 minutes is the next reading taken. Four more readings are taken at five-minute intervals (20 minutes total).
    [0133] Subject rinses with 5 mL of a 6 mM solution of Cysteine for 25 seconds, gargles for 5 seconds (for a total of 30 seconds), and expectorates. The next reading is taken immediately. Four more readings are taken at five-minute intervals (20 minutes total).
    [0134] Subject rinses with 5 mL of a 6 mM solution of Cysteine for 25 seconds, gargles for 5 seconds (for a total of 30 seconds), and expectorates. The next reading is taken immediately. Eight more readings are taken at ten-minute intervals (80 minutes total).
    [0135] Subject rinses with 5 mL of a 6 mM solution of Cysteine for 25 seconds, gargles for 5 seconds (for a total of 30 seconds), and expectorates. The next reading is taken immediately. Nine more readings are taken at twenty minute intervals (180 minutes total).
    [0136] Subject rinses with 5 mL of a 6 mM Cysteine solution for 25 seconds, gargles for 5 seconds (for a total of 30 seconds), and sputum. The next reading is taken immediately. Six more readings are taken at ten-minute intervals (60 minutes total).
    [0137] Subject rinses with 5 mL of a 6 mM solution of Cysteine for 25 seconds, gargles for 5 seconds (for a total of 30 seconds), and expectorates. The next reading is taken immediately. Six more readings are taken at ten-minute intervals (60 minutes total).
    [0138] Subject rinses with 5 mL of a 6 mM Cysteine solution for 25 seconds, gargles for 5 seconds (for a total of 30 seconds), and expects. The next reading is taken immediately. Six more readings are finally taken at ten-minute intervals (60 minutes total).
    [0139] The testing time, not including mixing, rinsing, and so on, totals 500 minutes.
    [0140] Two examples of Halimeter performance are shown in Figures 1 and 2 of subjects being tested with distilled water and Listerine® respectively. Figures correspond to VSC Halimeter output graphs in ppb units shown on the vertical axis and time in minutes shown on the horizontal axis.
    [0141] For the cysteine challenge using distilled water as the mouthwash (shown in Figure 1), the mean of the 14 "high VSC values" above 1000 ppb on the vertical axis corresponds to 1360 ± 199 (15%) . Similarly, when using Listerine® as the mouthwash (shown in Figure 2), the 13" high VSC values above 1000 ppb on the vertical axis correspond to 1290 ± 149 (12%). of cysteine challenge with Listerine® and distilled water (Tables 1 and 2 below) are indistinguishable, so Listerine® is no better at preventing VSC formation in the mouth than distilled water.


    [0142] Specifically, the results shown in Figure 3 confirm the results of previous cysteine challenge studies that demonstrated the use of SmartMouth® results in remarkably extended time periods of VSC values below 400 ppb (>120 minutes) and more than 500 minutes of VSC values below 600 ppb.
    [0143] The distribution of time-dependent data (Halimeter Baseline and Peak Values) is Gaussian and the resulting "array" can best be summarized by reporting the Mean (also known as the Mean Value) and the Standard Deviation of the Mean . These results are reported as the Mean/Median ± the Standard Deviation.
    [0144] All of the reported measurements can easily be placed into two distinct groups: (a) a mouthwash that will reduce the number of Gram-negative anaerobes to a sufficient degree, or for a fairly long period of time, to provide fresh breath in less than one hour / prevent bad breath no more than one hour and (b) a mouth rinse that provides fresh breath longer than 6 - 12 hours (and in some instances even longer).
    [0145] The Halimeter data collected in this study is "well structured". For the purpose of comparing the similarities and differences in mouthwashes of varying characteristics, the statistical concept of "two different groups" suffices.
    [0146] Information limits are at the level of 10 - 15% (to a standard deviation of the Mean Value) which is sufficiently accurate to distinguish differences between various mouthwashes that differ in their "Fresh Breath" characteristics from less than an hour, or more than 12 hours.
    [0147] As noted above, baseline values for SmartMouth® over the 25 - 500 minute period correspond to 195 ± 96 ppb (49%) and are typical and consistent with our expectations. However, Figure 4 for ACF shows that all baseline values are at levels not exceeding 275 ppb during the entire 30 - 500 minute cysteine challenge testing period, including immediately after each of the six cysteine rinses. individual. This result has never been observed or previously reported. This is clear evidence of an enhanced effect, such as coercion activity, between SmartMouth® and SmartMouth ACF™.
    [0148] Additional comparisons with respect to this constraint are represented in Table 3. Using the statistical information collected during cysteine challenge testing, it is possible to calculate the "long term fresh breath potential" of a test rinse. Based on the Halimeter measurements reported in this study, direct comparisons show the time it will take (in minutes) to reach 25%, 50%, or 70% post-test peak with water, Listerine®, SmartMouth®, or SmartMouth ACF™ . Longer times denote longer fresh breath.

    [0149] With a water rinse given as a control, there was minimal change in the high VCS readings resulting from subsequent cysteine challenges (1500 ±75 ppb). When Listerine® was used as the mouthwash, again, there was minimal change in the high SCV readings. When testing was given with SmartMouth®, there was a significant reduction in VSC levels with each subsequent cysteine challenge throughout the 500 minute threshold.
    [0150] In addition, when the cysteine challenge test was given with SmartMouth ACF™, there was a continued reduction and an even more significant decrease in VSC levels continuing with each subsequent cysteine challenge to the 500 minute limit of these studies .
    [0151] This study demonstrates that distilled water and Listerine® do not impair the ability of Gram-negative anaerobes to metabolize cysteine and produce VSCs. With both of these test rinses, the first post-test peak (and all subsequent peaks) rise to approximately the same levels as the pre-test peak. This demonstrates that the ability of Gram-negative anaerobes to metabolize amino acids and produce VSCs was not affected by these rinses. These results are consistent and can be correlated with previous studies that prove that neither distilled water nor Listerine® provides fresh breath/prevents bad breath for longer than an hour.
    [0152] This study also demonstrates that SmartMouth® significantly impairs the ability of Gram-negative anaerobes to metabolize cysteine and produce VSCs over an extended period of time. With SmartMouth®, the first two post-test cysteine challenges did not result in any peaks and no subsequent peaks reached even 50% of the pre-test peak levels. This demonstrates that the ability of Gram-negative anaerobes to metabolize amino acids and produce VSCs was dramatically inhibited by SmartMouth®. This result is consistent and can be correlated with a previous study that proved that SmartMouth® provides fresh breath/prevents bad breath for at least 12 hours.
    [0153] A comparison of the cysteine challenge testing properties of SmartMouth® and SmartMouth ACF™ was evaluated to determine if a correlation existed between the previous SmartMouth® study and the cysteine challenge testing of SmartMouth ACF™. Figure 3 (SmartMouth®) shows that (1) the first test post-rinse peak occurred approximately 160 minutes and reached approximately 30% of the pre-test peak, and (2) the last test post-rinse peak occurred in approximately 470 minutes and reached approximately 41% of the pre-test peak. In comparison, Figure 4 (SmartMouth ACF™) shows that (1) the first test post-rinse peak occurred at approximately 320 minutes and reached approximately 25% of the pre-test peak, and (2) the last peak of test post-rinse occurred approximately 470 minutes and never exceeded 25% of pre-test peak. This demonstrates, initially and over time, that SmartMouth ACF™ has a greater effect on the ability of Gram-negative anaerobes to metabolize amino acids and produce VSCs than SmartMouth®. This study demonstrated that CPC in SmartMouth ACF™ also does not inhibit zinc ion technology. In fact, CPC enhances the zinc ion effect in SmartMouth ACF™. An intensified effect is observed when CPC is used, such that a coercion exists between the ingredients.
    [0154] The above description of the modalities has been provided for purposes of illustration and description. It is not intended to be exhaustive or limiting of the disclosure. Individual elements or features of a particular embodiment are generally not limited to that particular embodiment, but, where applicable, are interchangeable and may be used in a selected embodiment, even if not specifically shown or described. The same can also be varied in many ways. Such variations are not to be considered a deviation from the disclosure, and all such modifications are intended to be included within the scope of the disclosure.
    [0155] The terminology used herein is for the purpose of describing particular exemplary embodiments only and is not intended to be limiting. As used herein, the singular forms "a" and "the" may be intended to include the plural forms as well, unless the context clearly indicates otherwise. The terms "comprises", "comprising", "including" and "having" are inclusive and therefore specify the presence of the stated characteristics, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other characteristics, integers, steps, operations, elements, components, and/or groups thereof. The method steps, processes, and operations described herein are not to be interpreted as necessarily requiring their performance in the particular order discussed or illustrated, unless specifically identified as an order of performance. It is also to be understood that additional steps or alternatives may be employed.
    权利要求:
    Claims (14)
    [0001]
    1. Oral composition characterized in that it comprises: a first component comprising at least one oxidation-reduction potential (Eh) enhancing compound, such as sodium chlorite, and a pharmaceutically acceptable carrier, and a second component comprising (i) at least one zinc compound capable of providing freely available zinc ions, such as zinc chloride; (ii) cetylpyridinium chloride (CPC) and (iii) a pharmaceutically acceptable carrier, wherein the first component comprises 0.01% by weight to 3.0% by weight of the at least one Eh-enhancing compound, and wherein the second component comprises 0.02% by weight to 1.0% by weight of the zinc ion and 0.02% by weight to 0.6% by weight of CPC.
    [0002]
    2. Oral composition, according to claim 1, characterized in that the first and second components are stored separately.
    [0003]
    3. Oral composition according to any one of claims 1 to 2, characterized in that the oral composition additionally comprises at least one additional component selected from the group consisting of a desensitizing agent, a bleaching agent, an antimicrobial agent, an antibiotic, an anti-cavity agent, an anti-plaque agent, an anti-tartar agent, an agent for relieving or reducing dry mouth, a deodorant, a polishing agent, a detergent and a sweetener.
    [0004]
    4. Oral composition according to any one of claims 1 to 3, characterized in that the oral composition is in a form selected from the group consisting of a mouthwash, a breath spray and an oral solution.
    [0005]
    5. Oral care system characterized in that it comprises the oral composition as defined in any one of claims 1 to 4.
    [0006]
    6. Oral composition, according to any one of claims 1 to 4, characterized in that it is for use as a medicine.
    [0007]
    7. Oral composition, according to any one of claims 1 to 4, characterized in that it is for use in the reduction of oral bad breath.
    [0008]
    An oral composition for use according to claim 7, characterized in that it is effective to reduce bad breath for at least 2 hours, preferably 3 hours, preferably 4 hours, preferably 5 hours, preferably 6 hours, preferably 7 hours. , preferably 8 hours, preferably 9 hours, preferably 10 hours, preferably 11 hours, preferably 12 hours.
    [0009]
    9. Oral composition according to any one of claims 1 to 4, characterized in that it is for use in the treatment or relief of a dental disease.
    [0010]
    10. Oral composition for use, according to claim 9, characterized in that the dental disease is selected from the group consisting of gingivitis, periodontitis and tooth decay.
    [0011]
    11. Oral composition according to any one of claims 1 to 4, characterized in that it is for use in plaque reduction.
    [0012]
    12. Oral composition, according to any one of claims 1 to 4, characterized in that it is for use in the reduction of canker sores.
    [0013]
    13. Oral composition for use, according to any one of claims 6 to 12, characterized in that the first component and the second component are mixed before said use.
    [0014]
    14. Use of an oral composition as defined in any one of claims 1 to 4, characterized in that it is in the preparation of a medicament for the reduction of oral bad breath, the treatment or relief of a dental disease, the reduction of plaque and reduction of canker sores.
    类似技术:
    公开号 | 公开日 | 专利标题
    US10702463B2|2020-07-07|Oral compositions for anticavity and desensitization use
    US6696047B2|2004-02-24|Stable oral care compositions comprising chlorite
    US20050002876A1|2005-01-06|Oral care methods and products
    US20210260107A1|2021-08-26|Methods Of Inhibiting Microbial Infections Using Zinc-Containing Compositions
    RU2524631C2|2014-07-27|Changing of colour of chalcone-containing preparative forms for oral cavity care
    同族专利:
    公开号 | 公开日
    US9138428B2|2015-09-22|
    KR20180029104A|2018-03-19|
    KR20200065109A|2020-06-08|
    DK2600833T3|2017-05-08|
    AU2011289661B2|2014-08-21|
    ES2642324T3|2017-11-16|
    US20130164358A1|2013-06-27|
    JP2013538199A|2013-10-10|
    WO2012021415A2|2012-02-16|
    RU2581915C2|2016-04-20|
    KR101804718B1|2017-12-05|
    JP2017014214A|2017-01-19|
    NZ606354A|2015-02-27|
    AU2011289661A1|2013-02-14|
    KR20190029719A|2019-03-20|
    KR20160123391A|2016-10-25|
    US10702463B2|2020-07-07|
    WO2012021419A2|2012-02-16|
    KR20170133520A|2017-12-05|
    US20190000733A1|2019-01-03|
    KR101953076B1|2019-05-22|
    KR20130105622A|2013-09-25|
    EP2600833B1|2017-03-08|
    MX2013001493A|2013-08-27|
    US10071031B2|2018-09-11|
    CA2807806A1|2012-02-16|
    AU2011289661C1|2014-12-04|
    US9480635B2|2016-11-01|
    US9044466B2|2015-06-02|
    CN103221031A|2013-07-24|
    CA2807806C|2017-11-07|
    WO2012021415A3|2012-12-13|
    CN103221031B|2016-04-27|
    US20120034280A1|2012-02-09|
    SG187733A1|2013-03-28|
    WO2012021419A3|2012-12-20|
    BR112013003081A2|2021-02-09|
    RU2013110071A|2014-09-20|
    KR101911202B1|2018-10-23|
    PT2600833T|2017-06-07|
    US20160008250A1|2016-01-14|
    KR102120160B1|2020-06-08|
    JP6018059B2|2016-11-02|
    US20160338922A1|2016-11-24|
    US20200405599A1|2020-12-31|
    EP2600833A2|2013-06-12|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US2556567A|1949-04-01|1951-06-12|Tampax Inc|Douche composition|
    US4226851A|1979-07-11|1980-10-07|Sompayrac Hewitt A|Stable dental composition containing hydrogen peroxide|
    US4477438A|1982-11-12|1984-10-16|Surgikos, Inc.|Hydrogen peroxide composition|
    AU570439B2|1983-03-28|1988-03-17|Compression Labs, Inc.|A combined intraframe and interframe transform coding system|
    US4647452A|1985-11-08|1987-03-03|Lever Brothers Company|Oral compositions of salicylamides and zinc salts for the synergistic inhibition of dental plaque|
    US4692262A|1986-09-18|1987-09-08|Brown Robert L|Skin cleanser capable of softening and removing smegma|
    US4992259A|1990-01-03|1991-02-12|Johnson & Johnson Consumer Products, Inc.|Stable oral composition of zinc|
    US5310546A|1990-02-07|1994-05-10|7-L Corporation|Mouthrinse and method of preparation|
    US5174990A|1990-02-07|1992-12-29|7-L Corporation|Mouthrinse and method of preparation|
    EP0559425B1|1992-03-02|1999-01-07|Immuno Japan Inc.|Use of proteins belonging to the transferrin/lactoferrin family for potentiating the immune system|
    US5958984A|1996-10-10|1999-09-28|Devillez; Richard L.|Method and composition for skin treatment|
    NZ335780A|1996-10-23|2001-01-26|Univ New York State Res Found|Compositions to control oral microbial oxidation-reduction levels and treat gingivitis-periodontitis|
    US20060171907A1|1996-11-21|2006-08-03|The Procter & Gamble Company|Oral care compositions providing enhanced whitening and stain prevention|
    US6350438B1|1998-02-27|2002-02-26|The Procter & Gamble Company|Oral care compositions comprising chlorite and methods|
    GB9810806D0|1998-05-21|1998-07-22|Boots Co Plc|Odour absorbing agent|
    US20020150630A1|1999-02-19|2002-10-17|Brooks Norman A.|Zinc chloride composition, unit dose packaging, applicator, and method of use in treating cancer and other skin diseases|
    NO990975A|1999-03-01|2000-02-21|Orix As|Oral preparation that is effective against halitosis|
    PE20020237A1|2000-06-30|2002-04-18|Procter & Gamble|TOPICAL ORAL COMPOSITION|
    US6723305B2|2002-03-04|2004-04-20|Colgate Palmolive Company|Anti-microbial breath freshening mouthrinse|
    JP4583148B2|2004-11-22|2010-11-17|住友大阪セメント株式会社|Mud reforming method|
    US20060140881A1|2004-12-22|2006-06-29|Guofeng Xu|Oral care compositions containing flavonoids and flavans|
    US8071077B2|2004-12-29|2011-12-06|Colgate-Palmolive Company|Oral compositions containing biphenol antibacterial compounds|
    AU2007212345A1|2006-02-06|2007-08-16|Irm Llc|Compounds and compositions as protein kinase inhibitors|
    US20070292531A1|2006-05-15|2007-12-20|Tim Clarot|Composition for oral use and methods for application of same|
    US9072673B2|2006-05-15|2015-07-07|Zicare, Llc|Method for measurably improving oral health|
    CN101938978A|2008-02-08|2011-01-05|高露洁-棕榄公司|Oral care product and methods of use and manufacture thereof|
    WO2010068428A1|2008-11-25|2010-06-17|The Procter & Gamble Company|Oral care compositions with improved aesthetics and fused silica|
    CN101780016B|2009-01-16|2012-05-16|上海交通大学医学院附属第九人民医院|Compound formula mouth wash of chlorine dioxide, cetylpyridinium chloride and zinc ion and preparation method thereof|
    KR102120160B1|2010-08-07|2020-06-08|더 리서치 파운데이션 포 더 스테이트 유니버시티 오브 뉴욕|Oral composition|US20100233101A1|2009-02-13|2010-09-16|Micropure, Inc.|Composition and method for the oxidative consumption of salivary biomolecules|
    KR102120160B1|2010-08-07|2020-06-08|더 리서치 파운데이션 포 더 스테이트 유니버시티 오브 뉴욕|Oral composition|
    US9387969B2|2011-04-14|2016-07-12|Edward Schapiro|Toothpaste composition and method of applying a single serving of toothpaste to a toothbrush|
    CN102670822A|2012-04-29|2012-09-19|李月英|Chinese herba preparation for treating oral ulcer|
    AU2012396916B2|2012-12-21|2015-10-01|Gaba International Holding Ag|Oral care composition|
    US20150290107A1|2013-03-14|2015-10-15|3 In 1 Dental Pllc|Compositions for treatment of xerostomia and for tooth treatment|
    US20150011653A1|2013-07-03|2015-01-08|Abby Aronowitz|Novel Microbial Pathogen inhibitor|
    US9403181B2|2013-07-26|2016-08-02|Paul O'Malley|Oral care product formulation|
    EP3076921B1|2013-12-02|2020-03-04|Colgate-Palmolive Company|Oral care zinc compositions|
    CN103830303B|2014-03-11|2016-03-02|北京德默高科医药技术有限公司|A kind of compositions of pre-counteracting bedsores|
    KR101666659B1|2014-06-12|2016-10-14|한국생명공학연구원|Pharmaceutical composition for preventing or treating muscle weakness diseases comprising Butylpyridinium or derivatives thereof|
    EP3171850B1|2014-07-21|2018-12-26|Colgate-Palmolive Company|Abrasive oral care composition|
    AR102640A1|2014-11-14|2017-03-15|Colgate Palmolive Co|COMPOSITION FOR ORAL CARE CONTAINING ZINC SALTS AND CALCIUM CARBONATE|
    EP3223781B1|2014-12-18|2021-07-07|GABA International Holding GmbH|Mouthrinse formulations comprising fluoride and a metal salt of pyrrolidone carboxylic acid|
    KR20170122743A|2015-02-26|2017-11-06|라이온 가부시키가이샤|Toothpaste composition|
    US20180117070A1|2015-04-27|2018-05-03|Japan Mode Co. Ltd.|Oral care composition|
    CA2935885A1|2015-07-09|2017-01-09|EWC & Associates, LLC|Toothpaste and mouth rinse|
    RU2713180C2|2015-12-14|2020-02-04|Колгейт-Палмолив Компани|Persistent oral teeth cleaning teeth whitening compositions for cleaning teeth|
    WO2017106763A1|2015-12-17|2017-06-22|Colgate-Palmolive Company|Oral care compositions comprising at least one phosphate/acrylate copolymer and at least one cationic active ingredient|
    KR101881636B1|2016-04-05|2018-07-24|주식회사 엘지생활건강|Composition for prevention or treatment of oral disease comprising Pueraria Extract|
    CN109414378A|2016-06-24|2019-03-01|高露洁-棕榄公司|Oral care composition and application method|
    RU2634347C1|2016-09-21|2017-10-25|Федеральное государственное бюджетное образовательное учреждение высшего образования "Кемеровский государственный медицинский университет" Министерства здравоохранения Российской Федерации|Therapeutic tooth paste|
    RU2635992C1|2016-10-10|2017-11-17|Общество с ограниченной ответственностью "Институт термологии"|Aerated mouthwash|
    CN106729656B|2016-12-07|2020-11-10|江山|Oral care composition for treating dry mouth and application of oral care composition in toothpaste|
    CN106729649B|2016-12-22|2020-11-10|江山|Oral care composition for treating xerostomia and application thereof|
    BR112019012551A2|2016-12-27|2019-11-12|Colgate Palmolive Co|oral care product and methods of use and manufacture|
    US10960129B2|2017-08-25|2021-03-30|AZ Solutions LLC|System and method for patient skin treatment and irrigation|
    RU2019114126A|2017-09-01|2021-02-01|Микропьюр, Инк.|ALIPHATIC ANIONIC COMPOUNDS AND OXIDATIVE COMPOUNDS WITH IMPROVED STABILITY AND EFFICIENCY FOR APPLICATION IN PHARMACEUTICAL COMPOSITIONS|
    RU2718554C1|2017-09-25|2020-04-08|Георгий Георгиевич Чумбуридзе|Thermostable composition, having antiviral and antibacterial activity and use thereof|
    CN107951764A|2017-11-14|2018-04-24|名臣健康用品股份有限公司|A kind of Chinese medicinal toothpaste for having effects that to prevent canker sore and repair mucous membrane of mouth|
    WO2019125829A1|2017-12-19|2019-06-27|Colgate-Palmolive Company|Oral care compositions|
    EP3810067A1|2018-06-25|2021-04-28|Triumph Pharmaceuticals Inc.|Methods of inhibiting microbial infections using zinc-containing compositions|
    EP3842041A1|2018-08-17|2021-06-30|Nibec Co., Ltd.|Composition for treating and preventing gingivoperiodontitis or peri-implantitis, and interdental brush coated with same|
    KR102117649B1|2018-08-17|2020-06-02|주식회사 나이벡|Composition for Treating and Preventing Gingivoperiodontitis or Periimplantitis and Proxabrush Coated with the Composition|
    KR20200098776A|2019-02-12|2020-08-21| 바이오에스텍|Slow-releasing type patch for relieving xerostomia|
    EP3714945A1|2019-03-29|2020-09-30|Applechem Inc.|Liquid thickener composition comprising polyalkoxylated polyols polyester having guerbet acid moieties|
    EP3714946A1|2019-03-29|2020-09-30|Applechem Inc.|Topical preparations comprising polyalkoxylated polyols polyester with guerbet acid|
    WO2022014675A1|2020-07-16|2022-01-20|国立大学法人大阪大学|Oral medicine|
    WO2022018478A1|2020-07-20|2022-01-27|Ghoreishi Javad|Oral hygiene compositions|
    RU2762506C1|2021-01-20|2021-12-21|Общество С Ограниченной Ответственностью «Диамед-Фарма»|Agent for applying oral and nasal cavities and method for its use as part of complex therapy of infectious and inflammatory diseases of nasal and oral cavities|
    法律状态:
    2021-03-02| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|
    2021-03-09| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|
    2021-03-09| B07D| Technical examination (opinion) related to article 229 of industrial property law [chapter 7.4 patent gazette]|Free format text: DE ACORDO COM O ARTIGO 229-C DA LEI NO 10196/2001, QUE MODIFICOU A LEI NO 9279/96, A CONCESSAO DA PATENTE ESTA CONDICIONADA A ANUENCIA PREVIA DA ANVISA. CONSIDERANDO A APROVACAO DOS TERMOS DO PARECER NO 337/PGF/EA/2010, BEM COMO A PORTARIA INTERMINISTERIAL NO 1065 DE 24/05/2012, ENCAMINHA-SE O PRESENTE PEDIDO PARA AS PROVIDENCIAS CABIVEIS. |
    2021-03-23| B06I| Publication of requirement cancelled [chapter 6.9 patent gazette]|Free format text: ANULADA A PUBLICACAO CODIGO 6.6.1 NA RPI NO 2618 DE 09/03/2021 POR TER SIDO INDEVIDA. |
    2021-04-13| B07G| Grant request does not fulfill article 229-c lpi (prior consent of anvisa) [chapter 7.7 patent gazette]|
    2021-04-20| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|
    2021-08-31| B06A| Patent application procedure suspended [chapter 6.1 patent gazette]|
    2021-12-07| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|
    2021-12-14| B350| Update of information on the portal [chapter 15.35 patent gazette]|
    2021-12-28| B09X| Republication of the decision to grant [chapter 9.1.3 patent gazette]|
    2022-02-01| B16A| Patent or certificate of addition of invention granted [chapter 16.1 patent gazette]|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 05/08/2011, OBSERVADAS AS CONDICOES LEGAIS. PATENTE CONCEDIDA CONFORME ADI 5.529/DF, QUE DETERMINA A ALTERACAO DO PRAZO DE CONCESSAO. |
    优先权:
    申请号 | 申请日 | 专利标题
    US37169510P| true| 2010-08-07|2010-08-07|
    US37169610P| true| 2010-08-07|2010-08-07|
    US61/371,695|2010-08-07|
    US61/371,696|2010-08-07|
    PCT/US2011/046831|WO2012021415A2|2010-08-07|2011-08-05|Oral compositions comprising a zinc compound and an anti-microbial agent|
    [返回顶部]