Patent Application
20220387279
Biofilms form when bacteria adhere to surfaces in some form of watery environment and begin to excrete a slimy, glue-like substance that can stick to all kinds of materials—metals, plastics, soil particles, medical implant materials, biological tissues. Dental plaque is a biofilm that adheres to tooth and other oral surfaces, particularly at the gingival margin, and is implicated in the occurrence of gingivitis, periodontitis, caries and other forms of periodontal disease. Dental plaque is cohesive and highly resistant to removal from teeth and/or oral surfaces. Bacteria associated with dental plaque convert sugar to glucans, which are insoluble polysaccharides that provide plaque with its cohesive properties. Anaerobic bacteria in plaque metabolize sugar to produce acids which dissolve tooth minerals, damaging the enamel and eventually forming dental caries. Saliva can buffer acids produced by bacteria and promote remineralization of the enamel, but extensive plaque can block the saliva from contact with the enamel. Redeposition of minerals in the biofilm forms a hard deposit on the tooth called calculus (or tartar), which becomes a local irritant for the gums, causing gingivitis.
Various antibacterial agents can retard the growth of bacteria and thus reduce the formation of biofilm on oral surfaces. In many cases, these antibacterial agents are cationic, for example quaternary ammonium surfactants such as cetyl pyridinium chloride (CPC), bisbiguanides such as chlorhexidine, metal cations such as zinc or stannous ions, and guanidines such as arginine.
However, while those in the field have explored the use of certain antiseptic and bactericidal agents such as bisbiguanide agents (e.g., chlorhexidine) in oral care products (e.g., mouthwash), one challenge in these formulations is to stabilize it in a higher-complex system such as gels and toothpaste. Chlorhexidine can be a very sensitive compound which is often required to be in a positive-charged form to provide the therapeutic benefits. Anything in the formula, for example anionic compounds, some impurities coming from raw materials or certain conditions (pH), have the potential to deactivate chlorhexidine which can make it ineffective from a therapeutic standpoint.
Accordingly, there is a need for an oral care product that contains a bisbiguanide agent (e.g., chlorhexidine) that can be formulated in a higher-complex system such as gels and toothpaste and allow for effective delivery to a consumer.
It is surprisingly found that the addition of a stabilizing amount of a nonionic gelling and thickening agent, e.g., a nonionic cellulose ether, (e.g., hydroxyethyl cellulose (HEC)), to formulations comprising a bisbiguanide (e.g., chlorhexidine (CHX)) agent allows for proper structure and consistency to the formulation to allow it to be used as a gel or a toothpaste and facilities delivery of a bisbiguanide (e.g., chlorhexidine) to the teeth or gums. For example, in one aspect, formulas containing 1.75% of HEC demonstrate acceptable consistency and structure while providing excellent CHX recovery (min. 90%) when it is added at 0.12% and 0.20%. In another aspect, formulas of the present invention containing 0.12% CHX and 0.20% CHX were submitted to aging tests and completed the studies (13 weeks) with satisfactory results. CHX levels remained within the specification (min. 90% recovery) and p-chloroaniline (pCA), a toxic compound, below 3 ppm.
The disclosure thus provides, in one embodiment, oral care compositions comprising:
The disclosure further provides methods of treating and/or inhibiting dental plaque, gingivitis, dental erosion, staining, and/or biofilm formation comprising administering to the oral cavity a composition as described in any of Composition 1, et seq. In one aspect, the oral care composition described herein would be used in a professional setting to help the patient who, for instance, underwent a surgery (as a post-oral surgery) or is in need of intense care due to severe gum conditions and thus requiring product application on targeted areas.
In one aspect, the compositions of the would be for professional administration to a patient who, for instance, underwent a surgery (as a post-oral surgery) or is in need of intense care due to severe gum conditions and thus requiring product application on targeted area. In some aspects, the compositions of the present invention (e.g., any of Composition 1 et seq) is in the form of a gel that can be delivered using a syringe and/or gel pen applicator.
Further areas of applicability of the present invention will become apparent from the detailed description provided hereinafter. It should be understood that the detailed description and specific examples, while indicating the preferred embodiment of the invention, are intended for purposes of illustration only and are not intended to limit the scope of the invention.
The following description of the preferred embodiment(s) is merely exemplary in nature and is in no way intended to limit the invention, its application, or uses.
As used throughout, 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. In addition, all references cited herein are hereby incorporated by referenced in their entireties. In the event of a conflict in a definition in the present disclosure and that of a cited reference, the present disclosure controls.
Unless otherwise specified, all percentages and amounts expressed herein and elsewhere in the specification should be understood to refer to percentages by weight of the total composition. Unless specified otherwise, the amounts given are based on the active weight of the material.
As is usual in the art, the compositions described herein are sometimes described in terms of their ingredients, notwithstanding that the ingredients may disassociate, associate or react in the formulation. Ions, for example, are commonly provided to a formulation in the form of a salt, which may dissolve and disassociate in aqueous solution. It is understood that the invention encompasses both the mixture of described ingredients and the product thus obtained.
In a first embodiment, the disclosure provides oral care compositions (Composition 1) comprising:
For example, the disclosure provides embodiments of Composition 1 as follows:
wherein the water content is from 60%-90% by wt. of the composition.
wherein the water content is from 60%-90% by wt. of the composition.
wherein the water content is from 60%-90% by wt. of the composition.
wherein the water content is from 60%-90% by wt. of the composition
wherein the water content is from 60%-90% by wt. of the composition
wherein the water content is from 50%-90% by wt. of the composition.
Any of Composition 1 et seq where the composition is administered to a patient in need thereof who, e.g., has undergone a surgery (e.g., post-oral surgery).
Any of Composition 1 et seq where the composition is administered to a patient in need thereof wherein the patient in need thereof has severe gum conditions and wherein the product is applied to a targeted or specific area (e.g., using a pen system to deliver a gel).
In yet a further aspect, the invention contemplates a Delivery System (Delivery System 1) for administration of any of Composition 1, et seq to a patient in need thereof. In one aspect the delivery system comprises any of Composition 1, et seq, wherein the composition is a gel. In another aspect, the delivery system comprises a syringe for administration of the composition of any of Composition 1, et seq (e.g., wherein the syringe is used by a professional).
In another aspect the delivery system comprises both a syringe and a dental pen for administration of any of Composition 1, et seq.
As used herein, an “oral care composition” refers to a composition for which the intended use includes oral care, oral hygiene, and/or oral appearance, or for which the intended method of use comprises administration to the oral cavity, and refers to compositions that are palatable and safe for topical administration to the oral cavity, and for providing a benefit to the teeth and/or oral cavity. The term “oral care composition” thus specifically excludes compositions which are highly toxic, unpalatable, or otherwise unsuitable for administration to the oral cavity. In some embodiments, an oral care composition is not intentionally swallowed, but is rather retained in the oral cavity for a time sufficient to affect the intended utility. The oral care compositions as disclosed herein may be used in nonhuman mammals such as companion animals (e.g., dogs and cats), as well as by humans. In some embodiments, the oral care compositions as disclosed herein are used by humans. Oral care compositions include, for example, dentifrice and mouthwash. In some embodiments, the disclosure provides mouthwash formulations.
As used herein, “orally acceptable” refers to a material that is safe and palatable at the relevant concentrations for use in an oral care formulation, such as a mouthwash or dentifrice.
As used herein, “orally acceptable carrier” refers to any vehicle useful in formulating the oral care compositions disclosed herein. The orally acceptable carrier is not harmful to a mammal in amounts disclosed herein when retained in the mouth, without swallowing, for a period sufficient to permit effective contact with a dental surface as required herein. In general, the orally acceptable carrier is not harmful even if unintentionally swallowed. Suitable orally acceptable carriers include, for example, one or more of the following: water, a thickener, a buffer, a humectant, a surfactant, an abrasive, a sweetener, a flavorant, a pigment, a dye, an anti-caries agent, an anti-bacterial, a whitening agent, a desensitizing agent, a vitamin, a preservative, an enzyme, and mixtures thereof.
As used herein, “viscoelastic fluid” refers to a complex fluid that exhibits mechanical properties that are both elastic (solid-like, e.g., rubber) and viscous (liquid-like or flowable, e.g., water). A viscoelastic fluid composition may deform and flow under the influence of an applied shear stress (e.g., shaking or swishing in the mouth), but when the stress is removed, the composition will recover the deformation.
As used herein, “CHX” refers to chlorhexidine. As used herein “chlorhexidine gluconate” and “chlorhexidine digluconate” are used interchangeably, wherein the formula of chlorhexidine gluconate or chlorhexidine digluconate refers to: (1,1′-hexamethylene bis [5-(p-chlorophenyl) biguanide]di-D-gluconate).
In some embodiments the compositions of the disclosure, e.g., any of Composition 1 et seq, comprises an orally acceptable cationic active agent. As used herein, “orally acceptable cationic active agent” means an agent which is cationic in aqueous solution at neutral pH and which provides some benefit, e.g. antimicrobial, antigingivitis, and/or antierosion activity, to the teeth or oral cavity. While in aqueous formulation, the agent will generally be in solution, but it may be introduced to the formulation formulated in free or orally acceptable salt form. In certain embodiments, the orally acceptable cationic active agent is selected from one or more of quaternary ammonium surfactants (such as cetyl pyridinium chloride (CPC)), cationic amino acids (such as arginine), metal cations (such as zinc, calcium, or stannous ions), or combinations thereof.
In some embodiments the compositions of the disclosure, e.g., any of Composition 1 et seq, comprises an anionic surfactant. As used herein, “anionic surfactant” means those surface-active or detergent compounds that contain an organic hydrophobic group containing generally 8 to 26 carbon atoms or generally 10 to 18 carbon atoms in their molecular structure and at least one water-solubilizing group selected from sulfonate, sulfate, and carboxylate so as to form a water-soluble detergent. Usually, the hydrophobic group will comprise a C8-C22 alkyl, or acyl group. Such surfactants are employed in the form of water-soluble salts and the salt-forming cation usually is selected from sodium, potassium, ammonium, magnesium and mono-, di- or tri-C2-C3 alkanolammonium, with the sodium, magnesium and ammonium cations again being the usual ones chosen. Some examples of suitable anionic surfactants include, but are not limited to, the sodium, potassium, ammonium, and ethanolammonium salts of linear C8-C18 alkyl ether sulfates, ether sulfates, and salts thereof. Suitable anionic ether sulfates have the formula R(OC2H4)n OSO3M wherein n is 1 to 12, or 1 to 5, and R is an alkyl, alkylaryl, acyl, or alkenyl group having 8 to 18 carbon atoms, for example, an alkyl group of C12-C14 or C12-C16, and M is a solubilizing cation selected from sodium, potassium, ammonium, magnesium and mono-, di- and triethanol ammonium ions. Exemplary alkyl ether sulfates contain 12 to 15 carbon atoms in the alkyl groups thereof, e.g., sodium laureth (2 EO) sulfate. Some preferred exemplary anionic surfactants that may be used in the compositions of the present disclosure include sodium laurel ether sulfate (SLES), sodium lauryl sulfate, and ammonium lauryl sulfate. In certain embodiments, the anionic surfactant is present in an amount of 0.01 to 5.0%, 0.1 to 2.0%, 0.2 to 0.4%, or about 0.33%.
In some embodiments the compositions of the disclosure, e.g., any of Composition 1 et seq, comprises a nonionic surfactant. As used herein, “nonionic surfactant” generally refers to compounds produced by the condensation of alkylene oxide groups (hydrophilic in nature) with an organic hydrophobic compound which may be aliphatic or alkyl-aromatic in nature. Examples of suitable nonionic surfactants include polyethylene glycol (e.g., PEG-40 hydrogenated castor oil), poloxamers (sold under trade name PLURONIC®), polyoxyethylene, polyoxyethylene sorbitan esters (sold under trade name TWEENS®), Polyoxyl 40 hydrogenated castor oil, fatty alcohol ethoxylates, polyethylene oxide condensates of alkyl phenols, products derived from the condensation of ethylene oxide with the reaction product of propylene oxide and ethylene diamine, ethylene oxide condensates of aliphatic alcohols, alkyl polyglycosides (for example, fatty alcohol ethers of polyglycosides, such as fatty alcohol ethers of polyglucosides, e.g., decyl, lauryl, capryl, caprylyl, myristyl, stearyl and other ethers of glucose and polyglucoside polymers, including mixed ethers such as capryl/caprylyl (C8-10) glucoside, coco (C8-16) glucoside, and lauryl (C12-16) glucoside), long chain tertiary amine oxides, long chain tertiary phosphine oxides, long chain dialkyl sulfoxides, and mixtures of such materials.
In some embodiments the compositions of the disclosure, e.g., any of Composition 1 et seq, comprises a nonionic surfactant selected from the group consisting of: amine oxides, fatty acid amides, ethoxylated fatty alcohols, block copolymers of polyethylene glycol and polypropylene glycol, glycerol alkyl esters, polyoxyethytene glycol octylphenol ethers, sorbitan alkyl esters, polyoxyethylene glycol sorbitan alkyl esters, and mixtures thereof. Examples of amine oxides include, but are not limited to, laurylamidopropyl dimethylamine oxide, myristylamidopropyl dimethylamine oxide, and mixtures thereof. Examples of fatty acid amides include, but are not limited to, cocomonoethanolamide, lauramide monoethanolamide, cocodiethanolamide, and mixtures thereof. In certain embodiments, the nonionic surfactant is a combination of an amine oxide and a fatty acid amide. In certain embodiments, the amine oxide is a mixture of laurylamidopropyl dimethylamine oxide and myristylamidopropyl dimethylamine oxide. In certain embodiments, the nonionic surfactant is a combination of lauryl/myristylamidopropyl dimethylamine oxide and cocomonoethanolamide. In certain embodiments, the nonionic surfactant is present in an amount of 0.01 to 5.0%, 0.1 to 2.0%, 0.1 to 0.6%, 0.2 to 0.4%, about 0.2%, or about 0.5%
In some embodiments the compositions of the disclosure, e.g., any of Composition 1 et seq, can comprise a basic or neutral amino acid. The basic amino acids which can be used in the compositions and methods of the invention include not only naturally occurring basic amino acids, such as arginine, lysine, and histidine, but also any basic amino acids having a carboxyl group and an amino group in the molecule, which are water-soluble and provide an aqueous solution with a pH of 7 or greater.
For example, basic amino acids include, but are not limited to, arginine, lysine, serine, citrullene, ornithine, creatine, histidine, diaminobutanoic acid, diaminoproprionic acid, salts thereof or combinations thereof. In a particular embodiment, the basic amino acids are selected from arginine, citrullene, and ornithine.
In certain embodiments, the basic amino acid is arginine, for example, L-arginine, or a salt thereof.
In another aspect, the compositions of the invention (e.g., any of Compositions 1 et seq) can include a neutral amino acid, which can include, but are not limited to, one or more neutral amino acids selected from the group consisting of alanine, aminobutyrate, asparagine, cysteine, cystine, glutamine, glycine, hydroxyproline, isoleucine, leucine, methionine, phenylalanine, proline, serine, taurine, threonine, tryptophan, tyrosine, valine, and combinations thereof.
In some embodiments the compositions of the disclosure, e.g., any of Composition 1 et seq, comprises a tartar control agent. As used herein, a “tartar control agent” refers to a compound or a mixture of compounds that inhibit the formation of tartar, a mixture of calcium phosphates on organic matrices, and/or the deposition of plaque on teeth to form tartar (calculus).
In some embodiments the compositions of the disclosure, e.g., any of Composition 1 et seq, is administered as part of a method to treat or reduce staining of the enamel. As used herein, “staining” refers to a discoloration of a dental surface caused by adsorption or absorption of a color agent on or into the surface, or caused by reaction of material of the dental surface (e.g., dental enamel) with a color or noncolor agent contacting the surface.
As used herein, “dental surface” refers to a surface of a natural tooth or a hard surface of artificial dentition including a crown, cap, filling, bridge, dental implant and the like. In some embodiments, the dental surface is a natural tooth.
In some embodiments the compositions of the disclosure, e.g., any of Composition 1 et seq, are tooth gels. Any of the compositions of Composition 1, et seq. is suitable for oral care use, provided the ingredients are orally acceptable. In some embodiments, any of the compositions of the disclosure are a tooth gel, e.g, any of Composition 1, wherein the tooth gel comprises an effective amount of an orally acceptable bisbiguanide (e.g., chlorhexidine) (e.g., chlorhexidine digluconate), which is an antimicrobial, antigingivitis, anti-erosion and/or anti-caries agent, a nonionic cellulose ether (e.g., hydroxyethyl cellulose), and a pyridinium surfactant (e.g., cetyl pyridinium chloride), wherein the nonionic cellulose ether is in an amount effective to stabilize the bisbiguanide in the tooth gel.
The oral care composition used in the present disclosure can comprise significant levels of water. Water employed in the preparation of commercial oral compositions should be deionized and free of organic impurities. The amount of water in the compositions includes the free water that is added plus that amount which is introduced with other materials.
In certain embodiments the compositions of the disclosure, e.g., any of Composition 1 et seq, can comprise a humectant. Humectants can enhance the viscosity, mouthfeel, and sweetness of the product, and may also help preserve the product from degradation or microbial contamination. Suitable humectants include edible polyhydric alcohols such as glycerin, sorbitol, xylitol, propylene glycol as well as other polyols and mixtures of these humectants. Sorbitol may in some cases be provided as a hydrogenated starch hydrolysate in syrup form, which comprises primarily sorbitol (the product if the starch were completely hydrolyzed to glucose, then hydrogenated), but due to incomplete hydrolysis and/or presence of saccharides other than glucose, may also include other sugar alcohols such mannitol, maltitol, and longer chain hydrogenated saccharides, and these other sugar alcohols also function as humectants in this case. In some embodiments, humectants are present at levels of 5% to 30%, e.g., 10% to 20% by weight.
In certain embodiments the compositions of the disclosure, e.g., any of Composition 1 et seq, can comprise a flavoring. Flavorings for use in the present invention may include extracts or oils from flavorful plants such as peppermint, spearmint, cinnamon, wintergreen, and combinations thereof, cooling agents such as menthol, methyl salicylate, as well as sweeteners, which may include polyols (which also function as humectants), saccharin, acesulfame, aspartame, neotame, stevia and sucralose.
Further provided is a method (Method A) for the treatment and/or inhibition of a gingivitis, plaque, and/or tartar on a dental surface, comprising contacting the dental surface with any of the preceding oral care compositions.
Further provided herein is Method A as follows:
Further provided is a method (Method B) for the treatment and/or inhibition of gum disease comprising contacting the oral cavity with any of the preceding oral care compositions.
Further provided herein is Method B as follows:
Further provided is a method (Method C) for the treatment and/or inhibition of halitosis comprising contacting the oral cavity with any of the preceding oral care compositions.
Further provided herein is Method C as follows:
Further provided is a method (Method D) for inhibiting biofilm formation on a dental surface comprising contacting the dental surface with any of the preceding oral care compositions.
Further provided herein is Method D as follows:
Further provided is a method (Method E) for treating and/or inhibiting bacteria from aggregating and forming bigger colonies in an oral cavity comprising contacting the oral cavity with any of the preceding oral care compositions.
Further provided herein is Method E as follows:
Further provided are any of Composition 1, et seq. for use in any of Methods A-E.
As used herein, “inhibition” refers to reduction of stains that would otherwise form or develop subsequent to the time of the treatment. Such inhibition can range from a small but observable or measurable reduction to complete inhibition of subsequent staining, by comparison with an untreated or placebo-treated dental surface.
A randomized, examiner blind clinical study is conducted to assess the clinical efficacy the chlorhexidine delivery system of the present invention. The study is designed to assess the reduction of periodontal outcomes in non-surgical periodontal adults.
The study looks at three separate treatments:
The study is designed as a phase II, randomized, examiner-blind, three-cell, parallel-group design. Dental plaque and gingivitis are assessed via Silness and Loe Plaque Index and Loe-Silness Gingival Index for each of the regimen groups. Periodontal parameters include probing pocket depths and clinical attachment level measurements. All subjects are provided with their assigned regimen at baseline. They are instructed to brush their teeth for one minute twice daily (morning and evening) with the toothpaste and toothbrush provided. Subjects in the rinsing regimens were instructed to rinse for 30 seconds with 15 ml of their assigned mouthwash twice daily (morning and evening) after brushing their teeth. Subjects assigned to the gel pen regimen are instructed to brush their teeth followed by use of the gel pen as per instructions provided by the study personnel.
Participants are instructed to repeat the same procedure twice daily for the duration of the study. The use of the mouthwash and gel treatment starts with the periodontal therapy and continues for a period of 2 weeks. After 2 weeks of product use, participants are instructed to discontinue use of their mouthwash/gel and to continue using the toothpaste and toothbrush provided for the duration of the study. Subsequent evaluations are performed at the 2-month examination. After the 2-month evaluation, all subjects discontinued product use and returned to their normal oral hygiene regime.
Generally, the results of the study indicate that the primary endpoint demonstrate significant reductions in dental plaque and gingivitis for the novel chlorhexidine delivery system (“Treatment 1”) as compared to a test regimen comprising of an in-office syringe containing 0.12% chlorhexidine gel, a mouthwash containing 0.12% chlorhexidine gluconate, commercial toothpaste and soft bristle toothbrush (“Treatment 2”) and a Commercial mouthwash regimen including only a commercial mouthwash containing 0.12% chlorhexidine gluconate and commercial toothpaste and a soft bristle toothbrush (“Treatment 3”). The results of the study are detailed in Tables 1-7 described below:
(*Note: A positive value in “% change” or “% difference” indicates a reduction in index scores in that column for Tables 1-7)
Gingival Index
Table 1 presents a summary of the baseline-adjusted mean gingival index scores measured at the 2-week examination.
Comparisons versus baseline: The baseline-adjusted mean gingival index scores at the 2-week examination were 0.54 for subjects assigned to the Treatment 1 Regimen, 0.57 for subjects assigned to the Treatment 2 Regimen and 0.71 for subjects assigned to the Treatment 3 (control) Regimen. The percent changes from baseline were 73.6% for the Treatment 1, 71.9% for the Treatment 2 Regimen and 65.4% for the Treatment 3 Regimen (control), of which all of the regimen groups were statistically significant (p<0.001).
Comparison between treatment groups: Relative to subjects in the Treatment 3 regimen (control), subjects in the Treatment 1 and Treatment 2 groups did show trends in reductions in the Index Score but did not exhibit statistically significant reductions 23.9% (p=0.209) and 19.7% (p=0.342), respectively, in gingival index scores at the 2-week examination. Relative to subjects in the Treatment 2 Regimen, subjects in the Treatment 1 did also show trends in the reduction in the Index Score but did not exhibit a statistically significant reduction 5.3% (p=0.949) in gingival index scores at the 2-week examination.
Plaque Index
Table 1 presents a summary of the baseline-adjusted mean plaque index scores measured at the 2-week examination.
Comparisons versus baseline: The baseline-adjusted mean plaque index scores at the 2-week examination were 0.46 for subjects assigned to the Treatment 1, 0.51 for subjects assigned to the Treatment 2 regimen and 0.58 for subjects assigned to the Treatment 3 regimen. The percent changes from baseline were 70.2% for the Treatment 1 group, 67.7% for the Mouthwash Regimen and 63.5% for the Commercial mouthwash regimen, of which all of the regimen groups were statistically significant (p<0.001).
Comparison between treatment groups: Relative to subjects in the Treatment 3 regimen, subjects in the Treatment 1 and Treatment 2 regimens did show a trend in reduction of the Index Score but did not exhibit statistically significant reductions 20.7% (p=0.475) and 12.1% (p=0.805), respectively, in plaque index scores at the 2-week examination.
Relative to subjects in the Treatment 2 regimen, subjects in the Treatment 1 did show trends in the reduction of the Index Score but did not exhibit a statistically significant reduction 9.8% (p=0.852) in plaque index scores at the 2-week examination.
Gingival Severity Index
Table 2 presents a summary of the baseline-adjusted mean gingival severity index scores measured at the 2-week examination.
Comparisons versus baseline: The baseline-adjusted mean gingival severity index scores at the 2-week examination were 0.02 for subjects assigned to the Treatment 1, 0.06 for subjects assigned to the Treatment 2 Regimen and 0.11 for subjects assigned to the Treatment 3 Regiment. The percent changes from baseline were 97.8% for the Treatment 1 Regimen, 93.5% for the Treatment 2 Regimen and 88.0% for the Treatment 3 regimen, of which all of the regimen groups were statistically significant (p<0.001).
Comparison between treatment groups: Relative to subjects in the Treatment 3 Control Regimen, subjects in the Treatment 1 exhibit a statistically significant reduction of 81.8% (p=0.042) in gingival severity index scores at the 2-week examination. Whereas, relative to subjects in the Treatment 3 control regimen, subjects in the Treatment 2 regimen did show a trend to a reduction in the Index Score but did not exhibit a statistically significant reduction 45.5% (p=0.341) in gingival severity index scores at the 2-week examination.
Relative to subjects in the Treatment 2 regimen, subjects in the Treatment 1 did show a trend in the reduction of the Index Score but did not exhibit a statistically significant reduction 66.7% (p=0.524) in gingival severity index scores at the 2-week examination.
Plaque Severity Index
Table 2 presents a summary of the baseline-adjusted mean plaque severity index scores measured at the 2-week examination.
Comparisons versus baseline: The baseline-adjusted mean plaque severity index scores at the 2-week examination were 0.06 for subjects assigned to the Treatment 1, 0.09 for subjects assigned to the Treatment 2 and 0.12 for subjects assigned to the Treatment 3 (control) Regiment. The percent changes from baseline were 89.1% for the Treatment 1 Regimen, 85.0% for the Treatment 2 regimen and 79.3% for the Treatment 3 regimen (control), of which all of the regimen groups were statistically significant (p<0.001).
Comparison between treatment groups: Relative to subjects in the Treatment 3 (control), subjects in the Treatment 1 and Treatment 2 Regimens did show trends in the reductions of the Index Scores but did not exhibit statistically significant reductions 50.0% (p=0.347) and 25.0% (p=0.734), respectively, in plaque severity index scores at the 2-week examination.
Relative to subjects in the Treatment 2 Regimen, subjects in the Treatment 1 did show a trend in the reduction of the Index Score but did not exhibit a statistically significant reduction 33.3% (p=0.792) in plaque severity index scores at the 2-week examination.
Gingival Interproximal Index
Table 3 presents a summary of the baseline-adjusted mean gingival interproximal index scores measured at the 2-week examination.
Comparisons versus baseline: The baseline-adjusted mean gingival interproximal index scores at the 2-week examination were 0.68 for subjects assigned to the Treatment 1, 0.72 for subjects assigned to the Treatment 2 Regimen and 0.87 for subjects assigned to the Treatment 3 regimen. The percent changes from baseline were 67.5% for the Treatment 1, 65.6% for the Treatment 2 regiment and 58.8% for the Treatment 3 regimen (control), of which all of the regimen groups were statistically significant (p<0.001).
Comparison between treatment groups: Relative to subjects in the Treatment 3 regimen (control), subjects in the Treatment 1 and Treatment 2 regimens did show trends in the reduction of the Index Scores but did not exhibit statistically significant reductions 21.8% (p=0.223) and 17.2% (p=0.387), respectively, in gingival interproximal index scores at the 2-week examination.
Relative to subjects in the Treatment 2 regimen, subjects in the Treatment 1 did show a trend to a reduction in the Index Score but did not exhibit a statistically significant reduction 5.6% (p=0.933) in gingival interproximal index scores at the 2-week examination.
Plaque Interproximal Index
Table 3 presents a summary of the baseline-adjusted mean plaque interproximal index scores measured at the 2-week examination.
Comparisons versus baseline: The baseline-adjusted mean plaque interproximal index scores at the 2-week examination were 0.63 for subjects assigned to the Treatment 1, 0.67 for subjects assigned to the Treatment 2 Regimen and 0.74 for subjects assigned to the Treatment 3 (control) regimen. The percent changes from baseline were 62.2% for the Treatment 1, 60.7% for the Treatment 2 Regimen and 56.0% for the Treatment 3 regimen, of which all of the regimen groups were statistically significant (p<0.001).
Comparison between treatment groups: Relative to subjects in the Treatment 3 (control) Regimen, subjects in the Treatment 1 and Treatment 2 Regimens did show trends to a reduction in Index Scores but did not exhibit statistically significant reductions 14.9% (p=0.581) and 9.5% (p=0.802), respectively, in plaque interproximal index scores at the 2-week examination.
Relative to subjects in the Treatment 2 Regimen, subjects in the Treatment 1 did show a trend to the a reduction in the Index Score but did not exhibit a statistically significant reduction 5.9% (p=0.931) in plaque interproximal index scores at the 2-week examination.
Gingival Index
Table 4 presents a summary of the baseline-adjusted mean gingival index scores measured at the 2-month examination.
Comparisons versus baseline: The baseline-adjusted mean gingival index scores at the 2-month examination were 0.18 for subjects assigned to the Treatment 1, 0.32 for subjects assigned to the Treatment 2 Regimen and 0.47 for subjects assigned to the Treatment 3 (control) Regimen. The percent changes from baseline were 92.0% for the Treatment 1 Regimen, 84.2% for the Treatment 2 Regimen and 76.1% for the Treatment 3 mouthwash regimen (control), of which all of the regimen groups were statistically significant (p<0.001).
Comparison between treatment groups: Relative to subjects in the Treatment 3 (control) Regimen, subjects in the Treatment 1 exhibited a statistically significant reduction 61.7% (p=0.009) in gingival index scores at the 2-month examination. Whereas, relative to the subjects in the Treatment 3 regimen, subjects in the Treatment 2 Regimen did show a trend to a reduction in the Index Score but did not exhibit a statistically significant reduction 31.9% (p=0.240) in gingival index scores at the 2-month examination.
Relative to subjects in the Treatment 2 Regimen, subjects in the Treatment 1 did show a trend to a reduction in the Index Score but did not exhibit a statistically significant reduction 43.8% (p=0.306) in gingival index scores at the 2-month examination.
Plaque Index Table 4 presents a summary of the baseline-adjusted mean plaque index scores measured at the 2-month examination.
Comparisons versus baseline: The baseline-adjusted mean plaque index scores at the 2-month examination were 0.32 for subjects assigned to the Treatment 1, 0.47 for subjects assigned to the Treatment 2 Regimen and 0.65 for subjects assigned to the Treatment 3 Regimen (control). The percent changes from baseline were 79.5% for the Treatment 1 Regimen, 69.5% for the Treatment 2 Regimen and 58.3% for the Treatment 3 regimen, of which all of the regimen groups were statistically significant (p<0.001).
Comparison between treatment groups: Relative to subjects in the Treatment 3 (control) Regimen, subjects in the Treatment 1 exhibited a statistically significant reduction 50.8% (p=0.003) in plaque index scores at the 2-month examination. Whereas, relative to the subjects in the Treatment 3 regimen, subjects in the Treatment 2 Regimen demonstrated a trend in the reduction of the Index Score but did not exhibit a statistically significant reduction 27.7% (p=0.141) in plaque index scores at the 2-month examination.
Relative to subjects in the Treatment 2 Regimen, subjects in the Treatment 1 demonstrated a trend in the reduction of the Index Score but did not exhibit a statistically significant reduction 31.9% (p=0.267) in plaque index scores at the 2-month examination.
Gingival Severity Index
Table 5 presents a summary of the baseline-adjusted mean gingival severity index scores measured at the 2-month examination.
Comparisons versus baseline: The baseline-adjusted mean gingival severity index scores at the 2-month examination were 0.00 for subjects assigned to the Treatment 1, 0.01 for subjects assigned to the Treatment 2 Regimen and 0.04 for subjects assigned to the Treatment 3 Regimen (control). The percent changes from baseline were 100.0% for the Treatment 1 Regimen, 98.5% for the Treatment 2 Regimen and 95.7% for the Treatment 3 regimen (control), of which all of the regimen groups were statistically significant (p<0.001).
Comparison between treatment groups: Relative to subjects in the Treatment 3 (control) Regimen, subjects in the Treatment 1 and Treatment 2 demonstrated trends in the reduction of the Index Scores but did not exhibit statistically significant reductions 100.0% (p=0.279) and 75.0% (p=0.543), respectively, in gingival severity index scores at the 2-month examination.
Relative to subjects in the Treatment 2 Regimen, subjects in the Treatment 1 demonstrated a trend in the reduction of the Index Score but did not exhibit a statistically significant reduction 100.0% (p=0.876) in gingival severity index scores at the 2-month examination.
Plaque Severity Index
Table 5 presents a summary of the baseline-adjusted mean plaque severity index scores measured at the 2-month examination.
Comparisons versus baseline: The baseline-adjusted mean plaque severity index scores at the 2-month examination were 0.04 for subjects assigned to the Treatment 1, 0.08 for subjects assigned to the Treatment 2 and 0.13 for subjects assigned to the Treatment 3 (control) Regimen. The percent changes from baseline were 92.7% for the Treatment 1 Regimen, 86.7% for the Treatment 2 Regimen and 77.6% for the Treatment 3 regimen, of which all of the regimen groups were statistically significant (p<0.001).
Comparison between treatment groups: Relative to subjects in the Treatment 3 (control) Regimen, subjects in the Treatment 1 exhibited a statistically significant reduction 69.2% (p=0.012) in plaque severity index scores at the 2-month examination. Whereas, relative to the subjects in the Treatment 3 regimen (control), subjects in the Treatment 2 Regimen demonstrated a trend in the reduction of the Index Score but did not exhibit a statistically significant reduction 38.5% (p=0.235) in plaque severity index scores at the 2-month examination.
Relative to subjects in the Treatment 2 Regimen, subjects in the Treatment 1 demonstrated a trend in the reduction of the Index Score but did not exhibit a statistically significant reduction 50.0% (p=0.378) in plaque severity index scores at the 2-month examination.
Gingival Interproximal Index
Table 6 presents a summary of the baseline-adjusted mean gingival interproximal index scores measured at the 2-month examination.
Comparisons versus baseline: The baseline-adjusted mean gingival interproximal index scores at the 2-month examination were 0.22 for subjects assigned to the Treatment 1, 0.41 for subjects assigned to the Treatment 2 Regimen and 0.59 for subjects assigned to the Treatment 3 regimen (control). The percent changes from baseline were 89.5% for the Treatment 1, 80.9% for the Treatment 2 Regimen and 71.6% for the Treatment 3 Regimen (control), of which all of the regimen groups were statistically significant (p<0.001).
Comparison between treatment groups: Relative to subjects in the Treatment 3 (control) Regimen, subjects in the Treatment 1 exhibited a statistically significant reduction 62.7% (p=0.008) in gingival interproximal index scores at the 2-month examination. Whereas, relative to the subjects in the Commercial mouthwash regimen, subjects in the Treatment 2 Regimen demonstrated a trend in the reduction of the Index Score but did not exhibit a statistically significant reduction 30.5% (p=0.269) in gingival interproximal index scores at the 2-month examination.
Relative to subjects in the Treatment 2 Regimen, subjects in the Treatment 1 exhibited a trend in the reduction of the Index Score but did not exhibit a statistically significant reduction 46.3% (p=0.258) in gingival interproximal index scores at the 2-month examination.
Plaque Interproximal Index
Table 6 presents a summary of the baseline-adjusted mean plaque interproximal index scores measured at the 2-month examination.
Comparisons versus baseline: The baseline-adjusted mean plaque interproximal index scores at the 2-month examination were 0.45 for subjects assigned to the Treatment 1 Regimen, 0.60 for subjects assigned to the Treatment 2 Regimen and 0.81 for subjects assigned to the Treatment 3 regimen (control). The percent changes from baseline were 73.8% for the Treatment 1, 64.2% for the Treatment 2 Regimen and 51.2% for the Treatment 3 regimen (control), of which all of the regimen groups were statistically significant (p<0.001).
Comparison between treatment groups: Relative to subjects in the Treatment 3 Regimen (control), subjects in the Treatment 1 exhibited a statistically significant reduction 44.4% (p=0.006) in plaque interproximal index scores at the 2-month examination. Whereas, relative to the subjects in the Commercial mouthwash regimen, subjects in the Treatment 2 Regimen demonstrated a trend in the reduction of the Index Score but did not exhibit a statistically significant reduction 29.5% (p=0.151) in plaque interproximal index scores at the 2-month examination.
Relative to subjects in the Treatment 2 Regimen, subjects in the Treatment 1 demonstrated a trend in the reduction of the Index Score but did not exhibit a statistically significant reduction 25.0% (p=0.379) in plaque interproximal index scores at the 2-month examination.
Probing Depth
Comparison between treatment groups: Table 7 shows probing depth reduction at 2-week and 2-month evaluation after non-surgical periodontal treatment, for each regimen Subjects assigned to the Treatment 1, at the 2-week examination, exhibited a mean probing depth reduction of 2.6 (+/−0.7) mm, while Treatment 2 Regimen and Treatment 3 (control) regimen showed 2.7(+/−0.8) mm and 2.4 (+/−0.7) mm, respectively, with no statistically significant differences among regimens (p=0.544). Similarly, at the 2-month examination, no statistically significant difference among groups were noted (p=0.826) with Treatment 1 subjects exhibiting a mean probing depth reduction of 3.2(+/−0.5) mm and Treatment 2 Regimen and Treatment 3 regimen (control) showing 3.2(+/−0.5) mm and 3.1(+/−0.5) mm, respectively.
Clinical Attachment Levels
Comparison between treatment groups: Table 7 shows the clinical attachment level gains after non-surgical periodontal treatment, at 2-week and 2-month evaluation for each regimen, At the 2-week examination, Treatment 1 exhibited a mean clinical attachment level gain of 2.7(+/−1.0) mm, while Treatment 2 Regimen and Treatment 3 (control) regimen showed 2.7(+/−0.8 mm and 2.4(+/−0.7) mm, respectively, with no statistically significant difference among the regimens (p=0.589). At the 2-month examination, no statistically significant differences among groups were noted (p=0.753). Treatment 1 showed a mean clinical attachment level gain of 3.3(+/−0.7) mm while Treatment 2 and the Treatment 3 (control) regimen showed 3.3(+/−0.5) mm and 3.1(+/−0.5) mm, respectively.
The following are representative formulations of the present invention:
This application claims the benefit of priority to U.S. Provisional Patent Application Ser. No. 63/193,479, filed May 26, 2021, the contents of which are incorporated herein by reference in its entirety.
| Number | Date | Country | |
|---|---|---|---|
| 63193479 | May 2021 | US |
