Methods for evaluating oral care products and apparatuses thereof

Abstract

Methods and apparatuses for evaluating the barrier properties of an oral care product disposed on a mucosal surface are disclosed herein. In accordance with one aspect, provided is a method comprising obtaining an oral care product; positioning the oral care product to have a first surface contacting a permeable substrate; contacting the permeable substrate and the first surface of the oral care product with a first solution, the first solution being selected from a media or an inoculum; and contacting a second surface of the oral care product with a second solution, the second solution being selected from the other of the media or the inoculum.

Description

Docket No. 1017189-00- WO-Ol-OCMETHODS FOR EVALUATING ORAL CARE PRODUCTS AND APPARATUSES THEREOFCROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of priority from U.S. Patent Application No. 63 / 729,029, titled Methods For Evaluating Oral Care Products And Apparatuses Thereof, which was filed on December 6, 2024, the content of which is hereby incorporated herein by reference in their entirety.BACKGROUND

[0002] Tissue health in the oral cavity is a constant concern for many individuals. However, various factors including the high degree of moisture in the oral cavity and an individual’s personal oral sensitivity level makes it difficult to properly treat certain oral conditions. Hyaluronic acid is the most abundant glycosaminoglycan of higher molecular weight in the extracellular matrix of soft periodontal tissues and has been linked to improved tissue health through actions such as reducing inflammation.

[0003] Although there has been recent improvements in creating patches and pads that can improve health in the oral cavity, there is still a need in creating a more stable and beneficial product that can deliver additional benefits. The research and development process for such patches and pads, which can provide health benefits to the oral cavity, can be time consuming and expensive. In addition, certain patches and pads providing health benefits to the oral cavity can require regulator review and approval, which can increase the cost of developing such patches and pads.BRIEF SUMMARY

[0004] This summary is intended merely to introduce a simplified summary of some aspects of one or more implementations of the present disclosure. Further areas of applicability of the present disclosure will become apparent from the detailed description provided hereinafter. This summary is not an extensive overview, nor is it intended to identify key or critical elements of the present teachings, nor to delineate the scope of the disclosure. Rather, its purpose is merely to present one or more concepts in simplified form as a prelude to the detailed description below.

[0005] Aspects of the invention are directed to methods for evaluating the barrier properties of anDocket No. 1017189-00- WO-Ol-OC oral care product disposed on a mucosal surface. Tn accordance with an aspect, provided is a method comprising obtaining an oral care product; positioning the oral care product to have a first surface contacting a permeable substrate; contacting the permeable substrate and the first surface of the oral care product with a first solution, the first solution being selected from a media or an inoculum; and contacting a second surface of the oral care product with a second solution, the second solution being selected from the other of the media or the inoculum.

[0006] In accordance with another aspect, provided is a method comprising obtaining an oral care product having a first surface and a second surface opposed the first surface; positioning the oral care product to have the first surface of the oral care product contacting a permeable substrate; contacting the permeable substrate and the first surface of the oral care product with a first solution, the first solution being selected from a media or an inoculum; contacting the second surface of the oral care product with a second solution, the second solution being selected from the other of the media or the inoculum.

[0007] In accordance with additional aspects, provided is an apparatus for evaluating the barrier properties of an oral care product. The apparatus typically comprises a first chamber comprising a permeable wall and an inner surface defining a first cavity, the permeable wall comprising a first surface and an opposed second surface and one or more aperture extending from the first surface to the second surface; and a second chamber comprising an inner surface defining a second cavity, the second cavity being fluidically coupled to the first cavity by way of the one or more aperture of the permeable wall.

[0008] In accordance with further aspects, provided is a method for evaluating the barrier properties of an oral care product disposed on a mucosal surface using apparatus according to the present disclosure. The method may comprise positioning an oral care product to have a first surface contacting the permeable wall of the first chamber of the apparatus; at least partially filling the first chamber of the apparatus with a first solution such that the first solution is in fluidic communication with the first surface of the oral care product, wherein the first solution is selected from a media or an inoculum; and at least partially filling the second chamber of the apparatus with a second solution such that the second solution is in fluidic communication with a second surface of the oral care product, wherein the second solution is selected from the other of the media or the inoculum, and wherein the second solution is not in direct contact with the first solution.

[0009] A list of non-limiting embodiments in accordance with aspects of the invention is providedDocket No. 1017189-00- WO-Ol-OC below:

[0010] In accordance with an embodiment 1, a method is provided for evaluating the barrier properties of an oral care product disposed on a mucosal surface, the method comprising: obtaining an oral care product; positioning the oral care product to have a first surface contacting a permeable substrate; contacting the permeable substrate and the first surface of the oral care product with a first solution, the first solution being selected from a media or an inoculum; and contacting a second surface of the oral care product with a second solution, the second solution being selected from the other of the media or the inoculum.

[0011] In accordance with an embodiment 2, provided is the method according to embodiment 1, wherein the first solution is the media.

[0012] In accordance with an embodiment 3, provided is the method according to embodiment 1 or embodiment 2, wherein the second solution is the inoculum.

[0013] In accordance with an embodiment 4, provided is the method according to any foregoing embodiment further comprising: maintaining the contact of the first solution with the first surface of the oral care product and the contact of the second solution with the second surface of the oral care product for a period of time.

[0014] In accordance with an embodiment 5, provided is the method according to embodiment 4, wherein the period of time is from about 30 minutes to about 72 hours.

[0015] In accordance with an embodiment 6, provided is the method according to any embodiment 4 or embodiment 5 further comprising: evaluating the media after the period of time.

[0016] In accordance with an embodiment 7, provided is the method according to embodiment 6, wherein the media is evaluated by determining the optical density of the media.

[0017] In accordance with an embodiment 8, provided is the method according to embodiment 6 or embodiment 7, wherein the media is evaluated to determine the total amount of bacteria cells in the media.

[0018] In accordance with an embodiment 9, provided is the method according to embodiment 8, wherein the total amount of bacterial cells in the media is evaluating using at least SYTO9 dye.

[0019] In accordance with an embodiment 10, provided is the method according to any one of embodiments 6 to 9, wherein the media is evaluated to determine the total number of dead bacteria cells in the media.

[0020] In accordance with an embodiment 11, provided is the method according to embodimentDocket No. 1017189-00- WO-Ol-OC10, wherein the total amount of dead bacterial cells in the media is evaluating using at least a propidium iodide dye.

[0021] In accordance with an embodiment 12, provided is the method according to any foregoing embodiment, wherein the second solution is not initially in direct contact with the first solution.

[0022] In accordance with an embodiment 13, provided is an apparatus for evaluating the barrier properties of an oral care product comprising: a first chamber comprising a permeable wall and an inner surface defining a first cavity, the permeable wall comprising a first surface and an opposed second surface and one or more aperture extending from the first surface to the second surface; a second chamber comprising an inner surface defining a second cavity, the second cavity being fluidically coupled to the first cavity by way of the one or more aperture of the permeable wall.

[0023] In accordance with an embodiment 14, provided is the method according to embodiment 13, wherein the first chamber is positioned at least partially within the cavity of the second chamber.

[0024] In accordance with an embodiment 15, provided is the method according to embodiment 13 or embodiment 14, wherein the first chamber is positioned within the cavity of the second chamber.

[0025] In accordance with an embodiment 16, provided is the method according to any one of embodiments 13 to 15, wherein the first surface of the permeable wall forms at least a portion of the inner surface of the first chamber.

[0026] In accordance with an embodiment 17, provided is the method according to any one of embodiments 13 to 16, wherein the permeable wall is flat.

[0027] In accordance with an embodiment 18, provided is the method according to any one of embodiments 13 to 17, wherein the permeable wall is convex such that an apex of the permeable wall extends in the direction of the center of the first chamber.

[0028] In accordance with an embodiment 19. provided is a method for evaluating the barrier properties of an oral care product disposed on a mucosal surface using the apparatus according to any one of embodiments 13 to 18, the method comprising: positioning an oral care product to have a first surface contacting the permeable wall of the first chamber of the apparatus; at least partially filling the first chamber of the apparatus with a first solution such that the first solution is in fluidic communication with the first surface of the oral care product, wherein the first solution is selected from a media or an inoculum; and at least partially filling the second chamber of the apparatusDocket No. 1017189-00- WO-Ol-OC with a second solution such that the second solution is in fluidic communication with a second surface of the oral care product, wherein the second solution is selected from the other of the media or the inoculum, and wherein the second solution is not in direct contact with the first solution.

[0029] In accordance with an embodiment 20, provided is the method according to embodiment 19, wherein the first solution is the media.

[0030] In accordance with an embodiment 21, provided is the method according to embodiments 19 or 20, wherein the second solution is the inoculum.

[0031] In accordance with an embodiment 22, provided is the method according to any one of embodiments 19 to 21 further comprising: maintaining the first solution in contact with the first surface of the oral care product and the second solution in contact with the second surface of the oral care product for a period of time.

[0032] In accordance with an embodiment 23, provided is the method according to embodiment 22, wherein the period of time is from about 30 minutes to about 72 hours.

[0033] In accordance with an embodiment 24, provided is the method according to any one of embodiments 19 to 23 further comprising: evaluating the media after the period of time.

[0034] In accordance with an embodiment 25, provided is the method according to embodiment 24, wherein the media is evaluated by determining the optical density of the media.

[0035] In accordance with an embodiment 26, provided is the method according to embodiment 24 or embodiment 25, wherein the media is evaluated to determine the total amount of bacteria cells in the media.

[0036] In accordance with an embodiment 27, provided is the method according to embodiment 26, wherein the total amount of bacterial cells in the media is evaluating using at least S YTO9 dye.

[0037] In accordance with an embodiment 28, provided is the method according to any one of embodiments 24 to 27, wherein the media is evaluated to determine the total number of dead bacteria cells in the media.

[0038] In accordance with an embodiment 29, provided is the method according to embodiment 28, wherein the total amount of dead bacterial cells in the media is evaluating using at least a propidium iodide dye.

[0039] In accordance with an embodiment 30, a method is provided for evaluating the barrier properties of an oral care product disposed on a mucosal surface, the method comprising: obtaining an oral care product having a first surface and a second surface opposed the first surface;Docket No. 1017189-00- WO-Ol-OC positioning the oral care product to have the first surface of the oral care product contacting a permeable substrate; contacting the permeable substrate and the first surface of the oral care product with a first solution, the first solution being selected from a media or an inoculum; contacting the second surface of the oral care product with a second solution, the second solution being selected from the other of the media or the inoculum.BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Implementation of the present technology will now be described, by way of example only, with reference to the attached figures, wherein:

[0041] FIG. 1 is a schematic of an exemplary, non-limiting apparatus in accordance with aspects of the invention; and

[0042] FIG. 2 is a flow chart of an exemplary, non-limiting method in accordance with aspects of the invention;

[0043] FIGS. 3A and 3B show a bilayer hyaluronic acid patch in accordance with aspects of the present invention.

[0044] It should be understood that the various aspects are not limited to the arrangements and instrumentality shown in the drawings.DETAILED DESCRIPTION

[0045] For illustrative purposes, the principles of the present invention are described by referencing various exemplary embodiments thereof. Although certain embodiments of the invention are specifically described herein, one of ordinary skill in the art will readily recognize that the same principles are equally applicable to, and can be employed in other compositions and methods. Before explaining the disclosed embodiments of the present invention in detail, it is to be understood that the invention is not limited in its application to the details of any particular embodiment disclosed herein. The terminology used herein is for the purpose of description and not of limitation.

[0046] As used herein and in the appended claims, the singular forms “a”, “an”, and “the” include plural references unless the context dictates otherwise. The singular form of any class of the ingredients refers not only to one chemical species within that class, but also to a mixture of those chemical species. The terms “a” (or “an”), “one or more” and “at least one” may be used interchangeably herein. The terms “comprising”, “including”, and “having” may be usedDocket No. 1017189-00- WO-Ol-OC interchangeably. The term “include” should be interpreted as “include, but are not limited to”. The term “including” should be interpreted as “including, but are not limited to”.

[0047] 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. Thus, a range from 1-5, includes specifically 1, 2, 3, 4 and 5, as well as subranges such as 2-5, 3-5, 2-3, 2-4, 1-4, etc.

[0048] The term “about” when referring to a number means any number within a range of 10% of the number. For example, the phrase “about 2 wt.%” refers to a number between and including 1.8 wt.% and 2.2 wt.%.

[0049] All references cited herein are hereby incorporated by reference 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.

[0050] The abbreviations and symbols as used herein, unless indicated otherwise, take their ordinary meaning. The abbreviation “wt.%” means percent by weight with respect to the oral care composition. The symbol “°” refers to a degree, such as a temperature degree or a degree of an angle. The symbols “h”, “min”, “mb”, “nm”, and “pm” refer to hour, minute, milliliter, nanometer, and micrometer, respectively. The abbreviation “UV-VIS” as referring to a spectrometer or spectroscopy, means Ultraviolet-Visible. The abbreviation “rpm” means revolutions per minute.

[0051] When referring to chemical structures, and names, the symbols “C”, “H”, and “O” mean carbon, hydrogen, and oxygen, respectively. The symbols “=” and “=” mean single bond, double bond, and triple bond, respectively.

[0052] “Volatile”, as used herein, means having a flash point of less than about 100° C. “Nonvolatile”, as used herein, means having a flash point of greater than about 100° C.

[0053] Any member in a list of species that are used to exemplify or define a genus, may be mutually different from, or overlapping with, or a subset of, or equivalent to, or nearly the same as, or identical to, any other member of the list of species. Further, unless explicitly stated, such as when reciting a Markush group, the list of species that define or exemplify the genus is open, and it is given that other species may exist that define or exemplify the genus just as well as, or better than, any other species listed.

[0054] The phrases, “a mixture thereof,” “a combination thereof.” or a combination of two or more thereof’ do not require that the mixture include all of A, B, C, D, E, and F (although all of A, B,Docket No. 1017189-00- WO-OLOCC, D, E, and F may be included). Rather, it indicates that a mixture of any two or more of A, B, C,D, E, and F can be included. In other words, it is equivalent to the phrase “one or more elements selected from the group consisting of A, B, C. D, E, F, and a mixture of any two or more of A, B, C, D, E, and F.” Likewise, the term “a salt thereof’ also relates to “salts thereof.” Thus, where the disclosure refers to “an element selected from the group consisting of A, B, C, D, E, F, a salt thereof, and a mixture thereof.” it indicates that that one or more of A. B, C, D, and F may be included, one or more of a salt of A, a salt of B, a salt of C, a salt of D, a salt of E, and a salt of F may be included, or a mixture of any two of A, B. C, D, E, F, a salt of A, a salt of B, a salt of C, a salt of D, a salt of E, and a salt of F may be included.

[0055] All components and elements positively set forth in this disclosure can be negatively excluded from the claims. In other words, the oral care compositions of the instant disclosure can be free or essentially free of all components and elements positively recited throughout the instant disclosure. In some instances, the oral care compositions of the present disclosure may be substantially free of non-incidental amounts of the ingredient(s) or compound(s) described herein. A non-incidental amount of an ingredient or compound is the amount of that ingredient or compound that is added into the oral care composition by itself. For example, an oral care composition may be substantially free of a non-incidental amount of an ingredient or compound, although such ingredient(s) or compound(s) may be present as part of a raw material that is included as a blend of two or more compounds.

[0056] Some of the various categories of components identified may overlap. In such cases where overlap may exist and the oral care composition includes both components (or the composition includes more than two components that overlap), an overlapping compound does not represent more than one component. For example, certain compounds may be characterized as both a polyol and a sweetener. If a particular oral care composition recites both a polyol and a sweetener, xylitol will serve only as either a polyol or a sweetener — not both.

[0057] For readability purposes, the chemical functional groups are in their adjective form; for each of the adjectives, the word “group” is assumed. For example, the adjective “alkyl” without a noun thereafter, should be read as “an alkyl group.”

[0058] Aspects of the invention are directed to an apparatus for evaluating the barrier properties of an oral care product. Referring to FIG. 1, provided is a schematic of an exemplary, non-limiting apparatus 100 in accordance with aspects of the invention. The apparatus 100 typically comprisesDocket No. 1017189-00- WO-Ol-OC a first chamber 110 and a second chamber 120. The first chamber 110 includes an inner surface 112 defining a first cavity 114 and a permeable wall 116. The first chamber may comprise an aperture and / or opening for receiving a liquid solution, such as first solution 140 and / or second solution 150, which are further discussed below. The first chamber 110 may also comprise a lid to fully encompass and / or surround first cavity 114.

[0059] The permeable wall 116 has a first surface 118a and an opposed second surface 118b and one or more aperture 120 extending from the first surface 118a to the second surface 118b. The first surface 118a of the permeable wall 116 may form at least a portion of the inner surface 112, which defines the first cavity 114, of the first chamber 110. Although the permeable wall 116 may be flat as illustrated in FIG. 1, in certain embodiments permeable wall 116 may be concave or convex. For instance, the permeable wall 116 may be convex such that an apex associated with a center portion 122 of the permeable wall 116 extends in the direction of the center of the first cavity 114 of the first chamber 110. In other embodiments, the permeable wall 116 is concave such that an apex of the permeable wall 116 extends in the direction of the center of the second cavity 134 of the second chamber 130.

[0060] The one or more aperture 120 may be configured as one or more hole(s), slot(s), opening(s), and / or the like. The one or more aperture(s) 120 may extend from the first surface 118a to the second surface 118b of the permeable wall 116. Preferably, each of the one or more aperture(s) 120 may extend from the first surface 118a to the second surface 118b of the permeable wall 116. The one or more apertures 120 may preferably be configured to permit fluid to pass through such aperture 120.

[0061] The second chamber 130 comprises an inner surface 132 defining a second cavity 134. The second cavity 134 may be fluidically coupled to the first cavity 114 by way of the one or more aperture 120 extending through permeable wall 116. The second chamber 130 may also include an aperture and / or opening for receiving a liquid solution, such as first solution 140 and / or second solution 150. The second chamber 130 may also comprise a lid to fully encompass and / or surround first cavity 134.

[0062] As illustrated in FIG. 1, the first chamber 110 may be positioned at least partially within the cavity of the second chamber 120. In at least one embodiment, the first chamber 110 is positioned within the cavity 132 of the second chamber 130. For example, the first chamber 110 may be completely positioned within the cavity 132 of the second chamber 130, such that the firstDocket No. 1017189-00- WO-Ol-OC chamber may be enclosed or encompassed by the second chamber 130. Tn some embodiments, however, the first chamber 110 is not at least partially positioned within the cavity 134 of the second chamber 130, while maintaining a fluidic connection to the cavity 134 of the second chamber 130, preferably, via the permeable wall 116.

[0063] Apparatus 100 may be formed from suitable materials, such as metal, ceramics, plastics (e.g., polyethylene, polypropylene, polyvinyl chloride, or the like). One of ordinary skill in the art would readily be able to identify and employ suitable materials for apparatus 100.

[0064] Aspects of the invention are directed to methods for evaluating the barrier properties of an oral care product disposed on a mucosal surface. Referring to FIG. 2, provided is a method 200 for evaluating the barrier properties of an oral care product 300 disposed on a mucosal surface. As a brief overview, method 200 comprises obtaining an oral care product in step 210; positioning the oral care product to have a first surface contacting a permeable substrate in step 220; in step 230, contacting the permeable substrate and the first surface of the oral care product with a first solution, the first solution being selected from a media or an inoculum; and in step 240, contacting a second surface of the oral care product with a second solution, the second solution being selected from the other of the media or the inoculum. Without necessarily being limited to methods employing apparatus 100 and oral care product 300, method 200 may be described below with reference to apparatus 100 and oral care product 300 to elucidate aspects of method 200.

[0065] In step 210, an oral care product is obtained. The oral care product may be an oral care product disclosed herein, such as oral care product 300, which is further disclosed below. The oral care product may be in the form of a film, strip, pad, or the like having a first surface and opposed second surface. The oral care product may be a liquid, a pseudo solid, a pseudo liquid, or the like. For example, the oral care product may be a gel that has a first surface that contacts the permeable substrate (e.g., permeable wall 116) when the oral care product is positioned on the permeable substrate. In certain embodiments, such as when the oral care product is a gel. the oral care product may be positioned on a permeable substrate (e.g., permeable wall 116) such that the oral care product has a first surface contacting the permeable substrate and a second surface opposed the first surface.

[0066] In step 220, the oral care product is positioned to have the first surface of the oral care product contacting a permeable substrate, such as permeable wall 116 of apparatus 100. Preferably, the oral care product is positioned to cover the one or more apertures of the permeable substrate,Docket No. 1017189-00- WO-Ol-OC e.g., to prohibit a fluid from passing through the permeable substrate and into the cavity of the first chamber. The oral care product may be positioned using forceps, preferably sterile forceps.

[0067] Without reference to a non-limiting method employing apparatus 200 and oral care product 300, the oral care product 300 may be positioned to have the first surface 3 of the oral care product 300 contacting the first surface 118a of the permeable wall 116. For example, the oral care product 300 may be positioned within the first cavity 114 of the first chamber 110 on the surface of the permeable wall 116 that forms the inner surface 112 of the first chamber 110. Preferably, the oral care product 300 is positioned to cover the one or more apertures 120 of the permeable wall 116, such that a fluid from the first chamber 110 is prevented from flowing through the one or more aperture 120 to contact a fluid in the second chamber 130.

[0068] In step 230, the permeable substrate and the first surface 3 of the oral care product 300 is contacted with a first solution in 140. The first solution 140 may be disposed in either the first chamber 110 or the second chamber 130, such that the first solution 140 is contacting a first surface 3 of the oral care product 300. The first solution 140 may comprise a media or an inoculum. In some embodiments, the first solution 140 is selected from the group consisting of a media or an inoculum. In at least one embodiment, the first solution 140 is the media.

[0069] In step 240, the second surface 4 of the oral care product 300 is contacted with a second solution 150, the second solution 150 being selected from the other of the media or the inoculum. The second solution 150 may be selected from the group consisting of the media or the inoculum. In at least one embodiment, the second solution 150 is the inoculum. The oral care product 300 may have a first surface 3 in contact with the first solution 140 and a second surface 4 in contact with the second solution 150.

[0070] Method 200 may further comprise maintaining the contact of the first solution 140 with the first surface 3 of the oral care product 300 and the contact of the second solution 150 with the second surface 4 of the oral care product 300 for a period of time. Preferably, the period of time is a predetermined period of time. In some instances, the period of time that the first surface 3 of the oral care product 300 is in contact with the first solution 140 is from about 30 minutes to about 72 hours, e.g., preferably, from about 30 minutes to about 60 hours, about 30 minutes to about 48 hours, about 30 minutes to about 36 hours, about 30 minutes to about 24 hours about 30 minutes to about 8 hours, about 30 minutes to about 6 hours, about 30 minutes to about 4 hours, about 30 minutes to about 2 hours; from about 1 hour to about 60 hours, about 1 hour to about 48 hours,Docket No. 1017189-00- WO-Ol-OC about 1 hour to about 36 hours, about 1 hour to about 24 hours about 1 hour to about 8 hours, about1 hour to about 6 hours, about 1 hour to about 4 hours, about 1 hour to about 2 hours; from about2 to about 72 hours, about 2 to about 60 hours, about 2 to about 48 hours, about 2 to about 36 hours, about 2 to about 24 hours about 2 to about 8 hours, about 2 to about 6 hours, about 2 to about 4 hours; from about 4 to about 72 hours, about 4 to about 60 hours, about 4 to about 48 hours, about 4 to about 36 hours, about 4 to about 24 hours about 4 to about 8 hours; from about 6 to about 72 hours, about 6 to about 60 hours, about 6 to about 48 hours, about 6 to about 36 hours, about 6 to about 24 hours about 6 to about 8 hours; from about 12 to about 72 hours, about 12 to about 60 hours, about 12 to about 48 hours, about 12 to about 36 hours, about 12 to about 24 hours; from about 24 to about 72 hours, about 24 to about 60 hours, about 24 to about 48 hours, about 24 to about 36 hours; from about 48 to about 72 hours, about 48 to about 60 hours, or any range or subrange thereof.

[0071] The period of time that the second surface 4 of the oral care product 300 is in contact with the second solution 150 may be from about 30 minutes to about 72 hours, e.g., preferably, from about 30 minutes to about 60 hours, about 30 minutes to about 48 hours, about 30 minutes to about 36 hours, about 30 minutes to about 24 hours about 30 minutes to about 8 hours, about 30 minutes to about 6 hours, about 30 minutes to about 4 hours, about 30 minutes to about 2 hours; from about 1 hour to about 60 hours, about 1 hour to about 48 hours, about 1 hour to about 36 hours, about 1 hour to about 24 hours about 1 hour to about 8 hours, about 1 hour to about 6 hours, about 1 hour to about 4 hours, about 1 hour to about 2 hours; from about 2 to about 72 hours, about 2 to about 60 hours, about 2 to about 48 hours, about 2 to about 36 hours, about 2 to about 24 hours about 2 to about 8 hours, about 2 to about 6 hours, about 2 to about 4 hours; from about 4 to about 72 hours, about 4 to about 60 hours, about 4 to about 48 hours, about 4 to about 36 hours, about 4 to about 24 hours about 4 to about 8 hours; from about 6 to about 72 hours, about 6 to about 60 hours, about 6 to about 48 hours, about 6 to about 36 hours, about 6 to about 24 hours about 6 to about 8 hours; from about 12 to about 72 hours, about 12 to about 60 hours, about 12 to about 48 hours, about 12 to about 36 hours, about 12 to about 24 hours; from about 24 to about 72 hours, about 24 to about 60 hours, about 24 to about 48 hours, about 24 to about 36 hours; from about 48 to about 72 hours, about 48 to about 60 hours, or any range or subrange thereof.

[0072] In some embodiments, the period of time that the first surface 3 of the oral care product 300 is in contact with the first solution 140 and the period of time that the second surface 4 of theDocket No. 1017189-00- WO-Ol-OC oral care product 300 is in contact with the second solution 150 substantially equal to each other, preferably within 2 hours, preferably within 1 hour, preferably within 30 minutes, preferably within 10 minutes, preferably within 5 minutes of each other.

[0073] Method 200 may include evaluating the media (e.g., either the first solution 140 or the second solution 150) after the oral care product has been in contact with the first solution 140 and the second solution 150 for a period of time, such as one of the period of times and / or one described above. The media may be evaluated by determining the optical density of the media. Additionally or alternatively, the media may be evaluated to determine the total amount of bacteria cells in the media. For instance, the total amount of bacterial cells in the media may be evaluated using at least SYTO9 dye. Method 200 may include evaluating the media to determine the total number of dead bacteria cells in the media. In some embodiments, the total amount of dead bacterial cells in the media is evaluated using at least a propidium iodide dye.

[0074] In some embodiments of method 200, the second solution 150 is not initially in direct contact with the first solution 140. In some embodiments of method 200, the media (e.g., first solution or second solution) is not in direct contact with the inoculum before the media is evaluated, e.g., to determine the optical density, total amount of bacteria cells, total amount of dead bacterial cells, and / or total amount of live bacteria cells.

[0075] In some embodiments, the present invention is directed to oral care products having customizable and suitable barrier properties whereby the product is characterized by a process having the following steps of: providing an oral care product having a first surface and a second surface opposed the first surface; positioning the oral care product to have the first surface contacting a permeable substrate comprising one or more aperture extending from a first surface to a second surface of the permeable substrate; contacting the permeable substrate and the first surface of the oral care product with a first solution selected from a media or an inoculum; contacting the second surface of the oral care product with a second solution selected from the other of the media or the inoculum, the first and second solutions not initially being in direct contact with one another; maintaining the first solution in contact with the first surface of the oral care product and the second solution in contact with the second surface of the oral care product for a period of time from about 30 minutes to about 72 hours; and evaluating the media after the period of time by at least determining the optical density of the media and quantifying bacterial cells using SYTO9 dye and / or quantifying dead bacterial cells using propidium iodide dye; wherein the oralDocket No. 1017189-00- WO-Ol-OC care product, when obtained by the process, exhibits barrier properties sufficient to maintain separation of the first and second solutions and to reduce microbial transfer into the media. In certain embodiments, the oral care product may have a bilayer patch including a first layer comprising hyaluronic acid and a water-soluble film forming polymer. In some embodiments, the oral care product has non-sticky second layer comprising a humectant and a water-soluble film forming polymer.

[0076] Referring to FIGS. 3 A and 3B, the oral care product is generally directed towards a bilayer patch comprising a first layer 1 and a second layer 2. The first layer 1 generally comprises a hyaluronic acid and / or salt thereof, a humectant, and a water-soluble film forming polymer. In some embodiments, the first layer 1 may further comprise an active agent, a sweetener, and / or water. The second layer 2 generally comprises a humectant and a water-soluble film forming polymer. The second layer 2 may be configured to not be sticky, even when touched by a wet surface, such as a wet finger. In certain embodiments, the second layer may further comprise a thickening agent, a fiber source, and a sweetener. The patch may be applied so that one side of first layer is in contact with the oral tissue of a user and the other side of the first layer is in contact with one side of the second layer. The patch may be formed by any means currently known in the art. It should be appreciated that the term “patch” may refer to a variety of forms including, but not limited to, a strip, cover, pad, or ribbon.

[0077] In some embodiments, the first layer may have a thickness ranging from about 50 to about 150 microns, from about 50 to about 140 microns, from about 50 to about 130 microns, from about 50 to about 125 microns, from about 50 to about 120 microns, from about 50 to about 115 microns, from about 50 to about 110 microns, from about 50 to about 100 microns, from about 60 to about 150 microns, from about 60 to about 140 microns, from about 60 to about 130 microns, from about 60 to about 125 microns, from about 60 to about 120 microns, from about 60 to about 115 microns, from about 60 to about 110 microns, from about 60 to about 100 microns, from about 70 to about 150 microns, from about 70 to about 140 microns, from about 70 to about 130 microns, from about 70 to about 125 microns, from about 70 to about 120 microns, from about 70 to about 115 microns, from about 70 to about 110 microns, from about 70 to about 100 microns, from about 80 to about 150 microns, from about 80 to about 140 microns, from about 80 to about 130 microns, from about 80 to about 125 microns, from about 80 to about 120 microns, from about 80 to about 115 microns, from about 80 to about 110 microns, from about 80 to about 100 microns, from about 90 to aboutDocket No. 1017189-00- WO-Ol-OC150 microns, from about 90 to about 140 microns, from about 90 to about 130 microns, from about 90 to about 125 microns, from about 90 to about 120 microns, from about 90 to about 115 microns, from about 90 to about 110 microns, about 80 microns, about 90 microns, about 100 microns, about 110 microns, about 115 microns, or about 120 microns, or any range or subrange thereof.

[0078] In some embodiments, the second layer may have a thickness ranging from about 50 to about 200 microns, from about 50 to about 190 microns, from about 50 to about 180 microns, from about 50 to about 170 microns, from about 50 to about 160 microns, from about 50 to about 150 microns, from about 50 to about 140 microns, from about 50 to about 130 microns, from about 50 to about 120 microns, from about 50 to about 110 microns, from about 50 to about 100 microns, from about 60 to about 200 microns, from about 60 to about 190 microns, from about 60 to about 180 microns, from about 60 to about 170 microns, from about 60 to about 160 microns, from about 60 to about 150 microns, from about 60 to about 150 microns, from about 60 to about 140 microns, from about 60 to about 130 microns, from about 60 to about 120 microns, from about 60 to about 110 microns, from about 60 to about 100 microns, from about 70 to about 200 microns, from about 70 to about 190 microns, from about 70 to about 180 microns, from about 70 to about 170 microns, from about 70 to about 160 microns, from about 70 to about 150 microns, from about 70 to about 150 microns, from about 70 to about 140 microns, from about 70 to about 130 microns, from about 70 to about 120 microns, from about 70 to about 110 microns, from about 70 to about 100 microns,

[0079] from about 80 to about 200 microns, from about 80 to about 190 microns, from about 80 to about 180 microns, from about 80 to about 170 microns, from about 80 to about 160 microns, from about 80 to about 150 microns, from about 80 to about 150 microns, from about 80 to about 140 microns, from about 80 to about 130 microns, from about 80 to about 120 microns, from about 80 to about 110 microns, from about 80 to about 100 microns, about 80 microns, from about 90 to about 200 microns, from about 90 to about 190 microns, from about 90 to about 180 microns, from about 90 to about 170 microns, from about 90 to about 160 microns, from about 90 to about 150 microns, about 90 microns, about 100 microns, about 110 microns, or about 120 microns, or any range or subrange thereof.

[0080] The oral care product typically comprises hyaluronic acid. As used herein, “hyaluronic acid” is an anionic, non-sulfated glycosaminoglycan (GAG) widely distributed throughout connective tissues of vertebrates, being the most abundant glycosaminoglycan of higher molecular weight in the extracellular matrix of soft periodontal tissues. Hyaluronic acid can exist in its freeDocket No. 1017189-00- WO-Ol-OC acid form, or in the form of a salt (such as an alkali metal salt). Hyaluronic acid has important hygroscopic, rheological and viscoelastic properties that fluctuate with changes in temperature, pH, ionic environment, and binding partners. However, these properties are also highly dependent on chain length.

[0081] Hyaluronan has been found to be effective in the treatment of inflammatory processes in medical fields such as orthopedics, dermatology and ophthalmology, and it has been further found to be anti-inflammatory and antibacterial in gingivitis and periodontitis therapy. Due to its tissue healing properties, it has been suggested for use as an adjunct to mechanical therapy in the treatment of periodontitis. Hyaluronan affects endothelial cell proliferation and monolayer integrity, and also has effects on angiogenesis.

[0082] It should be appreciated that the hyaluronic acid, as referenced herein, may refer to hyaluronic acid of different average molecular weights, and / or different salts of hyaluronic acid including, alkali metal hyaluronate or alkali metal hyaluronate polymer, acetylated hyaluronic acid, sodium acetylated hyaluronate, sodium hyaluronate, potassium hyaluronate, acetylated hyaluronic acid, sodium acetylated hyaluronate, sodium hyaluronate, potassium hyaluronate, cross-linked sodium hyaluronate, hydrolyzed sodium hyaluronate, zinc hyaluronate, and / or blends thereof.

[0083] The first layer of the oral care product may comprise a hyaluronic acid and / or salt thereof present in an amount ranging from about 20 to about 40 wt. %, from about 20 to about 35 wt.%, from about 25 to about 40 wt.%, from about 25 to about 35 wt. %, from about 30 to about 35 wt. %, about 25 wt. %, about 30 wt. %, about 33 wt. %, about 35 wt. %, about 38 wt. %, or about 40 wt. %„ or any range or subrange thereof, based on the total weight of the first layer of the oral care product.

[0084] In some embodiments, the oral care product comprises a hyaluronic acid and / or salt thereof with an average molecular weight of about 100 kDa or more, about 200 kDa or more, or about 400 kDa or more, based on the total weight of the oral care product. In other embodiments, the average molecular weight of the hyaluronic acid and / or salt thereof is from about 100 kDa to about 800 kDa, from about 100 kDa to 700 kDa, about 100 kDa to about 600 kDa, about 100 kDa to about 500 kDa, about 100 kDa to about 450 kDa, about 200 kDa to about 800 kDa, from about 200 kDa to 700 kDa, about 200 kDa to about 600 kDa, about 200 kDa to about 500 kDa, about 200 kDa to about 450 kDa, about 250 kDa to about 800 kDa, from about 250 kDa to 700 kDa, about 250 kDaDocket No. 1017189-00- WO-Ol-OC to about 600 kDa, about 250 kDa to about 500 kDa, about 250 kDa to about 450 kDa, about 300 kDa to about 800 kDa, from about 300 kDa to 700 kDa, about 300 kDa to about 600 kDa, about 300 kDa to about 500 kDa. about 300 kDa to about 450 kDa, about 350 kDa to about 800 kDa, from about 350 kDa to 700 kDa, about 350 kDa to about 600 kDa, about 350 kDa to about 500 kDa, about 350 kDa to about 450 kDa, or any range or subrange thereof. In some embodiments, the average molecular weight of the hyaluronic acid and / or salt thereof is about 200 kDa. about 250 kDa, about 300 kDa, about 350 kDa, about 400 kDa, about 450 kDa, about 500 kDa, about 550 kDa, or about 600 kDa. In at least one embodiment, the hyaluronic acid and / or salt thereof has an average molecular weight of 400 kDa.

[0085] The oral care product generally comprises at least one humectant. The humectant may be in the first layer, the second layer, or in both layers of the oral care product. In at least one embodiment, both the first layer and second layer comprise a humectant. It should be understood that when there is a humectant in the second layer, the humectant in the second layer may be referred to as the second humectant, even if there is no humectant in the first layer. In general, humectants include, but are not limited to, polyhydric alcohols such as glycerin, butylene glycol, propanediol such as 1,3-propanediol, sorbitol, xylitol or low molecular weight polyethylene glycols (PEGs), polyoxyethylenes or combinations thereof. In some embodiments, the humectant may be sorbitol (preferably, non-crystal sorbitol), butylene glycol, propanediol such as 1,3- propanediol, glycerin (e.g., vegetable refined glycerin), polyoxyethylene glycol or combinations thereof. In at least one embodiment, the humectant is glycerin.

[0086] The first layer of the oral care product may comprise a humectant in an amount ranging from about 12 to about 35 wt. %. from about 12 to about 33 wt. %, from about 12 to about 30 wt. %, from about 12 to about 27 wt. %, from about 12 to about 25 wt. %, from about 12 to about 23 wt. %, from about 12 to about 20 wt. %, from about 15 to about 35 wt. %, from about 15 to about 33 wt. %, from about 15 to about 30 wt. %, from about 15 to about 27 wt. %, from about 15 to about 25 wt. %, from about 15 to about 23 wt. %, from about 15 to about 20 wt. %, from about 19 to about 35 wt. %, from about 19 to about 33 wt. %, from about 19 to about 30 wt. %, from about 19 to about 27 wt. %, from about 19 to about 25 wt. %, from about 19 to about 23 wt. %, from about 20 to about 35 wt. %, from about 20 to about 33 wt. %, from about 20 to about 30 wt. %, from about 20 to about 27 wt. %. from about 20 to about 25 wt. %, from about 20 to about 23 wt. %, from about 23 to about 35 wt. %, from about 23 to about 33 wt. %, from about 23 to about 30Docket No. 1017189-00- WO-Ol-OC wt. %, from about 23 to about 27 wt. %, or any range or subrange thereof, based on the total weight of the first layer of the oral care product.

[0087] The second layer of the oral care product may comprise a humectant in an amount ranging from about 0.1 to about 12 wt. %, from about 0.5 to about 12 wt. %, from about 1 to about 12 wt. %, from about 2 to about 12 wt. %, from about 3 to about 12 wt. %„ from about 4 to about 12 wt. % from about 5 to about 12 wt. %., from about 6 to about 12 wt. % from about 7 to about 12 wt. %, from about 10 to about 12 wt. %, from about 0.1 to about 8 wt. %, from about 0.5 to about 8 wt. %, from about 1 to about 8 wt. %, from about 2 to about 8 wt. %, from about 3 to about 8 wt. %, from about 4 to about 8 wt. %, from about 5 to about 8 wt. %, from about 6 to about 8 wt. %, from about 0.1 to about 6 wt. %, from about 0.5 to about 6 wt. %, from about 1 to about 6 wt. %, from about 2 to about 6 wt. %, from about 3 to about 6 wt. %, from about 4 to about 6 wt. %, or any range or subrange thereof, based on the total weight of the second layer of the oral care product.

[0088] The oral care product generally comprises a water-soluble film forming polymer. The water-soluble film forming polymer may be in the first layer, the second layer, or in both layers of the oral care product. In at least one embodiment, both the first layer and second layer comprise a water-soluble film forming polymer. It should be understood that when there is a water-soluble film forming polymer in the second layer, the water-soluble film forming polymer in the second layer may be referred to as the second water-soluble film forming polymer, even if there is no water-soluble film forming polymer in the first layer. The water-soluble film forming polymer may include, but is not limited to, starches, chitin and chitosan, pectin, alginate, xanthan gum , carrageenan, and polysaccharides such as cellulose or cellulose derivatives, for example carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, ethyl cellulose, microcrystalline cellulose, and pullulan. In some embodiments, the water-soluble film forming polymer is selected form cellulose or cellulose derivatives, starch or starch derivatives, carboxymethylcellulose, hydroxyethyl cellulose, polyethylene glycol, polyacrylamide, polyacrylic acid copolymer, polyvinyl alcohol, alginate, chitosan, pectin, collagen, gelatin, and pullulan. In at least one embodiment, the water-soluble film forming polymer is a pullulan.

[0089] Pullulan typically refers to a polysaccharide linear polymer consisting of maltotriose units. Three glucose units of maltotriose are connected by an a- 1,4 glycosidic bond, whereas consecutive maltotriose units are connected to each other by an a- 1,6 glycosidic bond. The pullulan may beDocket No. 1017189-00- WO-Ol-OC obtained through a fermentation process from starch by the fungus Aureobasidium pullulans.

[0090] The water-soluble film forming polymer may be present in the first layer of the oral care product in an amount ranging from about 30 to about 55 wt. %, from about 30 to about 50 wt. %, from about 30 to about 48 wt. %, from about 30 to about 45 wt. %, from about 30 to about 43 wt. %, from about 30 to about 40 wt. %, from about 30 to about 38 wt. %, from about 35 to about 55 wt. %, from about 35 to about 50 wt. %. from about 35 to about 48 wt. %, from about 35 to about 45 wt. %, from about 35 to about 43 wt. %, from about 35 to about 40 wt. %, from about 38 to about 55 wt. %, from about 38 to about 50 wt. %, from about 38 to about 48 wt. %, from about 38 to about 45 wt. %, from about 38 to about 43 wt. %, from about 40 to about 55 wt. %, from about 40 to about 50 wt. %, from about 40 to about 48 wt. %, from about 40 to about 45 wt. %, from about 40 to about 43 wt. %, or any range or subrange thereof, based on the total weight of the first layer of the oral care product.

[0091] The water-soluble film forming polymer may be present in the second layer of the oral care product in an amount ranging from about 15 to about 40 wt. %, from about 15 to about 38 wt. %, from about 15 to about 35 wt. %, from about 18 to about 40 wt. %, from about 18 to about 38 wt. %, from about 18 to about 35 wt. %, from about 20 to about 40 wt. %, from about 20 to about 38 wt. %, from about 20 to about 35 wt. %, from about 23 to about 40 wt. %, from about 23 to about 38 wt. %, from about 23 to about 35 wt. %, from about 25 to about 40 wt. %, from about 25 to about 38 wt. %, from about 25 to about 35 wt. %, or any range or subrange thereof, based on the total weight of the second layer of the oral care product.

[0092] The first layer of the oral care product may, in some embodiments, be specifically formulated to have certain weight ratios of the hyaluronic acid to the humectant. For instance, the oral care product may have a weight ratio of the hyaluronic acid to the humectant from about 5:4 to about 8:4. In some embodiments, the weight ratio of the hyaluronic acid to the humectant is about 5:4 to about 8:4, about 5:4 to about 7:4, about 5:4 to about 6:4, about 1: 1 to about 1:1.5; from about 1:2 to about 1:4, about 1:2 to about 1:3, about 5:4; about 3:2, about 2:1, or any range or subrange formed therefrom. In at least one embodiment, the weight ratio of the hyaluronic acid to the humectant is about 3:2.

[0093] The first layer of the oral care product may, in some embodiments, be specifically formulated to have certain weight ratios of the hyaluronic acid to the water-soluble film forming polymer. For instance, the oral care product may have a weight ratio of the hyaluronic acid to theDocket No. 1017189-00- WO-Ol-OC water-soluble film forming polymer from about 1 :2 to about 1 : 1 . In some embodiments, the weight ratio of the hyaluronic acid to the water-soluble film forming polymer is about 2:4 to about 4:4, about 2:4 to about 3:4, about 1:2 to about 1:1.5, about 1:2 to about 1:3; about 1:2; about 3:4, about 2:3, or any range or subrange formed therefrom. In at least one embodiment, the weight ratio of the hyaluronic acid to the water-soluble film forming polymer is about 3:4.

[0094] The first layer of the oral care product may, in some embodiments, be specifically formulated to have certain weight ratios of the humectant to the water-soluble film forming polymer. For instance, the oral care product may have a weight ratio of the humectant to the water- soluble film forming polymer from about 1:1 to about 1:3. In some embodiments, the weight ratio of the humectant to the water-soluble film forming polymer is about 1:1 to about 1:3, about 1:1 to about 1:2.5, about 1:1 to about 1:2, about 1:1.5 to about 1:3, about 1:1.5 to about 1.5:2.5, about 1:1.5 to about 1:2, about 1:1, about 1:1.5, about 1:2, about 1:2.5, about 3:5, or any range or subrange formed therefrom. In at least one embodiment, the weight ratio of the humectant to the water-soluble film forming polymer is about 1:2.

[0095] The second layer of the oral care product may, in some embodiments, be specifically formulated to have certain weight ratios of the humectant to the water-soluble film forming polymer. As previously stated, it should be understood that when there is a humectant and / or water- soluble film forming polymer in the second layer, the humectant and water-soluble film forming polymer may be referred to as the second humectant and / or the second water-soluble film forming polymer, respectively. For instance, the oral care product may have a weight ratio of the humectant to the water-soluble film forming polymer from about 1:3 to about 1:9. In some embodiments, the weight ratio of the humectant to the water-soluble film forming polymer is about 1:3 to about 1:9, about 1:3 to about 1:8, about 1:3 to about 1:7, about 1:3 to about 1:6; about 1:3 to about 1:5, about 1:3 to about 1:4, about 1:5 to about 1:9, about 1:5 to about 1:8, about 1:5 to about 1:7, about 1:3, about 1:4, about 1:5, about 1:6. about 1:7. about 1:8. about 1:9. or any range or subrange formed therefrom. In at least one embodiment, the weight ratio of the humectant to the water-soluble film forming polymer in the second layer of the oral care product is about 1:6.

[0096] In some embodiments, the first or second layer of oral care product may include water. The first or second layer of the oral care product may, in some cases, be free or substantially free of water. In some embodiments, only the first layer or only the second layer may be substantially free of water. In certain embodiments, the first or second layer of the oral care product comprises aboutDocket No. 1017189-00- WO-Ol-OC15 wt. % or less of water, about 12 wt. % or less of water, about 10 wt. % or less of water, about9 wt. % or less of water, about 8 wt. % or less of water, about 7 wt. % or less of water, about 6 wt. % or less of water, or about 5 wt. % or less of water, based on the total weight of the first or second layer of oral care product. In other embodiments, water may be present in the oral care product in an amount ranging from about 1 to about 15 wt. %, from about 1 to about 12 wt. %, from about 1 to about 10 wt. %. from about 1 to about 8 wt. %, from about 1 to about 7 wt. %, from about 1 to about 6 wt. %, from about 1 to about 5 wt. %, from about 1 to about 4 wt. %, from about 1 to about3 wt. %, from about 2 to about 15 wt. %, from about 2 to about 12 wt. %, from about 2 to about10 wt. %, from about 2 to about 8 wt. %, from about 2 to about 7 wt. %, from about 2 to about 6 wt. %, from about 2 to about 5 wt. %, from about 3 to about 15 wt. %, from about 3 to about 12 wt. %, from about 3 to about 10 wt. %. from about 3 to about 8 wt. %. from about 3 to about 7 wt. %, from about 3 to about 6 wt. %, from about 3 to about 5 wt. %, from about 4 to about 15 wt. %, from about 4 to about 12 wt. %, from about 4 to about 10 wt. %, from about 4 to about 8 wt. %, from about 4 to about 7 wt. %. from about 4 to about 6 wt. %. from about 5 to about 15 wt. %, from about 5 to about 12 wt. %, from about 5 to about 10 wt. %, from about 5 to about 8 wt. %, from about 5 to about 7 wt. %, from about 5 to about 6 wt. %, about 15 wt. %, about 12 wt. %, about 10 wt. %, about 9 wt. %, about 8 wt. %, about 7 wt. %, about 6 wt. %, about 5 wt. %, about4 wt. %, about 3 wt. %, or any range or subrange thereof, based on the total weight of the first or second layer of the oral care product.

[0097] The oral care product may optionally comprise a sweetener. The sweetener may be in the first layer, the second layer, in both layers, or in no layers of the oral care product. In at least one embodiment, both the first layer and second layer comprise a sweetener. The sweetener may include, but is not limited to, stevia, sugars such as sucrose, glucose, invert sugar, fructose, ribose, tagalose, sucralose, maltitol, erythritol, xylitol, and mixtures thereof, saccharin and its various salts (e.g., sodium and calcium salt of saccharin), dipeptide sweeteners (e.g., aspartame), and sugar alcohols including, e.g., sorbitol, sorbitol syrup, mannitol and xylitol, and combinations thereof. In certain embodiments, the sweetener may include sodium saccharin, stevia rebaudioside A (“stevia reb-A”), and prostevia. In one embodiment, the sweetener is a combination of stevia reb- A and prostevia.

[0098] The sweetener may be present in the first of the oral care product in an amount ranging from about 0.01 to about 1.5 wt. %, from about 0.01 to about 1.3 wt. %, from about 0.01 to aboutDocket No. 1017189-00- WO-Ol-OC1.0 wt. %, from about 0.01 to about 0.8 wt. %, from about 0.01 to about 0.5 wt. %, from about 0.05 to about 1.5 wt. %, from about 0.05 to about 1.3 wt. %, from about 0.05to about 1.0 wt. %, from about 0.05 to about 0.8 wt. %, from about 0.05 to about 0.5 wt. %, from about 0.1 to about 1.5 wt. %, from about 0.1 to about 1.3 wt. %, from about 0.1 to about 1.0 wt. %, from about 0.1 to about 0.8 wt. %, from about 0.1 to about 0.5 wt. %, from about 0.3 to about 1.5 wt. %, from about 0.3 to about 1.3 wt. %, from about 0.3 to about 1.0 wt. %, from about 0.3 to about 0.8 wt. %, from about 0.3 to about 0.5 wt. %, from about 0.5 to about 1.5 wt. %, from about 0.5 to about 1.3 wt. %, from about 0.5 to about 1.0 wt. %, from about 0.5 to about 0.8 wt. %, from about 0.6 to about 1.5 wt. %, from about 0.6 to about 1.3 wt. %, from about 0.6 to about 1.0 wt. %, or any range or subrange thereof, based on the total weight of the first layer of the oral care product.

[0099] The sweetener may be present in the second layer of the oral care product in an amount ranging from about 0.01 to about 1.0 wt. %, from about 0.01 to about 0.8 wt. %, from about 0.01 to about 0.6 wt. %, from about 0.01 to about 0.5 wt. %, from about 0.01 to about 0.4 wt. %, from about 0.05 to about 1.0 wt. %, from about 0.05 to about 0.8 wt. %. from about 0.05 to about 0.6 wt. %, from about 0.05 to about 0.5 wt. %, from about 0.05 to about 0.4 wt. %, from about 0.1 to about 1.0 wt. %, from about 0.1 to about 0.8 wt. %, from about 0.1 to about 0.6 wt. %, from about 0.1 to about 0.5 wt. %, from about 0.1 to about 0.4 wt. %, from about 0.2 to about 1.0 wt. %, from about 0.2 to about 0.8 wt. %, from about 0.2 to about 0.6 wt. %, from about 0.2 to about 0.5 wt. %, from about 0.2 to about 0.4 wt. %, from about 0.3 to about 1.0 wt. %, from about 0.3 to about 0.8 wt. %, from about 0.3 to about 0.6 wt. %, from about 0.3 to about 0.5 wt. %, or any range or subrange thereof, based on the total weight of the second layer of the oral care product.

[0100] The oral care product may optionally comprise a thickener or thickening agent. In at least one embodiment, the thickener or thickening agent is in the second layer of the oral care product. The thickener or thickening agent may include, but is not limited to xanthan gum, guar gum, biosaccharide gum, cellulose, acacia seneca gum, sclerotium gum, agarose, pectin, and gellan gum. In at least one embodiment, the thickener or thickening agent is pectin. The thickener or thickening agent may be present in the oral care product in an amount ranging from about 15 to about 40 wt. %, from about 15 to about 38 wt. %, from about 15 to about 35 wt. %, from about 18 to about 40 wt. %, from about 18 to about 38 wt. %, from about 18 to about 35 wt. %, from about 20 to about 40 wt. %, from about 20 to about 38 wt. %, from about 20 to about 35 wt. %, from about 23 to about 40 wt. %, from about 23 to about 38 wt. %, from about 23 to about 35 wt. %, from about 25Docket No. 1017189-00- WO-Ol-OC to about 40 wt. %, from about 25 to about 38 wt. %, from about 25 to about 35 wt. %, or any range or subrange thereof, based on the total weight of the first or second layer of the oral care product.

[0101] The oral care product may optionally comprise a fiber or fiber source. In at least one embodiment, the fiber source is in the second layer of the oral care product. The fiber source may include, but is not limited to, carboxymethylcellulose, oat fiber, starch or modified starch, maltodextrin, amylose, high amylose starch, corn starch, potato starch, rice starch, tapioca starch, pea starch, sweet potato starch, barley starch, wheat starch, waxy corn starch, hydroxypropylated high amylose starch, or a combination of two or more thereof.

[0102] The fiber source may be present in the oral care product in an amount ranging from about 15 to about 40 wt. %, from about 15 to about 38 wt. %, from about 15 to about 35 wt. %, from about 18 to about 40 wt. %, from about 18 to about 38 wt. %, from about 18 to about 35 wt. %, from about 20 to about 40 wt. %, from about 20 to about 38 wt. %, from about 20 to about 35 wt. %, from about 23 to about 40 wt. %, from about 23 to about 38 wt. %, from about 23 to about 35 wt. %, from about 25 to about 40 wt. %, from about 25 to about 38 wt. %, from about 25 to about 35 wt. %, or any range or subrange thereof, based on the total weight of the first or second layer of the oral care product.

[0103] The oral care product may optionally comprise an active agent. In at least one embodiment, the active agent is in the first layer of the oral care product. The active agent may include, but is not limited to. zinc ion sources, green tea extract, cranberry extract, beta-glucan, curcumin, eugenol, one or more vitamins, and antibacterial agents.

[0104] Zinc ion source may include a chemical compound, a complex, or a zinc salt capable of or configured to provide the zinc ions. Zinc ion sources may include, but are not limited to, zinc sulfate, zinc chloride, zinc acetate, zinc phenolsulfonate, zinc borate, zinc bromide, zinc nitrate, zinc glycerophosphate, zinc benzoate, zinc carbonate, zinc citrate (e.g., zinc citrate trihydrate), zinc hexafluorosilicate, zinc phosphate hydrate, zinc lactate trihydrate, zinc oxide, zinc peroxide, zinc salicylate, zinc silicate, zinc stannate, zinc tannate, zinc tartrate, zinc titanate, zinc tetrafluoroborate, or a combination thereof.

[0105] Vitamins may include, but are not limited to, vitamin C and vitamin C derivatives, vitamin D and vitamin D derivatives, vitamin E and vitamin E derivatives, and any combination thereof. The vitamins may include compounds or substances that release the desired vitamin, in vivo or in vitro, solvates, hydrates, and salts thereof. The vitamins may be capable of or configured toDocket No. 1017189-00- WO-Ol-OC promote gum health. Illustrative vitamin C derivatives may be or include, but are not limited to, glucosides of ascorbic acid or ascorbyl glucoside (ASG), phosphates of ascorbic acid, in particular magnesium ascorbyl phosphate, sodium ascorbyl phosphate, calcium ascorbyl phosphate, potassium ascorbyl phosphate, mixed salts, such as sodium magnesium ascorbyl phosphate or sodium calcium ascorbyl phosphate, or the like, or a combination thereof

[0106] The active agent may be present in the oral care product in an amount ranging from about 0.1 to about 20 wt. %, from about 0.1 to about 18 wt. %, from about 0.1 to about 15 wt. %, from about 0.1 to about 12 wt. %, from about 0.1 to about 10 wt. %, from about 0.1 to about 7.5 wt. %, from about 0.1 to about 5 wt. %, from about 0.1 to about 2.5 wt. %, from about 0.1 to about 1 wt. %, from about 0.1. to about 0.5 wt. %, from about 0.5 to about 20 wt. %, from about 0.5 to about 18 wt. %. from about 0.5 to about 15 wt. %, from about 0.5 to about 12 wt. %, from about 0.5 to about 10 wt. %, from about 0.5 to about 7.5 wt. %, from about 0.5 to about 5 wt. %, from about 0.5 to about 2.5 wt. %, from about 0.5 to about 1 wt. %, from about 1 to about 20 wt. %, from about 1 to about 18 wt. %, from about 1 to about 15 wt. %, from about 1 to about 12 wt. %, from about 1 to about 10 wt. %, from about 1 to about 7.5 wt. %, from about 1 to about 5 wt. %, from about 3 to about 20 wt. %, from about 3 to about 18 wt. %, from about 3 to about 15 wt. %, from about 3 to about 12 wt. %, from about 3 to about 10 wt. %, from about 3 to about 7.5 wt. %, from about 3 to about 5 wt. %, from about 5 to about 20 wt. %, from about 5 to about 18 wt. %, from about 5 to about 15 wt. %, from about 5 to about 12 wt. %, from about 5 to about 10 wt. %, from about 5 to about 7.5 wt. %, or any range or subrange thereof, based on the total weight of the first or second layer of the oral care product.

[0107] The oral care product may optionally comprise one or more flavorants or flavoring agents. The one or more flavorants or flavoring agents may include, but are not limited to, flavoring oils or essential oils including include oils of spearmint, peppermint, Wintergreen, menthol, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon, lime, grapefruit, and orange. The flavorants or flavoring agents may be present in an amount ranging from about 1 wt. % or less, about 0.8 wt. % or less, about 0.7 wt. % or less, about 0.6 wt. %, about 0.5 wt. % or less, about 0.4 wt. % or less, about 0.3 wt. % or less, about 0.20 wt. % or less, about 0.1 wt. % or less, about 0.05 wt. % or less, or any range or subrange thereof. In at least one embodiment, the one or more flavorant or flavoring agent is selected from menthol or clove oil.

[0108] It should be appreciated by one having ordinary skill in the art, that the oral care productDocket No. 1017189-00- WO-Ol-OC may include other additional ingredients / components. For example, the oral care product may include any one or more of the following: anti-caries agents, diluents, surface active agents or surfactants, mouth feel agents, colorants or coloring agents, preservatives, antifoam agents (e.g., benzoic acid, sulfuric acid, glyceryl monostearate, etc.), or the like, or a combination thereof. It should further be appreciated by one having ordinary skill in the art that while general attributes of each of the above categories of materials may differ, there may be some common attributes and any given material may serve multiple purposes within two or more of such categories of materials.EXAMPLESExample 1

[0109] A non-limiting example apparatus configured in accordance with aspects of the invention (Example Apparatus) was prepared for evaluating the barrier properties of an oral care product adapted for being disposed on a mucosal surface. As depicted in FIG. 1, the Example Apparatus had a first chamber and a second chamber, which are adapted to receive and contain liquids, such as a first solution and a second solution. The first and second chambers were configured to be fluidically coupled by way of a permeable wall forming part of the first chamber.Example 2

[0110] The Example Apparatus from Example 1 was employed to evaluate the barrier properties of a non-limiting, example oral care product (Example Oral Care Product A) and three comparative oral care products (Comparative Oral Care Products 1-3). Example Oral Care Product A and Comparative Oral Care Products 1-3 were adapted for adhering to a mucosal surface. Example Oral Care Product A was a bilayer patch according to aspects of the disclosure described herein. Comparative Oral Care Product 1 was a PerioGel product that was free of hyaluronate. Comparative Oral Care Product 2 was a PerioGel product that was free of cetylpyridinium chloride. Comparative Oral Care Product 3 was a PerioGel product that was free of hyaluronate and cetylpyridinium chloride.

[0111] Before starting the evaluation of the oral care product, the Example Apparatus was placed within a sterile laminar hood and sterile media (specifically, McBain media), which was warmed to a temperature of 37°C. The respective oral care products were then positioned on the permeable bottom wall of the first chamber using sterile forceps so that the respective oral care product would be in direct contact with the liquid from the first chamber and in direct contact with the liquid fromDocket No. 1017189-00- WO-OLOC the second chamber, but would preclude the liquid in the first chamber from directly contacting the liquid in the second chamber if the oral care product maintains a fluidically tight seal with the permeable bottom wall and is non-permeable. Thus, the Example Apparatus enables the evaluation of the oral care products permeability and / or characteristics relating to maintenance of a fluidically tight seal with the permeable bottom wall (e.g., the oral care products adherence to a substrate).

[0112] After the respective oral care product was positioned and set on the permeable bottom wall, warm saliva was added on top of the oral care product and a cell culture insert was transferred into the sterile media using sterile forceps. Independent plates were incubated for 2 times periods; namely, 1 hour and 24 hours. At 1 hour, the cell culture inserts were removed and the incubated McBain media is portioned into a 96 well plate.

[0113] A subset of wells were then assessed by optical density and using dyes to evaluate the incubated McBain media. To evaluate the optical density of the incubated McBain media, 100 pL of the incubated McBain media was measured in a 96 well plate at each time point (namely, 1 hour and 24 hours) at a wavelength of 610 nm. The optical density at 610 nm is a measure of turbidity, which is correlated with bacterial count.

[0114] As mentioned above, the incubated McBain media was evaluated using dyes to quantify the amounts of live and dead bacteria. Specifically, bacteria was quantified with an Invitrogen BacLight Live / Dead viability kit. The kit includes two fluorescent dyes — specifically, propidium iodide and SYTO9. Propidium iodide is a red-fluorescent DNA stain that can only penetrate bacteria whose cell membranes have been permeabilized (“dead”). SYTO9 is a green-fluorescent DNA dye that is able to stain all bacteria. Incubated McBain media samples were stained by adding 100 pl of equal parts Live / Dead dye solution (prepared according to the manufacturer's manual) to each well of a 96-well plate. The plates were then incubated for 15 minutes at room temperature while being protected from light. Fluorescence is determined by exciting the samples at 485 nm and then reading the emission at 535 nm and 635 nm. Results are represented as total biomass detected using the SYTO9 green-fluorescent dye alone.

[0115] Table 2 provides the optical density at 24 hours for the Example Oral Care Product A and Comparative Oral Care Products 1-3.Docket No. 1017189-00- WO-Ol-OCTable 20116] Table 3 provides the total amount of bacteria cells in Example Oral Care Product A andComparative Oral Care Products 1-3.Table 3

Claims

Docket No. 1017189-00- WO-Ol-OCCLAIMSWhat is Claimed is:

1. A method for evaluating the barrier properties of an oral care product disposed on a mucosal surface, the method comprising: obtaining an oral care product; positioning the oral care product to have a first surface contacting a permeable substrate; contacting the permeable substrate and the first surface of the oral care product with a first solution, the first solution being selected from a media or an inoculum; and contacting a second surface of the oral care product with a second solution, the second solution being selected from the other of the media or the inoculum.

2. The method according to claim 1, wherein the first solution is the media.

3. The method according to claim 1 or claim 2 further comprising: maintaining the contact of the first solution with the first surface of the oral care product and the contact of the second solution with the second surface of the oral care product for a period of time; and evaluating the media after the period of time.

4. The method according to claim 3, wherein the period of time is from about 30 minutes to about 72 hours.

5. The method according to claim 3 or claim 4, wherein the media is evaluated by determining the optical density of the media.

6. The method according to any one of claims 3 to 5, wherein the media is evaluated to determine the total amount of bacteria cells in the media and evaluated to determine the total number of dead bacteria cells in the media.

7. The method according to claim 6, wherein the total amount of bacterial cells in the media is evaluating using at least SYTO9 dye.Docket No. 1017189-00- WO-Ol-OC8. The method according to claim 7, wherein the total amount of dead bacterial cells in the media is evaluating using at least a propidium iodide dye.

9. The method according to any foregoing claim, wherein the second solution is not initially in direct contact with the first solution.

10. An apparatus for evaluating the barrier properties of an oral care product comprising: a first chamber comprising a permeable wall and an inner surface defining a first cavity, the permeable wall comprising a first surface and an opposed second surface and one or more aperture extending from the first surface to the second surface; and a second chamber comprising an inner surface defining a second cavity, the second cavity being fluidically coupled to the first cavity by way of the one or more aperture of the permeable wall.

11. The apparatus according to claim 10, wherein the first chamber is positioned at least partially within the cavity of the second chamber.

12. The apparatus according to claim 10 or claim 11, wherein the first chamber is positioned within the cavity of the second chamber.

13. The apparatus according to any one of claims 10 to 12, wherein the first surface of the permeable wall forms at least a portion of the inner surface of the first chamber.

14. The apparatus according to any one of claims 10 to 13, wherein the permeable wall is flat.

15. The apparatus according to any one of claims 10 to 14, wherein the permeable wall is convex such that an apex of the permeable wall extends in the direction of the center of the first chamber.Docket No. 1017189-00- WO-Ol-OC16. A method for evaluating the barrier properties of an oral care product disposed on a mucosal surface using the apparatus according to any one of claims 10 to 15, the method comprising: positioning an oral care product to have a first surface contacting the permeable wall of the first chamber of the apparatus; at least partially filling the first chamber of the apparatus with a first solution such that the first solution is in fluidic communication with the first surface of the oral care product, wherein the first solution is selected from a media or an inoculum; and at least partially filling the second chamber of the apparatus with a second solution such that the second solution is in fluidic communication with a second surface of the oral care product, wherein the second solution is selected from the other of the media or the inoculum, and wherein the second solution is not in direct contact with the first solution.

17. The method according to claim 16 further comprising: maintaining the first solution in contact with the first surface of the oral care product and the second solution in contact with the second surface of the oral care product for a period of time; and evaluating the media after the period of time to determine the total amount of bacteria cells in the media and / or the total amount of dead bacteria cells in the media.

18. The method according to claim 17, wherein the period of time is from about 30 minutes to about 72 hours.

19. The method according to claim 17 or claim 18, wherein the media is evaluated by determining the optical density of the media.

20. A method for evaluating the barrier properties of an oral care product disposed on a mucosal surface, the method comprising: obtaining an oral care product having a first surface and a second surface opposed the first surface;Docket No. 1017189-00- WO-Ol-OC positioning the oral care product to have the first surface of the oral care product contacting a permeable substrate; contacting the permeable substrate and the first surface of the oral care product with a first solution, the first solution being selected from a media or an inoculum; and contacting the second surface of the oral care product with a second solution, the second solution being selected from the other of the media or the inoculum.

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