WO2020058837A1

WO2020058837A1 - An orally chewable gum composition having cosmetic and therapeutic effects for improving overall oral health of betel nut consumer

Info

Publication number: WO2020058837A1
Application number: PCT/IB2019/057804
Authority: WO
Inventors: Arnaud de YRIGOYEN
Original assignee: Ko Shwe Ventures
Priority date: 2018-09-18
Filing date: 2019-09-17
Publication date: 2020-03-26
Also published as: TW202021482A

Abstract

The present invention relates to an orally chewable gum composition having cosmetic and therapeutic effects comprising aloe vera, turmeric extract, vitamin C, and a cleaning agent for topical administration to a subject in need of oral health improvement, in particular the betel nut consumers.

Description

AN ORALLY CHEWABLE GUM COMPOSITION HAVING COSMETIC AND

THERAPEUTIC EFFECTS FOR IMPROVING OVERALL ORAL HEALTH OF BETEL NUT

CONSUMER

Technical Field

The present invention relates to orally chewable gum compositions comprising active cosmetic and therapeutic ingredients that improve the overall oral health of a subject. Specifically, the orally chewable gum compositions are designed to relieve symptoms of heavy betel nut consumption, reduce the impact of staining, reduce sensitivity, reduce tooth decay and speed up healing of the oral wounds of the betel nut chewers.

Background of the Invention

It is estimated that 600 million people worldwide chew betel regularly (Bull World Health Organ 2015;93:684-692 | doi: http://dx.doi.org/10.2471/BLT.14.149484). In Myanmar, a recent Ministry of Health and World Health Organization survey showed that 62% of men and 24% of women use smokeless tobacco products such as betel, which contains both tobacco and areca nut (Myanmar Times, 15/06/2016, "Government back-peddles on much- derided betel ban"). Most betel chewers are low-income and spend significant proportions of their household income on betel quid (7.5-10% on average).

Typically, a betel nut preparation is made by wrapping pieces of chopped areca nut, slaked lime (calcium hydroxide) often with tobacco and spices in a betel leaf that is usually chewed for 3-6 minutes. Areca nut contains a psychoactive drug, Arecoline, which is considered to be the fourth most consumed psychoactive drug in the world, after tobacco, alcohol, and caffeine (University of Florida. 21/10/2015, "Researcher finds key clues about 'betel nut' addiction that plagues millions worldwide", Science Daily), and slaked lime causes the mean pH to rise to 10 at which reactive oxygen species are generated from betel nut ingredients.

Chewing betel nut causes a wide range of serious oral health issues, from severe dental staining and erosion, dependence on betel nut, pain and sensitivity when eating spicy or sour food, to chronic inflammation, to a pre-malignant inflammatory disease called oral submucous fibrosis which latterly restricted oral opening and protrusion of the tongue, and oral cancer. Regular chewers of betel nut suffer these significant long-term debilitating effects upon their day-to-day quality of life.

While in some cultures the teeth and gum staining, sometimes reddish-brown, can be seen in a neutral or even positive light (Norton, S.A. 1998, "Betel: Consumption and consequences", Journal of the American Academy of Dermatology, Vol. 38, No.1 pp 81- 87), in urban areas or more developed countries public perceptions of this staining tend to be negative. A disease that could arise from the chewing of betel nut is oral submucous fibrosis, which is a potentially malignant and crippling disorder of the oral mucosa. It causes significant morbidity in terms of loss of mouth function as tissues become rigid and mouth opening becomes difficult. An imbalance in collagen synthesis and degradation in oral mucosa is generally believed to be the main cause of the oral submucous fibrosis. This disease is considered a type of collagen metabolism disorder as it causes disturbance in the homeostatic equilibrium between synthesis and degradation of extra cellular matrix. Other conditions arising from long-term betel nut consumption includes periodontitis, betel chewer’s mucosa (BCM), leukoplakia, and lichenoid lesions each of which may severely impact upon quality of life. In Myanmar, oral cancer is one of the most common cancers, and it is believed to be almost entirely caused by betel chewing.

On a wider societal level, oral diseases arising from the chewing of betel nut have become a widespread public health problem which has placed a significant economic burden upon the public health care system and infrastructure of certain South Asian, South East Asian and Pacific Rim regions. In Myanmar, the government has made a well-publicized attempt to tackle the betel nut problem through legislation (Radio Free Asia, 14/06/2016,“Myanmar Government Issues New Guidance for Reducing Betel Nut Chewing”), but the campaign seems to be unsuccessful (Myanmar Times, 15/06/2016,“Government back-peddles on much-derided betel ban”). Also, it appears that state efforts have tended to only provide limited solutions, especially in countries where government resources are limited. Thus, it seems that there is no single method to reduce the impact or prevalence of betel nut. The solution should be found in a holistic approach from governments, the market, and healthcare providers.

In recent years, nicotine gums have been marketed at betel nut users in India and elsewhere, but these attempts have so far not received widespread commercial success. A specific barrier to the success of nicotine gums aimed at the Indian market has been the restrictions on the points of sale - that is, it is common for nicotine gum to only be available on prescription and it is a relatively expensive product. Another product marketed in India is betel nut-flavored gum, however, this has neither the stimulating power of the nut, nor therapeutic or addiction-weaning effects. Furthermore, most chewers of betel nut products tend to fall within a relatively low-income bracket in less economically developed countries (LEDCs) where health service provisions are irregular, and accordingly, accessibility to ameliorative products is limited. Chewing gums with a teeth cleaning effect are well known and a number of products are and have been on the market. These products in general have been claimed to be able to whiten and clean the teeth through the action of mechanical cleansing, oxidation and rebuilding of the tooth enamel. Stains that existing products are able to remove or reduce are in most cases directly or indirectly mentioned to be the result of smoking and/or coffee or tea intake. Coffee and tea contain tannins, which are said to be the cause of staining. Tannins belong to a large group of phenolic substances widely distributed across plant families, and the definition is largely practical. Tannins are substances which react positively in the very unspecific tannin tests. They are divided into subgroups based on their chemical structures. The tannins contained in betel nut are obviously different from those contained in tea and coffee, apparent from their different colors. Red stains derived from betel nut usage are stated to be caused by red tannins. Although the existing oral care chewing gums have been shown to have effects against stains caused by coffee and tea, it is not clear whether they also could be effective against the different stains caused by betel nut consumption.

In addition, after an extensive research across major betel nut consuming countries, it is clear that there are currently no products on the market specifically designed to provide relief and improvement to the dental and oral health of betel nut consumers who are still addicted to betel nut chewing.

Accordingly, there exists a need for a new product that could meet the demand of improving the overall dental and oral health of betel nut chewers, which is specifically designed to be consumed alongside with betel nuts to provide not only aesthetic but also therapeutic effects to the dental and oral health of betel nut consumers.

Summary of the Invention

The present invention seeks to alleviate at least one of the above-described problems.

A primary objective of the present invention is to provide an orally chewable gum composition comprising the active cosmetic and therapeutic ingredients to be consumed alongside with betel nut to effectively combat some of the damages caused by betel nut consumption, such as to reduce stains, to reduce plaque and calculus, to reduce sensitivity and inflammation, and ultimately offer some longer term oral health benefits.

Accordingly, the present invention provides an orally chewable gum composition having cosmetic and therapeutic effects comprising aloe vera, turmeric extract, vitamin C, and a cleaning agent, for topical administration to a subject in need of oral health improvement. In an embodiment of the present orally chewable gum composition, aloe vera constitutes from about 0.2 to about 4.0%, turmeric extract constitutes from about 0.8 to about 8.0%, and vitamin C constitutes from about 0.6 to about 2.0%, by total weight of the orally chewable gum composition.

In another embodiment of the present orally chewable gum composition, the cleaning agent comprises sodium hydrogen carbonate and silicon dioxide.

In the preferred embodiment of the present orally chewable gum composition, sodium hydrogen carbonate constitutes from about 0.2 to about 0.8%, and silicon dioxide constitutes from about 0.2 to about 0.6%, by total weight of the orally chewable gum composition.

In the most preferred embodiment of the present orally chewable gum composition, aloe vera constitutes about 0.8%, turmeric extract constitutes about 1.4%, vitamin C constitutes about 1 .0%, sodium hydrogen carbonate constitutes about 0.4%, and silicon dioxide constitutes about 0.4%, by total weight of the orally chewable gum composition.

In another aspect, the present invention provides the use of the above-mentioned orally chewable gum composition for the improvement of the oral health of a subject in need thereof.

In yet another aspect, the present invention provides a method of improving the oral health of a subject, comprising topically administering to the subject the above-mentioned orally chewable gum composition.

In the preferred embodiments, the subject is a betel nut consumer.

In the preferred embodiments, the orally chewable gum compositions according to the invention are to be chewed alongside with the betel nuts in a minimal amount of 1 piece for every 5 betel nuts.

Brief Description of the Drawings

Figure 1 shows the age composition of 72 subjects completing the 14-day home-use stepwise study to assess the efficacy of an orally chewable gum product in accordance with a preferred embodiment of the present invention.

Figure 2 shows digital images of teeth of three example subjects before and after using an orally chewable gum product in accordance with a preferred embodiment of the present invention. Detailed Description of the Preferred Embodiments

Before the present orally chewable gum compositions of the invention are described, it is to be understood that this invention is not limited to particular orally chewable gum compositions described, since such gum composition may, of course, vary. It is also to be understood that the terminology used herein is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims.

Unless otherwise defined, all terms used in disclosing the invention, including technical and scientific terms, have the meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. By means of further guidance, term definitions are included to better appreciate the teaching of the present invention.

As used herein, the singular forms "a", "an", and "the" include plural reference, and the plural include singular forms, unless the context clearly dictates otherwise.

The terms "comprising", "comprises" and "comprised of as used herein are synonymous with "including", "includes" or "containing", "contains", and are inclusive or open-ended and do not exclude additional, non-recited members, elements or method steps. It will be appreciated that the terms "comprising", "comprises" and "comprised of as used herein comprise the terms "consisting of, "consists" and "consists of.

The recitation of numerical ranges by endpoints includes all numbers and fractions subsumed within the respective ranges, as well as the recited endpoints.

The term“about” when applied to values indicates that the calculation or the measurement allows some slight imprecision in the value (with some approach to exactness in the value; approximately or reasonably close to the value; nearly). If, for some reason, the imprecision provided by“about” is not otherwise understood in the art with this ordinary meaning, then “about” as used herein indicates at least variations that may arise from ordinary methods of measuring or using such parameters. For example, the terms “generally,” “about,” and “substantially,” may be used herein to mean within manufacturing tolerances. Or, for example, the term “about” as used herein when modifying a quantity of an ingredient or reactant of the invention or employed refers to variation in the numerical quantity that can happen through typical measuring and handling procedures used, for example, when making concentrates or solutions in the real world through inadvertent error in these procedures, through differences in the manufacture, source, or purity of the ingredients employed to make the compositions or carry out the methods, and the like. The term “about” also encompasses amounts that differ due to different equilibrium conditions for a composition resulting from a particular initial mixture. Whether or not modified by the term“about,” the claims include equivalents to the quantities.

Reference throughout this specification to "one embodiment" or "an embodiment" means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of the phrases "in one embodiment" or "in an embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment, but may. Furthermore, the particular features, structures or characteristics may be combined in any suitable manner, as would be apparent to a person skilled in the art from this disclosure, in one or more embodiments. Furthermore, while some embodiments described herein include some but not other features included in other embodiments, combinations of features of different embodiments are meant to be within the scope of the invention, and form different embodiments, as would be understood by those in the art. For example, in the appended claims, any of the claimed embodiments can be used in any combination.

In the following passages, different aspects of the invention are defined in more detail. Each aspect so defined may be combined with any other aspect or aspects unless clearly indicated to the contrary. In particular, any feature indicated as being preferred or advantageous may be combined with any other feature or features indicated as being preferred or advantageous.

The present invention provides an orally chewable gum composition having cosmetic and therapeutic effects comprising aloe vera, turmeric extract, vitamin C, and a cleaning agent for topical administration to a subject in order to improve the overall oral health. The oral health improvement may include, but not limited to, at least one of reduction of teeth staining, reduction of calculus, reduction of plaque, reduction of gum sensitivity, reduction of gingivitis, alleviation and prevention of oral diseases and/or disorders selected from oral submucous fibrosis, periodontitis, betel chewer’s mucosa (BCM), leukoplakia, and lichenoid lesions. Accordingly, also provided are the use of the said orally chewable gum composition for the improvement of the oral health of a subject in need thereof and method of improving the oral health of a subject in need thereof comprising topically administering to the subject the above-mentioned orally chewable gum composition. Preferable, the subject is a betel nut consumer.

In view of the disclosure herein, it would be appreciated that the present invention may assist in providing one or more advantages. The present invention may conveniently assist in providing a synergistic effect of cleaning, whitening, and soothing the oral region of a subject rather than simply providing one of these effects.

In particular, stained teeth and oral wounds resulting from betel nut consumption may have a tendency to create a social stigma for betel nut consumers. The present invention’s ability to improve the aesthetic appearance and oral health of the betel nut consumer may therefore assist in improving the social confidence and mental wellbeing of such consumers. Accordingly, teeth staining, plaque, calculus, oral wounds and gum soreness, resulting for instance from betel nut consumption or otherwise, together may be treated by way of a topical administration of a combination comprising the active cosmetic and therapeutic ingredients by way of a non-invasive and familiar chewing action so as to improve the likelihood of uptake as a treatment by betel nut chewers. Furthermore, the delivery of the active cosmetic and therapeutic ingredients in the form of an orally chewable gum composition may be considered a convenient and relatively easily adopted treatment by existing betel nut users as such users may already be accustomed to chewing upon betel nut and the act of chewing the dental gum may not be considered an unusual or undesirable act. Furthermore, a combination of aloe vera, turmeric extract, vitamin C, and a cleaning agent may present itself as a relatively accessible and cost-effective approach for treatment of betel nut oral ailments and improvement of one’s aesthetic appearance with relatively low manufacturing costs and complexity associated therewith. As such, the use of a combination comprising the active cosmetic and therapeutic ingredients in a chewable gum format lends itself to a cost-effective solution to treatment or prevention of certain diseases arising from betel nut chewing particularly amongst lower-income earning individuals.

In addition, contrary to a primary concern that chewing a gum may encourage greater betel nut chewing, it has been surprisingly found that the orally chewable gum composition according to the invention encourages the majority of betel nut consumers to reduce their betel nut consumption, although it is designed as a complement rather than a substitute or an addiction therapy to betel nut.

Useful ingredients are now described more closely.

Aloe vera

Advantageously, the active properties of the aloe vera constituent may be released from the orally chewable gum composition which provides anti-inflammatory soothing properties to assist in the healing of oral wounds as the orally chewable gum composition is being chewed. The orally chewable gum composition according to the invention comprises aloe vera in solid form or preferably in gel form, which constitutes from about 0.2% to about 4.0%, preferably from about 0.2% to about 3.0%, more preferably from about 0.2% to about 2.0%, still more preferably from about 0.3% to about 1.3%, most preferably about 0.8% by total weight of the orally chewable gum composition.

Turmeric extract

In the present application, the turmeric extract (also known as curcuma extract) contains total curcuminoids, of which curcumin (also known as diferuloylmethane) is the primary active component which has some important biological properties such as anti-inflammatory, antioxidant and anti-cancer activity. Turmeric extract containing curcumin is seen as one of the most effective ingredients to help betel chewers who are suffering from inflammation and oral submucous fibrosis thanks to its soothing and anti-inflammatory properties. It is also believed to offer significant chemo-prevention effects although more research is required. In addition, turmeric extract is also mildly abrasive, which can reduce staining.

The orally chewable gum composition according to the invention comprises turmeric extract from about 0.8% to about 8.0%, preferably from about 0.8% to about 4.0%, more preferably from about 0.8% to about 3.0%, still more preferably from about 1.0% to about 2.0%, most preferably about 1.4%, by total weight of the orally chewable gum composition.

Vitamin C

Vitamin C (also known as ascorbic acid) is seen as important for overall oral health because it aids collagen production, which is essential for oral health. Oral sub mucous and oral cancer sufferers face issues with the production of collagen.

In this context, since betel nut chewers are often low income and do not necessarily have a balanced diet, vitamin C is also designed to reinforce the longer term oral health benefits.

The orally chewable gum composition according to the invention comprises vitamin C from about 0.6% to about 2.0%, preferably from about 0.6% to about 1.5%, more preferably from about 0.8% to about 1.2%, most preferably about 1.0% by total weight of the orally chewable gum composition.

Cleaning agent

According to the invention, the cleaning agent comprises at least one of xylitol, aluminum carbonate, titanium dioxide, aluminum oxide, alkali metal and alkali earth metal carbonates and oxides such as calcium carbonate, sodium hydrogen carbonate, magnesium carbonate, barium carbonate, silicas such as talc, silicon dioxide, aluminum silicate, microline, albite, tremolite, zirconium silicate and kieselguhr, alkali metal and alkali earth metal phosphates such as calcium pyrophosphate, calcium hydrogen phosphate dehydrate, anhydrous calcium hydrogen phosphate, sodium metaphosphate, sodium tripolyphosphate and sodium hexametaphosphate, tricalcium phosphate, dicalcium phosphate, tetrasodium pyrophosphate, sodium tripolyphosphate, calcium hydrogen phosphate dehydrate, and calcium pyrophosphate, and other mineral materials such as olivine, kaolinite, and chromite, or any combinations thereof. If xylitol is used, by the virtue of its nature, it may act as both a cleaning agent and a sweetening agent.

When the orally chewable gum composition is chewed, the cleaning agent(s) will contact with the teeth so as to provide mechanical cleansing of the teeth. In certain embodiments, the cleaning agent(s) may be contained in microgranules incorporated in the gum base when manufacturing the gum composition. The microgranules may be relatively fragile, such that they break up directly upon contact with the teeth during the chewing, releasing the cleaning agent(s) at the site at which they are to perform their cleansing action. Typically, the particles of the cleaning agent(s) have a diameter of between 2 and 100 pm.

In a preferred embodiment of the orally chewable gum composition according to the invention, the cleaning agent comprises sodium hydrogen carbonate and silicon dioxide.

In the more preferred embodiment of the above-mentioned orally chewable gum composition, the above-mentioned cleaning agent further comprises xylitol and/or titanium dioxide.

Typically the total amount of the cleaning agent constitutes from about 0.2 to about 55.5% (the high level of up to 55.5% of cleaning agents may be relevant with respect to, for example, xylitol, which may be added in very high amount to act as both a cleaning agent and a sweetening agent), by total weight of the orally chewable gum composition.

In the preferred embodiment of the orally chewable gum composition according to the invention, the amount of sodium hydrogen carbonate constitutes preferably from about 0.2 to about 0.8%, preferably from about 0.2% to about 0.7%, more preferably from about 0.3% to about 0.6%, most preferably about 0.4%, and the amount of silicon dioxide constitutes preferably from about 0.2 to about 0.6%, preferably from about 0.2% to about 0.5%, more preferably from about 0.3% to about 0.5%, most preferably about 0.4%, by total weight of the orally chewable gum composition. In addition to the above active agents, the orally chewable gum composition according to the invention further comprises the following components.

Gum base

The orally chewable gum composition according to the present invention includes a gum base which serves as a carrier for the active cosmetic and therapeutic ingredients. The particular gum base selected as the carrier is not critical and any commercially available gum base may be satisfactorily employed so long as it allows an effective amount of active ingredients to be incorporated therein using conventional manufacturing methods, the gum base allows release of the active ingredients during chewing, and, the gum base does not adversely affect the cosmetic and therapeutic effects of the active ingredients during chewing of the orally chewable gum composition. The gum base normally comprises natural and/or synthetic resins and optionally other ingredients such as elastomers, waxes, fats, emulsifiers, antioxidants, and fillers.

Resins provide a cohesive body or strength to the gum base. Any suitable resin known in the art can be used in a suitable amount, and the exemplary resins are most often glycerol esters of gum, terpene resins, and/or polyvinyl acetate.

Elastomers provide the elasticity or bounce to the gum base. Any suitable elastomer known in the art can be used in a suitable amount, and the exemplary elastomers are natural latexes such as couma macrocarpa, loquat, tunu, jelutong, or chicle or synthetic rubbers such as styrene-butadiene rubber, butyl rubber, polyisobutylene.

Waxes act as softening agents in the gum base. Any suitable wax known in the art can be used in a suitable amount, and the exemplary waxes are most usually paraffin or microcrystalline wax.

Fats act as plasticizers in the gum base. Any suitable fat known in the art can be used in a suitable amount, and the exemplary fats mainly come from hydrogenated vegetable oils.

Emulsifiers help in hydrating the gum base. Any suitable emulsifier known in the art can be used in a suitable amount, and the most common are lecithin or glycerol monostearate.

Antioxidants protect the gum base from oxidation and extend its shelf-life. Any suitable antioxidant known in the art can be used in a suitable amount, and the most common type is butylated hydroxytoluene (BHT). Fillers impart a specific texture and/or consistency to the gum base. Any suitable filler known in the art can be used in a suitable amount, and the most commonly used are calcium carbonate or talc.

Many gum base formulations are well known in the art, and can be used suitably in the present invention, including both natural and synthetic gum base formulations. Suitable conventional stick gum bases (i.e., as opposed to bubble gum bases) include Paloja, Firm Paloja, Berguna, and Dreyco, all available from the L. A. Dreyfus Corporation, and Synthetic Base No. 2939 and Natural Base No. SC319, which have been obtained from the American Chicle Company. Suitable bubble gum bases include D.C., Extra Soft, Oak, Grande, Soft Ideal, Ideal, Model, and Ladco, all available from the L. A. Dreyfus Corporation.

The amount of the gum base is not critical. For example, the gum base may typically constitute from about 15% to about 50% by total weight of the orally chewable gum composition.

Other optional components Non-active ingredients

The orally chewable gum composition of the present invention may optionally contain nonactive ingredients, such as taste agents including sweetening agents and flavoring agents. In a preferred embodiment, these non-active ingredients are incorporated into the gum base when manufacturing the orally chewable gum composition.

The addition of taste agents selected from sweetening agents and flavoring agents act to make the user chew on the orally chewable gum composition for longer time since it is pleasant to do so. These taste ingredients do in this manner increase the effects of the cosmetic and therapeutic agents. Any conventional sweetening agent or flavoring agent may be used. Combinations of sweetening agents, flavoring agents, or sweetening agents and flavoring agents may likewise be used.

Sweetening agents may be used which may typically include any one of sugar alcohols such as xylitol, sorbitol, mannitol, maltitol, lactitol, erythritol, isomalt or other sugar alcohols, synthetic sweetening agents such as saccharin, aspartame, acesulfame potassium, sucralose and natural sweeteners such as corn syrup or cane sugar. If xylitol is used, by the virtue of its nature, it may act as both a sweetening agent and a cleaning agent. A natural or artificial flavor agent may be used to provide flavor such as mint, spearmint, peppermint, menthol, levomenthol, exotic flavor, or the like. While a nice tasting flavor is preferred, it could be changed according to specific circumstances.

In general, the sweetening and/or flavoring agents may present in an effective amount sufficient to provide a generally pleasant taste to the orally chewable gum composition.

Other non-active ingredients may also be contained in the orally chewable gum composition of the present invention. These include, but not limited to, binding agents, moisture absorbing components, film forming agents, dispersing agents, anti-sticking components, bulking agents, coloring agents, wax components, emulsifying agents, softening agents, stabilizing agents, thickening agents, and the like.

Any of the above-mentioned non-active ingredients is known in the art and can be added in a suitable amount into the chewable gum composition. In a preferred embodiment, these non-active ingredients are incorporated into the gum base when manufacturing the orally chewable gum composition.

Chewable gum coating

The orally chewable gum composition may or may not be coated by a chewable gum coating. If present, the chewable gum coating may serve to protect the active agents from decomposition, e.g., caused by oxygen. Moreover, the chewable gum coating may contribute to maintain desired moisture content in the orally chewable gum composition. The chewable gum coating may be any conventional coating used in the field of chewing gum and may be a hard coating or a soft coating.

When the orally chewable gum composition has a chewable gum coating, the chewable gum coating may contain at least one of the above-mentioned active agents, preferably at least one of the above-mentioned cleaning agents. Such an embodiment may for instance be advantageous when a rapid release of active agents is desirable.

The chewable gum coating may also comprise at least one non-active ingredient selected from, but not limited to, the above-mentioned group consisting of binding agents, moisture absorbing components, film forming agents, dispersing agents, anti-sticking components, bulking agents, flavoring agents, coloring agents, sweetening agents, wax components, emulsifying agents, softening agents, stabilizing agents, thickening agents, and the like. Any of the above-mentioned non-active ingredients is known in the art and can be added in a suitable amount into the chewable gum coating. The above-mentioned orally chewable gum composition according to the invention is a formulated composition which is ready to use by the consumers for improving their overall oral health.

The above-mentioned orally chewable gum compositions according to the invention can be a gum piece in the form of slabs, sticks, pellets, balls, pillows, and the like, wherein the preferred shape is a rectangle or square pillow. The composition of the different forms of the orally chewable gum compositions will be similar but can vary with regard to the ratio of the ingredients.

In order to achieve the improvement of the overall oral health as desired, the above- mentioned orally chewable gum compositions according to the invention are to be chewed alongside with the betel nuts in a minimal amount of 1 piece for every 5 betel nuts.

Preferably, the above-mentioned orally chewable gum compositions according to the invention have an average weight of about 0.5 to 5.0 g, more preferably from 1.0 to 3.0 g.

Methods of manufacture the orally chewable gum composition

The orally chewable gum compositions of the embodiments of the present invention may be manufactured in accordance with any suitably adapted conventional manufacturing methods of mixing the gum base with the active cosmetic and therapeutic ingredients such as aloe vera, turmeric extract, vitamin C, and cleaning agent(s). In addition, other non-active ingredients such as sweetening agents and flavoring agents may be mixed into the gum base. Next, the formulated chewable gum composition may be formed in any desired shape. This gum composition may be coated by a chewable gum coating.

Examples

The invention will now be further illustrated with reference to the examples.

The following Table 1 shows the active ingredients and their respective amounts (% by weight) of an exemplary orally chewable gum product in accordance with a preferred embodiment of the present invention which was manufactured according to a conventional method.

TABLE 1 - Active ingredients of an exemplary orally chewable gum product

Active ingredients % by weight

Curcuma ES 95% 1.0-2.0 Ascorbic acid (Vitamin C) 0.6-1.5

Aloe vera ES 15% 0.3-1.3

Sodium hydrogen carbonate 0.2-0.8

Silicon dioxide 0.2-0.6

Other cleaning agents including xylitol and/or titanium dioxide, the gum base, and non-active ingredients including sweetening agent(s), flavoring agent(s), emulsifying agent(s), softening agent(s), film forming agent(s), and thickening agent(s), which have been set forth in the detailed description above, are further contained in the above exemplary orally chewable gum product in appropriate amounts. For example, xylitol constitutes about 28.0-32.0% by total weight of the above exemplary orally chewable gum product to act as a cleaning agent as well as a sweetening agent. Other cleaning agent(s) may constitutes about 0.1 -2.0%, other sweetening agent(s) may constitutes about 39.0-43.0%, the flavoring agent(s) may constitutes about 1.0-3.0%, and the gum base may constitutes about 18.0-22.0% by total weight of the above exemplary orally chewable gum product. Additionally, sunflower lecithin may constitute about 0.5-1.5% and gum arabic may constitutes about 0.1-1.0% by total weight of the above exemplary orally chewable gum product. The balance amount is emulsifying agent(s), softening agent(s), film forming agent(s), and/or thickening agent(s).

Product study and survey

A study was performed at Palal Phyu, Yadanar rd, South Oakkalapa Tsp, Yangon between week commencing 26^th November 2018 and week ending 25^th January 2019 in order to assess the efficacy of the above-mentioned orally chewable gum product for its potential as an oral care product for betel nut users, as compared to a standard market product (an inactive control product).

Materials and methods

This was a double-blind within subject comparison study conducted in healthy betel nut using volunteers. The study included dental assessments by an independent consultant dentist and self-perception questionnaires (SPQ) by the volunteers.

Test and control articles

1. Zingo Chewing gum - ZG001 (test article), the orally chewable gum product which was manufactured in accordance with a preferred embodiment of the present invention.

2. Clorets (control article), the standard market product. The above articles had been tested to comply with applicable regulations, and considered to be safe for human use.

Test subjects

Subjects were recruited in a stepwise fashion with 70 subjects in the first phase and additional 20 subjects in the second phase (i.e., 90 recruited subjects in total). A stepwise method of recruitment was used to ensure appropriate subject numbers. The recruited subjects had to satisfy the following inclusion and exclusion criteria, had to be prepared to accept the prohibitions and restrictions and had to have given written informed consent.

Inclusion criteria

Healthy subjects of either gender aged at least 18 years at the start of the study active phase.

Frequent or regular users of betel nut (defined as a minimum of 5 years usage at an average of no less than 15 quids a day) as reported by the subjects.

Having written informed consents completed.

Exclusion criteria

- Pregnancy or lactation.

Inadequate or non-existent contraception (women of child bearing potential only).

- An unrelated current oral disease of any type defined as impairment of normal oral function not related to physical injury or an observed condition of the study.

- Current use of specific dental improvement products (excluding toothpaste without additional efficacious benefits) or use within the previous three months.

- Evidence of recent dental work.

- Anticipated non-compliance during the study or a change in circumstances that would have caused them to meet exclusion criteria.

Heavy alcohol consumption (i.e. more than 21 units per week or 8 units a day for men, more than 14 units per week or 4 units for women).

Current use or history of repeated use of street drugs at the study start date. A febrile illness within the last 12 hours, prior to the study start.

- Significant past medical history of hepatic, renal, cardiac, pulmonary, digestive, haematological, neurological, locomotor or psychiatric disease, which would have compromised the safety of the subject.

- History of malignant disease.

- Insulin dependent diabetes.

- Concurrent medication likely to have affected the response to the test and control articles or confuse the results of the study.

Participation in a dental study 28 days prior to the study start date.

Prohibitions and restrictions in the duration of the study

Must be willing to apply the test or control articles to the designated test sites as instructed.

Must not change the product currently used for personal dental cleansing in the duration of the study.

Must not apply any other product to the application sites other than the test or control articles or the current personal cleansing product in the duration of the study.

Must not complete or schedule dental works without informing the person in charge and withdrawing from the study.

Withdrawal

The participation of a subject in this study may have been discontinued for any of the following reasons:

- the subject wished to withdraw.

- if it was for the best interests of the subject.

- suspected adverse effects from the test or control articles. inter-current illness. violation of the prohibitions and restrictions. development of an exclusion criterion.

Subjects were free to withdraw at any time and needed not give a reason, but every reasonable attempt was made to ascertain such reasons. The data for those subjects who were withdrawn from the study is excluded from final data analysis. Withdrawn subjects were not replaced.

Study procedure

Study flow chart

The test and control articles were used at home regularly throughout the day for 14 days. Two dental assessments were performed for each subject on Day 1 (baseline) and Day 14 (end-point) for plaque, calculus, inflammation, sensitivity, and staining.

Day 1

Subjects reported to the test center on Day 1 at which time they underwent dental assessments of plaque, calculus, inflammation, sensitivity, and staining. Macrophotography was completed for the test sites, and self-perception questionnaires (SPQ) were completed. Upon completion of the assessments, subjects were issued with instruction sheets, diary cards and test or control articles randomly. They were asked to follow the instructions and use the articles they had been issued at home after chewing betel as per their instruction sheet.

Day 7

Subjects reported to the test center on Day 7 to collect the second dose of the articles and to check their compliance. They also completed a further SPQ.

Day 14

Subjects returned to the test center on Day 14 to undergo post-treatment dental assessments of plaque, calculus, inflammation, sensitivity, and staining. They were asked to complete a final SPQ and macrophotography was performed. Additionally they returned any unused articles and their completed diary cards.

Usage instructions

The test and control articles were used in accordance with the following usage instructions.

1 . Chew the articles after betel quids

2. Chew 10-15 mins per article. Do not chew for more than 20 mins.

3. Do not swallow the articles.

4. Chew 8 pieces of articles per day in total, no more or less.

5. Complete the diary sheet with the date and the number of quids and gum pieces chewed.

6. Repeat steps 1-5 each day of the study.

Dental assessments

Dental assessments of plaque, calculus, inflammation, sensitivity, and staining were conducted by an independent consultant dentist in accordance with the below scales.

Plaque was assessed using the Silness and Loe Plaque Index (PI) (1964) as shown below:

Score 0 = The tooth surface is clean.

Score 1 = The tooth surface appears clean, but dental plaque can be removed from the gingival third with a sharp explorer.

Score 2 = Plaque is visible along the gingival margin.

Score 3 = The tooth surface is covered with abundant plaque.

Calculus was assessed using the Silness and Loe Calculus index (Cl) (1964) as shown below:

Score 0 = No observable calculus

Score 1 = Scattered calculus covering less than 1/3 of the buccal surface of the tooth Score 2 = Calculus covering between 1/3 and 2/3 of the buccal tooth surface with minimal subgingival calculus.

Score 3 = Calculus covering greater than 2/3 of the buccal tooth surface and extending subgingivally.

Inflammation was assessed using the Silness and Loe Gingival index (Gl) (1963) as shown below:

Score 0 = Normal gingiva

Score 1 = Mild inflammation - slight change in color, slight edema. No bleeding on probing.

Score 2 = Moderate inflammation - redness, edema, glazing. Bleeding on probing.

Score 3 = Severe inflammation - marked redness and edema, ulceration. Tendency toward spontaneous bleeding.

Tooth sensitivity was assessed using a Visual Assessment Scale (VAS) of 0-10, where 0 represented no pain to temperature, tactile or chemical changes to the tooth and 10 represented extreme pain in response to a change in any of the aforementioned stimuli.

Staining was assessed using a Visual Assessment Scale (VAS) of 0-10, where 0 represented no visible staining to the tooth and 10 represented long-term staining.

Self-perception questionnaires (SPQ)

Alongside the dental assessments, self-perception questionnaires (SPQ) were collected from subjects based on their observation of the product efficacy and its market acceptance. The primary objective of the SPQ data was to validate clinically assessed claims based on dental assessments. The secondary objective was to provide internal reference on subject perception regarding several attributes of the product to guide the product development. Where possible, questions were asked on a modified 5-point unforced directional Likehart scale of agreement. No claims were based on SPQ data due to sample size.

The SPQ data indicated whether users agreed or strongly agreed with the following statements:

I like this gum • It made a positive different to the feeling of my mouth/gums

• It made a positive different to my teeth

• My gums feel better since using the product

• My dental health has improved

• I feel less sensitivity in my teeth/mouth

• My teeth getting whiter

• The stains less than previous

• It made more clean in my mouth

• I would recommend the product to others

• I would pay for the product

• It encouraged me to change my betel habits

Responses were considered to indicate a favorable response if an average score of greater than 3.5 was expressed by the subject group.

Macrophotography

Digital images for each subject were taken using a Canon 70D camera under standard lighting conditions. Images of the test site were taken from a standardized distance of 10cm from the base of the jawline using a distance setting.

Results

No adverse events were reported. Out of the total 90 recruited subjects, 18 (9 in the test group and 9 in the control group) withdrew from the study for reasons unrelated to the study. The data analysis was performed for 72 healthy subjects who completed the study (36 in the test group and 36 in the control group). The age composition of these subjects is presented in Figure 1.

Evaluation of results

Individual scores, mean scores and standard deviations for each assessment point were calculated for 72 subjects who completed the study. For between-treatment analysis of results, a student’s two-tailed t-test was performed on the data. The mean result was used to indicate direction of significance where observed. This method was selected based on the constant size of the samples, the actual sample size and the low level of standard deviation indicating normal distribution.

The results of dental assessments before and after 14 days of using the test articles as well as the control articles are presented in the following tables 1 and 2.

Table 1 : Between-treatment data for the test articles

Table 2: Between-treatment data for the control articles

In addition, the SPQ data after 14 days of using the test articles as well as the control articles are presented in the following tables 3 and 4. Table 3: SPQ data for the test articles

Table 4: SPQ data for the control articles

Furthermore, digital images of teeth of example subjects before and after using the test articles are presented in Figure 2.

Data discussion

As can be seen from the above tables, both test and control articles showed a statistically significant difference to the untreated baseline sites (p<0.05) in all assessed criteria, as would be expected. However, the test article was more effective than the control article in several assessed criteria such as reduction of plaque, inflammation, and sensitivity.

Staining

The test article showed statistically significant reduction in staining, as determined by direction mean values (p<0.05), under between-treatment comparisons. This supports the claim that“The test article significantly reduces staining caused by chewing betel”.

Plaque, calculus, and inflammation

Both test and control articles showed statistically significant reduction in the level of plaque, calculus, and inflammation (p<0.05) as would be expected. Within-treatment comparisons showed no significant variation between test groups’ mean differences of variation in any of the areas noted. The mean results showed that the test article performed with greater levels of efficacy compared to the control article for both plaque and inflammation reduction.

Sensitivity

For between-treatment analysis, both groups showed a statistically significant reduction (p<0.05) in the level of sensitivity. The control group showed the least variation between- treatment points whilst the test group showed the greatest level of variation. Thus the test article showed greater efficacy in reducing sensitivity.

SPQs

SPQ data showed subject favorability for both products as expected to support quantifiable data.

Particularly, for each of the above-mentioned statement, subjects were asked to rate their agreement on a scale of 1-5, with 3 being neither positive or negative. Statements were considered positive if an average of greater than 3.5 was expressed by the cohort. For both groups, subjects responded favorably. By Day 14 SPQ subjects in the test article group expressed stronger favorability than the control article group for each of the above- mentioned statements.

Macrophotography

As depicted in Figure 2, the pre- and post-trial digital images of teeth of three example subjects A-C after using the test articles demonstrate that the whitening effects of the test articles appeared to be visually significant, i.e., the stain removal effects were evident after consuming the test articles for 14 days.

Conclusion

It could be concluded that the claims of“reducing inflammation”,“whitening teeth”,“reducing pain”, “reducing sensitivity”, “reducing plaque”, and thus “improving betel chewers’ oral health/hygiene”,“dentist recommended” and“dentist approved” are valid for the test article as statistically significant difference (p<0.05) was observed for between-treatment comparisons of baseline and endpoint assessments. These claims were further supported to some extent by the SPQ data and digital images in connection with the test articles.

Those skilled in the art will appreciate that the invention described herein is susceptible to variations and modifications other than those specifically described without departing from the scope of the invention. All such variations and modification which become apparent to persons skilled in the art should be considered to fall within the spirit and scope of the invention as broadly hereinbefore described. It is to be understood that the invention includes all such variations and modifications. The invention also includes all of the steps and features, referred or indicated in the specification, individually or collectively, and any and all combinations of any two or more of said steps or features.

The reference to any prior art in this specification is not, and should not be taken as, an acknowledgment or any form of suggestion that that prior art forms part of the common general knowledge.

Claims

What is claimed is:

1. An orally chewable gum composition having cosmetic and therapeutic effects comprising aloe vera, turmeric extract, vitamin C, and a cleaning agent for topical administration to a subject in need of oral health improvement.

2. The orally chewable gum composition of claim 1 , wherein the aloe vera constitutes from about 0.2 to about 4.0%, the turmeric extract constitutes from about 0.8 to about 8.0%, and the vitamin C constitutes from about 0.6 to about 2.0%, by total weight of the orally chewable gum composition.

3. The orally chewable gum composition of any one of the preceding claims, wherein the cleaning agent comprises sodium hydrogen carbonate and silicon dioxide.

4. The orally chewable gum composition of claim 3, wherein sodium hydrogen carbonate constitutes from about 0.2 to about 0.8%, and silicon dioxide constitutes from about 0.2 to about 0.6%, by total weight of the orally chewable gum composition.

5. The orally chewable gum composition of any one of the preceding claims, wherein aloe vera constitutes about 0.8%, turmeric extract constitutes about 1.4%, vitamin C constitutes about 1.0%, sodium hydrogen carbonate constitutes about 0.4%, and silicon dioxide constitutes about 0.4%, by total weight of the orally chewable gum composition.

6. The orally chewable gum composition of any one of the preceding claims, wherein the gum composition comprises a gum base.

7. The orally chewable gum composition of any one of the preceding claims, wherein the gum composition further comprises a flavoring agent.

8. The orally chewable gum composition of any one of the preceding claims, wherein the gum composition further comprises a sweetening agent.

9. The orally chewable gum composition of any one of the preceding claims, wherein the gum composition is coated by a chewable gum coating.

10. The orally chewable gum composition of any one of the preceding claims, wherein the subject is a betel nut consumer.

11. The orally chewable gum composition of any one of the preceding claims, wherein the orally chewable gum composition is to be chewed alongside with a betel nut in a minimal amount of 1 piece for every 5 betel nuts.

12. The orally chewable gum composition of any one of the preceding claims, wherein the oral health improvement includes at least one of reduction of teeth staining, reduction of calculus, reduction of plaque, reduction of gum sensitivity, reduction of gingivitis, alleviation and prevention of oral diseases and/or disorders selected from oral submucous fibrosis, periodontitis, betel chewer’s mucosa (BCM), leukoplakia, and lichenoid lesions.

13. A use of the orally chewable gum composition of any one of claims 1-12 for an improvement of the oral health of a subject in need thereof.

14. The use of claim 13, wherein the subject is a betel nut consumer.

15. The use of claims 13 or 14, wherein the orally chewable gum composition is to be chewed alongside with a betel nut in a minimal amount of 1 piece for every 5 betel nuts.

16. The use of any one of claims 13-15, wherein the oral health improvement includes at least one of reduction of teeth staining, reduction of calculus, reduction of plaque, reduction of gum sensitivity, reduction of gingivitis, alleviation and prevention of oral diseases and/or disorders selected from oral submucous fibrosis, periodontitis, betel chewer’s mucosa (BCM), leukoplakia, and lichenoid lesions.

17. A method of improving the oral health of a subject, wherein the method comprises topically administering to the subject the orally chewable gum composition of any one of claims 1-12.

18. The method of claim 17, wherein the subject is a betel nut consumer.

19. The method of claims 17 or 18, wherein the orally chewable gum composition is to be chewed alongside with a betel nut in a minimal amount of 1 piece for every 5 betel nuts.

20. The method of any one of claims 17-19, wherein the oral health improvement includes at least one of reduction of teeth staining, reduction of calculus, reduction of plaque, reduction of gum sensitivity, reduction of gingivitis, alleviation and prevention of oral diseases and/or disorders selected from oral submucous fibrosis, periodontitis, betel chewer’s mucosa (BCM), leukoplakia, and lichenoid lesions.