RELATED APPLICATION

This application claims the benefit of priority under 35 USC § 119(e) of U.S. Provisional Patent Application No. 62/814,027 filed 9 April 2019, the contents of which are incorporated herein by reference in their entirety.

FIELD AND BACKGROUND OF THE INVENTION

The present invention, in some embodiments thereof, relates to a composition and method for controlling food consumption in humans and, more particularly, but not exclusively, to a perceived sweetness- suppressing composition obtained from plant origin and method of preparing and using the same.

Obesity and the more general condition known as the metabolic syndrome, is increasing significantly in recent years. For example, a reports estimate that about 65 % of Americans are overweight and more than 35 % are obese. Similar reports suggest that unhealthy diets and immobility are likely to be the leading cause of preventable deaths. Thus, obesity and obesity- related diseases such as type II diabetes, hypercholesterolemia, and / or all other forms of the metabolic syndrome are significant problems for modern society.

Weight control, by way of appetite suppression, is considered one of the tools for treating obesity and obesity-related diseases. Several formulations that can suppress appetite are commercially available, from traditional/altemative medicine to evidence-based pharmaceuticals. Some known natural (non-synthetic) appetite-suppressing formulations contain botanical products, such as maize, caffeine, tobacco, Trichocauron, Hoodia, Stapelia, Cairo, Milkweed, Stapelia, Orbea, Towata, Asclepias and many other herbs.

Another pathway for suppressing appetite is the reduction of the mental reward obtained from consumption of sweet foodstuff. Overeating foods such as chocolate, candy and pastry, which are calorie-dense, may lead to hyperglycemia and loss of control in weight-loss program, especially when emotional eating and binge eating takes place. The leaves and extracts of the Gymnema sylvestre plant, referred to herein and throughout as“gymnema”, contain gymnemic acids, major bioactive phytochemical constituents that interact with taste receptors on the tongue to temporarily suppress the taste of sweetness. Gymnema leaves contain triterpenoid saponins, flavonols and gurmarin, whereas the major biologically active plant molecules are gymnemic acids, a class of triterpenoid saponins, which have the effect of suppressing the taste of sweetness on the tongue from sucrose (sugar), stevia, xylitol, and artificial sweeteners such as aspartame. The sweet-blocking effect of gymnema in humans lasts from 15 to 50 minutes and may even persist for several hours. Gymnemic acids apparently have no long-term effects on taste and they do not influence bitter, salty, or sour taste perception. Today it is known that gurmarin is the taste modifying protein from Gymnema sylvestre.

In addition, gynnemic acid compounds in gymnema can also attach to receptors on the intestinal walls, helping to reduce absorption of sugar molecules in the gut. This process can lower blood sugar and promote insulin secretion and release. Indeed, researchers have shown that consumption of gymnema lead to a decrease of blood sugar in rats [Okabayashi, Y. et al., Diabetes Research and Clinical Practice , 1990, 9, 143-148]. Gymnema extracts with appetite suppressing properties have been proposed for use in body weight control, and a systematic review of double blind randomized controlled clinical trials has been published [Astell, K.J. et al., Complementary Therapies in Medicine , 2013, 21, 407— 416]. Aqueous extracts of gymnema depressed the sweetness of amino acids, glycine and dl-alanine in a way very similar to that of sucrose. Temporary suppressing of sweet taste is found to be more prominent although it influences the bitter taste modalities.

Background art further include a report on the use of gymnema in chewing gum [Nakamura, Y. et al., [Shokuhin Eiseigaku Zasshi (Food Hygiene and Safety Science), 1997, 38, 178], and an overview on the advances of gymnema chemistry, pharmacology and patents [Porchezhian, E. and Dobriyal, R. M., Pharmazie, 2003, 58, 1].

Additional background art includes U.S. Patent Nos. 10,314,326, 9,789,151, 9,737,082, 9,585,905, 9,504,722, 9,446,063, 9,421,217, 9,387,168, 9,253,991, and 9,387,168, as well as U.S. Patent Application Publication Nos. 20180027860, 20180193400, 20190336555 and 20190351000.

SUMMARY OF THE INVENTION

Aspect so the present invention are drawn to a food product that is typically kept in the mouth when consumed, such as chewing gum, toffee or hard candy, which contains gymnema plant parts or extracts, and a bitterness-masking agent, so as to facilitate the use thereof and increase user compliance for using the product. Also provided are method of controlling or reducing food craving in humans, by consumption of the presently provided products.

Hence, according to an aspect of some embodiments of the present invention there is provided chewing gum, comprising a gum base, gymnema, and a bitterness-masking agent. In some embodiments, the gymnema is in the form selected from the group consisting of dried ground leaves of Gymnema sylvestre plant, dried Gymnema sylvestre plant extract, liquid Gymnema sylvestre plant or a combination thereof.

In some embodiments, the bitterness-masking agent is a fungi-derived product.

In some embodiments, the bitterness-masking agent is ClearTaste™.

In some embodiments, the bitterness-masking agent is encapsulated in capsules.

In some embodiments, the gymnema is encapsulated in capsules.

In some embodiments, the amount of the gymnema in the composition ranges 3-6 % by weigh of the total weight of the composition.

In some embodiments, the amount of the bitterness-masking agent in the composition ranges 10-50 ppm by weight.

In some embodiments, the chewing gum provided herein further includes additional ingredients selected from the group consisting of flavor agents, aroma agents, softeners, hardeners, colorants, coating and any combination thereof.

According to another aspect of some embodiments of the present invention there is provided method for controlling food craving in a subject, comprising administering the chewing gum presented herein to the subject.

In some embodiments, administration of the chewing gum is effected by the subject.

In some embodiments, administration of the chewing gum is effected before or while the subject is experiencing food craving.

In some embodiments, administration of the chewing gum is effected at a predetermined time of day known to the subject as prone to food craving.

In some embodiments, administration of the chewing gum is effected at regular intervals during a time period such that the subject is experiencing loss of perception of sweetness during the period.

Unless otherwise defined, all technical and/or scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of the invention, exemplary methods and/or materials are described below. In case of conflict, the patent specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be necessarily limiting. DESCRIPTION OF SOME SPECIFIC EMBODIMENTS OF THE INVENTION

The present invention, in some embodiments thereof, relates to a composition and method for controlling food consumption in humans and, more particularly, but not exclusively, to a perceived sweetness- suppressing composition obtained from plant origin and method of preparing and using the same.

Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not necessarily limited in its application to the details set forth in the following description or exemplified by the Examples. The invention is capable of other embodiments or of being practiced or carried out in various ways.

Mitigation of adverse characteristics inherent to gymnema:

As been reported in the literature and presented hereinabove, gymnema has a profound action on the modulation of taste. Gymnema extract selectively suppress the response to sweeteners like sucrose, fructose, saccharin, and cyclamate. Fifty percent of this action is extended against the sweet taste caused by water-after-citric acid. Sweet taste of the glycoside, methyl a-d- mannopyranoside is suppressed without any alteration in the response to its bitterness.

Indeed, unpleasant bitter and astringent taste makes it difficult to administer gymnema as anti-diabetic or anti-obesity agent for oral administration even when the medicament is swallowed immediately. To overcome the bitter taste before swallowing, dried leaf powder is mixed with powdered chitosan and packed in water-permeable bags that can be consumed as tea. Mixing with chitosan can be employed to food and pharmaceutical preparations containing gymnemic acid. Another way of masking bitter taste perceived before rapidly swallowing is mixing gymnema with cyclodextrin. This technique can also be employed to food or food additives but addition of cyclodextrin to gymnema further enhances the blood sugar-lowering effect of the extract. Gymnema can be mixed with natural water-soluble polymers, natural oil and lecithins to prepare an encapsulated food to overcome the off-taste that can be used as antidiabetic and anticarcinogenic .

However, none of the known solutions that attempt to mitigate the unpleasant bitter and astringent taste of gymnema, when formulated for rapid swallowing, is effective for application that require the plant to stay in the mouth for a few minutes in order to achieve sweetness- perception suppression. In order to enlist patient for compliance in using a gymnema-containing product that has to stay in the mouth for several minutes, the formulation of the product should comprise effective amount of gymnema and at the same comprise a bitterness-perception suppression agent; none of the known bitterness-lowering compositions are suitable for composition that are meant for use as a gum, hard candy or toffee, all of which are referred to herein as mouth-lingering edible compositions.

The present inventors have found that in order to obtain an effective perceived sweetness suppression in human subjects, the plant or its extract should be kept in the oral cavity for at least two minutes without swallowing the whole product, and therefore a hard candy or a chewing gum would provide that duration without changing the subject’s habits of using such products. Thus, a feature of the present invention is the form of the product, being mouth-lingering edible product, such as a chew able (chewing gum) masticatory candy (toffee) or lickable (hard candy). In the context of some embodiments of the present invention, the term “mouth-lingering edible composition” refers to food products that are consumed by keeping the product in the mouth for an extended period of time, as opposed to a food product that is swallowed as a liquid or chewed and swallowed thereafter. Exemplary mouth-lingering edible compositions include, without limitation, chewing gum, hard candy, toffee, and gummy candies (jelly candies).

Another feature of the present invention is the amount of gymnema in the product, which needs to be effective in order to effect loss of sweetness perception in the subject. In the context of the present disclosure, the term“gymnema” is collectively used to refer to any perceived- sweetness suppressing form of the botanical known as Gymnema sylvestre (a plant), including leaves, extracts, gymnemic acids, or any combination thereof in which at least one contains the bioactive phytochemical constituents that interact with taste receptors on the tongue to temporarily suppress the perception of sweetness.

Yet another feature of the presence of a bitterness masking agent in the product that is essential for rendering the product usable by the subject having to keep the product in its mouth far longer than known gymnema formulations for rapid or immediate swallowing, such as in teas and other medicaments that are formulated for the internal effect of gymnema. In the context of embodiments of the present invention, the term“bitterness masking agent” refers to an additive in the composition that mitigates the adverse bitter taste of gymnema, such that a subject consuming the composition as a chewing gum, toffee or hard candy, will keep the product in the mouth for a duration of time sufficient to exert the desired effect of gymnema in the subject.

In some embodiments, the bitterness-masking agent is a product derived from a mushroom extract. Preferably, the bitterness-masking agent is marketed under the trade name ClearTaste™ by MycoTechnology, which effectively acts by temporarily blocking bitter tastes from being perceived by blocking 17 of the 25 bitter receptors found on the human tongue.

Thus, according to an aspect of some embodiments of the present invention, there is provided a mouth-lingering edible compositions for suppressing perceived sweetness in a subject, which includes a base, gymnema, and a bitterness masking agent, wherein the bitterness masking agent is capable of masking the bitterness of gymnema for at least the duration of the time required for the perceived sweetness suppression take effect.

The base, according to some embodiments of the present invention, is a typical base used in any mouth-lingering composition, as known in the art. In addition, the mouth-lingering composition may include flavor and aroma agents, coating, softeners or hardeners, and any additional ingredient that is typically used in any mouth-lingering composition, as known in the art.

In some embodiments the amount of gymnema in the composition ranges from 2 % (percent symbol indicates weight percent throughout the disclosure, unless stated otherwise) to 10 %. Preferably, the amount of gymnema in the composition ranges 3-8 %. More preferably, gymnema is about 6+1 % in the composition.

In some embodiments the amount of the bitterness masking agent in the composition ranges from 10-40 ppm, or 10-30 ppm, or 20+5 ppm.

Ingredient encapsulation:

According to some embodiments of the present invention, the gymnema and/or the bitterness-masking agent are each independently encapsulated in a vesicle or a capsule, such that the ingredient encapsulated within the capsule is released gradually as the composition is being chewed or sucked upon by the subject.

Encapsulation of the gymnema and/or the bitterness-masking agent, each in a microcapsule, allows for the sustained release thereof, which contributes to the lingering effect of each of the ingredients, while exposing the subject to controlled concentrations of each of the ingredients, allowing a more pleasant subject’s experience and thus a more compliant subject’s response.

In some embodiments of the present invention the composition is in a form of a chewing gum, which provides a longer lasting effect masking the bitter taste of gymnema. In one approach to prolonging the bitterness-masking effect, the bitterness-masking agent is encapsulated in a polymeric coating to delay and prolong is release. U.S. Patent Nos. 4,931,293, 5,057,328, 5,064,658 and 5,110,608 are exemplary sources for additional information regarding such encapsulation.

In another approach, the bitterness-masking effect is extended by providing a chewing gum composition that includes a gum base, gymnema, a bitterness-masking agent, and at least one encapsulated surfactant, where the surfactant increases the amount of bitterness-masking agent released from the chewing gum composition, as described, for example, U.S. Patent Application Publication No. 20060263474.

In cases where the bitterness-masking agent is highly soluble in water, making its encapsulation more challenging, the soluble agent is encapsulated in poly(vinyl acetate) and a fatty acid salt, as described, for example, in U.S. Patent No. 9,737,082. The poly(vinyl acetate) and fatty acid salt encapsulated ingredient can further be incorporated into a chewing gum composition in order to more precisely control the intensity of and timing of the bitterness-masking effect as experienced by the subject without deteriorating the late chewy texture of the chewing gum.

Additional guidance and information regarding encapsulation of ingredients that is useful for mouth-lingering edible compositions such as chewing gum include, for example, U.S. Patent Nos. 5,013,557, 6,174,514, 6,589,562, 7,067,152, 8,455,033 and 9,186,640.

A method of controlling food craving in a subject:

According to an aspect of some embodiments of the present invention, there is provided a method for reducing or controlling food craving in a subject, which is effected by consuming the mouth-lingering composition described herein, before or during a period of food craving. The composition can be used by administration or by self-administration of the composition to the subject as soon as the subject is sensing loss of self-control and the beginning of food cravings. Alternatively, the mouth-lingering composition described herein is administered to the subject or self-administered by the subject at regular intervals such that the perceived-sweetness suppression is effected over an extended period of time. Alternatively, the mouth-lingering composition described herein is administered to the subject or self-administered by the subject at a predetermined time of day during which the subject is known to be prone to food cravings.

It is expected that during the life of a patent maturing from this application many relevant non-bitter gymnema-containing mouth-lingering compositions will be developed and the scope of the that phrase is intended to include all such new technologies a priori.

As used herein the term“about” refers to ± 10 %.

The terms "comprises", "comprising", "includes", "including", “having” and their conjugates mean "including but not limited to".

The term“consisting of’ means“including and limited to”.

The term "consisting essentially of" means that the composition, method or structure may include additional ingredients, steps and/or parts, but only if the additional ingredients, steps and/or parts do not materially alter the basic and novel characteristics of the claimed composition, method or structure. As used herein, the phrases "substantially devoid of" and/or "essentially devoid of" in the context of a certain substance, refer to a composition that is totally devoid of this substance or includes less than about 5, 1, 0.5 or 0.1 percent of the substance by total weight or volume of the composition. Alternatively, the phrases "substantially devoid of" and/or "essentially devoid of" in the context of a process, a method, a property or a characteristic, refer to a process, a composition, a structure or an article that is totally devoid of a certain process/method step, or a certain property or a certain characteristic, or a process/method wherein the certain process/method step is effected at less than about 5, 1, 0.5 or 0.1 percent compared to a given standard process/method, or property or a characteristic characterized by less than about 5, 1, 0.5 or 0.1 percent of the property or characteristic, compared to a given standard.

The term“exemplary” is used herein to mean “serving as an example, instance or illustration”. Any embodiment described as“exemplary” is not necessarily to be construed as preferred or advantageous over other embodiments and/or to exclude the incorporation of features from other embodiments.

The words“optionally” or“alternatively” are used herein to mean“is provided in some embodiments and not provided in other embodiments”. Any particular embodiment of the invention may include a plurality of“optional” features unless such features conflict.

As used herein, the singular form "a", "an" and "the" include plural references unless the context clearly dictates otherwise. For example, the term "a compound" or "at least one compound" may include a plurality of compounds, including mixtures thereof.

Throughout this application, various embodiments of this invention may be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.

Whenever a numerical range is indicated herein, it is meant to include any cited numeral (fractional or integral) within the indicated range. The phrases“ranging/ranges between” a first indicate number and a second indicate number and“ranging/ranges from” a first indicate number “to” a second indicate number are used herein interchangeably and are meant to include the first and second indicated numbers and all the fractional and integral numerals therebetween. As used herein the terms“process” and "method" refer to manners, means, techniques and procedures for accomplishing a given task including, but not limited to, those manners, means, techniques and procedures either known to, or readily developed from known manners, means, techniques and procedures by practitioners of the chemical, material, mechanical, computational and digital arts.

As used herein, the term“treating” includes abrogating, substantially inhibiting, slowing or reversing the progression of a condition, substantially ameliorating clinical or aesthetical symptoms of a condition or substantially preventing the appearance of clinical or aesthetical symptoms of a condition.

It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination or as suitable in any other described embodiment of the invention. Certain features described in the context of various embodiments are not to be considered essential features of those embodiments, unless the embodiment is inoperative without those elements.

Various embodiments and aspects of the present invention as delineated hereinabove and as claimed in the claims section below find experimental and/or calculated support in the following examples.

EXAMPLES

Reference is now made to the following examples, which together with the above descriptions illustrate some embodiments of the invention in a non limiting fashion.

Example 1

Materials and Methods

A proof of concept of some embodiments of the present invention was carried out by preparing chewing gum samples comprising dried and ground gymnema leaves, a gum base, wherein the amount of gymnema ranges from 1 to 9 % of the total weight of the chewing gum.

The gum base was purchased from Amazon LTD.

ClearTaste™ was purchased from MycoTechnology® Aurora, Colorado, USA.

Additional ingredients added to the chewing gum included flavoring agents, sweeteners and coloring agents. The gum was prepared as bits weighing 1-3 grams each, and the subject was requested to chew the gum for at least 3 minutes before tasting chocolate and reporting the level of sweetness perceived thereby.

50 mg of ClearTaste™ powder were suspended in 50 ml of purified water to afford a 1000 ppm stock solution, and 1, 2, and 5 ml of this stock solution were added to 100 grams of gum base to give a final concentration of 10 ppm, 20 ppm and 50 ppm in the final product.

The gum was prepared in the batches, a batch with 2 %, 5 %, 7 %, 9 % gymnema, each having 10 ppm, 20 ppm and 50 ppm ClearTaste™ and another series of the same batches having a similar formulation except the bitterness-masking agent (control).

Example 2

Results

A group of adult individuals, 5 females and 5 males, age 35-67, were asked to chew on a piece of gum, prepared as described hereinabove, for at least 3 minutes, and thereafter each a small piece of chocolate and report the organoleptic sensation, in particular to sweetness and to bitterness.

Each member of the group was given a sample of both the gum with the bitterness-masking agent, and the control gum without it, in an arbitrary order, and with at least three hours between each sample.

The results have shown that gymnema is effective starting from 3 % and up, and that the bitterness-masking agent improved subject’s experience in all batches, allowing the high percentage gymnema samples to be tolerated for the duration of the experiment (3 minutes).

Optimal perceived sweetness suppressing gum was obtained with 3-6 % gymnema, and 20 ppm ClearTaste™.

Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims.

All publications, patents and patent applications mentioned in this specification are herein incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention. To the extent that section headings are used, they should not be construed as necessarily limiting.

In addition, any priority document(s) of this application is/are hereby incorporated herein by reference in its/their entirety.