Oral formulation

Abstract

The present disclosure relates to oral formulations, methods for preparing oral formulations, and uses of the oral formulations, which are chewable solids containing a combination of active ingredients, including L-theanine, ginseng, and lemon balm, and the formulations include at least one binder and at least one excipient selected from the group consisting of a sugar alcohol, a sugar, or a combination of at least one sugar alcohol and at least one sugar.

Description

[Technical Field]

[0001] The present disclosure relates to oral formulations, methods for making oral formulations, and uses of said oral formulations. [Background technology]

[0002] The present disclosure relates to formulations and compositions intended for human use. The formulations are configured for oral use and deliver substances such as flavorings and / or active ingredients during use.

[0003]

[0003] Pharmaceutical preparations that are easy to administer orally and can have a beneficial effect on specific mood states in humans or animals have become popular in recent years. For example, confectionery-type preparations (e.g., gummies or soft lozenges) containing vitamins or other mood-improving active ingredients provide a convenient and comfortable mode of administration for such active ingredients. Other convenient modes of administration are foods and beverages, such as energy drinks. Such preparations can contain active ingredients that are delivered to the user to elicit a biological response in the user that can improve the user's physical or mental function.

[0004] Beverages containing theanine and caffeine are described in U.S. Patent Nos. 5,780,086 and 6,268,009. More recently, European Patent No. 1819241 describes a beverage containing theanine and caffeine in a ratio of 5:1 to 1:1.5. Other beverages, such as chamomile tea and other herbal teas, are consumed by some users to aid sleep and relaxation. A method for treating extreme physical or mental stress using L-theanine is described in U.S. Patent Application Publication No. 20050090512.

[0005] It would be desirable to provide an oral dosage form adapted for oral use that can deliver an active ingredient to the recipient in a palatable and effective form, such as in the form of a solid chew. Summary of the Invention

[0006] The present disclosure generally provides formulations adapted for oral use, comprising a combination of active ingredients, at least one binder and at least one sugar, or at least one sugar alcohol, or a combination of at least one sugar and at least one sugar alcohol. The oral formulations are solid and may be in any form suitable for oral use, for example, a chewable form such as a dissolving chew or soft lozenge.

[0007] According to some embodiments described herein, there is provided a chewable solid oral formulation comprising a combination of active ingredients, at least one binder, and at least one excipient selected from the group consisting of a sugar alcohol, or a sugar, or a combination of at least one sugar alcohol and at least one sugar, wherein the combination of active ingredients comprises (i) L-theanine, (ii) ginseng, and (iii) lemon balm.

[0008] According to some embodiments described herein, there is provided a method of preparing an oral formulation, comprising: (a) contacting at least one binder with at least one excipient selected from the group consisting of a sugar alcohol, or a sugar, or a combination of at least one sugar alcohol and at least one sugar, and optionally adding water; (b) heating a mixture of a binder, a sugar alcohol and / or a sugar, and optionally water; (c) adding a combination of active ingredients, the combination of active ingredients including L-theanine, ginseng, and lemon balm; (d) solidifying the resulting mixture to provide an oral chew formulation. The present invention provides a method for preparing an oral formulation, comprising:

[0009] According to some embodiments described herein, there is provided use of a combination of active ingredients to provide a relaxation effect to a human or animal, the combination of active ingredients comprising: (i) L-theanine; (ii) ginseng; and (iii) lemon balm.

[0010] According to some embodiments described herein, there is provided a use of a combination of active ingredients for sedating a human or animal, the combination of active ingredients comprising: (i) L-theanine; (ii) ginseng; and (iii) lemon balm.

[0011] According to some embodiments described herein, there is provided a chewable solid oral formulation comprising a combination of active ingredients, wherein the combination of active ingredients comprises lemon balm in an amount of about 1000 ppm to about 10000 ppm.

[0012] According to some embodiments described herein, there is provided a chewable solid oral formulation comprising a combination of active ingredients, the combination of active ingredients comprising (i) lemon balm and (ii) ginseng.

[0013] According to some embodiments described herein, there is provided a chewable solid oral formulation comprising a combination of active ingredients, the combination of active ingredients comprising (i) L-theanine and (ii) ginseng, wherein the L-theanine and ginseng are present in a weight ratio of about 150:1 to about 100:1.

[0014] In a preferred embodiment, each oral dosage form of the above embodiments may be provided in the form of a dissolvable chew.

[0015] These and other features, aspects, and advantages of the present disclosure will become apparent upon reading the following detailed description. The present invention includes any combination of two, three, four, or more of the above-described embodiments, as well as combinations of any two, three, four, or more features or elements described in this disclosure, regardless of whether such features or elements are explicitly combined in the description of a particular embodiment herein. The present disclosure is intended to be read as a whole such that any separable features or elements of the disclosed invention, in any of its various aspects and embodiments, should be considered as intended to be combinable unless the context clearly dictates otherwise.

[0016] For ease of reference, these and further aspects of the present invention are discussed herein under appropriate section headings, however, the teachings under each section are not necessarily limited to each particular section. DETAILED DESCRIPTION OF THE INVENTION

[0017] It is to be understood that the invention is not limited to the particular configurations, method steps, and materials disclosed herein, as the configurations, method steps, and materials may vary slightly. It is also to be understood that the terminology used herein is used for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the invention will be limited only by the appended claims and their equivalents.

[0018] As used herein and in the claims, the singular forms "a," "an," and "the" include the plural forms unless the context clearly dictates otherwise. References to "% by weight" or "dry weight basis" refer to weight based on dry ingredients (i.e., all ingredients excluding water). References to "wet weight" refer to the weight of the formulation or composition including water. Unless otherwise specified, references to "% by weight" (or "wt %") of a formulation or composition reflect the total wet weight (i.e., including water) of the formulation or composition.

[0019] As used herein, unless otherwise specified, the term "about" modifying the amount of an ingredient in an oral formulation or used in a method of the present invention refers to variations in numerical value that may occur due, for example, to typical measuring procedures and liquid handling procedures used to prepare the actual concentrate or use the solution, inadvertent errors in these procedures, differences in the manufacture, source, or purity of the ingredients used to prepare the oral formulation or practice the method, etc. The term "about" also encompasses amounts that differ due to different equilibrium conditions for a formulation or composition resulting from a particular initial mixture. Whether modified by the term "about," the claims include equivalents of the amounts.

[0020] Oral formulation As described herein, there is provided a chewable solid oral formulation comprising a combination of active ingredients, at least one binder, and at least one excipient selected from the group consisting of a sugar alcohol, or a sugar, or a combination of at least one sugar alcohol and at least one sugar, wherein the combination comprises (i) L-theanine, (ii) ginseng, and (iii) lemon balm.

[0021] Oral formulations are designed for oral use, and thus for insertion into the user's mouth (i.e., oral cavity). As used herein, unless otherwise specified, the term "oral" in relation to a formulation refers to a formulation that is suitable for ingestion or retention anywhere in the user's oral cavity in normal use. For example, the formulation may be retained in the oral cavity, or may be chewed in the oral cavity, for example, in the form of a chew or chewing gum.

[0022] The ranges provided herein provide preferred amounts of each component. Each of these ranges can be used alone or in combination with one or more other component ranges to provide preferred embodiments of the present invention.

[0023] Active ingredient combination The formulations disclosed herein comprise an active ingredient.

[0024] As used herein, an active substance may be a physiologically active substance, which is a substance intended to achieve or enhance a physiological response. The active substance may be selected from, for example, nutritional active substances, nootropic substances, and psychoactive substances. The active substance may be naturally derived or synthetically obtained.

[0025] The active ingredient combinations include suitable active ingredients that elicit a biological response in humans or animals. As used herein, an active ingredient may be a physiologically active substance, which is a substance intended to achieve or enhance a physiological response.

[0026] According to the present invention, the combination of active ingredients comprises at least L-theanine, ginseng, and lemon balm.

[0027] Each active ingredient may be present in an amount suitable to induce the desired biological response in human animals. The inventors have discovered that a specific combination of active ingredients contained in an oral formulation provides improved relaxation effects to the user compared to conventional known formulations. The inventors have discovered that a specific combination of active ingredients of the present invention can improve relaxation and calmness and reduce stress and anxiety. For example, the combination of active ingredients allows the user to restore mental and physical harmony after tension or stress, and provides the user with short-term mood improvement upon ingestion. In some instances, the combination of active ingredients can also aid sleep.

[0028] It has also been found that the combination of active ingredients described herein can provide a safe formulation with desirable pharmacokinetics (Tmax, Cmax, half-life), bioavailability, and metabolism.

[0029] L-theanine is a compound of L-γ-glutamylethylamide and N 5L-theanine is an amino acid analogue also known as α-ethyl-L-glutamine. The inclusion of L-theanine can enhance the relaxation effects of oral formulations. For example, the inclusion of L-theanine can help reduce anxiety and stress levels.

[0030] L-theanine can be present in any suitable amount, such as at least about 0.001%, at least about 0.01%, or at least about 0.1% by weight of the oral formulation, hi some embodiments, L-theanine can be present in an amount of no more than about 10%, or no more than about 5% by weight of the oral formulation.

[0031] L-theanine may be present in an amount of about 0.001% to about 10% by weight of the oral formulation. In some embodiments, L-theanine is present in an amount of about 0.01% to about 5% by weight of the oral formulation.

[0032] Preferably, L-theanine may be present in an amount of about 0.01% to about 5% by weight of the oral formulation. In some embodiments, L-theanine is present in an amount of about 0.1% to about 4% by weight of the oral formulation, e.g., about 0.25% to about 3% by weight of the oral formulation, e.g., about 0.5% to about 2.5% by weight of the oral formulation. In some embodiments, L-theanine is present in an amount of about 1% to about 5% by weight of the oral formulation.

[0033] Ginseng is the root of plants in the Panax genus, characterized by the presence of unique steroidal saponin phytochemicals (ginsenosides) and gintonin. The putative major active ingredients of ginseng include over 100 specific triterpene saponins, or "ginsenosides." Ginseng and ginseng extracts also contain a variety of other potentially bioactive compounds, including alkaloids, phytosterols, sesquiterpenes, and polyphenols. Ginseng is used as a nutritional supplement in energy drinks and herbal teas, and in traditional medicine.

[0034] Ginseng may include any suitable form of ginseng, such as Panax ginseng (Korean ginseng), Panax notoginseng (Tenshichi ginseng), and Panax quinquefolius (American ginseng).

[0035] Ginseng may also include Ashwagandha (Withania somnifera), commonly known as Indian Ginseng. Ginseng may be present in the form of ginseng extract, chopped ginseng, shredded ginseng, or powdered ginseng. Preferably, ginseng is included in the form of ginseng extract or powdered ginseng extract. Ginseng may be white ginseng, fresh ginseng, or red ginseng. In some embodiments, the ginseng is red ginseng, such as red ginseng extract or powdered red ginseng extract. The inclusion of ginseng has been found to be beneficial in enhancing the cognitive effects of the composition and increasing calmness / reducing stress in users. For example, ginseng can reduce stress and blood pressure, improving cognitive function and mood. Ginseng has also traditionally been found to improve quality of life.

[0036] In particular, it is believed that the combination of L-theanine and ginseng may improve the relaxation effect on users and reduce stress and anxiety levels after administration.

[0037] Ginseng can be present in any suitable amount, such as at least about 0.0001% by weight, at least about 0.001% by weight, or at least about 0.01% by weight of the oral formulation. In some embodiments, ginseng is present in an amount of about 0.001% to about 5% by weight of the oral formulation. In some embodiments, ginseng is present in an amount of about 0.001% to about 3% by weight of the oral formulation. In some embodiments, ginseng is present in an amount of about 0.001% to about 1% by weight of the oral formulation. In some embodiments, ginseng is present in an amount of about 0.001% to about 0.5% by weight of the oral formulation, or about 0.001% to about 0.25% by weight of the oral formulation. Ginseng can be present in an amount of about 5% by weight or less of the oral formulation, e.g., about 1% by weight or less.

[0038] In some preferred embodiments, ginseng is present in an amount of about 0.001% to about 3% by weight of the oral formulation. In some preferred embodiments, ginseng is present in an amount of about 0.001% to about 0.1% by weight of the oral formulation.

[0039] Ginseng may be present in some embodiments (e.g., when the oral formulation is a solid oral dosage form such as a chew or soft lozenge) in an amount of from about 0.001% to about 1% by weight of the oral formulation, such as from about 0.01% to about 0.5% by weight, such as from about 0.01% to about 0.25% by weight, for example, from about 0.01% to about 0.1% by weight.

[0040] Lemon balm, also known as Melissa officinalis, is a perennial herbaceous plant in the Lamiaceae family. Lemon balm contains a complex mixture of terpenes, terpenoids, flavonoids, polyphenols, and other molecules. Lemon balm can be in the form of leaves, stems, or roots from the lemon balm plant. In some embodiments, lemon balm is included in the form of lemon balm leaf, such as chopped, shredded, or powdered lemon balm leaf. In some embodiments, lemon balm is included in the form of lemon balm extract, such as lemon balm water extract. In some embodiments, lemon balm is included in the form of lemon balm essential oil. The inclusion of lemon balm can improve stress levels and aid sleep in users. Lemon balm has previously been found to exhibit antioxidant, anti-inflammatory, and neuroprotective properties.

[0041] Lemon balm can be present in any suitable amount, such as at least about 0.001%, at least 0.01%, or at least 0.1% by weight of the oral formulation. In some embodiments, lemon balm is present in an amount of about 0.001% to about 10% by weight of the oral formulation. In some embodiments, lemon balm is present in an amount of about 0.001% to about 5% by weight of the oral formulation. In some embodiments, lemon balm is present in an amount of about 0.01% to about 3% by weight of the oral formulation. Lemon balm can be present in an amount of about 5% or less by weight of the oral formulation, e.g., about 3% or less by weight.

[0042] Preferably, lemon balm may be present in an amount of about 0.01% to about 3% by weight of the oral formulation, hi some embodiments, lemon balm is present in an amount of about 0.05% to about 2%, e.g., about 0.1% to about 1%, e.g., about 0.5% to about 0.75% by weight.

[0043] In some embodiments, the amount of lemon balm may be at least 0.1% by weight of the oral formulation, i.e., the oral formulation may contain at least about 1000 ppm of lemon balm. In some embodiments, the amount of lemon balm may be at least 0.5% by weight of the oral formulation, i.e., the oral formulation may contain at least about 5000 ppm of lemon balm. In some embodiments, the amount of lemon balm is about 0.5% to about 1% by weight of the oral formulation (i.e., 5000 ppm to 10000 ppm).

[0044] In addition to L-theanine, ginseng, and lemon balm, the active ingredient combination may include one or more additional active ingredients. The additional active ingredient may be any suitable active ingredient that aids relaxation or calmness, and may be selected from, for example, nutritional active ingredients, nootropic ingredients, and psychoactive ingredients. The additional active ingredient may be naturally occurring or synthetically obtained.

[0045] Non-limiting examples of additional active ingredients include those in the categories of botanical ingredients, amino acids, nicotine ingredients, and / or nutritional active ingredients, and pharmaceutical ingredients (e.g., vitamins such as vitamins A, B3, B6, B12, and C and / or cannabinoids such as tetrahydrocannabinol (THC) and cannabidiol (CBD)).

[0046] Additional active ingredients may include, for example, taurine, theine, vitamins such as B vitamins (e.g., B2, B3, B6, B9, and / or B12), vitamin A, vitamin D, vitamin E, vitamin K, or vitamin C, melatonin, gamma aminobutyric acid (GABA), cannabinoids, or components, derivatives, or combinations thereof.

[0047] In some embodiments, the one or more additional active ingredients are selected from botanicals (e.g., lavender, peppermint, chamomile, basil, rosemary, ginger, maca, and herbal tea ingredients), amino acids (e.g., taurine, phenylalanine, tyrosine, GABA, and tryptophan), cannabinoids, and / or nutritional or pharmaceutical active ingredients (e.g., vitamins such as B vitamins and / or vitamin C).

[0048] In some preferred embodiments, the combination of active ingredients further includes vitamin C (ascorbic acid). Vitamin C acts as an antioxidant, helping to protect cells from damage caused by free radicals. The body also utilizes vitamin C for the production of collagen, a protein that can aid in wound healing. Additionally, vitamin C promotes iron absorption from plant-based foods and helps the immune system function properly, protecting the body from disease.

[0049] The inclusion of vitamin C may reduce tiredness and fatigue.

[0050] Vitamin C may be present in an amount of about 0.001% to about 10% by weight of the oral formulation, such as about 0.01% to about 5% by weight, for example, about 0.05% to about 2.5% by weight, for example, about 0.1% to 2% by weight, for example, about 0.5% to 1% by weight. When present, vitamin C may be included preferably in an amount of about 0.01% to about 5% by weight, more preferably about 0.1% to about 2% by weight of the oral formulation.

[0051] In some embodiments, the combination of active ingredients further comprises chamomile. Chamomile (Matricaria recuita) is a flowering plant of the daisy family (Asteraceae). It is native to Europe and Western Asia and is now found throughout the world. There are two different species of chamomile plants: German chamomile and Roman chamomile. German chamomile is generally considered to be the more effective variety and the most widely used type for medical purposes. Various types of bioactive components are present in chamomile, such as flavanols (apigenin, luteolin, quercetin), coumarins, and terpenoids. Research has shown that chamomile is beneficial in reducing anxiety.

[0052] Chamomile may be in the form of a chamomile extract. Chamomile (e.g., chamomile extract) may be present in an amount of about 0.0001% to about 5% by weight of the oral formulation, for example, about 0.0001% to about 3% by weight, for example, about 0.0001% to about 1% by weight. Chamomile (e.g., chamomile extract) may be present in an amount of about 0.001% to about 5% by weight of the oral formulation, for example, about 0.01% to about 2.5% by weight, for example, about 0.02% to about 1%, for example, about 0.03% to about 0.5% by weight. When present, chamomile (e.g., chamomile extract) may preferably be present in an amount of about 0.01% to about 3% by weight of the oral formulation.

[0053] In some preferred embodiments, the active ingredient combination further comprises L-tryptophan. L-tryptophan may be present in an amount of about 0.001% to about 10% by weight of the oral formulation, e.g., about 0.01% to about 5% by weight, e.g., about 0.05% to about 2.5% by weight, e.g., about 0.1% to 1% by weight, e.g., about 0.1% to 0.5% by weight. When present, L-tryptophan is preferably present in an amount of about 0.05% to about 3% by weight of the oral formulation.

[0054] In some preferred embodiments, the combination of active ingredients includes L-theanine, ginseng, lemon balm, and vitamin C.

[0055] In some embodiments, the combination of active ingredients includes L-theanine, ginseng, lemon balm, and chamomile extract. In some embodiments, the combination of active ingredients includes L-theanine, ginseng, lemon balm, vitamin C, and chamomile extract.

[0056] In some preferred embodiments, the combination of active ingredients includes L-theanine, ginseng, lemon balm, and L-tryptophan. In some preferred embodiments, the combination of active ingredients includes L-theanine, ginseng, lemon balm, vitamin C, and L-tryptophan.

[0057] In some embodiments, the active ingredient combination includes (i) about 0.01% to about 5% L-theanine by weight of the oral formulation, (ii) about 0.001% to about 0.25% ginseng by weight of the oral formulation, and (iii) about 0.01% to about 3% lemon balm by weight of the oral formulation. In some embodiments, the active ingredient combination includes (i) about 1% to about 5% L-theanine by weight of the oral formulation, (ii) about 0.01% to about 1% ginseng by weight of the oral formulation, and (iii) about 0.1% to about 1% lemon balm by weight of the oral formulation.

[0058] In any of these embodiments, the active ingredient combination may further include vitamin C in an amount of about 0.1% to about 5% by weight of the oral formulation. In any of these embodiments, the active ingredient combination may further include L-tryptophan in an amount of about 0.05% to about 3%.

[0059] In some embodiments, the active ingredient combination includes: (i) L-theanine in an amount of from about 0.1% to about 2.5% by weight of the oral formulation; (ii) ginseng in an amount of from about 0.001% to about 0.25% by weight of the oral formulation; (iii) lemon balm in an amount of from about 0.1% to about 1% by weight of the oral formulation; and (iv) vitamin C in an amount of from about 0.1% to about 2.5% by weight of the oral formulation.

[0060] In some embodiments, the active ingredient combination includes (i) L-theanine in about 0.1% to about 2.5% by weight of the oral formulation; (ii) ginseng in about 0.01% to about 1% by weight of the oral formulation; (iii) lemon balm in about 0.1% to about 1% by weight of the oral formulation; (v) chamomile (e.g., chamomile extract) in about 0.01% to about 3% by weight of the oral formulation; and optionally (iv) vitamin C in about 0.1% to about 2.5% by weight of the oral formulation. In some embodiments, the active ingredient combination includes (i) L-theanine in about 0.1% to about 2.5% by weight of the oral formulation; (ii) ginseng in about 0.01% to about 1% by weight of the oral formulation; (iii) lemon balm in about 0.1% to about 1% by weight of the oral formulation; (v) chamomile (e.g., chamomile extract) in about 0.0001% to about 1% by weight of the oral formulation; and optionally (iv) vitamin C in about 0.1% to about 2.5% by weight of the oral formulation.

[0061] In some embodiments, the active ingredient combination includes (i) L-theanine in about 1% to about 5% by weight of the oral formulation; (ii) ginseng in about 0.01% to about 1% by weight of the oral formulation; (iii) lemon balm in about 0.1% to about 1% by weight of the oral formulation; (v) L-tryptophan in about 0.05% to about 3% by weight of the oral formulation; and optionally (iv) vitamin C in about 0.1% to about 2.5% by weight of the oral formulation.

[0062] The inventors have found that the above amounts of active ingredient provide a formulation that provides a beneficial effect of relaxation / stress reduction to the user while also providing a highly safe formulation. The amount of active ingredient can be adjusted so that the formulation is highly effective while ensuring safety for the user and avoiding overdosing on the active ingredient.

[0063] Other suitable additional active ingredients are described below.

[0064] In some embodiments, the combination of active ingredients further comprises a botanical active ingredient. As used herein, the terms "botanical ingredient" or "botanical material" refer to any plant or fungal-derived material, including plant material in its natural form and plant material derived from natural plant material, such as an extract or isolate of the plant material, or processed plant material (e.g., plant material that has been subjected to heat treatment, fermentation, bleaching, or other treatment processes that can alter the physical and / or chemical properties of the material). For purposes of this disclosure, "botanical material" includes, but is not limited to, "herbal material," which refers to seed-producing plants that do not develop permanent woody tissue and are typically valued for their pharmacological or organoleptic properties (e.g., tea or herbal tea). Botanical materials useful in this disclosure can include, but are not limited to, any of the compounds and materials (including mixtures thereof) described herein. Certain botanical materials of this type are sometimes referred to as supplements, dietary supplements, "phytochemicals," or "functional foods." Certain botanical materials, either as plant materials or extracts thereof, are used in traditional herbal medicine and are further described herein.Non-limiting examples of botanical or plant-derived materials include ashwagandha, bacopa monniera, baobab, basil, Centella asiatica, Bupleurum Root, chamomile, cherry blossom, chlorophyll, cinnamon, citrus fruits, clove, cocoa, cordyceps, curcumin, damiana, Dorstenia arifolia, Dorstenia odorata, essential oils, eucalyptus, fennel, Galphimia glauca, ginger, ginkgo biloba, ginseng (e.g., ginseng), griffonia simplicifolia, guarana, cannabis, hemp, hops, jasmine, Kaempferia parviflora, black ginger (Thai ginseng), kava, lavender, lemon balm, lemongrass, licorice, lutein, maca, matcha green tea, pepper (Nardostachys chinensis), oily violet extract, peppermint, quercetin, resveratrol, tema (Rhizoma gastrodiae), rhodiola, rooibos, rose essential oil, rosemary, kana (Sceletium tortuosum), schisandra, skullcap, spearmint extract, spikenard, terpenes, herbal tea ingredients, turmeric, damiana (Turnera aphrodisiaca), valerian, white mulberry, echinacea, and yerba mate.

[0065] The active ingredient combination may include B vitamins (e.g., one or more of vitamin B1, vitamin B2, vitamin B3, vitamin B5, vitamin B6, vitamin B7, vitamin B9, vitamin B12, preferably vitamin B6 and vitamin B12). When present, the B vitamins (such as vitamin B6 and / or vitamin B12) may be present in an amount of about 0.001% to about 5% by weight of the oral formulation, preferably about 0.01% to about 2.5% by weight of the oral formulation.

[0066] The combination of active ingredients may further comprise a vitamin selected from vitamin A, vitamin D, vitamin E, and vitamin K, or a mixture thereof.

[0067] The combination of active ingredients may include melatonin, which, if present, may be present in an amount of from about 0.001% to about 5% by weight of the oral formulation.

[0068] The active ingredient combination may further include an amino acid, such as an amino acid selected from the group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, gamma-aminobutyric acid (GABA), taurine (2-aminoethanesulfonic acid), hydroxyproline, and beta-alanine. In some embodiments, the active ingredient combination includes GABA.

[0069] In some embodiments, the combination of active ingredients includes a cannabinoid. The cannabinoid may be a derivative or extract of cannabis. Cannabinoids are a group of natural or synthetic chemical compounds that act on intracellular cannabinoid receptors (i.e., CB1 and CB2) to inhibit the release of neurotransmitters in the brain. Cannabinoids are cyclic molecules that exhibit certain properties, such as the ability to easily cross the blood-brain barrier. Cannabinoids may be naturally occurring in plants such as cannabis (phytocannabinoids), present in animals (endocannabinoids), or artificially produced (synthetic cannabinoids). Cannabis species exhibit at least 85 different phytocannabinoids, which can be subdivided into cannabigerol, cannabichromene, cannabidiol, tetrahydrocannabinol, cannabinol, and cannabinodiol, as well as other cannabinoids.In some embodiments, the cannabinoid is selected from the group consisting of cannabigerol (CBG), cannabichromene (CBC), cannabidiol (CBD), tetrahydrocannabinol (THC), cannabinol (CBN), and cannabinodiol (CBDL), cannabicyclol (CBL), cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM), cannabinerolic acid, cannabidiolic acid (CBDA), cannabinol propyl variants (Cannabinol propyl variant (CBNV), cannabitriol (CBO), tetrahydrocannabimolic acid (THCA), tetrahydrocannabivarinic acid (THCV A), and mixtures thereof. In some embodiments, the cannabinoid is tetrahydrocannabinol (THC) or comprises at least tetrahydrocannabinol (THC). In some embodiments, the cannabinoid is cannabidiol (CBD) or comprises at least cannabidiol (CBD).

[0070] In some embodiments, the active ingredient combination comprises a cannabinoid (such as cannabidiol) in an amount ranging from at least about 0.001% by weight of the oral formulation, e.g., from about 0.001% to about 10% by weight of the oral formulation, e.g., from about 0.01% to about 5% by weight, e.g., from about 0.1% to about 2.5% by weight, e.g., from 0.5% to about 1% by weight.

[0071] In some embodiments, the active ingredient combination includes magnesium glycinate, which, when present, may be included in an amount of about 0.1% to about 10% by weight of the oral formulation, such as about 0.5% to about 5% by weight, or about 0.5% to about 1% by weight.

[0072] For the avoidance of doubt, combinations of the above final formulation amounts are expressly contemplated by this disclosure, as are any of the ranges disclosed herein.

[0073] Active ingredient ratio The ratio of active ingredients in the oral formulation may be selected to enhance the relaxation effect of the oral formulation on the recipient.

[0074] In some embodiments, the L-theanine and ginseng are present in a weight ratio of about 250:1 to about 100:1, for example, about 150:1 to about 100:1.

[0075] In some embodiments, the L-theanine and ginseng are present in a weight ratio of about 100:1 to about 130:1, for example, about 110:1 to about 120:1.

[0076] The inventors have found that the amount of lemon balm included in the formulation can have a desirable effect on reducing stress and anxiety levels. In some embodiments, the L-theanine and lemon balm are present in a weight ratio of about 1:1 to about 10:1, such as about 2.5:1 to about 7.5:1. Preferably, the L-theanine and lemon balm are present in a weight ratio of about 3:1 to about 4:1.

[0077] In some embodiments, the ginseng and lemon balm are present in a weight ratio of about 1:1 to about 1:100, such as about 1:5 to about 1:75, such as about 1:10 to about 1:50.

[0078] When present, vitamin C may be included such that the weight ratio of vitamin C to lemon balm is from about 1:1 to about 10:1. In some preferred embodiments, the weight ratio of vitamin C to lemon balm is from about 1:1 to about 5:1.

[0079] When present, vitamin C may be included such that the weight ratio of vitamin C to L-theanine is about 1:1 to about 1:5. In some preferred embodiments, the weight ratio of vitamin C to L-theanine is about 1:1 to about 1:2.

[0080] In some embodiments, the oral formulation comprises: A combination of active ingredients comprising: (i) L-theanine; (ii) ginseng; and (iii) lemon balm, The weight ratio of L-theanine to ginseng is about 100:1 to about 130:1. The weight ratio of L-theanine to lemon balm is about 5:1 to about 7.5:1, It contains a combination of active ingredients, with a weight ratio of ginseng and lemon balm of about 1:5 to about 1:75.

[0081] In some embodiments, the oral formulation comprises: A combination of active ingredients comprising: (i) L-theanine; (ii) ginseng; and (iii) lemon balm, The weight ratio of L-theanine to ginseng is about 110:1 to about 120:1. The weight ratio of L-theanine to lemon balm is about 4:1 to about 3:1, It contains a combination of active ingredients, with a weight ratio of ginseng and lemon balm of about 1:10 to about 1:50.

[0082] In some embodiments, the oral formulation comprises: A combination of active ingredients comprising: (i) L-theanine; (ii) ginseng; (iii) lemon balm; and (iv) vitamin C; It contains a combination of active ingredients in which the weight ratio of vitamin C to L-theanine is about 1:1 to about 1:10.

[0083] In some embodiments, the oral formulation comprises: A combination of active ingredients comprising: (i) L-theanine; (ii) ginseng; (iii) lemon balm; and (iv) vitamin C; The weight ratio of L-theanine to ginseng is about 110:1 to about 120:1. The weight ratio of L-theanine to lemon balm is about 4:1 to about 3:1, The weight ratio of ginseng to lemon balm is about 1:10 to about 1:50. It contains a combination of active ingredients in which the weight ratio of vitamin C to L-theanine is about 1:1 to about 1:10.

[0084] additives Depending on the type of oral formulation being processed, the formulation may contain one or more additional ingredients in addition to the combination of active ingredients. For example, the oral formulation may further contain an additive selected from the group consisting of flavorings, sweeteners, buffering agents, acidifying agents, thickeners, fillers, binders, humectants, preservatives, salts, coloring agents, oral care additives, disintegration aids, antioxidants, water, or mixtures thereof. In some embodiments, the oral formulation further contains one or more additives selected from the group consisting of flavorings, sweeteners, acidifying agents, thickeners, fillers, binders, humectants, preservatives, and mixtures thereof.

[0085] Fillers or excipients Depending on the formulation, oral formulations may contain fillers or excipients, which can serve multiple functions, for example, improving certain sensory properties such as texture and mouthfeel, or improving the cohesiveness or compressibility of the formulation.

[0086] In some embodiments, the filler is a porous granular material and is cellulosic. For example, the filler or excipient may be a non-tobacco plant material or derivative thereof, including cellulosic materials derived from the sources described below. Examples of cellulosic non-tobacco plant materials include grains (e.g., corn, oats, barley, rye, buckwheat, etc.), sugar beet (e.g., FIBREX® brand filler available from International Fiber Corporation), bran fiber, and mixtures thereof. In some embodiments, the filler is a cellulosic material selected from the group consisting of corn fiber, oat fiber, barley fiber, rye fiber, buckwheat fiber, sugar beet fiber, bran fiber, bamboo fiber, wood pulp fiber, cotton fiber, citrus pulp fiber, grass fiber, willow fiber, poplar fiber, cocoa fiber, derivatives thereof, and combinations thereof. In some embodiments, the filler is a cellulosic material selected from the group consisting of sugar beet fiber, wood pulp fiber, bamboo fiber, derivatives thereof, and combinations thereof.

[0087] In some embodiments, the filler is derived from wood pulp fibers. One particularly suitable filler for use in the formulations described herein is microcrystalline cellulose (MCC). MCC can be synthetic, semi-synthetic, or derived entirely from natural cellulose. MCC can be selected from the group consisting of AVICEL® PH-100, PH-101, PH-102, PH-103, PH-105, PH-112, PH-113, PH-200, PH-300, PH-301, and PH-302 grades, VIVACEL® 101, 102, 12, and 20 grades, and EMOCEL® 50M and 90M grades, and mixtures thereof.

[0088] In some embodiments, the filler is a non-tobacco plant material or a derivative thereof. Non-limiting examples of derivatives of non-tobacco plant materials include starch (e.g., from potato, wheat, rice, corn), natural cellulose, and modified cellulosic materials. Additional examples of fillers that can be used include maltodextrin, dextrose, calcium carbonate, calcium phosphate, lactose, mannitol, xylitol, and sorbitol. Combinations of these fillers can also be used.

[0089] As used herein, "starch" can refer to pure starch, modified starch, or starch derivatives derived from any source. Starch, typically in granular form, is present in almost all green plants in various plant tissues and organs (e.g., seeds, leaves, rhizomes, roots, tubers, shoots, fruits, grains, and stems). Starch composition, granule shape, and particle size can vary. Starches derived from different sources often have different chemical and physical properties. A particular starch can be selected for inclusion in a formulation based on the ability of the starch-based material to impart specific sensory properties to the formulation. Starch derived from a variety of sources can be used. For example, major sources of starch include cereals (e.g., rice, wheat, and corn) and root vegetables (e.g., potato and cassava). Other examples of starch sources include acorn, arrowroot, arracacha, banana, barley, beans (e.g., broad beans, lentils, mung beans, peas, chickpeas), breadfruit, buckwheat, canna, chestnut, taro, potato, kudzu, malanga, millet, oats, oka, Polynesian arrowroot, sago, sorghum, sweet potato, quinoa, rye, tapioca, taro, tobacco, water chestnut, and yam. Certain starches are modified starches. Modified starches have undergone one or more structural modifications, i.e., generally designed to alter their high-temperature properties. Some starches have been developed through genetic engineering and are considered "modified" starches. Other starches are modified after they are obtained. For example, modified starches can be starches that have undergone chemical reactions such as esterification, etherification, oxidation, acid-catalyzed or base-catalyzed depolymerization (thinning), bleaching, transglycosylation and depolymerization (e.g., dextrinization in the presence of a catalyst), cross-linking, enzyme treatment, acetylation, hydroxypropylation, and / or partial hydrolysis. Other starches are modified by pregelatinization, dextrinization, and / or thermal treatments such as cold water swelling.Specific modified starches include phosphated starch, glycerol cross-linked starch, phosphate cross-linked starch esterified with sodium trimetaphosphate, phosphate monoesterified phosphate cross-linked starch, acetylated phosphate cross-linked starch, starch acetate esterified with acetic anhydride, starch acetate esterified with vinyl acetate, acetylated adipate cross-linked starch, acetylated glycerol cross-linked starch, hydroxypropyl starch, hydroxypropylglycerol cross-linked starch, and starch sodium octenyl succinate.

[0090] Other suitable fillers or excipients include sugar alcohols. Sugar alcohols are polyols derived from monosaccharides or disaccharides, either partially or fully hydrogenated. Sugar alcohols have, for example, from about 4 to about 20 carbon atoms and include erythritol, arabitol, ribitol, isomalt, maltitol, dulcitol, iditol, mannitol, xylitol, lactitol, sorbitol, and combinations thereof. In some embodiments, the filler, if present, may be selected from the group consisting of isomalt, maltitol, and mixtures thereof.

[0091] water The moisture content (eg, water content) of an oral formulation can be varied depending on the desired properties prior to use by the recipient of the formulation.

[0092] Typically, for solid oral dosage forms, prior to insertion into the user's oral cavity, the moisture content is less than about 60% by weight, generally about 1 to about 60% by weight, e.g., about 5 to about 55% by weight, about 10 to about 50% by weight, about 20 to about 45% by weight, or about 25 to about 40% by weight of the oral dosage form, including at least about 5% by weight, at least about 10% by weight, at least about 15% by weight, and at least about 20% by weight of the oral dosage form.

[0093] fragrance As used herein, the term "flavoring agent" (or "flavor" or "flavorant") refers to an ingredient that can be used, where local regulations permit, to evoke a desired taste, aroma, or other somatosensory sensation in a formulation intended for adult consumption. Examples of somatosensory sensations that can be altered by flavorings include taste, mouthfeel, moistness, cool / warm sensation, and / or scent / aroma. Flavorings can be natural or synthetic, and the flavor characteristics imparted by flavorings can be described as, but are not limited to, cool, sweet, herbal, confectionery, floral, fruity, or spicy.

[0094] Flavoring agents may be naturally occurring flavoring materials, botanical materials, extracts of botanical materials, synthetically derived materials, or combinations thereof (e.g., tobacco, cannabis, licorice, hydrangea, eugenol, magnolia leaf, chamomile, fenugreek, clove, maple, matcha green tea, menthol, Japanese mint, aniseed, cinnamon, turmeric, Indian spices, Asian spices, herbs, wintergreen, cherry, berry, red berry, cranberry, raspberry, strawberry, peach, apple, orange, mango, pineapple, etc.). Lemon, clementine, lemon, lime, tropical fruits, papaya, rhubarb, grapes, durian, dragon fruit, cucumber, blueberry, mulberry, citrus fruits, Drambuie, bourbon, scotch, whiskey, gin, tequila, rum, spearmint, peppermint, lavender, aloe vera, cardamom, coconut, celery, cascarilla, nutmeg, sandalwood, bergamot, geranium, khat, eggplant, betel nut, shisha, pine, honey essence, rose oil, vanilla, lemon oil, orange oil, orange blossom, cherry blossom, cassia, kimchi Challaway, cognac, jasmine, ylang-ylang, sage, fennel, wasabi, bell pepper, ginger, coriander, coffee, hemp, peppermint oil from any species of the genus Mentha, eucalyptus, star anise, cocoa, lemongrass, rooibos, flax, ginkgo, hazel, hibiscus, bay leaf, yerba mate, orange peel, rose, tea such as green tea or black tea, thyme, juniper, elderflower, basil, bay leaf, cumin, oregano, paprika, rosemary, saffron, lemon peel, mint, shiso, curcuma, cilantro, myrtle squid, blackcurrant, valerian, pimento, mace, damiane, marjoram, olive, lemon balm, lemon basil, chives, Calvi, verbena, tarragon, limonene, thymol, camphene), flavor enhancers, bitter taste receptor antagonists, sensory receptor activators or stimulants, sugars and / or sugar substitutes (e.g., honey, sucralose, acesulfame potassium, aspartame, saccharin, cyclamate, lactose, sucrose, glucose, fructose, sorbitol, or mannitol), as well as charcoal, chlorophyll, minerals, botanical ingredients,or other additives such as breath fresheners. The flavoring agent may be an imitation, synthetic, or natural ingredient, or a combination thereof. The flavoring agent may be in any suitable form, for example, a liquid such as an oil, a solid such as a powder, or a gas.

[0095] In some embodiments, the flavoring agent comprises a natural flavoring agent, such as berry (e.g., raspberry, blueberry, or strawberry), honey, citrus (e.g., lemon, bergamot, orange, or lime), or other botanical source.

[0096] In some embodiments, the flavoring agent comprises menthol, spearmint, and / or peppermint. In some embodiments, the flavoring agent comprises cucumber, blueberry, citrus, and / or red berry flavor components. In some embodiments, the flavoring agent comprises eugenol. In some embodiments, the flavoring agent comprises flavor components extracted from tobacco. In some embodiments, the flavoring agent comprises flavor components extracted from cannabis.

[0097] In some embodiments, fragrances may include sensuous ingredients intended to produce somatosensory sensations, typically chemically induced and perceived by stimulating the fifth cranial nerve (trigeminal nerve), in addition to or instead of the nerves involved in aroma or taste, and may include ingredients that produce a warming effect, a cooling effect, a tingling sensation, or a numbing sensation. A suitable warming ingredient may be, but is not limited to, vanillyl ethyl ether, and a suitable cooling ingredient may be, but is not limited to, eucalyptol, WS-3.

[0098] In some embodiments, the fragrance may comprise a terpene. In some embodiments, the fragrance may comprise a monoterpene, and / or a diterpene, and / or a sesquiterpene. In some embodiments, the fragrance may comprise a monoterpene. In some embodiments, the terpene is selected from pinene (alpha and beta), geraniol, linalool, limonene, carvone, eucalyptol, menthone, isomenthone, piperitone, myrcene, beta-bourbonene, germacrene, thymol, citral, eugenol, and mixtures thereof. In some embodiments, the fragrance is selected from the group consisting of geraniol, citronellol, nerol, maltol, ethyl maltol, fenchol, homofuraneol, furaneol, norfuraneol, 1-octen-3-ol, borneol, linalool, farnesol, hydroxycyclonerol, 3,7-dimethyloctanol, myrcenol, lavandulol, nerolidol, terpineol, alpha terpineol, menthol, thymol, carvacrol, myrtenol, carveol, san The hydroxybenzoate is selected from the group consisting of talol, piperitol, perillyl alcohol, patchouli alcohol, hexanol, 1-hexanol, 3-cis-hexanol, cis-3-hexen-1-ol, phenylethanol, eugenol, sesamol, sotolon, maple furanone, methyl anthranilate, guaiacol, raspberry ketone, 2-methoxy-4-vinylphenol, 4-ethylguaiacol, benzyl alcohol, homofuranol, vanillin, ethyl vanillin, and combinations thereof.In some embodiments, the fragrance is selected from the group consisting of geraniol, citronellol, nerol, maltol, ethyl maltol, fenchol, homofuraneol, furaneol, norfuraneol, 1-octen-3-ol, borneol, linalool, farnesol, hydroxycyclonerol, 3,7-dimethyloctanol, myrcenol, lavandulol, nerolidol, terpineol, alpha terpineol, menthol, thymol, carvacrol, myrtenol, carveol, santalol, piperitol, perillyl alcohol, patchouli alcohol, hexanol, 1-hexanol, 3-cis-hexanol, cis-3-hexen-1-ol, phenylethanol, eugenol, sesamol, sotolon, maple furanone, methyl anthranilate, guaiacol, raspberry ketone, 2-methoxy-4-vinylphenol, 4-ethylguaiacol, benzyl alcohol, homofuranol, and combinations thereof.

[0099] When present, flavoring agents may be included in the oral formulation in an amount of up to about 10% by weight of the oral formulation, such as up to about 5% by weight, e.g., up to about 1% by weight. In some embodiments, flavoring agents are present in an amount of about 0.01% to about 5% by weight, preferably about 0.1% to about 2.5% by weight of the oral formulation, and more preferably about 0.25% to about 1% by weight of the oral formulation.

[0100] Binder In some embodiments, the oral dosage form may further comprise at least one binder. A binder (or combination of binders) may be used in the dosage form in certain embodiments in an amount sufficient to impart desired physical properties and physical integrity to the dosage form.

[0101] The binder can be organic or inorganic, or a combination thereof. Representative binders include cellulose derivatives, povidone, sodium alginate, starch-based binders, pectin, carrageenan, pullulan, zein, and the like, and combinations thereof. The amount of binder used in the formulation can vary but may be up to about 30% by weight, with certain embodiments being characterized by a binder content of at least about 0.1% by weight, e.g., from about 1% to about 30% by weight, or from about 1% to about 10% by weight, based on the total weight of the oral formulation.

[0102] In some embodiments, the binder comprises pectin. Pectin is a natural polymer that is an acidic heteropolysaccharide (a polysaccharide composed of multiple monosaccharide units) related to carbohydrates. Unlike common carbohydrates, pectin contains a carboxylic acid group (or the corresponding methyl ester or carboxamide group) at the C-6 position instead of a hydroxymethyl group. The main subunit is known as galacturonic acid, which can copolymerize with L-rhamnose. Other sugars are present as side-chain substituents. Pectin acts as a thickening and gelling agent. Pectin isolated from raw materials, such as apple pomace, citrus peel, sugar beet waste from the sugar processing process, sunflower flower discs discarded after seed harvesting, mango residue, and other commercially available pectins, can be used. In combination with certain sugars, under acidic conditions (e.g., pH of about 2.5 to about 5) or in the presence of gelling agents (calcium or other divalent alkaline earth elements), pectin can impart a gel-like or gummy consistency to the formulations disclosed herein. In some embodiments, the binder comprises low-methoxy pectin. Suitable low-methoxy pectins include, for example, "GENU® pectin type LM-104 AS" available from CP Kelco, Atlanta, GA, USA. In some embodiments, the binder comprises low-methoxy pectin in combination with a gelling agent. In some embodiments, the gelling agent comprises calcium ions, such as, but not limited to, calcium diphosphate. In some embodiments, the binder comprises high-methoxy pectin in combination with an organic acid, as described herein below. In some embodiments, the binder comprises high-methoxy pectin in combination with citric acid.

[0103] When present, the pectin-based binder is typically present in an amount of up to about 3% by weight, e.g., about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.6%, about 1.7%, about 1.8%, about 1.9%, about 2%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, or about 3% by weight, based on the total weight of the oral dosage form.

[0104] In some embodiments, the binder comprises a cellulose derivative. In certain embodiments, a cellulose derivative is a cellulose ether (including a carboxyalkyl ether), which refers to a cellulose polymer in which the hydrogen atoms of one or more hydroxyl groups in the cellulose structure have been replaced with an alkyl group, a hydroxyalkyl group, or an aryl group. Non-limiting examples of such cellulose derivatives include methylcellulose, hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), hydroxyethyl cellulose, and carboxymethylcellulose (CMC). In some embodiments, the cellulose derivative is or includes HPC. In some embodiments, the cellulose derivative is a combination of HPC and HPMC. In some embodiments, the oral formulation comprises about 1% to about 10% by weight of the cellulose derivative (e.g., HPC), and in certain embodiments, about 1% to about 5% by weight of the cellulose derivative (e.g., HPC) based on the weight of the formulation.

[0105] In certain embodiments, the binder comprises a gum, such as a natural gum. As used herein, natural gum refers to a naturally occurring polysaccharide material that has binding properties and is also useful as a thickening or gelling agent. Representative natural gums derived from plants, which are typically somewhat water-soluble, include xanthan gum, guar gum, gum arabic, gum ghatti, gum tragacanth, gum karaya, locust bean gum, gellan gum, and combinations thereof. When present, the natural gum binder material may be present in an amount of up to about 5% by weight, e.g., from about 0.1% by weight, from about 0.2% by weight, from about 0.3% by weight, from about 0.4% by weight, from about 0.5% by weight, from about 0.6% by weight, from about 0.7% by weight, from about 0.8% by weight, from about 0.9% by weight, from about 1% by weight to about 2% by weight, from about 3% by weight, from about 4% by weight, or from about 5% by weight, based on the total weight of the formulation.

[0106] Wetting agent In some embodiments, the oral formulation comprises at least one humectant. Examples of suitable humectants that may be included in the formulation include, but are not limited to, glycerin, 1,2-propanediol (propylene glycol), 1,3-propanediol, dipropylene glycol, sorbitol, xylitol, mannitol, and the like. In some embodiments, the humectant is or includes glycerin. In some embodiments, the oral formulation comprises glycerin. In some embodiments, the humectant is or includes propylene glycol. In some embodiments, the oral formulation comprises propylene glycol. The amount of humectant used in the oral formulation can vary but may be up to about 5% by weight, with certain embodiments being characterized by a humectant content of at least about 1% by weight of the oral formulation, e.g., from about 2 to about 5% by weight. In some embodiments, the humectant (such as glycerin and / or propylene glycol) may be present in an amount of about 0.01% to about 25% by weight of the oral formulation, e.g., about 0.1% to about 20% by weight of the oral formulation, e.g., about 0.5% to about 15% by weight of the oral formulation, e.g., about 1% to about 10% by weight of the oral formulation, e.g., about 5% to about 10% by weight of the oral formulation.

[0107] sweetener One or more sweeteners may be added to improve the sensory properties of the oral formulation. The sweetener may be any sweetener or combination of sweeteners, whether natural or artificial, or a combination of natural and artificial sweeteners. Examples of natural sweeteners include fructose, sucrose, glucose, maltose, mannose, galactose, lactose, stevia, honey, etc. Examples of artificial sweeteners include sucralose, isomaltulose, maltodextrin, saccharin, aspartame, acesulfame K, neotame, etc.

[0108] In some embodiments, the sweetener comprises one or more sugar alcohols. The sugar alcohols may comprise erythritol, arabitol, ribitol, isomalt, maltitol, dulcitol, iditol, mannitol, xylitol, lactitol, sorbitol, or a combination thereof. In some embodiments, the sweetener is selected from the group consisting of fructose, sucrose, glucose, maltose, mannose, galactose, lactose, stevia, honey, sucralose, isomaltulose, maltodextrin, saccharin, aspartame, acesulfame K, neotame, erythritol, arabitol, ribitol, isomalt, maltitol, dulcitol, iditol, mannitol, xylitol, lactitol, sorbitol, and mixtures thereof.

[0109] In some embodiments, the sweetener is selected from the group consisting of sucralose, acesulfame K, aspartame, maltodextrin, mannitol, sucrose, and mixtures thereof. Preferably, the sweetener can be sucralose and / or acesulfame K. When present in the oral formulation, the sweetener (such as sucralose and / or acesulfame K) can be present in an amount of about 0.001% to about 5% by weight of the oral formulation, for example, about 0.01% to about 3% by weight, and preferably about 0.01% to about 1% by weight.

[0110] buffer Non-limiting examples of suitable buffering agents that may be included in the oral formulation include alkali metal acetates, glycinates, phosphates, glycerophosphates, citrates, carbonates, bicarbonates, borates, or mixtures thereof. In some embodiments in which a buffering agent is present, the buffering agent is selected from the group consisting of sodium carbonate, sodium bicarbonate, sodium phosphate, ammonium phosphate, dicalcium phosphate, tricalcium phosphate, and mixtures thereof. In some embodiments, the buffering agent is sodium bicarbonate and / or sodium carbonate. When present, the buffering agent (e.g., sodium bicarbonate and / or sodium carbonate) may be included in an amount less than about 5% by weight of the oral formulation, such as about 0.5% to about 5% by weight, e.g., about 0.75% to about 4% by weight, about 0.75% to about 3% by weight, or about 1% to about 2% by weight, based on the total weight of the oral formulation.

[0111] organic acid In some embodiments, the formulation includes an organic acid. As used herein, the term "organic acid" refers to an organic (i.e., carbon-based) compound characterized by acidic properties. Typically, organic acids are relatively weak acids (i.e., they do not completely dissociate in the presence of water), such as carboxylic acids (-COH) or sulfonic acids (-SOHO). As used herein, reference to an organic acid refers to an organic acid that is intentionally added. In this regard, the organic acid may be intentionally added as a particular mixed component, rather than being inherently present simply as a component of another mixed component (e.g., a small amount of organic acid that may be inherently present in a mixed component such as tobacco raw material). In some embodiments, one or more organic acids are added neat (i.e., in free acid form, or in native solid or liquid form) or as a solution, such as, for example, an aqueous solution. In some embodiments, one or more organic acids are added in the form of a salt.

[0112] In some embodiments, the organic acid is a carboxylic acid or a sulfonic acid. The carboxylic acid or sulfonic acid functional group can be, for example, a group having 1 to 20 carbon atoms (C1 to C6). 20In some embodiments, the organic acid is an alkyl carboxylic acid, a cycloalkyl carboxylic acid, a heterocycloalkyl carboxylic acid, an aryl carboxylic acid, a heteroaryl carboxylic acid, an alkyl sulfonic acid, a cycloalkyl sulfonic acid, a heterocycloalkyl sulfonic acid, an aryl sulfonic acid, or a heteroaryl sulfonic acid.

[0113] In some embodiments, the organic acid is an alkyl carboxylic acid. Non-limiting examples of alkyl carboxylic acids include formic acid, acetic acid, propionic acid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid, dodecanoic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, etc. In some embodiments, the organic acid is an alkyl sulfonic acid. Non-limiting examples of alkyl sulfonic acids include propane sulfonic acid and octane sulfonic acid.

[0114] In some embodiments, the alkyl carboxylic acid or alkyl sulfonic acid is substituted with one or more hydroxyl groups. Non-limiting examples include glycolic acid, 4-hydroxybutyric acid, and lactic acid.

[0115] In some embodiments, the organic acid may contain two or more carboxylic acid groups or two or more sulfonic acid groups (e.g., two, three, or more carboxylic acid groups). Non-limiting examples include oxalic acid, fumaric acid, maleic acid, and glutaric acid. In organic acids containing multiple carboxylic acids (e.g., two to four carboxylic acid groups), one or more carboxylic acid groups may be esterified. Non-limiting examples include succinic acid monoethyl ester, monomethyl fumarate, monomethyl citrate, dimethyl citrate, etc.

[0116] In some embodiments, the organic acid may contain two or more carboxylic acid groups and one or more hydroxyl groups. Non-limiting examples of such acids include tartaric acid, citric acid, etc. In some preferred embodiments, the organic acid is citric acid, sodium citrate, calcium citrate, or a combination thereof.

[0117] In some embodiments, the organic acid is an aryl carboxylic acid or aryl sulfonic acid. Non-limiting examples of aryl carboxylic acids and aryl sulfonic acids include benzoic acid, toluic acid, salicylic acid, benzenesulfonic acid, and p-toluenesulfonic acid.

[0118] Additional non-limiting examples of suitable organic acids include 2,2-dichloroacetic acid, 2-hydroxyethanesulfonic acid, 2-oxoglutaric acid, 4-acetamidobenzoic acid, 4-aminosalicylic acid, acetic acid, adipic acid, ascorbic acid (L), aspartic acid (L), camphoric acid (+), camphor-10-sulfonic acid (+), capric acid, caproic acid, caprylic acid, cinnamic acid, cyclamic acid, decanoic acid, dodecyl sulfuric acid, ethane-1,2-disulfonic acid, ethanes ... Sulfonic acid, formic acid, fumaric acid, galactaric acid, gentisic acid, glucoheptonic acid, gluconic acid, glucuronic acid, glutamic acid, glycerophosphoric acid, glycolic acid, hippuric acid, isobutyric acid, lactobionic acid, lauric acid, malonic acid, mandelic acid, methanesulfonic acid, naphthalene-1,5-disulfonic acid, naphthalene-2-sulfonic acid, oleic acid, palmitic acid, pamoic acid, pyroglutamic acid, sebacic acid, stearic acid, and undecylenic acid.

[0119] Preferably, the organic acid is selected from the group consisting of citric acid, malic acid, lactic acid, benzoic acid, tartaric acid, and mixtures thereof, hi some preferred embodiments, the organic acid is or includes citric acid or a salt thereof.

[0120] In some embodiments, the formulation includes an alkali metal salt of an organic acid. For example, at least a portion of the organic acid may be present in the formulation in the form of an alkali metal salt. Suitable alkali metal salts include lithium, sodium, and potassium. In some embodiments, the alkali metal is sodium or potassium. In some embodiments, the alkali metal is sodium. In some embodiments, the formulation includes an organic acid and a sodium salt of the organic acid. In some embodiments, the organic acid is or includes sodium citrate, such as trisodium citrate.

[0121] The amount of organic acid present in the formulation can vary. The oral formulation can contain from about 0.01% to about 10% by weight of an organic acid present as one or more organic acids, based on the total weight of the oral formulation. In some embodiments, the oral formulation contains at least about 0.01%, at least about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or at least about 10% by weight of an organic acid, based on the total weight of the oral formulation. In some preferred embodiments, the oral formulation contains from about 0.01% to about 5% by weight of an organic acid, based on the weight of the oral formulation. For example, the oral formulation may contain an organic acid in an amount of about 0.1% to about 2.5% by weight of the oral formulation. When a salt of an organic acid is added (e.g., citric acid anhydrous), the weight percent is calculated based on the weight of the free acid, without any counterion that may be present.

[0122] In certain embodiments, the inclusion of an organic acid is sufficient to adjust the pH of the formulation to about 4.0 to about 9.0, e.g., about 4.5 to about 7.0, or about 5.5 to about 7.0, about 4.0 to about 5.5, or about 7.0 to about 9.0. In some embodiments, the inclusion of an organic acid is sufficient to adjust the pH of the formulation to about 4.5 to about 6.5, e.g., about 4.5 to about 5.0 to about 5.5 to about 6.0, or about 6.5. In some embodiments, the organic acid is used in an amount sufficient to adjust the pH of the formulation to about 5.5 to about 6.5, e.g., about 5.5 to about 5.6 to about 5.7 to about 5.8 to about 5.9 to about 6.0 to about 6.1, to about 6.2 to about 6.3 to about 6.4, or to about 6.5.

[0123] In other embodiments, the pH of the formulation is adjusted to the desired value by adding a mineral acid (eg, hydrochloric acid, sulfuric acid, phosphoric acid, etc.).

[0124] The organic acid (e.g., citric acid) can be added neat (i.e., as a solid) or as a solution, such as an aqueous solution. In some embodiments, the organic acid is added as a 50% aqueous solution.

[0125] salt The oral formulation may further comprise a salt. The salt may be included in an amount sufficient to impart desired organoleptic properties to the formulation. Non-limiting examples of suitable salts include sodium chloride, potassium chloride, ammonium chloride, flour salt, sodium acetate, sodium citrate, and the like. The salt may be included in any suitable amount, for example, at least about 0.5% by weight of the oral formulation, for example, at least about 1% by weight, for example, at least about 1.5% by weight. In some embodiments, the oral formulation may comprise the salt in an amount of about 0.5% by weight to about 10% by weight, for example, about 1% by weight to about 7.5% by weight, for example, about 1.5% by weight to about 5% by weight, based on the total weight of the oral formulation.

[0126] thickener In some embodiments, the oral formulation may contain a thickener. Suitable thickeners may include hydrocolloids such as xanthan gum, guar gum, konjac gum, tragacanth gum, and gum arabic. For example, xanthan gum is understood to be a thickener that thickens the composition when added during non-heat processing (i.e., without the application of heat).

[0127] If present, thickening agents (eg, xanthan gum) may be included in an amount from about 0.001% to about 5%, preferably from about 0.01% to about 1% by weight of the oral dosage form.

[0128] coloring agent Coloring agents can be used in an amount sufficient to impart the desired physical properties to the formulation. Examples of coloring agents include various dyes and pigments, such as caramel coloring and titanium dioxide. In addition to natural coloring agents such as curcumin, beet juice extract, and spirulina, various synthetic pigments may also be used. The amount of coloring agent used in oral formulations can vary, but when present, is typically up to about 3% by weight, e.g., about 0.1% to about 0.5% by weight, or about 1% to about 3% by weight, based on the total weight of the oral formulation.

[0129] Other additives Other ingredients, such as preservatives (e.g., potassium sorbate), disintegration aids (e.g., croscarmellose sodium, crospovidone, sodium starch glycolate, pregelatinized corn starch, etc.), and / or antioxidants, can also be used. Typically, such ingredients, when used, are used in an amount of up to about 10% by weight of the oral formulation, e.g., at least about 0.1% by weight, e.g., about 0.5 to about 10% by weight. Disintegration aids can be used in an amount sufficient to adjust the desired physical properties of the oral formulation, for example, by causing the formulation to lose its physical integrity upon contact with water, dispersing various components (e.g., by swelling upon contact with water), etc.

[0130] Further exemplary types of additives include zinc or magnesium salts, or combinations thereof, selected to be relatively water-soluble to provide a highly water-soluble composition (e.g., magnesium gluconate or zinc gluconate), or relatively insoluble to provide a less water-soluble composition (e.g., magnesium oxide or zinc oxide). See, for example, U.S. Pat. No. 9,237,769 to Mua et al., U.S. Pat. No. 7,861,728 to Holton, Jr. et al., U.S. Patent Application Publication No. 2010 / 0291245 to Gao et al., and U.S. Patent Application Publication No. 2007 / 0062549 to Holton, Jr. et al., each of which is incorporated herein by reference, for exemplary additive components, combinations of components, relative amounts of components, and aspects and methods of using the components. Typical content ranges of such additional additives can vary depending on the nature and function of the additive and the intended effect on the final formulation, and include, for example, a range of up to about 10% by weight (e.g., about 0.1 to about 5% by weight) based on the total weight of the oral formulation.

[0131] In some embodiments, the oral formulation comprises a magnesium salt. A non-limiting example of a suitable magnesium salt is magnesium gluconate. In some embodiments, the oral formulation comprises magnesium in an amount of about 0.1% to about 2% by weight, or about 0.2% to about 1% by weight, based on elemental magnesium.

[0132] The aforementioned additives can be used together (e.g., as an additive blend) or separately (e.g., individual additive components can be added at different stages in the preparation of the final formulation). Additionally, additives of the aforementioned types can be encapsulated for addition to the final formulation or composition. For example, exemplary encapsulated additives are described in International Publication No. 2010 / 132444 by Atchley, which is incorporated herein by reference.

[0133] Oral formulation The formulations or compositions described herein are adapted for oral use. As used herein, the term "adapted for oral use" means that the formulation is provided in a form such that, during use, one or more components of the formulation (e.g., active ingredient) are dispersed in the user's oral cavity by saliva in the user's mouth. In certain embodiments, the formulation is designed to deliver the active ingredient and optionally a flavoring agent to the user through the user's oral mucosa, the user's digestive system, or both. In some examples, the active ingredient and optionally a flavoring agent can be absorbed through the oral mucosa or through the digestive tract upon use of the formulation.

[0134] In some embodiments, the oral formulation comprises the combination of active ingredients in an amount of at least about 0.01% by weight of the oral formulation, e.g., at least about 0.1% by weight, preferably at least about 1% by weight. The oral formulation may comprise, for example, at least about 0.25% by weight, at least about 0.3% by weight, at least about 0.5% by weight, at least about 0.75% by weight, at least about 1% by weight, at least about 1.5% by weight, at least about 2% by weight, or at least about 3% by weight of the oral formulation. The combination of active ingredients may be present in an amount of about 50% by weight or less of the oral formulation, e.g., about 40% by weight or less, e.g., about 30% by weight or less, e.g., about 20% by weight or less, e.g., about 10% by weight or less.

[0135] The active ingredient combination may be present in an amount of about 0.01% to about 20% by weight. For example, the active ingredient combination may be present in an amount of about 0.05% to about 15% by weight of the oral formulation, such as about 0.1% to about 10% by weight, or about 0.5% to about 5% by weight. Preferably, the active ingredient combination is present in an amount of about 0.1% to about 10% by weight of the oral formulation. Preferably, the active ingredient combination is present in an amount of about 0.5% to about 5% by weight of the oral formulation, more preferably about 1% to about 5% by weight of the oral formulation.

[0136] In some embodiments, the combination of active ingredients may be present in an amount of about 1.5% to about 20% by weight of the oral formulation, such as about 2.5% to about 15% by weight, or about 2.5% to about 10% by weight.

[0137] The oral formulation can take any form suitable for application to the oral cavity of a human or animal, hi some embodiments, the oral formulation is a solid oral dosage form.

[0138] The oral formulations described herein can take a variety of forms, including soft lozenges and chews.

[0139] solid oral dosage forms As described herein, the oral formulation is in a solid form. As used herein, the term "solid" means that the formulation can substantially maintain its physical shape when not supported by external means, such as packaging. Thus, the formulation is considered to be solid, solid-like, solid-form, or solid-like at room temperature. For the avoidance of doubt, a solid formulation remains substantially solid up to 30°C. In some embodiments, the oral formulation is in a solid form, such as a chew or soft lozenge. In some embodiments, the oral formulation is a chew or soft lozenge. In some embodiments, the oral formulation may be a chewing gum product.

[0140] The oral dosage forms disclosed herein can be formed into a variety of shapes, including various tablets, spheres, strips, films, sheets, coins, cubes, beads, ovoids, ellipsoids, cylinders, beans, sticks, or rods. The cross-sectional shape of the dosage form can vary, with exemplary cross-sectional shapes including circle, square, oval, rectangle, etc. Such shapes can be formed in a variety of ways using equipment such as moving belts, nip devices, extruders, granulators, and compactors.

[0141] In some embodiments, the solid oral formulation is in a form selected from the group consisting of a chew or a soft lozenge.

[0142] In other embodiments, the oral formulation is in a solid form such as moist loose snuff, dry loose snuff, chewing tobacco-type forms, pellet-like pieces, extruded or molded strips, pieces, rods or sticks, finely divided powders, powder-like pieces and micronized or comminuted agglomerates of ingredients, flake-like pieces, molded pieces, gums, films, films or strips that are readily soluble or dispersible in water, capsule-like articles, tablets, lozenges, etc. In some embodiments, the oral formulation is a tablet or lozenge. In some embodiments, the oral formulation may be a chewing gum product. In some embodiments, the oral formulation is in the form of moist snuff or snus, which may or may not contain tobacco.

[0143] Kiss In some embodiments, the formulations can be chewable, meaning that the formulation has a gentle elasticity or "bounce" when chewed and a desirable degree of plasticity. Chewable formulations can dissolve completely or can be in the form of a non-dissolving gum in which only certain ingredients (e.g., active ingredients, flavors, sweeteners) dissolve, leaving a non-dissolving matrix.

[0144] As described herein, a "chew" may be a confectionery-type formulation that can be chewed by the user before dissolving in the oral cavity (i.e., a dissolvable chew) or may be a chewing gum. Preferably, the "chew" completely dissolves in the user's oral cavity. The formulation may be dissolvable. As used herein, the terms "dissolve," "dissolving," and "dissolvable" refer to a formulation having water-soluble components that interact with the moisture in the oral cavity and go into solution, allowing the formulation to be gradually ingested. In one embodiment, a dissolvable formulation can remain in the user's oral cavity for a given period of time until completely dissolved. Dissolution rates can vary over a wide range, from about 1 minute or less to about 60 minutes. For example, a rapid-release formulation typically dissolves and / or releases the desired ingredient (e.g., active ingredient, flavor, etc.) in about 2 minutes or less, often about 1 minute or less (e.g., about 50 seconds or less, about 40 seconds or less, about 30 seconds or less, or about 20 seconds or less). Dissolution can occur by melting, mechanical disruption (eg, chewing), enzymatic or other chemical degradation, or by disruption of interactions between components of the formulation.

[0145] In other embodiments, the formulation does not dissolve while the formulation resides in the user's mouth.

[0146] Chewable embodiments generally include a binder such as a natural gum, pectin, agar, carrageenan, starch, or a combination thereof. In some embodiments, the binder includes or is pectin.

[0147] In some embodiments, the chewable formulation (i.e., "chew") comprises a combination of active ingredients, at least one excipient selected from the group consisting of a sugar alcohol, or at least one sugar, or a combination of at least one sugar alcohol and at least one sugar, and at least one binder. In some embodiments, the chewable formulation (i.e., "chew") comprises a combination of active ingredients, at least one excipient selected from the group consisting of a sugar alcohol, or at least one sugar, or a combination of at least one sugar alcohol and at least one sugar, and at least one binder in an amount of about 0.1% to about 10% by weight of the oral formulation. The chewable formulation or chew may also optionally include a sweetener and / or a flavoring agent.

[0148] Representative chew compositions and formulations may incorporate, based on the total weight of the oral formulation, about 0.1% to about 20% by weight of the active ingredient combination, about 0.1% to about 10% by weight of a binder (e.g., pectin, agar, carrageenan, starch, or a combination thereof), and at least about 30% by weight of at least one excipient selected from the group consisting of a sugar alcohol, or at least one sugar, or a combination of at least one sugar alcohol and at least one sugar. Optionally, the oral formulation may further comprise about 0.01 to about 2% by weight of a sweetener and / or about 0.1% to about 5% by weight of at least one flavoring, based on the total weight of the oral formulation. The specific proportions and selection of ingredients will vary depending on the desired flavor, texture, and other characteristics. For example, the active ingredient combination may be present in the chew in an amount of about 0.1% to about 10% by weight of the oral formulation.

[0149] In some embodiments, the oral chew formulation comprises pectin and an organic acid along with one or more sugar alcohols in an amount of at least 30% by weight of the oral formulation.

[0150] In some embodiments, the oral chew formulation comprises at least one excipient selected from the group consisting of a sugar alcohol, or a sugar, or a combination of at least one sugar alcohol and at least one sugar. In some embodiments, the at least one excipient is selected from a sugar alcohol or a sugar. In some embodiments, the at least one excipient is selected from a sugar alcohol. In some embodiments, the at least one excipient is selected from a sugar. In some embodiments, the at least one excipient is selected from a combination of at least one sugar alcohol and at least one sugar.

[0151] The total amount of excipients (preferably sugar alcohols) may be at least about 30% by weight of the oral formulation, such as at least about 40% by weight, for example at least about 45% by weight, hi some preferred embodiments, the total amount of excipients (preferably sugar alcohols) may be at least about 50% by weight of the oral formulation.

[0152] In some embodiments, the total amount of sugar alcohol is present in an amount of about 30% to about 99% by weight of the oral formulation, e.g., about 40% to about 99% by weight, e.g., about 45% to about 99% by weight, e.g., about 50% to about 99% by weight, e.g., about 60% to about 95% by weight, preferably about 70% to about 90% by weight. Preferably, the sugar alcohol is present in an amount of about 80% to about 95% by weight of the oral formulation.

[0153] In some preferred embodiments, the total amount of excipients (preferably sugar alcohols) is present in an amount of about 40% to about 60% by weight of the oral formulation.

[0154] Alternatively, in some preferred embodiments, the total amount of sugar alcohol is about 50% to about 90% by weight of the oral formulation, in such embodiments, the excipient may consist entirely of sugar alcohol.

[0155] The sugar alcohol may be selected from the group consisting of isomalt, erythritol, sorbitol, arabitol, ribitol, maltitol, dulcitol, iditol, mannitol, xylitol, lactitol, or mixtures thereof. In some embodiments, the sugar alcohol is selected from the group consisting of maltitol, sorbitol, erythritol, mannitol, lactitol, xylitol, isomalt, and mixtures thereof. In some embodiments, the sugar alcohol is selected from the group consisting of maltitol, isomalt, and mixtures thereof. In some embodiments, the sugar alcohol is or comprises isomalt. In some embodiments, the sugar alcohol is or comprises maltitol. In some embodiments, the sugar alcohol comprises a combination of isomalt and maltitol.

[0156] In some embodiments, the sugar substitute may be a substitute for a sugar alcohol or may be used in combination with one or more sugar alcohols. Suitable sugar substitutes include allulose, water-soluble tapioca fiber, inulin, and combinations thereof.

[0157] In some embodiments, sugars are included as a substitute for sugar alcohols or are used in combination with one or more sugar alcohols. When present, sugars may be included in the form of glucose, fructose, galactose, sucrose, or mixtures thereof. In some embodiments, the oral chew formulation includes a sugar (e.g., sucrose) in combination with at least one sugar alcohol (e.g., maltitol and / or isomalt). The sugar may be present in any suitable amount, such as from 10% to about 50% by weight of the oral formulation, e.g., from about 20% to about 40% by weight.

[0158] In some embodiments, the excipient comprises at least one sugar alcohol selected from maltitol and / or isomalt and sucrose. In some embodiments, the at least one excipient comprises maltitol and sucrose. In some embodiments, the at least one excipient comprises isomalt and sucrose.

[0159] In some embodiments, the excipient comprises a combination of maltitol and a sugar, wherein the maltitol may be present in an amount of about 20% to about 50% by weight of the oral formulation, and the sugar may be present in an amount of about 10% to about 50% by weight.

[0160] In some embodiments, the excipient comprises a combination of isomalt and a sugar, wherein the isomalt may be present in an amount of about 20% to about 50% by weight of the oral formulation, and the sugar may be present in an amount of about 10% to about 50% by weight.

[0161] In some embodiments, the binder is selected from the group consisting of pectin, agar, carrageenan, starch, and mixtures thereof. In some preferred embodiments, the binder is or includes pectin. In some embodiments, the binder (e.g., pectin) is present in an amount of about 0.1% to about 10% by weight of the oral formulation. Preferably, the binder (e.g., pectin) is present in an amount of about 1% to about 5% by weight of the oral formulation.

[0162] The oral formulation may also include an organic acid to cross-link the pectin, a gelling agent, or both.

[0163] In some embodiments, the oral chew formulation includes an acidifying agent. The acidifying agent may be an organic acid or an inorganic acid. The organic acid may be any suitable organic acid. Suitable organic acids are described herein above in the section entitled "Additives." For example, the organic acid may be selected from the group consisting of citric acid, malic acid, lactic acid, benzoic acid, tartaric acid, and mixtures thereof or salts thereof. The organic acid may include, for example, a combination of citric acid and a salt (e.g., sodium salt) of citric acid.

[0164] The chew-form oral formulation of the present disclosure may contain various amounts of water. For example, the moisture content of the chew formulation may be provided within a specific range to determine the final form of the formulation. The moisture content of the chew formulations described herein can be varied within the ranges described below before use by a consumer, depending on the desired properties and characteristics, to determine the final form of the formulation. For example, the chew-form formulation may have a moisture content ranging from about 1% to about 20% by weight of the oral formulation, for example, from about 1% to about 10% by weight.

[0165] Oral formulations in chew form include: (a) a combination of active ingredients described herein in an amount of about 0.1% to about 10% by weight of the oral formulation; (b) at least one excipient selected from the group consisting of a sugar alcohol, or a sugar, or a combination of at least one sugar alcohol and at least one sugar, wherein the total amount of the sugar alcohol and / or sugar is from about 40% to about 99% by weight of the oral formulation; (c) at least one binder in an amount of about 0.1% to about 10% by weight of the oral dosage form; and optionally, (d) flavorings, organic acids and / or sweeteners; may include:

[0166] Oral formulations in chew form include: (a) a combination of active ingredients described herein in an amount of about 0.1% to about 10% by weight of the oral formulation; (b) at least one excipient selected from the group consisting of a sugar alcohol, or a sugar, or a combination of at least one sugar alcohol and at least one sugar, wherein the total amount of the sugar alcohol and / or sugar is from about 40% to about 99% by weight of the oral formulation; (c) at least one binder in an amount of about 0.1% to about 10% by weight of the oral dosage form; and (d) an organic acid in an amount of about 0.1% to about 5% by weight of the oral formulation; optionally, (e) flavoring and / or sweetening agents; may include:

[0167] Oral formulations in chew form include: (a) a combination of active ingredients described herein in an amount of about 0.1% to about 10% by weight of the oral formulation; (b) at least one sugar alcohol, wherein the total amount of sugar alcohol is about 50% to about 90% by weight of the oral formulation, and the at least one sugar alcohol is selected from the group consisting of isomalt, maltitol, and mixtures thereof; (c) at least one binder in an amount of about 0.1% to about 10% by weight of the oral formulation, wherein the at least one binder is or comprises pectin; optionally, (d) flavorings, organic acids, and / or sweeteners; may include:

[0168] Oral formulations in chew form include: (a) a combination of active ingredients described herein in an amount of about 0.1% to about 10% by weight of the oral formulation; (b) at least one sugar alcohol, optionally in combination with a sugar, wherein the total amount of sugar alcohols is about 40% to about 60% by weight of the oral formulation, and the at least one sugar alcohol is or comprises maltitol; (c) at least one binder in an amount of about 0.1% to about 10% by weight of the oral formulation, wherein the at least one binder is or comprises pectin; optionally, (d) flavorings, organic acids, and / or sweeteners; may include:

[0169] In some embodiments, the combination of active ingredients in the oral chew formulation includes (i) L-theanine, (ii) ginseng, (iii) lemon balm, (iv) vitamin C, and optionally (v) L-tryptophan. The combination of active ingredients in the oral chew formulation can include (i) L-theanine, (ii) ginseng, (iii) lemon balm, (iv) vitamin C, and (v) L-tryptophan.

[0170] The oral chew formulation may have a weight of about 0.1 g to about 10 g, for example, about 0.5 g to about 5 g. Preferably, the oral chew formulation has a weight of about 1 g to about 5 g. An exemplary chew formulation may have a weight of about 4 g.

[0171] An oral chew formulation (eg, having a total weight of about 1 g to about 5 g) can contain L-theanine in an amount of about 25 mg to about 150 mg, preferably about 50 mg to about 100 mg.

[0172] An oral chew formulation (e.g., having a total weight of about 1 g to about 5 g) may contain ginseng in an amount of about 0.01 mg to about 10 mg, preferably about 0.1 mg to about 5 mg, and more preferably about 0.5 mg to about 1 mg. The amount of ginseng in the oral chew formulation may be about 5 mg or less, for example, about 1 mg or less. The amount of ginseng in the oral chew formulation may be about 0.5 mg to about 1 mg.

[0173] An oral chew formulation (e.g., having a total weight of about 1 g to about 5 g) may contain lemon balm in an amount of about 0.1 mg to about 100 mg, preferably about 1 mg to about 50 mg, and more preferably about 5 mg to about 30 mg.

[0174] When present, oral chew formulations (e.g., having a total weight of about 1 g to about 5 g) may contain vitamin C in an amount of about 10 mg to about 60 mg. In some preferred embodiments, oral chew formulations (e.g., having a total weight of about 1 g to about 5 g) may contain vitamin C in an amount of about 25 mg to about 50 mg.

[0175] When present, an oral chew formulation (eg, having a total weight of about 1 g to about 5 g) may contain L-tryptophan in an amount of about 0.1 mg to about 50 mg, such as about 1 mg to about 25 mg.

[0176] In some embodiments, the oral chew formulation (e.g., having a total weight of about 1 g to about 5 g) comprises: (i) about 25 mg to about 150 mg of L-theanine, and / or (ii) about 0.01 mg to about 10 mg of ginseng, and / or (iii) about 0.1 mg to about 100 mg of lemon balm, and / or Optionally, (iv) about 10 mg to about 60 mg of vitamin C, and / or Optionally, (v) about 0.1 mg to about 50 mg of L-tryptophan.

[0177] In some embodiments, the oral chew formulation (e.g., having a total weight of about 1 g to about 5 g) comprises: (i) about 50 mg to about 100 mg of L-theanine, and / or (ii) about 0.5 mg to about 10 mg of ginseng, and / or (iii) about 5 mg to about 30 mg of lemon balm, and / or Optionally, (iv) about 25 mg to about 100 mg of vitamin C, and / or Optionally, (v) about 1 mg to about 25 mg of L-tryptophan.

[0178] In some embodiments, the oral chew formulation (e.g., having a total weight of about 1 g to about 5 g) comprises: (i) about 50 mg to about 100 mg of L-theanine; (ii) about 0.5 mg to about 10 mg of ginseng; (iii) about 5 mg to about 30 mg of lemon balm, (iv) about 25 mg to about 100 mg of vitamin C, and (v) containing about 1 mg to about 25 mg of L-tryptophan.

[0179] In any of the above embodiments, the active ingredient combination in the oral chew formulation may optionally further comprise magnesium glycinate in an amount of about 0.1% to about 10% by weight of the oral formulation, e.g., about 0.5% to about 5% by weight, or about 0.5% to about 1% by weight. If present, the amount of magnesium glycinate in the oral chew formulation may be about 1 mg to about 50 mg, preferably about 10 mg to about 30 mg.

[0180] The oral chew formulation may contain any additional suitable additives. Suitable additives are described in more detail above, and all of the additives described herein may be included in the oral chew formulation. In some embodiments, the oral chew formulation may further contain an additive selected from the group consisting of a flavoring agent, a sweetener, an acidifying agent, a preservative, and a mixture thereof. Examples of the various additives mentioned above are described herein above.

[0181] In some embodiments, the chew may further comprise a coating, such as a coating oil. The coating may comprise, for example, an oil or wax, such as sunflower oil and / or carnauba wax. Suitable coatings are described in more detail with respect to the soft lozenge formulations, and this description applies entirely to the chews as well.

[0182] For example, the chews can be coated with an overcoat material. Equipment for applying outer coatings to compressed pelletized compositions is available from Thomas Engineering, including the CompuLab 24, CompuLab 36, Accela-Cota 48, and Accela-Cota 60.

[0183] If present, the coating may comprise a film-forming polymer such as a cellulose-based polymer, an optional plasticizer, and any flavoring, coloring, salt, sweetener, or other additive described herein. The coating composition may be aqueous in nature and may be applied using any pellet or tablet coating technique known in the art, such as pan coating. Examples of film-forming polymers include cellulose-based polymers such as methylcellulose, hydroxypropyl cellulose (HPC), hydroxypropylmethylcellulose (HPMC), hydroxyethyl cellulose, and carboxymethyl cellulose. Examples of plasticizers include aqueous solutions or emulsions of glyceryl monostearate and triethyl citrate. Additional coatings that may be used include food-grade shellac, oils such as sunflower oil, waxes such as carnauba wax, and combinations thereof.

[0184] Soft type lozenges In some embodiments, the formulations disclosed herein may be in the form of soft, dissolvable, lightly chewable lozenges for oral use. As used herein, the term "soft lozenge" refers to a dissolvable oral formulation made by solidifying a liquid or gel composition, such as a composition containing a gelling agent or binder, so that the final formulation becomes a hardened, solid gel. Alternatively, the soft lozenge formulation may be referred to as a soft lozenge. In certain embodiments, the soft lozenge formulations of the present disclosure are characterized by sufficient cohesion to withstand light chewing in the oral cavity without rapidly disintegrating. The soft lozenge formulations of the present disclosure typically do not exhibit the highly deformable chewing characteristics found in conventional chewing gums. See, for example, the smokeless tobacco soft lozenges, soft lozenge formulations, soft lozenge configurations, soft lozenge characteristics, and soft lozenge formulation or manufacturing techniques described in U.S. Patent Nos. 9,204,667 to Cantrell et al., 9,775,376 to Cantrell et al., and 10,357,054 to Marshall et al., each of which is incorporated herein by reference. Particular formulations may exhibit, for example, one or more of the following characteristics: crispy, granular, chewy, syrupy, pasty, fluffy, smooth, and / or creamy. In certain embodiments, the desired texture characteristic can be selected from the group consisting of adhesiveness, cohesiveness, density, dryness, friability, granularity, gumminess, hardness, weight, hygroscopicity, moisture release, mouthcoating, roughness, slipperiness, smoothness, viscosity, wettability, and combinations thereof.

[0185] The soft lozenge formulations of the present disclosure typically comprise a combination of active ingredients in an amount of about 0.1% to about 10% by weight of the oral formulation, a binder, and a sugar alcohol and / or sugar (e.g., as a filler component). Any active ingredient discussed herein is meant to be suitable for use as an active ingredient in a soft lozenge formulation according to the present disclosure.

[0186] In some embodiments, the active ingredients may be provided in the soft lozenge in liquid form or in dry powder or particulate form, hi some embodiments, each active ingredient in the active ingredient combination is provided in the soft lozenge in dry powder form.

[0187] The binder (or a combination of two or more binders) may be used in an amount sufficient to impart desired physical properties and physical integrity to the soft lozenge formulation. In some embodiments, the binder of the soft lozenge may include pectin or gum. A representative amount of binder (e.g., pectin or gum) may comprise at least about 5% or at least about 10% of the total weight of the soft lozenge formulation. In certain embodiments, the binder (e.g., pectin or gum) is present in an amount of at least about 30% by weight, at least about 35% by weight, at least about 40% by weight, at least about 45% by weight, or at least about 50% by weight, based on the total weight of the oral formulation. In some embodiments, the binder (e.g., pectin or gum) may be present in an amount of about 35% to about 55% by weight of the oral formulation. Preferably, the total amount of binder (e.g., pectin or gum) in the soft lozenge formulation does not exceed about 55% by weight of the oral formulation. In most cases, the amount of binder (eg, pectin or gum) in a desirable formulation will not exceed about 65% by weight of the oral formulation, and usually will not exceed about 60% by weight.

[0188] In some embodiments, the binder may include pectin. Soft lozenge formulations may include pectin as the only binder, or pectin may be included in combination with a gum.

[0189] In certain embodiments, the binder is or includes a gum. The gum may include a natural gum. In particular, a natural gum (e.g., gum arabic, etc.) may be incorporated into the soft lozenge formulation as a softener. Advantageously, the use of a natural gum as a softener provides the desired texture qualities necessary to form the soft lozenge formulation, particularly the formulations described herein. In particular, it is noted that increasing the amount of natural gum (e.g., gum arabic) and then decreasing the amount of sugar alcohol and / or sugar can advantageously increase the flexibility of the resulting soft lozenge formulation. As used herein, natural gum refers to a naturally occurring polysaccharide material useful as a softener. Representative natural gums of plant origin, which are typically water-soluble to some extent, include xanthan gum, guar gum, gum arabic, gum ghatti, gum tragacanth, gum karaya, locust bean gum, gellan gum, and combinations thereof. Preferably, gum arabic may be used as an exemplary natural gum that provides the above softening properties when incorporated into the soft lozenge formulations of the present disclosure.

[0190] As noted above, the soft lozenge formulations of the present disclosure may contain at least one sugar, or at least one sugar alcohol, or a combination of at least one sugar and at least one sugar alcohol (e.g., in the form of a filler component). Sugar alcohols are particularly advantageous as filler components in the soft lozenges of the present disclosure, because such materials contribute some sweetness without compromising the desired chewable properties of the final formulation. In some embodiments, the sugar alcohol may be selected from the group consisting of maltitol, sorbitol, erythritol, mannitol, lactitol, xylitol, and isomalt. In some embodiments, isomalt may be incorporated as the only filler component. The sugar alcohol and / or sugar are typically added to the formulations of the present disclosure in the form of an aqueous solution or suspension, such as a solution or suspension having a solids content of about 50 to about 90% by weight. Combinations of sugar alcohols and / or sugars with additional filler components may also be used. Bulking agents often serve multiple functions, such as improving certain sensory properties, such as texture and mouthfeel, and improving the cohesiveness or compressibility of the formulation. In some embodiments, the bulking agent comprises a sugar substitute, such as one or more of allulose, water-soluble tapioca fiber, and inulin. Such sugar substitutes may be substitutes for sugar alcohols or may be used in combination with one or more sugar alcohols.

[0191] Melt Type In some embodiments, the formulations can be meltable, for example, as described in U.S. Patent Application Publication No. 2012 / 0037175 to Cantrell et al., which is incorporated herein by reference in its entirety.

[0192] As used herein, "melt," "melting," and "meltable" refer to the ability of a formulation to change from a solid state to a liquid state. That is, melting occurs when a substance (e.g., a formulation disclosed herein) changes from a solid to a liquid, usually by heating.

[0193] The heating of the formulations disclosed herein is provided by the temperature inside the user's mouth. Thus, the term "meltable" refers to a formulation that can be liquefied in the user's mouth when the formulation undergoes a phase change from solid to liquid, and is intended to distinguish it from a formulation that simply disintegrates in the mouth due to the loss of cohesion of the formulation, which simply dissolves in the mouth when the water-soluble components of the formulation interact with moisture.

[0194] Generally, meltable formulations include lipids. In some embodiments, the composition includes lipids. Lipids are fatty, oily, or waxy components typically derived from animal or plant sources (e.g., plant-derived fats) and typically contain primarily triglycerides with minor amounts of free fatty acids and monoglycerides or diglycerides. In certain embodiments, the lipids are solid or semi-solid at room temperature (i.e., 25°C) and can be at least partially liquefied (i.e., "melted") upon exposure to the temperature of a user's mouth. Exemplary plant-derived fats are primarily composed of saturated or unsaturated fatty acid chains (mostly attached in triglyceride structures) having carbon chain lengths of about 10 to about 26 carbon atoms, or about 14 to about 20 carbon atoms, or about 14 to about 18 carbon atoms.

[0195] In some embodiments, the lipid comprises an oil, particularly a food-grade oil, including fractionated oils. Such oils include vegetable oils (e.g., acai oil, almond oil, amaranth oil, apricot oil, apple seed oil, argan oil, avocado oil, babassu oil, beechnut oil, ben oil, bitter melon seed oil, black seed oil, black currant seed oil, borage seed oil, Borneo taro nut oil, bottle gourd seed oil, Brazil nut oil, buffalo gourd oil, butternut squash seed oil, Cape chestnut oil, canola oil, carob oak seed oil, and the like). Dew oil, cocoa butter, oakleber oil, coconut oil, corn oil, cosun oil, coriander seed oil, cottonseed oil, date seed oil, zika oil, egus seed oil, evening primrose oil, eggplant oil, linseed oil, grape seed oil, grapefruit seed oil, hazelnut seed oil, hemp oil, kapok seed oil, kenaf seed oil, lalemantia oil, lemon oil, linseed oil, macadamia oil, mafra oil, marula oil, meadowfoam seed oil, mongongo nut Oil, Mustard Oil, Niger Seed Oil, Nutmeg Butter, Okra Seed Oil, Olive Oil, Orange Oil, Palm Oil, Papaya Seed Oil, Groundnut Oil, Pecan Oil, Perilla Seed Oil, Perilla Seed Oil, Pequi Oil, Pili Nut Oil, Pine Nut Oil, Pistachio Oil, Pomegranate Seed Oil, Poppy Seed Oil, Praxi Oil, Prune Seed Oil, Pumpkin Seed Oil, Quinoa Oil, Rapeseed Oil, Rice Bran Oil, Royle Oil, Sacha Inchi Oil, Safflower Oil, Sapote Oil, Seji oil, sesame oil, shea butter, soybean oil, sunflower oil, tarramilla oil, tea seed oil, thistle oil, tiger nut oil, tobacco seed oil, tomato seed oil, walnut oil, watermelon seed oil, wheat germ oil, and combinations thereof), animal oils (e.g., beef tallow, buffalo tallow, mutton tallow, goat tallow, lard, camel tallow, tallow, liquid margarine, fish oil, fish liver oil, whale oil, seal oil, and combinations thereof), and mineral oils.

[0196] In certain embodiments, the plant-derived fats of the present disclosure include palm oil, palm kernel oil (including fractionated palm oil), soybean oil, cottonseed oil, and mixtures thereof. In one embodiment, the lipid is a blend of palm oil and palm kernel oil. The lipid may be, for example, hydrogenated, partially hydrogenated, or non-hydrogenated. Exemplary embodiments of lipids can be purchased under the trade names CEBES®, CISAO®, or CONF AO®, available from AarhusKarlshamn USA Inc.

[0197] The melting point of the lipid is typically about 29°C or higher, e.g., about 29°C to about 49°C, or about 36°C to about 45°C, or about 38°C to about 41°C. In some embodiments, the use of lipids with melting points below about 36°C is not suitable due to the possibility of melting during storage or handling of the formulation. One test for determining the melting point of a lipid is the Mettler Dropping Point Method (ASTM D3954-15, Standard Test Method for Dropping Point of Waxes, ASTM International, West Conshohocken, PA, 2015, www.astm.org.).

[0198] When present, the amount of lipid in the composition may vary. In certain embodiments, the amount of lipid is at least about 10%, at least about 20%, or at least about 30% by dry weight of the composition. In certain embodiments, the amount of lipid is less than about 70%, less than about 60%, or less than about 50% by dry weight. Exemplary lipid weight ranges include about 10 to about 70% by dry weight, e.g., about 35 to about 50% by dry weight. In some embodiments, the amount of lipid is about 35, about 40, about 45, or about 50% by weight of the total oral formulation.

[0199] In some embodiments, the oral formulation comprises a lipid. In one embodiment, the lipid is an oil selected from the group consisting of palm oil, palm kernel oil, soybean oil, sunflower oil, cottonseed oil, coconut oil, and combinations thereof, and the oil may be hydrogenated, partially hydrogenated, or non-hydrogenated. In one embodiment, the lipid is a medium-hardness trans-hydrogenated filling fat such as Confao® 5, available from AarhusKarlshamn USA Inc., 131 Marsh Street, Port Newark, NJ 07114.

[0200] In some embodiments, the dissolvable formulation comprises lipid in an amount of about 35% to about 50% by weight of the oral formulation and sugar alcohol in an amount of about 35% to about 55% by weight of the oral formulation. In some embodiments, the sugar alcohol is isomalt, erythritol, sorbitol, arabitol, ribitol, maltitol, dulcitol, iditol, mannitol, xylitol, lactitol, or a combination thereof. In some embodiments, the sugar alcohol is or includes isomalt. In some embodiments, a sugar substitute may be a sugar alcohol substitute or may be used in combination with one or more sugar alcohols. Suitable sugar substitutes include allulose, water-soluble tapioca fiber, inulin, and combinations thereof.

[0201] tablet In certain embodiments, the formulation is in the form of a compressed or molded tablet. Exemplary tablet dosage forms have a weight of about 250 mg to about 1500 mg, e.g., about 250 mg to about 700 mg, or about 700 mg to about 1500 mg. Tablets can have any of a variety of shapes, including conventional tablet shapes.

[0202] Generally, tablet formulations comprise a glucose-polysaccharide blend and a sugar alcohol. In some embodiments, the glucose-polysaccharide blend is present in an amount of about 35 to about 50% by weight, based on the total weight of the formulation, and the sugar alcohol is present in an amount of about 30 to about 45% by weight, based on the total weight of the formulation. In some embodiments, the sugar alcohol is isomalt, erythritol, sorbitol, arabitol, ribitol, maltitol, dulcitol, iditol, mannitol, xylitol, lactitol, or a combination thereof. In some embodiments, the sugar alcohol is or comprises isomalt.

[0203] When in tablet form, the formulation may be dissolvable. As used herein, the terms "dissolve," "dissolving," and "dissolvable" refer to a formulation having water-soluble components that interact with the moisture in the oral cavity and dissolve into solution, allowing the formulation to be gradually ingested. In one aspect, a dissolvable formulation can remain in the user's oral cavity for a given period of time until completely dissolved. The dissolution rate can vary over a wide range, from about 1 minute or less to about 60 minutes. For example, immediate-release formulations typically dissolve and / or release the desired components (e.g., active ingredient, flavor, etc.) in about 2 minutes or less, often about 1 minute or less (e.g., about 50 seconds or less, about 40 seconds or less, about 30 seconds or less, or about 20 seconds or less). Dissolution can occur by melting, mechanical disruption (e.g., chewing), enzymatic or other chemical degradation, or by disruption of interactions between the components of the formulation. In other embodiments, the formulation does not dissolve while the formulation remains in the user's oral cavity.

[0204] Lozenges In some embodiments, the formulations disclosed herein may be in the form of dissolvable lozenges adapted for oral use. Exemplary lozenge-shaped formulations of the present invention have the form of lozenges, tablets, microtablets, or other tablet-like formulations. See, for example, U.S. Patent No. 4,967,773 to Shaw, U.S. Patent No. 5,110,605 to Acharya, U.S. Patent No. 5,733,574 to Dam, U.S. Patent No. 6,280,761 to Santus, U.S. Patent No. 6,676,959 to Andersson et al., U.S. Patent No. 6,248,760 and U.S. Patent No. 7,374,779 to Wilhelmsen, and U.S. Patent Application Publication No. 2001 / 0016593 to Wilhelmsen, all of which are incorporated herein by reference. and U.S. Patent Application Publication No. 2010 / 0004294 to Axelsson et al., ...

[0205] Troche formulations are generally described as "hard" and are distinguished from soft troches (i.e., soft-type troches) as follows: Hard troches are mixtures of sugars and / or carbohydrates in an amorphous state. Hard troches are made from an aqueous sugar solution; however, the water initially present evaporates as the sugar solution boils during processing, so the moisture content of the final formulation is very low, e.g., 0.5% to 1.5% by weight. To obtain a hard, non-sticky troche, the temperature of the melt must generally reach a hard crack stage, an exemplary temperature range of 149° to 154°C.

[0206] In some embodiments, the lozenge formulation may exhibit translucency or transparency. The desired transparency or translucency of a formulation can be quantified by any known technique. For example, optical measurements such as turbidity (or scattered light measurement) and colorimetry can be used to quantify the turbidity (light scattering) and color (light absorption) of the formulation, respectively. Translucency can also be confirmed by visual inspection by simply holding the formulation level with a light source and determining whether light diffusely passes through the material or formulation.

[0207] The lozenge formulations of the present disclosure can incorporate a variety of different additives in addition to the combination of active ingredients and can be prepared by a variety of different methods for preparing lozenges that are generally known in the art. Exemplary compositions, formulations, and methods for preparing such formulations are detailed herein below.

[0208] The lozenge formulations of the present disclosure typically comprise a composition comprising a combination of an active ingredient in an amount of less than about 2% by weight, a sugar substitute in an amount of at least about 80% by weight, and a sugar alcohol solution. Any active ingredient discussed herein is suitable for use as an active ingredient in the lozenge formulations provided herein. In some embodiments, the active ingredient may be provided in liquid form or in dry powder or particulate form. As described above, the active ingredient is typically present in an amount of about 0.1% by weight to about 10% by weight, for example, about 0.1% by weight to about 10% by weight, such as about 0.1% by weight, about 0.5% by weight, about 1% by weight, about 1.5% by weight, about 2% by weight, about 2.5% by weight, about 3% by weight, about 3.5% by weight, about 4% by weight, about 4.5% by weight to about 5.5% by weight, about 6% by weight, about 6.5% by weight, about 7% by weight, about 7.5% by weight, about 8% by weight, about 8.5% by weight, about 9% by weight, about 9.5% by weight, about 10% by weight, etc. In some embodiments, the active ingredient may be present in an amount of less than about 10% by weight, less than about 9% by weight, less than about 8% by weight, less than about 7% by weight, less than about 6% by weight, less than about 5% by weight, less than about 4% by weight, less than about 3% by weight, less than about 2% by weight, or less than about 1% by weight, based on the total weight of the formulation.

[0209] In some embodiments, the lozenge formulation comprises a sugar substitute. The sugar substitute is typically provided in a pure solid form (e.g., granular or powdered form). In certain embodiments, the sugar substitute is dry and has a very low moisture content. For example, the sugar substitute may contain less than about 5% water by weight, less than about 3% water by weight, less than about 2% water by weight, or less than about 1% water by weight. In certain embodiments, the sugar substitute is capable of forming a glassy matrix. The formation of a glassy matrix is ​​generally characterized by a translucent / transparent appearance.

[0210] Typically, sugar substitutes are substantially non-hygroscopic. Non-hygroscopic materials typically do not absorb, adsorb, and / or retain substantial amounts of moisture from the air. Non-hygroscopic materials can provide the advantage of reducing the tendency of the lozenge formulation to stick when exposed to moisture. Sugar substitutes can be any sugar-free material (i.e., sucrose-free material) and can be natural or synthetically produced. Sugar substitutes used in the formulations described herein can be nutritive or non-nutritive. For example, sugar substitutes are generally sugar alcohols. Sugar alcohols that may be useful according to the present invention include, but are not limited to, erythritol, threitol, arabitol, xylitol, ribotol, mannitol, sorbitol, dulcitol, iditol, isomalt, maltitol, lactitol, polyglycitol, and mixtures thereof. For example, in certain embodiments, the sugar alcohol is selected from the group consisting of erythritol, sorbitol, and isomalt. The amount of sugar substitute in a lozenge formulation can vary, but is typically at least about 75%, at least about 80%, at least about 85%, or at least about 90%, or at least about 95% by weight of the formulation.

[0211] In certain embodiments, the sugar substitute comprises one or more sugar alcohols, for example, in one embodiment the sugar substitute is isomalt.

[0212] In some embodiments, the sugar substitute is one or more of allulose, water-soluble tapioca fiber, and inulin. Such sugar substitutes may be substitutes for sugar alcohols or may be used in combination with one or more sugar alcohols.

[0213] In some embodiments, the lozenge formulations of the present disclosure may contain a sugar solution, such as a sugar syrup or a sugar alcohol solution. As used herein, "sugar alcohol solution" is intended to refer to a highly concentrated aqueous solution of a sugar alcohol, e.g., having a solids content of greater than about 40%, preferably greater than about 50%, greater than about 60%, greater than about 70%, or greater than about 80%. Typically, the solids of a sugar alcohol solution are predominantly composed of a particular sugar alcohol (i.e., a maltitol solution typically contains greater than about 80%, greater than about 85%, or greater than about 90% by weight of maltitol on a dry basis). Sugar alcohol solutions are generally prepared by heating an aqueous solution of a sugar alcohol and cooling the mixture to obtain a viscous composition. The resulting sugar solution is typically characterized by a relatively high concentration of sugar alcohol and a relatively high stability (i.e., the sugar alcohol typically does not crystallize from solution, e.g., at room temperature).

[0214] Sugar solutions, such as sugar alcohol solutions, can desirably affect the recrystallization of melted sugar substitutes. One example of a particularly useful sugar alcohol solution according to the present disclosure is maltitol solution. Other sugar alcohol solutions can be used, including, but not limited to, corn solution, golden syrup, molasses, xylitol solution, mannitol solution, glycerol solution, erythritol solution, threitol solution, arabitol solution, ribitol solution, mannitol solution, sorbitol solution, dulcitol solution, iditol solution, isomalt solution, lactitol solution, and polyglycitol solution. Such sugar alcohol solutions can be prepared or obtained commercially. For example, maltitol solution is commercially available from suppliers such as Corn Products Specialty Ingredients. While sugar alcohol solutions may be preferred, in certain embodiments, sugar syrups can be used in place of or in combination with the sugar alcohol solution. For example, in some embodiments, corn syrup, golden syrup, and / or molasses can be used.

[0215] The amount of sugar alcohol solution added to the lozenge formulation mixture is typically an amount necessary to slow the recrystallization of the molten sugar substitute. It should be noted that the amount of sugar alcohol solution can be varied depending on the composition of the remaining ingredients to ensure that recrystallization is sufficiently slow to yield a material with the desired properties (e.g., a desired level of translucency / transparency). Thus, the amount of sugar alcohol solution can vary, but typically ranges from about 0.1% to about 2% by weight of the lozenge formulation mixture, often from about 0.5% to about 1.5% by weight, and more often about 1% by weight. In certain embodiments, the amount of sugar alcohol solution is higher, e.g., up to about 2% by weight of the mixture, up to about 5% by weight of the mixture, up to about 10% by weight of the mixture, or up to about 20% by weight of the mixture.

[0216] Representative lozenge compositions and formulations may incorporate up to about 10% by weight of a combination of active ingredients, about 0.01 to about 2% by weight of an artificial sweetener, about 1% to about 5% by weight of a humectant, about 1% to about 5% by weight of a natural sweetener, at least about 80% by weight of a sugar substitute, about 0.1% to about 10% by weight of a sugar alcohol solution, one or more flavorings in an amount up to about 5% by weight, and salt in an amount up to about 3% by weight, based on the total weight of the formulation. The specific proportions and selection of ingredients will vary depending on the flavor, texture, and other characteristics desired.

[0217] The oral formulations in the form of lozenges of the present disclosure may contain various amounts of water. The water content of the lozenges described herein can vary within the ranges described below depending on the desired properties and characteristics, and can determine the final form of the formulation before use by a consumer. For example, lozenge-shaped formulations typically have a water content in the range of about 0.1 to about 5% by weight of the formulation. Preferably, the water content of the lozenge formulation present in one unit of formulation before insertion into the user's oral cavity is less than about 5%, less than about 3%, less than about 2%, or less than about 1% by weight of the formulation. In some embodiments, the water content of the lozenge formulations described herein can be within the range of about 0.1% to about 5%, about 0.5 to about 3%, or about 1 to about 2% by weight of the formulation.

[0218] Powder or pouch-packaged preparations In some embodiments, the oral formulation may be in the form of a powder. The powder may be a free-flowing powder. The powder may be contained in a loose form in a container and thus may be used in a form similar to snuff, when the user takes a pinch of powder from the container and retains it in the oral cavity. Alternatively or additionally, the powder may be incorporated into a moisture-permeable (e.g., saliva-permeable) pouch similar to snus-type products. The pouch-packaged formulation may be configured to be inserted into the oral cavity of the user, i.e., may be a pouch-packaged oral formulation.

[0219] In some embodiments, the formulations of the present disclosure are in the form of pouch-packaged oral formulations. Such pouch-packaged formulations include an oral formulation described herein placed in a moisture-permeable container (e.g., a water-permeable pouch or a saliva-permeable pouch). For example, the pouch-packaged formulation may include an oral formulation in powder form incorporated into a saliva-permeable pouch.

[0220] Such compositions in the form of breathable pouches are typically used by retaining one pouch containing the composition in the oral cavity of a human subject / user. Generally, the pouch is retained somewhere in the user's oral cavity, for example, under the lips, in a manner similar to the normal use of moist snuff products. The pouch is preferably not chewed or swallowed. Upon exposure to saliva, some of the components of the composition therein (e.g., active ingredient and / or any flavoring) pass through, for example, the breathable pouch, providing flavor and a satisfying sensation to the user, without the user having to expectorate any portion of the composition. After about 10 to about 60 minutes of use / enjoyment, typically about 15 to about 45 minutes, once a significant amount of the composition has been ingested by the human subject, the pouch can be removed from the human subject's mouth for disposal.

[0221] In some embodiments, the pouch is saliva-permeable. This means that the pouch is made of a saliva-permeable pouch material. Pouch materials used in oral pouch-packaged formulations are typically dry-bonded nonwovens containing viscose rayon fibers (i.e., regenerated cellulose) and an acrylic polymer, which acts as a binder in the nonwoven material and allows the pouch to be heat-sealed during manufacturing. The pouch material may also contain synthetic fibers (e.g., polyester) in addition to viscose fibers. The viscose nonwoven material typically used in smokeless tobacco pouches is similar to the fibrous material used in tea bags. Nonwovens are fibrous materials that are neither woven nor knitted. Methods for manufacturing nonwoven materials are generally known in the art. For more information on nonwovens, see "Handbook of Nonwovens" by S. Russell, published by Woodhead Pub I. Ltd. in 2007. In some embodiments, the pouch material is a fleece material. In some embodiments, the pouch material is a nonwoven material. In some embodiments, the pouch material is a nonwoven fleece material. In some embodiments, the pouch material comprises viscose, e.g., viscose rayon fibers. In some embodiments, the pouch material comprises regenerated cellulose fibers. In some embodiments, the pouch material comprises polyester fibers, which may comprise the pouch material or may be included in combination with viscose (e.g., regenerated cellulose fibers).

[0222] In some embodiments, the pouch material includes a binder that allows the pouch to be heat sealed during manufacturing. In some embodiments, the pouch material includes an acrylic binder. In some embodiments, the pouch material includes an acrylic binder in combination with viscose and / or polyester fibers.

[0223] Suitable sachets, pouches, or containers of the type used to manufacture smokeless tobacco products are available under the trade names CatchDry, Ettan, General, Granit, Goteborgs Rape, Grovsnus White, Metropol Kaktus, Mocca Anis, Mocca Mint, Mocca Wintergreen, Kicks, Probe, Prince, Skruf, and TreAnkrare. The composition can be contained and packaged in a pouch in a manner similar to that used to manufacture conventional snus-type products, using various ingredients used in the manufacture of conventional snus-type products. The pouch functions as a moisture-permeable container, the type of which may be considered similar in characteristics to the mesh material used to manufacture tea bags. The ingredients of the composition readily diffuse through the pouch into the user's mouth. Non-limiting examples of suitable types of pouches are described, for example, in U.S. Pat. No. 5,167,244 to Kjerstad, U.S. Pat. No. 8,931,493 to Sebastian, U.S. Patent Application Publication No. 2016 / 0000140 to Sebastian et al., U.S. Patent Application Publication No. 2016 / 0073689 to Sebastian et al., U.S. Patent Application Publication No. 2016 / 0157515 to Chapman et al., and U.S. Patent Application Publication No. 2016 / 0192703 to Sebastian et al., each of which is incorporated herein by reference. The pouches can be provided as individual pouches or multiple pouches (e.g., 2, 4, 5, 10, 12, 15, 20, 25, or 30 pouches) can be connected or joined together (e.g., end to end) so that a single pouch or individual portion can be easily removed for use from an integral band or matrix of pouches.

[0224] Exemplary pouches can be manufactured from materials that allow controlled dispersion or dissolution of the pouch during use by the user. Such pouch materials can be in the form of mesh, screen, perforated paper, permeable fabric, etc. For example, a pouch material made from mesh-like rice paper or perforated rice paper can dissolve in the user's mouth. As a result, the pouch and composition can each completely disperse in the user's mouth under normal use conditions, and thus both the pouch and the composition can be ingested by the user. Other examples of pouch materials can be manufactured using water-dispersible film-forming materials (e.g., binders such as alginate, carboxymethylcellulose, xanthan gum, pullulan, etc.) and combinations of water-dispersible film-forming materials with comminuted cellulose (e.g., finely divided wood pulp). While preferred pouch materials are water-dispersible or soluble, they may also be designed and manufactured so that a significant amount of the composition contents can permeate the pouch material under normal use conditions before the pouch loses its physical integrity. If desired, flavoring ingredients, disintegration aids, and other desired ingredients may be incorporated into or applied to the pouch material.

[0225] The amount of oral formulation contained in each pouch-packaged formulation unit, e.g., one pouch, can vary. In some embodiments, the weight of the composition in each pouch is at least about 50 mg, e.g., about 50 mg to about 1 gram (1000 mg), e.g., about 100 mg to about 900 mg, e.g., about 200 mg to about 800 mg, e.g., about 500 mg to about 700 mg. In some smaller embodiments, the weight of the composition in each pouch can be about 100 mg to about 300 mg. In larger embodiments, the weight of the composition in each pouch can be about 300 mg to about 700 mg. If desired, other ingredients can be included in each pouch.

[0226] The moisture content of an oral formulation may vary depending on the form in which the composition is provided. In some embodiments described hereinabove, the oral formulation may be in the form of moist snuff or snus, and may be provided in pouch form. In some embodiments (e.g., in the case of snus-like formulations), the moisture content of the composition (before inserting the formulation into the user's oral cavity) may be at least about 20% by weight of the oral formulation, such as at least 30% by weight, for example at least 40% by weight, for example at least 50% by weight. In some embodiments (e.g., in the case of snus-like formulations, e.g., non-pouch or pouch-packaged snus-like formulations), the moisture content of the composition (before inserting the formulation into the user's oral cavity) may be about 20% by weight to about 70% by weight of the oral formulation, such as about 30% by weight to about 60% by weight, for example about 40% by weight to about 55% by weight.

[0227] In some embodiments, the oral formulation may be a "dry" snus- or snuff-like formulation. In such embodiments, the moisture content of the oral formulation may be about 10% or less, e.g., about 5% or less, by weight of the oral formulation. For example, the moisture content may be about 0.1% to about 10% by weight of the oral formulation, e.g., about 1% to about 5% by weight.

[0228] When in the form of a pouch-packaged oral formulation, the oral formulation typically contains a filler. The filler may be a cellulosic material, preferably selected from the suitable materials described above. In some preferred embodiments, the filler is or includes at least MCC. The amount of filler can vary, but is typically at least about 5% to about 95% by weight of the oral formulation, based on the total weight of the oral formulation. In some embodiments, the filler (e.g., a cellulosic material such as MCC) may be present in the oral formulation in an amount of about 5% to about 95% by weight, e.g., about 10% to about 90% by weight, e.g., about 15% to about 85% by weight, e.g., about 20% to about 80% by weight, e.g., about 25% to about 75% by weight, e.g., about 30% to about 70% by weight, e.g., about 35% to about 65% by weight, e.g., about 40% to about 60% by weight. In some embodiments, the filler (eg, a cellulosic material such as MCC) may be present in an amount of about 45% to about 55% by weight of the oral dosage form.

[0229] packaging According to some embodiments described herein, a package containing the oral formulation described herein is provided. For example, the package may contain the oral formulation in powder form. In such embodiments, the package may be in the form of a tinplate or plastic container. Alternatively or additionally, the package may contain the oral formulation in the form of a chew, lozenge, soft lozenge, tablet, etc. The package may be in the form of a blister pack, tinplate, or plastic container containing such oral dosage forms.

[0230] According to some embodiments described herein, there is provided a package containing at least one pouch-packaged oral formulation described herein. The pouch-packaged formulation described herein can be packaged in any suitable inner wrapper and / or outer container. See, for example, U.S. Pat. No. 7,014,039 to Henson et al., U.S. Pat. No. 7,537,110 to Kutsch et al., U.S. Pat. No. 7,584,843 to Kutsch et al., U.S. Pat. No. 8,397,945 to Gelardi et al., U.S. Design Patent No. D592,956 to Thiellier, U.S. Design Patent No. D594,154 to Patel et al., U.S. Design Patent No. D625,178 to Bailey et al., U.S. Patent Application Publication No. 2008 / 0173317 to Robinson et al., U.S. Patent Application Publication No. 2009 / 0014343 to Clark et al., U.S. Patent Application Publication No. 2009 / 0014343 to Bjorkholm, all of which are incorporated herein by reference. See also various smokeless product containers described in U.S. Patent Application Publication Nos. 4450 to Bellamah et al., 2009 / 0250360 to Bellamah et al., 2009 / 0266837 to Gelardi et al., 2009 / 0223989 to Gelardi, 2009 / 0230003 to Thiellier, 2010 / 0084424 to Gelardi, 2010 / 0133140 to Bailey et al., 2010 / 0264157 to Bailey et al., and 2011 / 0168712 to Bailey et al. For example, the package may be a tinplate or plastic container containing a plurality of pouch-packaged oral dosage forms.

[0231] In some preferred embodiments, where the oral formulation is in liquid form, a package in the form of a bottle or can containing the liquid oral dosage form is provided. The package may be a bottle containing a desired volume of the liquid oral dosage form.

[0232] method The manner in which the various components of the composition (e.g., active ingredient and optional additives) are combined can vary. Thus, for example, the overall formulation, including powdered composition components, can be relatively uniform (e.g., homogeneous) in nature. The above components, which can be in liquid or dry solid form, can be added by mixing in a pre-processing step before mixing with any remaining components of the formulation, or can simply be mixed with all other liquid or dry ingredients.

[0233] The various components of the formulation can be contacted, combined, or mixed using any mixing technique or device known in the art. Any mixing method that allows for intimate contact of the formulation components can be used, such as a mixing device featuring an impeller or other agitating structure. Examples of mixing devices include casing drums, adjusting cylinders or drums, liquid spray devices, conical blenders, ribbon blenders, mixers such as FKM130, FKM600, FKM1200, FKM2000, and FKM3000 available from Littleford Day, Inc., plowshare-type mixing cylinders, Hobart mixers, and the like. See also, for example, the various techniques described in U.S. Pat. No. 4,148,325 to Solomon et al., U.S. Pat. No. 6,510,855 to Korte et al., and U.S. Pat. No. 6,834,654 to Williams, each of which is incorporated herein by reference. In some embodiments, the components forming the formulation are prepared so that the mixture can be used in the starch forming method to form the formulation.The manner and method of formulating the product will be clear to those skilled in the art.See, for example, the various methods described in U.S. Patent No. 4,148,325 by Solomon et al., U.S. Patent No. 6,510,855 by Korte et al., U.S. Patent No. 6,834,654 by Williams, U.S. Patent No. 4,725,440 by Ridgway et al., and U.S. Patent No. 6,077,524 by Bolder et al., each of which is incorporated herein by reference.

[0234] Method for preparing chew formulations As described herein, the formulation is in chewable form. In such embodiments, the method comprises: (a) contacting at least one binder with at least one excipient selected from the group consisting of a sugar alcohol, or a sugar, or a combination of at least one sugar alcohol and at least one sugar, and optionally adding water; (b) heating a mixture of binder, sugar alcohol and / or sugar, and optionally water; (c) adding the combination of active ingredients; (d) solidifying the resulting mixture to obtain an oral chew formulation. may include:

[0235] The combination of active ingredients may be as described herein above. The combination of active ingredients may also be as described below in connection with "Further Broad Aspects."

[0236] Step (b) of heating the mixture may include heating the mixture to a temperature of about 70° C. to about 150° C., such as about 80° C. to about 125° C., such as about 90° C. to about 100° C. Step (b) may include heating the mixture to boiling, optionally while stirring the mixture.

[0237] Step (d) preferably includes a cooling step. In some embodiments, the mixture resulting from step (c) is cooled to solidify and provide an oral chew formulation. For example, after adding the active ingredient in step (c), the resulting mixture may be filled into a mold and the heat removed. The mixture may be passively cooled to room temperature. Alternatively, the mixture may be placed in a cold water bath, refrigerator, or freezer to reduce the temperature. Preferably, cooling is performed at room temperature to solidify the formulation.

[0238] The active ingredient combination may be added during heating step (b). In some embodiments, the active ingredient combination is added while the mixture of binder, sugar alcohol and / or sugar, and optionally water is boiling. Alternatively, the active ingredient combination may be added after the mixture of binder, sugar alcohol and / or sugar, and optionally water has cooled.

[0239] Optional additives may be added at any stage during the above process. In some embodiments, an acidifying agent is added after heating of the mixture is terminated, i.e., during step (c) or (d). In some embodiments, flavoring and / or coloring agents are added after heating of the mixture is terminated, i.e., during step (c) or (d). In some embodiments, a sweetener is added during step (a). Thus, a sweetener may be included in the mixture heated in step (b).

[0240] To prepare chewable formulations, a binder (e.g., pectin, agar, carrageenan, starch, or a combination thereof) is generally preblended with all or part of the sugar alcohol / sugar, sweetener, or combination thereof. Water is added and the mixture is heated to a boil with stirring. The remaining sugar alcohol or sweetener is added to the boiling mixture along with the active ingredient, followed by the optional buffer. The mixture is heated until it reaches about 50 to about 80 Brix. Heating is stopped, and optional acidifiers and / or flavoring agents are added along with optional coloring agents, and the mixture is thoroughly mixed. The composition is filled into molds for storage at ambient temperature.

[0241] In some embodiments, the composition is filled into starch molds. A starch tray with a molded shape is prepared and preheated to 60°C for at least 1-2 hours. The starch can be any starch as disclosed hereinabove. In some embodiments, the starch is corn starch. In some starch-molded embodiments, the pectin binder is pre-blended with a portion of the sugar alcohol (e.g., isomalt or maltitol). Water is added, and the mixture is heated to a boil while stirring. Additional sugar alcohol (e.g., maltitol syrup and / or isomalt) is added to the boiling mixture along with the active ingredient. The mixture is heated to about 78 Brix. Heating is stopped, and optional sweeteners (e.g., sucralose or acesulfame K) and flavoring agents are added along with optional colorants and acidifiers (e.g., citric acid solution), and the mixture is thoroughly mixed. The hot mixture is filled into starch molds for storage at ambient temperature. The resulting chew is removed from the starch mold, and excess starch is removed.

[0242] In other starch molded embodiments, gum powder (e.g., pectin, agar, carrageenan, starch, or a combination thereof) is mixed with water until no lumps remain. Sugar alcohols and / or sugars (e.g., isomalt and / or maltitol syrup) and optional sweeteners (e.g., sucralose) are mixed together and the mixture is heated to 82-104°C. The gum powder solution is added to the sugar alcohol / sugar and mixed thoroughly. Active ingredients, optional colors and flavors are added to the solution and mixed thoroughly. The mixture is heated at 93-104°C until the Brix reaches 50-80. An aqueous solution of an acidifying agent (e.g., citric acid and / or trisodium citrate dihydrate) is prepared and added to the hot mixture. An optional gelling agent (e.g., dicalcium phosphate solution) is then added to the mixture, if desired. The hot mixture is filled into the prepared starch molds and placed in a 60°C oven overnight, or until properly set. The resulting chew is removed from the starch mold and excess starch is removed. In some embodiments, the chew is coated with, for example, a coating oil or CAPOL 410 (available from Centerchem, Inc.). The coating process can be carried out in the same manner as described in detail below for the soft lozenge formulation.

[0243] In other embodiments, the composition is filled into starch-free molds. In such embodiments, gum powder (e.g., pectin, agar, carrageenan, starch, or a combination thereof) is mixed with water until no lumps remain. Maltitol syrup, sucralose, and optionally isomalt are mixed together, and the mixture is heated to 82-104°C. The gum powder solution is added to the maltitol solution and mixed thoroughly. The active ingredient(s), optional colorants and flavoring agents are added, and the mixture is thoroughly mixed. The mixture is heated at 93-104°C until the Brix reaches 50-80. An aqueous solution of citric acid and, optionally, trisodium citrate dihydrate is prepared and added to the hot mixture to achieve a pH of 2.5-4. An optional gelling agent (e.g., dicalcium phosphate solution) is then added to the mixture, if desired. The hot mixture is filled into non-starch molds and allowed to stand at room temperature until properly set.

[0244] The chew formulation may be held in the mold (starch or non-starch) for a period of time, such as from about 10 minutes to about 24 hours, or even 48 hours, to allow the chew formulation to harden and set.

[0245] According to another aspect of the present disclosure, rather than using a mold to prepare the chew formulation, an extrusion process can be used in which the final chew formulation is extruded as described below with respect to the soft lozenge extrusion method.

[0246] Method for preparing soft lozenge formulation The methods and techniques used to formulate and manufacture the soft lozenge formulations described herein can vary. For example, the composition for forming the soft lozenge formulation can be prepared so that the mixture can be used in a starch molding method to form the soft lozenge formulation. Exemplary soft lozenge manufacturing processes are described in U.S. Pat. No. 4,725,440 to Ridgway et al. and U.S. Pat. No. 6,077,524 to Bolder et al., each of which is incorporated herein by reference. In some embodiments, the composition for forming the soft lozenge formulation can be prepared so that the mixture can be used in a non-starch molding method (e.g., a molding method that does not include starch-based components) to form the soft lozenge formulation.

[0247] In some embodiments, the method includes heating the gum, optionally hydrating the gum ingredients with water, and then stirring the active ingredient combination into the heated gum ingredients. Generally, the gum may be heated to a temperature ranging from about 60°C to about 80°C for a period of a few seconds to a few minutes. In some embodiments, the gum may be heated to a temperature of about 71°C before stirring with the active ingredient combination to dissolve the active ingredients therein. In some examples, the aqueous mixture is formed in a separate container by mixing one or more additives (e.g., salt, sweeteners, humectants, emulsifiers, flavors, etc.) with water to form the aqueous mixture.

[0248] The aqueous mixture can then be mixed with the heated gum (including at least one active ingredient added thereto) to form a mixture in the form of a slurry. In some embodiments, at least one sugar alcohol / sugar component can be added separately to this mixture, or in other embodiments, the at least one sugar alcohol / sugar can be mixed with the gum and active ingredient before being added to the mixture. In some examples, the at least one sugar alcohol / sugar can be heated in a separate container and added separately to the mixture. For example, in some embodiments, the at least one sugar alcohol / sugar (which may optionally include isomalt / maltitol / erythritol) can be heated to a temperature in the range of about 160°C to about 190°C before being added to the mixture. In some embodiments, the at least one sugar alcohol / sugar can be heated to a temperature of at least about 160°C, at least about 170°C, at least about 180°C, or at least about 190°C. In some examples, the heated sugar alcohol / sugar can be allowed to cool to a temperature in the range of about 120°C to about 160°C before being added to the mixture. In some embodiments, for example, the heated sugar alcohol / sugar may be cooled to a temperature of about 160°C or less, about 150°C or less, about 140°C or less, or about 130°C or less before being added to the mixture.

[0249] In some examples, the soft lozenge composition, which may be in the form of a slurry, may be obtained by mixing the heated (and optionally cooled) sugar alcohol / sugar with a mixture (e.g., including the heated gum, at least one active ingredient, and an aqueous mixture) and stirring using a high-shear mixer or a Hobart mixing bowl equipped with a whipping attachment. The soft lozenge composition may then be heated to an elevated temperature, e.g., from about 40°C to about 80°C, typically about 71°C, for about 1 minute to about 3 minutes, for example, to dissolve the dry ingredients within the soft lozenge composition. The heating step may be characterized as heating at a temperature of at least about 50°C, at least about 60°C, or at least about 70°C. The soft lozenge composition may typically have a moisture content of at least about 40% by weight, based on the total weight of the composition.

[0250] According to some embodiments, a soft lozenge composition in a slurry form may optionally undergo a degassing step or degassing process to reduce or remove air bubbles present in the slurry mixture before being poured into a mold or subjected to other processing steps. Air bubbles trapped in the slurry may affect the final weight of the soft lozenge formulation and may compromise the unit-to-unit weight uniformity of the final formulation. Therefore, any degassing method and system may be used to remove such air bubbles from the slurry material. For example, the slurry may be placed under reduced pressure (i.e., atmospheric pressure) to extract the air bubbles from the slurry mixture. In some examples, a vacuum degassing process may be employed in which the slurry mixture is placed in a vacuum degassing device to degas the slurry mixture by reducing the pressure. In some examples, the slurry mixture may be placed under vacuum for about 1 to about 10 minutes, typically about 3 to about 5 minutes. The degassing step may be monitored and adjusted as necessary to control the removal of gaseous components from the slurry mixture.

[0251] The viscosity of the heated and deaerated slurry mixture may be measured, for example, using a Brookfield HA series viscometer, an SC4 water jacket, a 27 / 13R sample chamber, and a No. 27 spindle. The soft lozenge composition may have a viscosity of about 5.7 Pascal seconds (Pa·s) to about 6.2 Pa·s when heated to a temperature of about 38° C., about 4.9 Pa·s to about 5.4 Pa·s when heated to a temperature of about 43° C., and about 4.2 Pa·s to about 4.7 Pa·s when heated to a temperature of about 50° C. In some examples, additional water may be added to the soft lozenge composition to provide the desired viscosity.

[0252] Once the desired viscosity is achieved, the heated soft lozenge composition may then be filled into molds, such as, for example, starch molds. It should be noted that while the process described further herein is directed to forming soft lozenge formulations using starch molds, other types of molds may also be used in the process, such as, for example, non-starch molds, pectin molds, plastic tray molds, silicone tray molds, metal tray molds, neoprene tray molds, etc.

[0253] When using a starch mold, the starch mold may be pre-dried to remove moisture from the starch mold itself. That is, the starch mold may be exposed to high temperatures to remove moisture from the starch mold before the slurry or viscous soft lozenge composition is poured into it. For example, in some instances, the starch mold may initially have a moisture content of about 10-15% by weight. Moisture at such levels may affect the uniformity of the resulting product. In this regard, certain moisture levels in the starch mold may cause the product to wrinkle or shrink, resulting in a deflated or otherwise wrinkled appearance of the final formulation. Thus, the starch mold may be dried at high temperatures to reduce the moisture content of the starch mold to about 4-10% by weight, preferably about 6-8% by weight, based on the total weight of the starch mold. Taking such a step may, in some instances, result in a more uniform and consistent appearance of the formulation. Additionally, the starch mold may be heated to a high temperature before being injected with the soft lozenge composition so that the starch mold itself is at a high temperature when it receives the lozenge composition.

[0254] The soft lozenge composition may be held in the starch mold at an elevated temperature, such as about 40°C to about 80°C (e.g., at least about 40°C or at least about 50°C), typically about 60°C. The soft lozenge composition may be held at the elevated temperature for a predetermined period of time, such as about 12 to 48 hours, typically about 24 hours, so that the soft lozenge composition hardens and solidifies into a soft lozenge shape, and the moisture content of the composition is reduced to a desired final moisture level. As noted above, in some embodiments, the desired final moisture level of the soft lozenge formulation may be within a range of about 5 to about 25% by weight, or about 8 to about 20% by weight, or about 10 to about 15% by weight, based on the total weight of the formulation unit. In this regard, hardening generally refers to the solidification process during which moisture loss occurs, the viscosity of the composition increases, and chemical and physical changes begin to occur (e.g., crystallization, crosslinking, gelation, film formation, etc.). The soft lozenge composition is cooled and then removed from the starch mold. In some instances, the soft lozenge composition may be cooled to refrigeration temperatures or below ambient temperature. A blower or shaker device may be used to remove starch residue from the soft lozenge composition after it has been removed from the starch mold.

[0255] The soft lozenge formulation is then post-cured for a time and temperature suitable to equilibrate the desired moisture, shape, and configuration. The time and temperature can vary without departing from the scope of the invention and depend, in part, on the desired final properties of the formulation. In one embodiment, post-curing occurs at ambient temperature for at least about 20 hours after removal from the mold.

[0256] The soft lozenge formulation may be provided as an individual unit weighing about 0.5 g to about 5 g, although embodiments of the present disclosure are not limited to such weights.

[0257] The curing time and temperature of the soft lozenge formulation can be varied as desired. In this regard, such variables can affect the final visual appearance of the soft lozenge formulation. For example, a long curing time and / or a low curing temperature can affect the final outer configuration or contour of the soft lozenge formulation. That is, the rate at which the product dries and / or hardens can affect the final properties of the product. In some instances, for example, by lowering the curing temperature and extending the curing time, the soft lozenge formulation can have a relatively smooth outer surface. In contrast, curing at a high temperature for a short time can result in the formulation appearing rough or wrinkled.

[0258] According to another aspect of the present disclosure, rather than using a mold to prepare the soft lozenge formulation, an extrusion process can be used in which the final soft lozenge formulation is extruded. In some examples, a soft lozenge composition in slurry form can be formed into a sheet and dried to a moisture content of, for example, about 15% to about 25% by weight to form a sticky or other paste-like material in a physically manageable form. The paste-like material can then be chopped or otherwise cut into small pieces, for example, using a mixer. The chopped material can then be extruded in an extrusion device into any desired shape / size, including shapes that may be difficult or impossible to achieve with a mold. In some examples, the extruded product can then be dried to achieve the desired moisture content. A similar process is described, for example, in U.S. Pat. No. 3,806,617 to Smylie et al., which is incorporated herein by reference in its entirety. Additionally, the soft lozenge composition can be subjected to a coextrusion process with another composition.

[0259] For example, shapes such as rods and cubes can be formed by first extruding the material through a die having the desired cross-section (e.g., circular or square), and then optionally cutting the extruded material to the desired length. Techniques and equipment for extruding tobacco feedstock are described in U.S. Patent No. 3,098,492 to Wursburg, U.S. Patent No. 4,874,000 to Tamol et al., U.S. Patent No. 2,488,018 to Graves et al., U.S. Patent No. 4,989,620 to Keritsis et al., U.S. Patent No. 5,072,744 to Luke et al., U.S. Patent No. 5,829,453 to White et al., and U.S. Patent No. 6,182,670 to White et al., each of which is incorporated herein by reference. Exemplary extrusion equipment suitable for use includes a food or gum extruder, or an industrial pasta extruder such as the Model TP200 / 300 available from Emiliomiti, LLC, Italy. In some instances, it may be possible to accomplish multiple steps of the methods described herein in a single machine, such as, for example, a kneading apparatus available from Buss AG.

[0260] The soft lozenge formulation can be provided in any suitable predetermined shape or form, most preferably in a form having a general shape such as a pill, pellet, tablet, coin, bead, ovoid, ellipsoid, or cube. The texture of the soft lozenge formulation preferably has a slightly chewable, dissolvable quality with a gentle elasticity or "bounce" upon chewing that gradually leads to greater flexibility during use. According to one embodiment, the soft lozenge formulation can preferably remain in the user's mouth for about 10 to 15 minutes until it is completely dissolved. Preferably, the formulation does not leave any residue in the user's mouth to a substantial extent and does not impart a smooth, waxy, or slimy feeling to the user's mouth.

[0261] According to some embodiments, the soft lozenge composition may be coated with a coating material after removal from the starch mold and before drying. For example, a glazing or anti-stick coating, such as CAPOL 410 (available from Centerchem, Inc.), may be applied to the soft lozenge composition to impart flowability. The coating composition may include, for example, an oil or wax, such as sunflower oil and / or carnauba wax.

[0262] The outer coating can also help improve the storage stability of the soft lozenge formulations of the present disclosure, as well as improve the packaging process by reducing friability and dusting. Equipment for applying the outer coating layer to the formulations of the present disclosure includes pan coaters and spray coaters, including Thomas Engineering's CompuLab 24, CompuLab 36, Accela-Cota 48, and Accela-Cota 60, among others. An example of an outer coating contains a film-forming polymer, such as a cellulose-based polymer, an optional plasticizer, and any flavor, color, salt, sweetener, or other additive described herein. The coating composition is typically aqueous in nature and can be applied using any pellet or tablet coating technique known in the art, such as pan coating. Examples of film-forming polymers include cellulose-based polymers such as methylcellulose, hydroxypropyl cellulose (HPC), hydroxypropylmethylcellulose (HPMC), hydroxyethyl cellulose, and carboxymethyl cellulose. Examples of plasticizers include aqueous solutions or emulsions of glyceryl monostearate and triethyl citrate.

[0263] In one embodiment, the coating composition comprises up to about 75 wt. % of a film-forming polymer solution (e.g., about 40 to about 70 wt. % based on the total weight of the coating formulation), up to about 5 wt. % of a plasticizer (e.g., about 0.5 to about 2 wt. %), up to about 5 wt. % of a sweetener (e.g., about 0.5 to about 2 wt. %), up to about 10 wt. % of one or more colorants (e.g., about 1 to about 5 wt. %), up to about 5 wt. % of one or more flavoring agents (e.g., about 0.5 to about 3 wt. %), up to about 2 wt. % of a salt such as NaCl (e.g., about 0.1 to about 15 wt. %), and the balance water. Exemplary coating compositions and application methods are described in U.S. Patent Application Serial No. 12 / 876,785, filed September 7, 2010, by Hunt et al., each of which is incorporated herein by reference.

[0264] While the above description focuses on a uniform composition throughout each dosage unit, a product can also be formed from multiple different formulations with different properties within the same dosage unit. For example, two different compositions can be filled into a single mold to produce a layered dosage form. Furthermore, two different compositions can be co-extruded to form a dosage form with different cross-sectional properties. Such a method can be used to provide a dosage form with two different compositions characterized by different dissolution rates, such that one portion of the dosage form dissolves at a first rate (e.g., a faster rate) and the second portion dissolves at a second, slower rate.

[0265] Method for preparing tablet formulations In some embodiments, the formulation is in the form of compressed pellets or tablets. In one embodiment, the method for making pellets or tablets involves first mixing the active ingredient with a bulk filler (e.g., EMDEX®). The remaining composition ingredients (e.g., sugar alcohol and any other desired ingredients such as binders, colorants, sweeteners, flavors, etc.) are then added. Optionally, the colorant can be added to one of the composition ingredients in a separate step before mixing with the remaining composition ingredients. Mixing of the composition can be accomplished using any mixing equipment. The final composition is then compressed into pellet or tablet form using conventional tableting techniques and optionally coated. Compressed pellets of the composition can be made by compressing the composition, including any relevant formulation ingredients, into pellet form and optionally coating each pellet with an overcoat material. Exemplary compaction equipment, such as compaction molding machines, are available from Vector Corporation as Colton 2216 and Colton 2247, and from Fette Compacting as 1200i, 2200i, 3200, 2090, 3090, and 4090. Equipment for applying outer coatings to compacted pelletized compositions is available from Thomas Engineering as CompuLab 24, CompuLab 36, Accela-Cota 48, and Accela-Cota 60.

[0266] If present, the coating typically comprises a film-forming polymer such as a cellulose-based polymer, an optional plasticizer, and any flavoring, coloring, salt, sweetener, or other additive described herein. The coating composition is usually aqueous in nature and can be applied using any pellet or tablet coating technique known in the art, such as pan coating. Examples of film-forming polymers include cellulose-based polymers such as methylcellulose, hydroxypropyl cellulose (HPC), hydroxypropylmethylcellulose (HPMC), hydroxyethyl cellulose, and carboxymethyl cellulose. Examples of plasticizers include aqueous solutions or emulsions of glyceryl monostearate and triethyl citrate. Additional coatings that can be used include food-grade shellac, waxes such as carnauba wax, and combinations thereof.

[0267] Method for preparing a lozenge formulation The methods and techniques used to formulate and manufacture the lozenge formulations described herein above can vary. For example, the compositions can be prepared by any method commonly used to manufacture hard-boiled confectionery. For example, exemplary methods for manufacturing hard candy can be found in LFRA Ingredients Handbook, Sweeteners, edited by Janet M. Dalzell, Leatherhead Food RA (December 1996), pages 21-44, which is incorporated herein by reference.

[0268] Typically, a first component mixture is prepared. The composition of the first component mixture can vary, but typically includes a sugar substitute and may contain various additional substances (e.g., sugar alcohol solution, NaCl, preservatives, additional sweeteners, water, and / or flavorings). In certain embodiments, the composition of the first component mixture includes a sugar substitute, salt, and vanillin. In other embodiments, the first mixture includes a sugar substitute and a sugar alcohol solution. Typically, the first component mixture does not contain an active ingredient, although in some embodiments, an active ingredient may be incorporated into the first component mixture.

[0269] The first component mixture is heated until melted, and then the mixture is heated to or past the hard crack stage. In confectionery, the hard crack stage is defined as the temperature at which a string-like strip of the heated mixture (obtained by pulling a cooled molasses sample between the thumb and index finger) becomes brittle or at which the molasses cracks when attempted to be molded. According to the present method, the temperature at which the hard crack stage is achieved may vary depending on the specific composition of the formulation mixture, but is generally between about 145°C and about 170°C. Typically, the mixture is not heated above about 171°C, the temperature at which caramelization begins to occur. In the method of the present disclosure, the mixture is typically cooled after being heated to or above the hard crack stage temperature. Heating can be performed at atmospheric pressure or under vacuum. Typically, the method of the present invention is performed at atmospheric pressure.

[0270] In one exemplary embodiment, the first component mixture includes a high percentage of isomalt, and the mixture is heated to about 143° C. Once all of the components have dissolved, the temperature is raised beyond the hard crack stage (e.g., to about 166° C.). After the mixture is heated to this temperature, heating is terminated and the mixture is allowed to cool.

[0271] In certain embodiments, the active ingredient(s) and optionally additional ingredients (e.g., additional sweeteners, fillers, flavors, and water) are individually combined in a second mixture. The second mixture is typically added to the first component mixture after the first component mixture has finished heating. In some embodiments, the addition of the second mixture may occur only after the heated first component mixture has cooled to a predetermined temperature (e.g., to about 132°C in certain embodiments). In certain embodiments, one or more flavors are added to the second mixture just before adding the second mixture to the heated first component mixture. Certain flavors are volatile, and therefore are preferably added after the mixture has cooled to a certain extent. The combined mixture is then formed into a desired shape. In certain embodiments, the mixture is poured directly into a mold, formed (e.g., rolled or pressed) into a desired shape, or extruded. If desired, the mixture can be extruded or injection molded. In certain embodiments, the mixture is formed into a mold of the desired shape or extruded in a closed system that requires low temperatures and can limit evaporation of certain mixture components. For example, such a system can limit evaporation of volatile ingredients, including, but not limited to, flavorings. Other methods of making lozenges are also intended to be encompassed herein.

[0272] Typical conditions associated with the manufacture of food-grade lozenge formulations as described herein include control of heat and temperature (i.e., the degree of heat to which the various ingredients are exposed during manufacture and the temperature of the manufacturing environment), moisture content (e.g., the degree of moisture present in the individual ingredients and in the final composition), humidity of the manufacturing environment, atmospheric control (e.g., nitrogen atmosphere), airflow experienced by the various ingredients during the manufacturing process, and other similar factors. Additionally, the various process steps involved in manufacturing the formulation may include selection of specific solvents and processing aids, use of heat and radiation, refrigeration and cryogenic conditions, ingredient mixing speed, etc. Manufacturing conditions can also be controlled by selection of the form (e.g., solid, liquid, or gas) of the various ingredients, the particle size or crystallinity of ingredients in solid form, the concentration of ingredients in liquid form, etc. The ingredients can be processed into the desired composition by techniques such as extrusion, compression, spraying, etc.

[0273] In certain embodiments, the lozenge formulation may be transparent or translucent. As used herein, "translucent" or "translucency" refers to a material that allows some light to pass through it diffusely. In certain embodiments, the lozenge formulations of the present disclosure may have a high degree of transparency, which may result in a material classified as "transparent" or exhibiting "transparency," which is defined as a material that allows light to pass freely through it without significant diffusion. The transparency of a lozenge formulation is in contrast to opacity, which refers to a material that cannot transmit light, and which exhibits some degree of translucency.

[0274] Transparency / translucency can be measured by any technique commonly used in the art, but is typically measured by spectrophotometric light transmittance over a wavelength range (e.g., about 400-700 nm). Optical techniques, such as turbidity (or scattered light measurement) and colorimetry, can also be used to quantify the turbidity (light scattering) and color (light absorption), respectively, of the lozenge formulations provided herein. Translucency can also be confirmed by visual inspection by simply holding a material (e.g., an extract) or formulation level with a light source and determining whether light diffusely passes through the formulation.

[0275] Method for preparing melt-type formulations In some embodiments, the formulation is in a meltable form. To prepare a meltable formulation, lipids are typically heated to just above their melting temperature so that the lipids are liquefied. Optionally, active ingredients, flavorings, and / or lecithin can be added to the liquefied lipid at this stage. All or part of the liquefied lipid can then be blended into the dry blend and mixed until the product reaches the desired homogeneity or until the desired texture characteristics are achieved. The mixture is milled (e.g., in a dry roll mill) until the particle size is less than about 20 microns. The milled isomalto-palm oil mixture is combined with any remaining lipids, and the dry ingredients and flavorings are mixed. The base is generally heated until a flowable consistency is achieved.

[0276] In some embodiments, a sugar alcohol (eg, isomalt) is added to a mixer bowl, and a portion of the total lipid (eg, melted palm oil) is added along with salt and an emulsifier.

[0277] Additional lipid is added with mixing until a cohesive clump forms. The clumped mixture is divided and transferred to a three-roll mill and processed to a particle size of less than 50 microns, or about 20 microns. The adjusted mixture is transferred to a mixer bowl and the remaining lipid is added with mixing. The mixture is warmed as needed to maintain fluidity.

[0278] The sweetener, flavoring, and active ingredient are added while mixing. Mixing is continued until a homogeneous composition is obtained. The mixture is allowed to stand for a period of time, for example, about 10-15 minutes. The composition can be divided into individual portions, for example, by pouring the composition into a sheet-like structure, cooling, and cutting the structure into individual portions, or by filling the composition into a mold and allowing it to cool. The mold can be starch or non-starch. In certain embodiments, the mold is non-starch.

[0279] The molten composition may be held in a mold (starch or non-starch) for a predetermined time, for example, about 1 to about 15 minutes, to cool and solidify the molten composition. Optionally, the mold containing the melt may be cooled by refrigeration to accelerate solidification.

[0280] According to another aspect of the present disclosure, rather than using a mold to prepare the melt formulation, an extrusion process can be used in which the final melt-type formulation is extruded as described herein above with respect to the soft-type lozenge extrusion method.

[0281] Method for preparing pouch-packaged oral preparations When the formulation is in the form of a pouch-packaged oral formulation, the method comprises: (a) combining active ingredients; (b) contacting the combination of active ingredients with at least one filler to obtain an oral dosage form; may include:

[0282] The combination of active ingredients may be as described herein above. The combination of active ingredients may also be as described below in connection with "Further Broad Aspects."

[0283] When the formulation is in the form of a pouch-packaged oral formulation, the method comprises: (a) combining active ingredients, the active ingredients including (i) L-theanine, (ii) ginseng, and (iii) lemon balm; (b) contacting the combination of active ingredients with at least one filler to obtain an oral dosage form; Includes.

[0284] In some embodiments, step (b) comprises mixing the active ingredient combination with at least one filler. In some embodiments, the active ingredient combination is in solid form (e.g., powder form). The active ingredient combination may be mixed directly with the filler to obtain an oral formulation. In some embodiments, the active ingredient combination may be dissolved in a hydrophilic solvent (e.g., water and / or alcohol) before contacting with the filler. For example, the active ingredient combination may be dissolved in water or alcohol (e.g., ethanol or propylene glycol) before mixing with the filler. In such embodiments, the method may comprise a step of drying the product to remove the solvent. For example, the product can be dried by heating, freeze-drying, spray-drying, or simply by leaving the product at room temperature for a period of time. Preferably, the drying step comprises leaving the product at room temperature for 1 hour to 48 hours to remove the solvent.

[0285] The method may then further comprise the step of pouching the oral formulation using a pouch material as described herein above.

[0286] use According to some embodiments described herein, there is provided use of a combination of active ingredients to provide a relaxation effect to a human or animal, the combination of active ingredients comprising: (i) L-theanine; (ii) ginseng; and (iii) lemon balm.

[0287] In some embodiments, the active ingredient combination further comprises any of the additional active ingredients described herein above. For example, the active ingredient combination may further comprise vitamin C, chamomile extract, and / or L-tryptophan. The active ingredient combination may further comprise vitamin C, among others.

[0288] The combination of active ingredients may provide improved relaxation benefits to the consumer compared to previously known formulations. The inventors have found that the particular combination of active ingredients of the present invention may improve relaxation and calmness, reduce stress and anxiety, and improve sleep.

[0289] According to some embodiments described herein, there is provided a use of a combination of active ingredients for sedating a human or animal, the combination of active ingredients comprising: (i) L-theanine; (ii) ginseng; and (iii) lemon balm.

[0290] Further broad aspects According to some embodiments described herein, there is provided a chewable solid oral formulation comprising a combination of active ingredients, wherein the combination of active ingredients comprises lemon balm in an amount of about 1000 ppm to about 2000 ppm.

[0291] Such oral formulations may further comprise other active ingredients. The active ingredients and / or additives described hereinabove with respect to the first aspect are equally applicable to such an embodiment and will not be repeated here for the sake of brevity. All amounts and combinations described hereinabove apply equally to this embodiment.

[0292] In some embodiments, the amount of lemon balm may be from about 5000 ppm to about 10000 ppm.

[0293] Also described herein is a chewable solid oral formulation comprising a combination of active ingredients, the combination of active ingredients comprising (i) lemon balm and (ii) ginseng.

[0294] Also described herein is a chewable solid oral formulation comprising a combination of active ingredients, the combination of active ingredients comprising (i) lemon balm and (ii) L-tryptophan.

[0295] Also described herein is a chewable solid oral formulation comprising a combination of active ingredients, the combination of active ingredients comprising (i) ginseng and (ii) L-tryptophan.

[0296] Also described herein is a chewable solid oral formulation comprising a combination of active ingredients, the combination of active ingredients comprising (i) L-theanine and (ii) ginseng, wherein the L-theanine and ginseng are present in a weight ratio of about 150:1 to about 100:1.

[0297] In any of the above embodiments, the oral dosage form may further comprise additional active ingredients as described herein above with respect to the first aspect. The ranges and combinations of these additional active ingredients described herein above apply equally to these embodiments.

[0298] The methods and uses herein above are equally applicable to the broader aspects described above.

[0299] Example Aspects of the present invention will be more fully described by the following examples, which are set forth to illustrate particular aspects of the invention and are not to be construed as limitations thereof.

[0300] Example 1 - Oral Chew Formulations Prepared with Starch Formulations according to embodiments of the present disclosure in chewable form are prepared from a composition comprising a mixture of fillers, a combination of active ingredients consisting of L-theanine, ginseng, lemon balm, and vitamin C, and additional ingredients disclosed herein (sucralose as a sweetener, flavoring, water, coloring, pectin as a binder, citric acid). The filler comprises a combination of isomalt and maltitol syrup.

[0301] The pectin binder is pre-blended with a portion of the isomalt. Water is added and the mixture is heated to a boil while stirring. Maltitol syrup and any remaining isomalt are added to the boiling mixture along with the active ingredients (e.g., L-theanine, ginseng, lemon balm, and vitamin C). The mixture is heated to 78 Brix. The heating is stopped, and the sweetener (e.g., sucralose), color, and flavor are added along with the citric acid. The mixture is thoroughly mixed, and the composition is filled into starch molds for storage at ambient temperature. Each chew weighs 2600 mg.

[0302] Example 2 - Non-starch oral chew formulation Formulations according to embodiments of the present disclosure in chewable form are prepared from compositions comprising a mixture of fillers disclosed herein, active ingredients, and additional ingredients (sucralose as a sweetener, flavoring, water, coloring, pectin as a binder, citric acid). The filler comprises a combination of isomalt and maltitol syrup.

[0303] Pectin is mixed with water until no lumps remain. Maltitol syrup, isomalt, and sucralose are mixed together and the mixture is heated to 82-104°C. The pectin solution is added to the maltitol / isomalt solution and mixed thoroughly. Active ingredients, colors, and flavors are added and the mixture is mixed thoroughly. The mixture is heated at 93-104°C until the Brix is ​​50-80. An aqueous solution of citric acid is prepared and added to the hot mixture to achieve a pH of 2.5-4. The hot mixture is filled into non-starch molds and allowed to stand at room temperature until properly set.

[0304] Example 3 - Oral soft lozenge formulation An oral formulation in the form of a soft lozenge adapted for oral use is provided as follows:

[0305] An aqueous mixture is prepared by mixing water, salt, a sweetener (sucralose), a humectant (glycerin), and flavorings. The gum (gum arabic) solution is then heated to a temperature of about 71°C, and a combination of active ingredients (e.g., L-theanine, ginseng, lemon balm, and optionally vitamin C) is stirred into the heated gum ingredients.

[0306] The heated gum (including at least one active ingredient therein) is then added to an aqueous composition to form a mixture. At least one sugar alcohol (including, for example, isomalt, maltitol, and erythritol) is then heated to a temperature of about 175° C. and then cooled to a temperature of about 150° C. The cooled sugar alcohol is then added to the mixture and stirred in a Hobart mixing bowl to form a soft lozenge composition and allowed to cool.

[0307] The soft lozenge composition is heated to about 71°C and then filled into a starch mold. The soft lozenge composition is held in the starch mold at about 60°C for about 24 hours. The soft lozenge composition is cooled and then removed from the starch mold. The oral formulation is then allowed to harden at ambient room temperature for about 24 hours to provide a soft lozenge formulation adapted for oral use.

[0308] Example 4 - Oral Melt-Type Formulation Compositions according to embodiments of the present disclosure in dissolvable form are prepared from compositions containing a filler (e.g., isomalt), a lipid (e.g., palm oil), a mixture of theanine, ginseng, lemon balm, and optionally vitamin C as active ingredients, and additional ingredients (salt, sweeteners, flavorings) disclosed herein.

[0309] A portion of the palm oil is melted in a mixer and mixed with the isomalt. The mixture is transferred to a dry roll mill and milled to a particle size of less than 20 microns. The milled isomalt-palm oil is mixed with the remaining palm oil in the mixer. The base is heated until a flowable consistency is achieved. Sunflower oil, dry ingredients, and flavorings are mixed. The isomalt-palm oil component mixture is transferred to a heated injection funnel. An appropriate weight of sample is filled into a non-starch mold. If necessary, the mold is placed on a vibrator to ensure uniform filling. The product is cooled and solidified, then removed from the mold. Each melt weighs 1300 mg.

[0310] The various embodiments described herein are presented solely to aid in the understanding and teaching of the claimed features. These embodiments are provided only as a representative sample of embodiments and are not exhaustive and / or exclusive. The advantages, embodiments, examples, functions, features, structures, and / or other aspects described herein should not be construed as limitations on the scope of the invention as defined by the claims or limitations on the equivalents of the claims, and it should be understood that other embodiments may be utilized and modifications may be made without departing from the scope of the claimed invention. Various embodiments of the present invention may suitably comprise, consist of, or consist essentially of any suitable combination of the disclosed elements, components, features, parts, steps, means, etc., other than those specifically described herein. Furthermore, the present disclosure may include other inventions not currently claimed but which may be claimed in the future.

[0311] Example 5 - Chew Dosage Form An oral formulation in chew form is prepared containing the following ingredients: ·water L-theanine 40mg Vitamin C 25mg Ginseng root extract 0.7mg L-tryptophan 10mg Acidifier Sucralose Pectin Isomalt Maltitol syrup ·Coloring agent ·Fragrance

[0312] The oral formulation has a mass of 4 gm per serving.

[0313] Oral formulations are prepared as described in Example 2.

[0314] Example 6 - Chew Dosage Form An oral formulation in chew form is prepared containing the following ingredients: ·water L-theanine – 70mg Vitamin C - 40mg Ginseng root extract L-tryptophan - 20mg Lemon balm extract Acidifier Sucralose Pectin Isomalt Maltitol syrup ·Coloring agent ·Fragrance

[0315] The oral formulation has a mass of 4 gm per serving.

[0316] Oral formulations are prepared as described in Example 1.

[0317] Terms 1. A solid oral dosage form in chewable form containing a combination of active ingredients, the combination of active ingredients being: (i) L-theanine, (ii) ginseng, (iii) lemon balm; at least one binder; at least one excipient selected from the group consisting of a sugar alcohol, or a sugar, or a combination of at least one sugar alcohol and at least one sugar; 1. A chewable solid oral formulation comprising: 2. The solid oral formulation of clause 1, wherein the L-theanine is present in an amount of about 0.01% to about 5% by weight of the oral formulation. 3. The solid oral formulation of clause 1 or 2, wherein the ginseng is present in an amount of about 0.001% to about 0.25% by weight of the oral formulation. 4. The solid oral formulation of any one of clauses 1-3, wherein the lemon balm is present in an amount of about 0.01% to about 3% by weight of the oral formulation. 5. The solid oral formulation of any one of clauses 1 to 4, wherein the L-theanine and ginseng are present in a weight ratio of about 150:1 to about 100:1. 6. The solid oral formulation of any one of clauses 1 to 5, wherein the L-theanine and lemon balm are present in a weight ratio of about 1:1 to about 10:1. 7. The solid oral formulation of any one of clauses 1 to 6, wherein the ginseng and lemon balm are present in a weight ratio of about 1:10 to about 1:50. 8. The solid oral formulation of any one of clauses 1 to 7, wherein the combination of active ingredients further comprises vitamin C, optionally wherein the vitamin C is present in an amount of about 0.1% to about 5% by weight of the oral formulation. 9. The solid oral formulation of clause 8, wherein the vitamin C and L-theanine are present in a weight ratio of about 1:1 to about 1:2. 10. The oral formulation of any one of clauses 1 to 10, wherein the combination of active ingredients further comprises L-tryptophan, optionally in an amount of about 0.01% to about 5% by weight of the oral formulation. 11. The solid oral formulation according to any one of clauses 1 to 10, wherein the oral formulation comprises the combination of active ingredients in an amount of about 0.1% to about 10% by weight of the oral formulation. 12. The solid oral dosage form of any one of clauses 1 to 11, further comprising one or more additives selected from the group consisting of flavorings, sweeteners, acidifying agents, fillers, humectants, preservatives, and mixtures thereof. 13. The solid oral dosage form according to clause 12, wherein the oral dosage form comprises an acidifying agent. 14. The solid oral formulation of any one of clauses 1 to 13, wherein the oral formulation comprises at least one sugar alcohol. 15. The solid oral formulation of any one of clauses 1 to 14, wherein at least one sugar alcohol is selected from the group consisting of erythritol, arabitol, ribitol, isomalt, maltitol, dulcitol, iditol, mannitol, xylitol, lactitol, sorbitol, and combinations thereof, optionally wherein the at least one sugar alcohol is or comprises maltitol. 16. The solid oral dosage form of any one of clauses 1-15, wherein the at least one sugar alcohol is present in an amount of about 40% to about 99% by weight of the oral dosage form. 17. The solid oral formulation of any one of clauses 1-16, wherein the oral formulation comprises at least one sugar alcohol comprising a combination of isomalt and maltitol, and optionally the at least one sugar alcohol is present in an amount of about 50% to about 99% by weight of the oral formulation. 18. A solid oral formulation according to any one of clauses 1 to 17, wherein the oral formulation comprises a combination of at least one sugar alcohol and a sugar, optionally wherein the at least one sugar alcohol is or comprises maltitol. 19. The solid oral dosage form of any one of clauses 1-18, wherein the at least one binder is selected from the group consisting of cellulose derivatives, povidone, sodium alginate, starch-based binders, pectin, carrageenan, pullulan, zein, and the like, and combinations thereof, and optionally the at least one binder is or comprises pectin. 20. The solid oral dosage form of any one of clauses 1-19, wherein the at least one binder is present in an amount of about 0.001% to about 5% by weight of the oral dosage form. 21. A solid oral dosage form according to any one of clauses 1 to 20, wherein the oral dosage form is in the form of a dissolvable chew. 22. The combination of active ingredients is (i) L-theanine, (ii) ginseng, (iii) lemon balm extract; (iv) Vitamin C; (v) L-tryptophan and 22. The solid oral formulation of any one of clauses 1 to 21, comprising: 23. (i) about 25 mg to about 150 mg of L-theanine, and / or (ii) about 0.01 mg to about 10 mg of ginseng, and / or (iii) about 0.1 mg to about 100 mg of lemon balm, and / or Optionally, (iv) about 10 mg to about 60 mg of vitamin C, and / or 23. The solid oral formulation of any one of clauses 1-22, optionally comprising: (v) about 0.1 mg to about 50 mg of L-tryptophan. 24. A method for producing an oral dosage form as defined in any one of clauses 1 to 23, comprising: (a) contacting at least one binder with at least one sugar, or at least one sugar alcohol, or a combination of at least one sugar and at least one sugar alcohol, and optionally adding water; (b) heating a mixture of a binder, a sugar alcohol and / or a sugar, and optionally water; (c) adding a combination of active ingredients, the combination of active ingredients comprising: (i) L-theanine; (ii) ginseng; and (iii) lemon balm; (d) solidifying the resulting mixture to provide an oral dosage form. 1. A method for preparing an oral formulation, comprising: 25. A chewable solid oral formulation comprising a combination of active ingredients, the combination of active ingredients comprising lemon balm in an amount of about 1000 ppm to about 10000 ppm. 26. A chewable solid oral formulation comprising a combination of active ingredients, the combination of active ingredients comprising (i) lemon balm and (ii) ginseng. 27. A chewable solid oral formulation comprising a combination of active ingredients, the combination of active ingredients comprising (i) L-theanine and (ii) ginseng, wherein the L-theanine and ginseng are present in a weight ratio of about 150:1 to about 100:1.

Claims

1. 1. A solid oral formulation in chewable form comprising a combination of active ingredients, said combination of active ingredients comprising: (i) L-theanine, (ii) ginseng, (iii) lemon balm; at least one binder; at least one excipient selected from the group consisting of a sugar alcohol, or a sugar, or a combination of at least one sugar alcohol and at least one sugar; 1. A solid oral formulation comprising:

2. 10. The solid oral formulation of claim 1, wherein the L-theanine is present in an amount of about 0.01% to about 5% by weight of the oral formulation.

3. 3. The solid oral formulation of claim 1, wherein the ginseng is present in an amount of about 0.001% to about 0.25% by weight of the oral formulation.

4. 4. The solid oral formulation of claim 1, wherein the lemon balm is present in an amount of about 0.01% to about 3% by weight of the oral formulation.

5. 5. The solid oral formulation of claim 1, wherein the L-theanine and the ginseng are present in a weight ratio of about 150:1 to about 100:1, or about 150:1 to about 40:

1.

6. 6. The solid oral formulation of claim 1, wherein the L-theanine and the lemon balm are present in a weight ratio of about 1:1 to about 10:

1.

7. 7. The solid oral formulation of claim 1, wherein the ginseng and lemon balm are present in a weight ratio of about 1:10 to about 1:

50.

8. 8. The solid oral formulation of claim 1, wherein the combination of active ingredients further comprises vitamin C, optionally present in an amount of about 0.1% to about 5% by weight of the oral formulation.

9. 9. The solid oral formulation of claim 8, wherein the vitamin C and the L-theanine are present in a weight ratio of about 1:1 to about 1:2, or about 1:1 to about 1:

5.

10. 10. The solid oral formulation of claim 8 or 9, wherein the vitamin C and the lemon balm are present in a weight ratio of about 1:2 to about 10:

1.

11. 11. The solid oral formulation of any one of claims 1 to 10, wherein the combination of active ingredients further comprises L-tryptophan, optionally in an amount of about 0.01% to about 5% by weight of the oral formulation.

12. 12. The solid oral formulation of claim 11, wherein the L-tryptophan and the L-theanine are present in a weight ratio of about 1:1 to about 1:

20.

13. 13. The solid oral formulation of claim 11 or 12, wherein the L-tryptophan and the lemon balm are present in a weight ratio of about 1:1 to about 1:

10.

14. 14. The solid oral formulation of any one of claims 1 to 13, wherein the oral formulation comprises the combination of active ingredients in an amount of about 0.1% to about 10% by weight of the oral formulation.

15. 15. The solid oral formulation of any one of claims 1 to 14, further comprising one or more additives selected from the group consisting of flavorings, sweeteners, acidifying agents, fillers, humectants, preservatives, and mixtures thereof, preferably wherein the oral formulation comprises an acidifying agent.

16. 16. The solid oral formulation of any one of claims 1 to 15, wherein the oral formulation comprises at least one sugar alcohol.

17. 17. The solid oral formulation of any one of claims 1 to 16, wherein the at least one sugar alcohol is selected from the group consisting of erythritol, arabitol, ribitol, isomalt, maltitol, dulcitol, iditol, mannitol, xylitol, lactitol, sorbitol, and combinations thereof, optionally wherein the at least one sugar alcohol is or comprises maltitol.

18. 18. The solid oral dosage form of any one of claims 1 to 17, wherein the at least one sugar alcohol is present in an amount of about 40% to about 99% by weight of the oral dosage form.

19. 19. The solid oral formulation of any one of claims 1 to 18, wherein the oral formulation comprises at least one sugar alcohol comprising a combination of isomalt and maltitol, optionally wherein the at least one sugar alcohol is present in an amount of from about 50% to about 99% by weight of the oral formulation.

20. 20. The solid oral formulation of any one of claims 1 to 19, wherein the oral formulation comprises a combination of at least one sugar alcohol and a sugar, optionally wherein the at least one sugar alcohol is or comprises maltitol.

21. 21. The solid oral formulation of any one of claims 1 to 20, wherein the at least one binder is selected from the group consisting of cellulose derivatives, povidone, sodium alginate, starch-based binders, pectin, carrageenan, pullulan, zein, and the like, and combinations thereof, optionally wherein the at least one binder is or comprises pectin.

22. 22. The solid oral dosage form of any one of claims 1 to 21, wherein the at least one binder is present in an amount of about 0.001% to about 5% by weight of the oral dosage form.

23. A solid oral formulation according to any one of claims 1 to 22, wherein the oral formulation is in the form of a dissolvable chew.

24. The combination of active ingredients is (i) L-theanine, (ii) ginseng, (iii) lemon balm extract; and (iv) Vitamin C; and (v) L-tryptophan and 24. The solid oral formulation of any one of claims 1 to 23, comprising:

25. (i) about 25 mg to about 150 mg of L-theanine, and / or (ii) about 0.01 mg to about 10 mg of ginseng, and / or (iii) about 0.1 mg to about 100 mg of lemon balm, and / or optionally, (iv) about 10 mg to about 100 mg of vitamin C, and / or 25. The solid oral formulation of any one of claims 1 to 24, optionally comprising: (v) about 0.1 mg to about 50 mg of L-tryptophan.

26. A method for producing the oral formulation according to any one of claims 1 to 25, comprising the steps of: (a) contacting at least one binder with at least one sugar, or at least one sugar alcohol, or a combination of at least one sugar and at least one sugar alcohol, and optionally adding water; (b) heating a mixture of a binder, a sugar alcohol and / or a sugar, and optionally water; (c) adding a combination of active ingredients, the combination of active ingredients comprising: (i) L-theanine; (ii) ginseng; and (iii) lemon balm; (d) solidifying the resulting mixture to provide an oral dosage form. A method comprising:

27. 1. A chewable solid oral formulation comprising a combination of active ingredients, wherein the combination of active ingredients comprises lemon balm in an amount of about 1,000 ppm to about 10,000 ppm, or the combination of active ingredients comprises (i) lemon balm and (ii) ginseng, or the combination of active ingredients comprises (i) L-theanine and (ii) ginseng, wherein the L-theanine and the ginseng are present in a weight ratio of about 150:1 to about 100:1, or about 150:1 to about 40:

1.

28. 1. Use of a combination of active ingredients for providing a relaxation effect to a human or animal, wherein the combination of active ingredients comprises (i) L-theanine, (ii) ginseng, and (iii) lemon balm, or comprises lemon balm in an amount of from about 1,000 ppm to about 10,000 ppm, (i) lemon balm and (ii) ginseng, or comprises (i) L-theanine and (ii) ginseng, wherein the L-theanine and the ginseng are present in a weight ratio of from about 150:1 to about 100:1, or from about 150:1 to about 40:1.

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