Methylcellulose as a humectant in the pouch base

Abstract

The present invention relates to the use of methylcellulose as a humectant in a pouch substrate and to an oral pouch containing a pouch substrate, wherein the aforementioned pouch substrate comprises one or more carriers, one or more active ingredients, and methylcellulose having a viscosity of about 200 to about 10,000 cP at 20°C and a 2% w / v concentration.

Description

Technical Field

[0001] The present invention relates to the use of methylcellulose as a humectant in a pouch substrate. The present invention also relates to an oral pouch comprising the pouch substrate, said pouch substrate comprising one or more carriers, one or more active ingredients, and methylcellulose having a viscosity of 200-10,000 cP at 20 °C at a concentration of 2% w / v.

Background Art

[0002] One product that is popular as a product for oral delivery of active ingredients such as nicotine without the accompanying smoke is the pouch. A pouch is a container formed of a water-permeable material that encloses a cavity. The pouch is filled with a pouch substrate and then sealed. The pouch substrate can be either dry, semi-moist, or moist. The pouch substrate often contains alginates and other similar polysaccharides as humectants. Alginates improve the processability of the pouch substrate and retain moisture. Oral compositions containing polysaccharides used in pouches (such as acacia gum, xanthan gum, alginates, carrageenan, etc.) are described in US2021 / 0169890A1.

[0003] A problem associated with the use of alginates or other similar polysaccharides in the pouch substrate is the reduced release rate of the active ingredients (such as nicotine) and flavoring agents contained in the pouch substrate. As a result, the delivery efficiency of the active ingredients and flavoring agents deteriorates.

[0004] Therefore, there is a need for a humectant that not only improves the processability of the pouch substrate (such as powder flowability, reduction of dust formation, etc.), but also enables more complete and rapid release of the active ingredients and flavoring agents contained in the pouch substrate.

[0005] Object of the Invention An object of the present invention is to provide a humectant that improves the processability of pouch substrates, retains moisture in the pouch substrate, and enables more complete and rapid release of active ingredients and flavorings contained in the pouch substrate compared to known humectants (e.g., alginates). Another object of the present invention is to provide an oral pouch that improves the delivery of active ingredients and flavorings contained therein, thereby providing a superior user experience.

[0006] The uses and oral pouches described below are intended to fulfill the purposes stated above. [Overview of the project]

[0007] In one embodiment, the present invention relates to the use of methylcellulose as a humectant in a pouch substrate.

[0008] In another embodiment, the present invention relates to an oral pouch comprising a pouch substrate, wherein the pouch substrate comprises one or more carriers, one or more active ingredients, and methylcellulose having a viscosity of about 200 to about 10,000 cP at 20°C and a 2% w / v concentration.

[0009] In preferred embodiments of each of the above-described aspects, the pouch substrate further comprises one or more carriers and one or more active ingredients.

[0010] In more preferred embodiments of each of the above-described models, the active ingredient is nicotine.

[0011] In more preferred embodiments of each of the above-described features, the methylcellulose has a viscosity of about 200 to about 10,000 cP at 20°C and a 2% w / v concentration.

[0012] In preferred embodiments of each of the above-described features, the methylcellulose contains about 27.5 to 31.5% by weight of methoxy groups.

[0013] In more preferred embodiments of each of the above-described aspects, the methylcellulose has a viscosity of about 300 to about 5000 cP at 20°C and a concentration of 2% w / v.

[0014] In preferred embodiments of each of the above-described aspects, methylcellulose is added in an amount of about 0.5% to 10% by weight, based on the total weight of the pouch substrate.

[0015] In more preferred embodiments of each of the above-described models, the pouch substrate further comprises one or more flavoring agents. [Brief explanation of the drawing]

[0016] [Figure 1] Figure 1 shows the release rate of nicotine contained in the pouch substrates of Examples 1 and 2 and Comparative Example 1 as a function of time. [Modes for carrying out the invention]

[0017] This invention is based on the finding that using methylcellulose (MC) as a humectant in the pouch substrate not only improves the processability and humectancy of the pouch substrate, but also improves the release of active ingredients and flavorings contained in the pouch substrate. Therefore, pouches containing methylcellulose as a humectant have improved efficacy and flavor intensity, providing a superior user experience.

[0018] Definitions and Terms Unless otherwise defined, all technical and scientific terms from this point forward have their commonly understood meanings.

[0019] Unless otherwise defined, any feature within any aspect or embodiment of the Invention may be combined with any feature within any other aspect or embodiment of the Invention, and those skilled in the art will understand that such combinations are encompassed in the original disclosure of this application. This also applies to the possibility of combining elements from lists of species within different broader definitions of terms, and such possibility of individualized combinations is expressly intended and within the direct and obvious disclosure of this application. This also applies, in particular, but not limited to, the endpoints of the scope disclosed herein. For example, if a given substance is disclosed as being present in a composition in a concentration range of XY% or AB%, this application should be understood to expressly disclose not only the ranges XY% and AB%, but also the ranges XB%, AY%, and, numerically, YA%, and BX%. Each of these ranges, and combinations of ranges, should be understood to be intended and directly and obviously disclosed in this application.

[0020] Similarly, it should be understood that the section headings used throughout this application are solely for organizational purposes and do not give any exclusive character to the disclosure relating to aspects or embodiments of the invention referred to in any particular section heading. Therefore, the section headings do not preclude any combination of the disclosures within any one section heading to a corresponding or similar context provided under another section heading. In fact, such in-section disclosures are explicitly within the disclosures of this application.

[0021] As used herein, each of the terms "comprising", "having", and "containing", including their grammatical variations, is intended in a non-exclusive sense to mean "including", but not necessarily "consisting of", and does not exclude elements in addition to those explicitly recited as being present. As used herein, the terms "comprising", "having", and "containing", and their grammatical variations, indicate that components other than those explicitly recited may be present, but are not essential. Thus, these terms, as a limiting case, include embodiments in which no elements other than those recited exist, for example, in the commonly accepted sense of "consisting of".

[0022] As used herein, the phrase "consisting of", and its grammatically related variations, mean that no other elements other than those recited exist. Thus, considering the above definition of "comprising" (and grammatically and semantically related terms), the term "consisting of" means a limiting scenario within the meaning of "comprising".

[0023] Unless otherwise indicated, the percentages indicating the degree to which a particular component is included in a mixture or composition refer to weight / weight (w / w) percentages. Similarly, unless otherwise indicated, the ratios specified herein are weight ratios.

[0024] Unless otherwise stated, any range designation in this application using two bracket values ​​X and Y, or a hyphen ("-") separating two bracket ratios, should be understood as meaning and disclosing a specific range that includes both endpoint values ​​X and Y. The same applies to ranges expressed as "X to Y". Thus, range expressions such as "XY", "X to Y", "X to Y", "of XY", and "X to Y" should be understood equally as meaning and disclosing a range that includes both endpoint values ​​X and Y, where all values ​​lie between X and Y. Unless otherwise stated, any range designation as "X or less" should be understood as meaning and disclosing a range whose upper limit is X and which includes the value X. Unless otherwise stated, any range designation as "greater than X and greater than Y" should be understood as meaning and disclosing a range whose lower limit does not include the value X, but which includes any value greater than or equal to X and which includes the upper limit Y. As used herein, "any value greater than X" may include values ​​that are 1.0% higher than X.

[0025] As used herein, the term “approximately” refers to a specific value, for example, the endpoint(s) of a range, and includes and discloses a specific amount of variation around that specifically enumerated value, in addition to the specifically enumerated value itself. Such variations may arise from normal measurement variations, such as in the weighing or distribution of various substances by methods known to those skilled in the art. The term “approximately” should be understood as including and disclosing a range of variation above and below the specific value indicated, where the percentage value is relative to the specific enumerated value itself, as follows: The term “approximately” may include and disclose a variation of ±5.0%. The term “approximately” may include and disclose a variation of ±4.5%. The term “approximately” may include and disclose a variation of ±4.0%. The term “approximately” may include and disclose a variation of ±3.5%. The term “approximately” may include and disclose a variation of ±3.0%. The term “approximately” may include and disclose a variation of ±2.5%. The term "approximately" may encompass and disclose a variation of ±2.0%. The term "approximately" may encompass and disclose a variation of ±1.5%. The term "approximately" may encompass and disclose a variation of ±1.0%. The term "approximately" may encompass and disclose a variation of ±0.5%. In relation to a particular enumerated value, the term "approximately" may encompass and disclose the exact specific value itself, regardless of any explicit reference that this exact specific value is included, and even in the absence of an explicit indication that the term "approximately" includes a particular exact enumerated value, this exact specific value is still included within the range of variation created by the term "approximately" and is therefore disclosed in this application. Unless otherwise stated, if the term "approximately" is written before the first endpoint of a numerical range but not before the second endpoint of that range, the term, and the variability it implies in the range and disclosure, refers to both the first endpoint and the second endpoint of the range. For example, the enumerated range "approximately X~Y" is: about X~ about It should be read as "Y". The same applies to the range of listed ratios. For example, the range of listed weight ratios "approximately X:YA:B" should be read as the weight ratio "(approximately X):(approximately Y)-(approximately A):(approximately B)".

[0026] As used in this specification, the term "the combination" refers to any combination thereof, in any proportion. That is, this term encompasses any combination of features listed in any relative amounts (e.g., any two listed features, any combination of any three listed features, etc.).

[0027] As used in this specification, the term "humectant" refers to a substance that has hygroscopicity (the property of absorbing water) and retains moisture in the pouch substrate.

[0028] As used in this specification, the term "pouch substrate" means a composition suitable for use in an oral pouch.

[0029] As used in this specification, the term "oral" means a product adapted for use in the user's oral cavity. During use, saliva in the user's mouth passes one or more of the components of the product (e.g., the pouch substrate) into the user's mouth.

[0030] As used in this specification, the term "dry" in the context of the pouch substrate means a water content of no more than 12% by weight.

[0031] As used in this specification, the term "semi-moist" in the context of the pouch substrate means a water content of 12% to 20% by weight.

[0032] As used in this specification, the term "moist" in the context of the pouch substrate means a water content of more than 20% and no more than 50% by weight.

[0033] As used in this specification, the term "water content" means the weight water content expressed by mass (weight) as follows: u = m w / m s where m w is the mass of water and m sis the mass of the solid. The water content can be determined by the Karl Fischer method, in particular according to ISO 6488:2021 - Tobacco and tobacco products - Determination of water content - Karl Fischer method.

[0034] As used herein, the term “pouch” refers to a container formed of a water-permeable material that seals a cavity. The pouch is adapted for oral use. The water-permeable material can be a fibrous material such as a woven or nonwoven fabric. The nonwoven fabric may be made of polyester fibers, viscose, sisal, wool fibers, or a combination thereof. The water-permeable material is not water-soluble. In one preferred embodiment, the fibrous material is a nonwoven fabric made of a combination of polyester and viscose. Preferably, the weight ratio of polyester to viscose is about 1:1 to 10:1, more preferably about 2:1 to 5:1, and most preferably about 4:1. In another preferred embodiment, the water-permeable material is a nonwoven fabric laminated with layers of a thermoplastic polymer (e.g., thermoplastic polyurethane).

[0035] As used herein, the term "water permeability" means that water can pass through the pouch material in both directions, namely from the oral cavity to the inside of the pouch and from the inside (rear) of the pouch to the oral cavity.

[0036] As used herein, the term "carrier" means a substance or group of substances whose content is 50% by weight or more of the pouch substrate. Non-limiting examples of carriers include water-insoluble dietary fiber, powdered cellulose, and sugar alcohols. Sugar alcohols may be selected from the group consisting of, for example, xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, and combinations thereof.

[0037] As used herein, the term "water-insoluble dietary fiber" means a substance that is water-insoluble and in the form of dietary fiber. Non-limiting examples may be selected from the group consisting of cellulose fiber (e.g., powdered cellulose), wheat fiber, pea fiber, rice fiber, corn fiber, oat fiber, tomato fiber, barley fiber, rye fiber, sugar beet fiber, buckwheat fiber, potato fiber, apple fiber, cocoa fiber, bran fiber, bamboo fiber, and combinations thereof.

[0038] As used herein, the term "water-insoluble" refers to the water solubility of a water-soluble composition or substance at less than 0.1 grams per 100 mL of water, measured at 25 degrees Celsius, atmospheric pressure, and pH 7.

[0039] As used herein, the term "powder form" refers to a composition in powder form, i.e., particulate matter having a relatively small average particle size of, for example, 1 to 1500 micrometers.

[0040] As used herein, the term “fibrous form” refers to a composition in the form of fibers, i.e., particles that are significantly longer than broad particles. The term “fibrous form” also encompasses all products referred to as dietary fiber in the art.

[0041] As used herein, the term “active ingredient” refers to a substance that modulates, for example, a stimulating effect on the user’s nervous system. In one preferred embodiment, the active ingredient is selected from the group consisting of nicotine, caffeine, anatabine, one or more cannabinoids, and any combination thereof in any proportion.

[0042] As used herein, the term “nicotine” refers to a nicotine source. A nicotine source can be any nicotine compound. Such nicotine compounds include nicotine in its free base form (i.e., unprotonated form), as a salt, as a complex, or as a solvate. An example of a nicotine complex is a nicotine resin complex, in which nicotine is bound to an ion-exchange resin such as nicotine polarilex. Examples of nicotine salts include benzoates, hydrochlorides, dihydrochlorides, monotartrates, bisartrates, sulfates, salicylates, citrates, stearates, glutarates, aspartates, palmitates, and lactates. Further possible forms of nicotine are discussed below. Their combinations in any proportion are also possible and disclosed in the context of this invention.

[0043] As used herein, “nicotine content” refers to the amount of nicotine from a nicotine source, calculated as free base nicotine in weight / weight (w / w) percentage, and is also referred to herein as “weight %”.

[0044] As used herein, the term “cannabinoid” refers to a diverse class of chemical compounds that act on cannabinoid receptors in cells that alter neurotransmitter release in the brain, also known as the endocannabinoid system. Ligands for these receptor proteins include endocannabinoids naturally produced in the bodies of animals, phytocannabinoids found in cannabis, and synthetic cannabinoids that are artificially produced. Cannabinoids found in cannabis include, but are not limited to, cannabigerol (CBG), cannabichromene (CBC), cannabidiol (CBD), tetrahydrocannabinol (THC), cannabinol (CBN), cannabinodiol (CBDL), cannabicyclol (CBL), cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromevaline (CBCV), cannabigerovaline (CBGV), cannabigerol monomethyl ether (CBGM), cannabinerol acid, cannabidiolic acid (CBDA), cannabinol propyl variant (CBNV), cannabitriol (CBO), tetrahydrocannabinolic acid (THCA), and tetrahydrocannabivaric acid (THCV A). Any combination thereof in any proportion is also possible and is disclosed in the context of this invention.

[0045] As used herein, the term “flavoring agent” refers to any flavoring or aromatic substance that can alter the sensory properties of a compound or composition. Examples of sensory properties that can be modified by flavoring agents include taste (e.g., sweet, salty, sour, bitter), mouthfeel, moisture, cooling / heating, and / or aroma / fragrance. Flavoring agents may be natural or synthetic, and the flavor characteristics they impart may be described as fresh, sweet, salty, umami, herbal, confectionery, floral, fruity, or spicy. Specific types of flavors include, but are not limited to, vanilla, coffee, chocolate / cocoa, cream, mint, spearmint, menthol, peppermint, bracken, adzuki bean, ginseng, kelp, dwarf spicebush, eucalyptus, lavender, cardamom, nutmeg, cinnamon, clove, cascarilla, sandalwood, honey, jasmine, ginger, anise, sage, licorice, lemon, orange, apple, peach, lime, cherry, strawberry, and any combination thereof in any proportion. Flavoring agents also include components considered as humectants, coolants, or smoothing agents, such as eucalyptus. Flavoring agents can mask the flavors of other components in the composition (e.g., bitterness). For example, sweeteners can be used as bitterness masking agents. Flavoring agents may include at least one volatile flavor component. As used herein, “volatile” means a chemical substance that readily forms vapor at ambient temperature (i.e., a chemical substance that has a higher vapor pressure at a given temperature compared to a non-volatile substance). Typically, volatile flavor compounds have a molecular weight of less than approximately 400 Da and often contain at least one carbon-carbon double bond, a carbon-oxygen double bond, or both. Examples of volatile flavor compounds include alcohols, aldehydes, aromatic hydrocarbons, ketones, esters, terpenes, terpenoids, trigeminal sensates, or combinations thereof. Non-exclusive examples of aldehydes include vanillin, ethyl vanillin, p-anisaldehyde, hexanal, furfural, isovaleraldehyde, cuminaldehyde, benzaldehyde, and citronellal.Non-limiting examples of ketones include 1-hydroxy-2-propanone and 2-hydroxy-3-methyl-2-cyclopentenone-1-one. Non-limiting examples of esters include allyl hexanoate, ethyl heptanoate, ethyl hexanoate, isoamyl acetate, and 3-methylbutyl acetate. Non-limiting examples of terpenes include sabinene, limonene, gamma-terpinene, beta-famecene, nerolidool, suzhon, myrcene, geraniol, nerol, citronellol, linalool, and eucalyptol. Any combination thereof in any proportion is also possible and disclosed in the context of this invention.

[0046] Use of methylcellulose as a humectant in pouch substrates This invention provides the use of methylcellulose as a humectant in pouch substrates. Methylcellulose is superior to conventional humectants (such as alginates) because it is excellent at releasing active ingredients and flavorings contained in the pouch substrate.

[0047] The pouch substrate may be dry, semi-moist, or wet. In one preferred embodiment, the pouch substrate is wet.

[0048] In one preferred embodiment, the pouch substrate further comprises one or more carriers and one or more active ingredients.

[0049] In a more preferred embodiment, the pouch substrate has a water content of about 13% to 35% by weight, preferably about 15% to 30% by weight, and more preferably about 17% to 25% by weight.

[0050] In a more preferred embodiment, the carrier comprises water-insoluble dietary fiber and / or sugar alcohol. The carrier content in the pouch substrate can be at least about 50% by weight, preferably about 50% to 90% by weight, more preferably about 60% to 85% by weight, and most preferably about 70% to 80% by weight.

[0051] In one preferred embodiment, in combination with any of the embodiments described above and below, the sugar alcohol is selected from the group consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, and any mixture thereof. Preferably, the sugar alcohol is a combination of xylitol and erythritol.

[0052] In a more preferred embodiment, in any combination of the embodiments described above or below, the water-insoluble dietary fiber is selected from the group consisting of cellulose fiber (e.g., powdered cellulose), wheat fiber, pea fiber, rice fiber, corn fiber, oat fiber, tomato fiber, barley fiber, rye fiber, sugar beet fiber, buckwheat fiber, potato fiber, apple fiber, cocoa fiber, bran fiber, bamboo fiber, and combinations thereof.

[0053] In one preferred embodiment, the active ingredient is nicotine. Any form of nicotine may also be used. Nicotine may be incorporated into a premix of liquid suspension before being added to the pouch substrate.

[0054] In one preferred embodiment, nicotine is a nicotine salt or a nicotine resin complex, and the nicotine is bound to an ion exchange resin (i.e., a nicotine / ion exchange resin complex). In another preferred embodiment, the nicotine salt is nicotine bitartrate, nicotine glutarate, nicotine aspartate, nicotine palmitate, or nicotine lactate, most preferably nicotine bitartrate. Any combination thereof in any proportion is also possible and disclosed in the context of the present invention.

[0055] In a further preferred embodiment, nicotine may be in a liquid form (e.g., free nicotine base) that is encapsulated (e.g., by a cyclodextrin).

[0056] In preferred embodiments, nicotine is selected from the group consisting of nicotine bitartrate, nicotine polarilex, nicotine betadex, nicotine o-salicylate, nicotine gentisate, nicotine gallate, nicotine phthalate, nicotine isophthalate, nicotine acesulfame H, nicotine benzoate, nicotine fumarate, nicotine R-mandelate, nicotine hydrochloride, nicotine L-lactic acid, nicotine levulinate, nicotine phosphate, nicotine ascorbate, nicotine ferrate, nicotine vanillate, nicotine picolinate, nicotine cuminate, nicotine nicotinate, nicotine pyruvate, and nicotine gamma-resorsilate. Any combination thereof in any proportion is also possible and is disclosed in the context of the present invention.

[0057] In one preferred embodiment, the active ingredient is nicotine, and its content in the pouch base is about 0.5 to 20 mg, preferably about 0.5 to 15 mg, and most preferably about 0.5 to 10 mg.

[0058] In one preferred embodiment, the methylcellulose has a viscosity of about 200 to about 10,000 cP at 20°C and a 2% w / v concentration. More preferably, the methylcellulose has a viscosity of about 300 to about 5,000 cP at 20°C and a 2% w / v concentration. The viscosity is measured according to the method described in Ph.Eur. 11.0, pages 3379-3380.

[0059] In a preferred embodiment, the methylcellulose has a viscosity of about 300 to about 500 cP at 20°C and a concentration of 2% w / v. An example of such methylcellulose is DuPont's Methocel® 4AC.

[0060] In another preferred embodiment, the methylcellulose has a viscosity of about 2000 to about 5000 cP at 20°C and a 2% w / v concentration, preferably 2500 to 5000 cP at 20°C and a 2% w / v concentration. An example of such methylcellulose is DuPont's Methocel® 4AM.

[0061] In a more preferred embodiment, methylcellulose contains approximately 27.5 to 31.5% by weight of methoxy groups. The methoxy group content can be measured by NMR spectroscopy.

[0062] In a more preferred embodiment, methylcellulose is added in an amount of about 0.5% to 10% by weight based on the total weight of the pouch substrate. More preferably, methylcellulose is added in an amount of about 1% to 8% by weight based on the total weight of the pouch substrate, even more preferably, about 1.2% to 6% by weight based on the total weight of the pouch substrate, and most preferably, about 1.3% to 5% by weight based on the total weight of the pouch substrate.

[0063] In one preferred embodiment, the pouch substrate further comprises one or more flavoring agents.

[0064] In a more preferred embodiment, the pouch base comprises methylcellulose having a viscosity of about 300 to about 5000 cP at 20°C and a 2% w / v concentration, one or more carriers, one or more active ingredients, and one or more flavoring agents, wherein the carrier is water-insoluble dietary fiber and the active ingredient is nicotine.

[0065] All of the preferred embodiments described above can be combined with one another, and such combinations are disclosed in the context of the present invention.

[0066] Oral pouch The present invention also provides an oral pouch comprising a pouch substrate, the aforementioned pouch substrate comprising one or more carriers, one or more active ingredients, and methylcellulose having a viscosity of about 200 to about 10,000 cP at 20°C and a 2% w / v concentration. The viscosity is measured according to the method described in Ph.Eur.11.0, pages 3379-3380.

[0067] The pouch substrate may be dry, semi-moist, or wet. In one preferred embodiment, the pouch substrate is wet.

[0068] In a more preferred embodiment, the pouch substrate has a water content of about 13% to 35% by weight, preferably about 15% to 30% by weight, and more preferably about 17% to 25% by weight.

[0069] In a more preferred embodiment, the carrier comprises water-insoluble dietary fiber and / or sugar alcohol. The carrier content in the pouch substrate can be at least about 50% by weight, preferably about 50% to 90% by weight, more preferably about 60% to 85% by weight, and most preferably about 70% to 80% by weight.

[0070] In one preferred embodiment, in combination with any of the embodiments described above and below, the sugar alcohol is selected from the group consisting of xylitol, maltitol, mannitol, erythritol, isomalt, sorbitol, lactitol, and any mixture thereof.

[0071] In a more preferred embodiment, in any combination of the embodiments described above or below, the water-insoluble dietary fiber is selected from the group consisting of cellulose fiber (e.g., powdered cellulose), wheat fiber, pea fiber, rice fiber, corn fiber, oat fiber, tomato fiber, barley fiber, rye fiber, sugar beet fiber, buckwheat fiber, potato fiber, apple fiber, cocoa fiber, bran fiber, bamboo fiber, and combinations thereof.

[0072] In one preferred embodiment, the active ingredient is nicotine. Any form of nicotine may also be used. Nicotine may be incorporated into a premix of liquid suspension before being added to the pouch substrate.

[0073] In one preferred embodiment, nicotine is a nicotine salt or a nicotine resin complex, and the nicotine is bound to an ion exchange resin (i.e., a nicotine / ion exchange resin complex). In another preferred embodiment, the nicotine salt is nicotine bitartrate, nicotine glutarate, nicotine aspartate, nicotine palmitate, or nicotine lactate, most preferably nicotine bitartrate.

[0074] In a further preferred embodiment, nicotine may be in a liquid form (e.g., free nicotine base) that is encapsulated (e.g., by a cyclodextrin).

[0075] In preferred embodiments, nicotine is selected from the group consisting of nicotine bitartrate, nicotine polarilex, nicotine betadex, nicotine o-salicylate, nicotine gentisate, nicotine gallate, nicotine phthalate, nicotine isophthalate, nicotine acesulfame H, nicotine benzoate, nicotine fumarate, nicotine R-mandelate, nicotine hydrochloride, nicotine L-lactic acid, nicotine levulinate, nicotine phosphate, nicotine ascorbate, nicotine ferrate, nicotine vanillate, nicotine picolinate, nicotine cuminate, nicotine nicotinate, nicotine pyruvate, and nicotine gamma-resorsilate. Any combination thereof in any proportion is also possible and is disclosed in the context of the present invention.

[0076] In one preferred embodiment, the active ingredient is nicotine, and its content in the pouch base is about 0.5 to 20 mg, preferably about 0.5 to 15 mg, and most preferably about 0.5 to 10 mg.

[0077] In one preferred embodiment, the methylcellulose has a viscosity of about 300 to about 5000 cP at 20°C and a 2% w / v concentration.

[0078] In one preferred embodiment, the methylcellulose has a viscosity of about 300 to about 500 cP at 20°C and a 2% w / v concentration. In another preferred embodiment, the methylcellulose has a viscosity of about 2000 to about 5000 cP at 20°C and a 2% w / v concentration, preferably about 2500 to about 5000 cP at 20°C and a 2% w / v concentration.

[0079] In a more preferred embodiment, methylcellulose contains approximately 27.5 to 31.5% by weight of methoxy groups. The methoxy group content can be measured by NMR spectroscopy.

[0080] In a more preferred embodiment, methylcellulose is added in an amount of about 0.5% to 10% by weight based on the total weight of the pouch substrate. More preferably, methylcellulose is added in an amount of about 1% to 8% by weight based on the total weight of the pouch substrate, even more preferably, about 1.2% to 6% by weight based on the total weight of the pouch substrate, and most preferably, about 1.3% to 5% by weight based on the total weight of the pouch substrate.

[0081] In one preferred embodiment, the pouch substrate further comprises one or more flavoring agents.

[0082] In a more preferred embodiment, the pouch base comprises methylcellulose having a viscosity of about 300 to about 5000 cP at 20°C and a 2% w / v concentration, one or more carriers, one or more active ingredients, and one or more flavoring agents, wherein the carrier is water-insoluble dietary fiber and the active ingredient is nicotine.

[0083] All of the preferred embodiments described above can be combined with one another, and such combinations are disclosed in the context of the present invention.

[0084] The pouch substrates described herein may optionally contain one or more pH adjusters, preservatives, flavor enhancers, and sweeteners. Examples of pH adjusters include sodium orthophosphate, potassium orthophosphate, calcium orthophosphate, sodium diphosphate, potassium diphosphate, calcium diphosphate, pentasodium triphosphate, pentasodium triphosphate, sodium polyphosphate, potassium polyphosphate, carbonic acid, sodium carbonate, sodium bicarbonate, potassium carbonate, calcium carbonate, magnesium carbonate, and combinations thereof. Examples of preservatives include sorbic acid and its salts (e.g., potassium sorbate), benzoic acid and its salts, sulfur dioxide, nitrates, nitrites, acetic acid and its salts, lactic acid and its salts, malic acid and its salts, and combinations thereof. An example of a flavor enhancer is sodium chloride. Examples of sweeteners include sugar sweeteners such as sucrose, dextrose, maltose, and lactose, as well as high-strength sweeteners such as sucralose, aspartame, salts of acesulfame (e.g., acesulfame potassium), alitarm, saccharin and its salts, cyclamic acid and its salts, glycyrrhizin, dihydrochalcone, thaumatin, monellin, stevioside, and combinations thereof. [Examples]

[0085] A pouch substrate having the composition shown in Table 1 was prepared and filled into pouches according to the method of Example 3A of WO2020 / 244721A1. The nicotine direct premix was prepared according to the method of Example 2B of WO2020 / 244721A1. [Table 1]

[0086] Nicotine release test: The amount of nicotine released from the pouches in Examples 1 and 2 and Comparative Example 1 was measured as a function of time according to the following method.

[0087] 2.72 g of potassium dihydrogen phosphate was dissolved in 950 ml of purified water, and the pH was adjusted to 7.4 with 2N KOH solution to prepare a chewing buffer. Purified water was added to obtain 1000 ml of the final buffer.

[0088] As described above, 10 liters of chewing buffer solution were degassed and heated to 38°C to prepare the solution (chewing buffer solution).

[0089] The resulting 900 ml of chewing buffer was transferred to individual containers in a USP dissolving apparatus 1 (for example, an Agilent 708-DS dissolving apparatus). The chewing buffer (pH 7.4) was then adjusted to 37°C within the containers.

[0090] The weighed pouches were transferred to a basket, and the dissolution device was started.

[0091] The buffer sampling times were set to 2, 6, 12, 20, and 30 minutes. The rotation speed was set to 100 rpm.

[0092] The release sample after 2 minutes was manually collected using a cannula. The release samples after 6, 12, 20, and 30 minutes were automatically collected using a dissolution device.

[0093] All samples were filtered and prepared for HPLC analysis.

[0094] As can be seen from Figure 1, Examples 1 (dotted line) and 2 (dashed line), which use methylcellulose as a humectant, show improved (faster) nicotine release compared to Comparative Example 1 (solid line), which uses sodium alginate as a humectant.

[0095] The present invention also covers the following embodiments.

[0096] Embodiment 1: Use of methylcellulose as a humectant in the pouch substrate. Embodiment 2: The use according to Embodiment 1, wherein the aforementioned pouch substrate further comprises one or more carriers and one or more active ingredients. Embodiment 3: The use according to Embodiment 1 or 2, wherein the active ingredient is nicotine. Embodiment 4: The use of methylcellulose according to any one of Embodiments 1 to 3, wherein the methylcellulose has a viscosity of approximately 200 to approximately 10,000 cP at 20°C and a 2% w / v concentration. Embodiment 5: The use according to any one of Embodiments 1 to 4, wherein the methylcellulose contains approximately 27.5 to 31.5% by weight of methoxy groups. Embodiment 6: The use of methylcellulose according to any one of Embodiments 1 to 5, wherein the methylcellulose has a viscosity of approximately 300 to approximately 5000 cP at 20°C and a 2% w / v concentration. Embodiment 7: The use according to any one of Embodiments 1 to 6, wherein methylcellulose is added in an amount of about 0.5% to 10% by weight, based on the total weight of the pouch substrate. Embodiment 8: The use according to any one of Embodiments 1 to 7, wherein the pouch base further comprises one or more flavoring agents. Embodiment 9: An oral pouch comprising a pouch substrate, wherein the pouch substrate comprises one or more carriers, one or more active ingredients, and methylcellulose having a viscosity of about 200 to about 10,000 cP at 20°C and a 2% w / v concentration. Embodiment 10: An oral pouch according to Embodiment 9, wherein the active ingredient is nicotine. Embodiment 11: An oral pouch according to Embodiment 9 or 10, wherein methylcellulose contains about 27.5 to 31.5% by weight of methoxy groups. Embodiment 12: An oral pouch according to any one of Embodiments 9 to 11, wherein the methylcellulose has a viscosity of approximately 300 to approximately 5000 cP at 20°C and a 2% w / v concentration. Embodiment 13: An oral pouch according to any one of embodiments 9 to 12, wherein the amount of methylcellulose in the pouch substrate is about 0.5% to 10% by weight based on the total weight of the pouch substrate. Embodiment 14: An oral pouch according to any one of embodiments 9 to 13, further comprising one or more flavoring agents.

Claims

1. Use of methylcellulose as a humectant in a pouch substrate, wherein the methylcellulose has a viscosity of about 200 to about 10,000 cP at 20°C and a 2% w / v concentration when measured as described herein, and the methylcellulose is added in an amount of about 0.5% to 6% by weight based on the total weight of the pouch substrate.

2. The use according to claim 1, wherein the pouch substrate further comprises one or more carriers and one or more active ingredients.

3. The use according to claim 1 or 2, wherein the active ingredient is nicotine.

4. The use according to any one of claims 1 to 3, wherein the methylcellulose contains about 27.5 to 31.5% by weight of methoxy groups.

5. The use according to any one of claims 1 to 4, wherein the methylcellulose has a viscosity of about 300 to about 5000 cP at 20°C and a 2% w / v concentration when measured as described herein.

6. The use according to any one of claims 1 to 5, wherein the pouch substrate further comprises one or more flavoring agents.

7. An oral pouch comprising a pouch substrate, wherein the pouch substrate comprises one or more carriers, one or more active ingredients, and methylcellulose having a viscosity of about 200 to about 10,000 cP at 20°C and a 2% w / v concentration, as measured according to this specification, and the methylcellulose is added in an amount of about 0.5% to 6% by weight based on the total weight of the pouch substrate.

8. The oral pouch according to claim 7, wherein the active ingredient is nicotine.

9. The oral pouch according to claim 7 or 8, wherein the methylcellulose contains about 27.5 to 31.5% by weight of methoxy groups.

10. The oral pouch according to any one of claims 7 to 9, wherein the methylcellulose has a viscosity of about 300 to about 5000 cP at 20°C and a 2% w / v concentration when measured as described herein.

11. An oral pouch according to any one of claims 7 to 10, further comprising one or more flavoring agents.

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