Methylcellulose as humectant in bag substrate

Abstract

The present invention relates to the use of methylcellulose as a humectant in a pouch substrate and to a pouch for oral use comprising a pouch substrate wherein the pouch substrate comprises one or more carriers, one or more active ingredients and methylcellulose having a 5 viscosity at 20 DEG C of from about 200 to about 10000 cP at a concentration of 2% w / v.

Description

Technical Field

[0001] This invention relates to the use of methylcellulose as a humectant in a bag matrix. The invention also relates to a bag for oral use comprising a bag matrix, wherein the bag matrix comprises one or more carriers, one or more active ingredients, and methylcellulose having a viscosity of 200 to 10000 cP at a concentration of 2% w / v and at 20°C. Background Technology

[0002] A popular product for smokeless oral delivery of active ingredients such as nicotine is a pouch. A pouch is a container formed of a water-permeable material that encapsulates a cavity. The pouch is filled with a pouch matrix and then sealed. The pouch matrix can be dry, semi-moist, or moist. The pouch matrix typically contains alginate or other similar polysaccharides as humectants. Alginate improves the processability of the pouch matrix and retains moisture. US 2021 / 0169890 A1 describes oral compositions containing polysaccharides (e.g., acacia gum, xanthan gum, alginate, carrageenan, etc.) for use in pouches.

[0003] One problem associated with using alginate or other similar polysaccharides in the bag matrix is ​​a reduced release rate of active ingredients (such as nicotine) and flavorings contained in the bag matrix. This results in inefficient delivery of active ingredients and flavorings.

[0004] Therefore, there is a need for humectants that not only improve the processability of the bag matrix (powder flowability, reduced dust formation, etc.) but also allow for a more complete and faster release of the active ingredients and flavorings contained in the bag matrix.

[0005] Purpose of the invention One object of the present invention is to provide a humectant that, compared with known humectants (e.g., alginate), improves the processability of the pouch matrix, retains moisture in the pouch matrix, and allows for a more complete and rapid release of active ingredients and flavorings contained in the pouch matrix. Another object of the present invention is to provide a pouch for oral use that exhibits improved delivery of the active ingredients and flavorings contained therein, and thus provides a superior user experience.

[0006] The uses and the bag for oral use described below fulfill the above purposes. Summary of the Invention

[0007] In one aspect, the present invention relates to the use of methylcellulose as a humectant in a bag matrix.

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

[0009] In a preferred embodiment of each of the above aspects, the bag matrix further comprises one or more carriers and one or more active ingredients.

[0010] In yet another preferred embodiment of each of the above aspects, the active ingredient is nicotine.

[0011] In yet another preferred embodiment of each of the above aspects, the methylcellulose has a viscosity of about 200 to about 10,000 cP at a concentration of 2% w / v and a temperature of 20°C.

[0012] In a preferred embodiment of each of the above aspects, methylcellulose contains about 27.5-31.5% by weight of methoxy groups.

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

[0014] In a preferred embodiment of each of the above aspects, methylcellulose is added in an amount of about 0.5% to 10% by weight based on the total weight of the bag matrix.

[0015] In yet another preferred embodiment of each of the above aspects, the bag matrix further comprises one or more flavoring agents. Attached Figure Description

[0016] Figure 1 The nicotine release from the bag matrix of Examples 1 and 2 and Comparative Example 1 over time. Detailed Implementation

[0017] This invention is based on the discovery that using methylcellulose (MC) as a humectant in the bag matrix not only improves the processability and moisture retention of the bag matrix, but also improves the release of active ingredients and flavorings contained in the bag matrix. Therefore, bags containing methylcellulose as a humectant have improved potency and flavor intensity, and provide an excellent user experience.

[0018] Definitions and Terms Unless otherwise defined, all technical and scientific terms used below shall have the meanings commonly understood by the words.

[0019] Unless otherwise defined, any feature in any aspect or embodiment of the invention may be combined with any feature in any other aspect or embodiment of the invention, and those skilled in the art will understand that such combinations are covered within the original disclosure of this application. This also applies to the possibility of combining fundamental portions of the class list within the definitions of broader terms that differ from each other, the possibility of such individualized combinations being clearly intended to fall within the direct and explicit disclosure scope of this application. This also applies particularly, but not only, to the endpoints of the scope disclosed herein. For example, if a given substance is disclosed to be present in a composition at a concentration range of X% to Y% or A% to B%, this application should be understood to explicitly disclose not only the range X% to Y% and A% to B%, but also the range X% to B%, A% to Y%, and, where numerically possible, Y% to A% and B% to X%. Each of these ranges and combinations of ranges is contemplated and should be understood to be directly and explicitly disclosed in this application.

[0020] Similarly, it should be understood that the section headings used throughout this application are for organizational purposes only and do not imply exclusivity to the disclosure relating to aspects or embodiments of the invention mentioned in a particular section heading. Therefore, section headings do not exclude combinations of disclosure within any section heading with the corresponding or similar context provided under another section heading. In fact, such disclosure within a section is explicitly within the disclosure of this application.

[0021] As used herein, each of the terms “comprising,” “having,” and “containing,” including its grammatical variations, means “comprising” in a non-extensive sense, but not necessarily “consisting of,” and does not exclude elements other than those explicitly stated to exist. Thus, as used herein, the terms “comprising,” “having,” and “containing,” and their grammatical variations, indicate that components other than those explicitly stated may exist, but are not necessarily present. Therefore, these terms include, as an extreme case, embodiments in which no other elements besides those stated exist, for example, in the generally accepted sense of “consisting of.”

[0022] As used in this paper, the expression “composed of” and its grammatically related variants mean that there are no other elements besides those described. Given the above definition of “contains” (and related grammatically and semantically), the term “composed of” therefore represents the extreme case within the meaning of “contains”.

[0023] Unless otherwise stated, percentages indicating the extent to which a particular ingredient is contained in a mixture or composition are weight / weight (w / w) percentages. Similarly, unless otherwise stated, ratios specified herein are weight ratios.

[0024] Unless otherwise stated, the use of a hyphen ("-") separating two enclosing values ​​X and Y or two enclosing ratios to specify a range in this application should be understood to indicate and disclose the range including the two endpoint values ​​X and Y. This also applies to ranges expressed as "X to Y". Therefore, ranges expressed as "X – Y", "X to Y", "from X to Y", "X to Y", and "from X to Y" should be understood equivalently to indicate and disclose a range covering endpoint X, all values ​​between X and Y, and endpoint Y. Unless otherwise stated, specifying a range as "not exceeding X" should be understood to indicate and disclose a range with an upper limit of X and including the value X. Unless otherwise stated, specifying a range as "greater than X and at most Y" should be understood to indicate and disclose a range whose lower limit does not include the value X but includes any value higher than X and includes the upper limit Y. As used herein, "any value higher than X" can cover values ​​1.0% higher than X.

[0025] As used herein, the term "about" encompasses and discloses, when referring to one or more endpoints of a particular value, such as a range, a certain variation around the specifically stated value, in addition to the value itself. Such variation may arise, for example, from normal measurement variability, such as when weighing or dispensing various substances by methods known to those skilled in the art. The term "about" should be understood to encompass and disclose a range of variation above and below the specific value indicated, the percentage value relative to the specific stated value itself, as follows: The term "about" may encompass and disclose ± 5.0% variability. The term "about" may encompass and disclose ± 4.5% variability. The term "about" may encompass and disclose ± 4.0% variability. The term "about" may encompass and disclose ± 3.5% variability. The term "about" may encompass and disclose ± 3.0% variability. The term "about" may encompass and disclose ± 2.5% variability. The term "about" may encompass and disclose ± 2.0% variability. The term "about" may encompass and disclose ± 1.5% variability. The term "about" may cover and disclose a variation of ±1.0%. The term "about" may cover and disclose a variation of ±0.5%. With respect to a particular stated value, the term "about" may cover and disclose that exact specific value itself, whether or not it is explicitly mentioned that the exact specific value is included; even if not explicitly indicated that the term "about" includes a specific exact stated value, that exact specific value is still included within the range of variation created by the term "about," and is therefore disclosed in this application. Unless otherwise stated, when the term "about" is stated before the first endpoint of a numerical range but not before the second endpoint of that range, the term and its implied variation in the range and disclosure refer to both the first endpoint and the second endpoint of the range. For example, the stated range of "about X to Y" should be interpreted as "... about X to about"Y". This also applies to the range of ratios described. For example, a weight ratio description of "approximately X:Y - A:B" should be interpreted as a weight ratio of "(approximately X):(approximately Y) -(approximately A):(approximately B)".

[0026] As used herein, the term "the combination thereof" means any combination thereof in any proportion. That is, the term covers any combination of the listed features in any relative amount (e.g., any combination of any two listed features, any three listed features, etc.).

[0027] As used herein, the term "humectant" refers to a substance that absorbs moisture and retains the moisture in the bag matrix.

[0028] As used herein, the term "bag matrix" refers to a composition suitable for use in bags intended for oral use.

[0029] As used herein, the term "for oral use" refers to a product suitable for use in a user's mouth. During use, saliva in the user's mouth transfers one or more components of the product (e.g., pouch matrix) into the user's mouth.

[0030] As used herein, in the context of bag substrate, the term “dry” means a water content of no more than 12% by weight.

[0031] As used herein, in the context of bag substrate, the term “semi-moist” means a water content of more than 12% by weight but not more than 20% by weight.

[0032] As used herein, in the context of bag substrate, the term “wet” means a water content of more than 20% by weight but not more than 50% by weight.

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

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

[0035] As used in this article, the term "permeable" means that water can pass through the material of the bag in both directions: from the mouth into the inside of the bag, and from the inside of the bag (back) into the mouth.

[0036] As used herein, the term "carrier" refers to a substance or group of substances comprising 50% by weight or more of the bag matrix. Non-limiting examples of carriers include water-insoluble fibers, powdered cellulose, and sugar alcohols. Sugar alcohols may be selected, for example, from xylitol, maltitol, mannitol, erythritol, isomaltitol, sorbitol, lactitol, and combinations thereof.

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

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

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

[0040] As used herein, the term "fiber form" refers to a composition in fibrous form, i.e., particles whose length is significantly greater than their width. The term "fiber form" also encompasses all products referred to in the art as dietary fiber.

[0041] As used herein, the term "active ingredient" refers to a substance that has a regulatory (e.g., stimulating) effect on the user's nervous system. In a preferred embodiment, the active ingredient is selected from nicotine, caffeine, neonicotinoids, and combinations 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), salt form, complex form, or solvate form. Examples of nicotine complexes are resin complexes of nicotine in which nicotine is bound to an ion-exchange resin, such as nicotine polycrylene (polacrilex). Examples of nicotine salts are benzoates, hydrochlorides, dihydrochlorides, monotartrates, bitartrates, sulfates, salicylates, citrates, stearates, glutarates, aspartates, palmitates, and lactates. Other possible forms of nicotine are discussed below. Combinations of these in any proportions are also possible and are disclosed in the context of this invention.

[0043] As used herein, “nicotine content” means the amount of nicotine source in terms of free nicotine, expressed as a weight / weight (w / w) percentage (also referred to herein as “weight %”).

[0044] As used herein, the term "flavoring agent" is any flavoring or aromatic substance capable of altering the sensory properties of a compound or composition. Examples of sensory properties that can be altered by a flavoring agent include taste (e.g., sweet, salty, sour, bitter, etc.), mouthfeel, moisture, cold / hot temperature, and / or aroma / odor. Flavoring agents can be natural or synthetic, and the flavor characteristics imparted thereby can be described, without limitation, as fresh, sweet, salty, umami, herbal, candy, floral, fruity, or spicy. Specific flavor types include, without limitation, vanilla, coffee, chocolate / cocoa, cream, mint, spearmint, menthol, peppermint, mustard, red bean, ginseng, seaweed, wintergreen, eucalyptus, lavender, cardamom, nutmeg, cinnamon, clove, cascarilla, sandalwood, honey, jasmine, ginger, fennel, sage, licorice, lemon, citrus, apple, peach, lime, cherry, strawberry, and any combination thereof in any proportion. Flavoring agents also include components that are considered humectants, coolants, or lubricants, such as eucalyptus. Flavoring agents can mask the flavors (e.g., bitterness) of other components in the composition. For example, sweeteners can be used as bitterness maskers. Flavoring agents may contain at least one volatile flavor component. As used herein, “volatile” means a chemical substance that readily vaporizes at ambient temperatures (i.e., a chemical substance that has a high vapor pressure relative to a non-volatile substance at a given temperature). Typically, volatile flavor components have a molecular weight of less than about 400 Da and typically contain at least one carbon-carbon double bond, a carbon-oxygen double bond, or both. Examples of volatile flavor components include alcohols, aldehydes, aromatic hydrocarbons, ketones, esters, terpenes, trigeminal agonists, or combinations thereof. Non-limiting 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 heptaate, ethyl hexanoate, isoamyl acetate, and 3-methylbutyl acetate. Non-limiting examples of terpenes include sapinene, limonene, γ-terpinene, β-farnesene, nerolidol, thujone, myrcene, geraniol, nerol, citronellol, linalool, and eucalyptol. Combinations of these in any proportions are also possible and are disclosed in the context of this invention.

[0045] Uses of methylcellulose as a humectant in bag matrix This invention provides the use of methylcellulose as a humectant in a pouch matrix. Surprisingly, methylcellulose has been found to be superior to conventional humectants (e.g., alginate) because it provides excellent release of active ingredients and flavorings contained in the pouch matrix.

[0046] The bag substrate can be dry, semi-damp, or damp. In a preferred embodiment, the bag substrate is damp.

[0047] In a preferred embodiment, the bag matrix further comprises one or more carriers and one or more active ingredients.

[0048] In yet another preferred embodiment, the bag substrate has a water content of about 13%-35% by weight, preferably about 15%-30% by weight, and more preferably about 17%-25% by weight.

[0049] In another preferred embodiment, the carrier comprises water-insoluble fibers and / or sugar alcohols. The carrier content in the bag matrix may be at least about 50% by weight, preferably about 50%-90% by weight, more preferably about 60%-85% by weight, and most preferably about 70%-80% by weight.

[0050] In a preferred embodiment, in combination with any of the embodiments described above or below, the sugar alcohol is selected from xylitol, maltitol, mannitol, erythritol, isomaltitol, sorbitol, lactitol, and combinations thereof. Preferably, the sugar alcohol is a combination of xylitol and erythritol.

[0051] In another preferred embodiment, in combination with any of the above or below embodiments, the water-insoluble fiber is selected from cellulose fibers (e.g., powdered cellulose), wheat fibers, pea fibers, rice fibers, corn fibers, oat fibers, tomato fibers, barley fibers, rye fibers, beet fibers, buckwheat fibers, potato fibers, apple fibers, cocoa fibers, bran fibers, bamboo fibers, and combinations thereof.

[0052] In a preferred embodiment, the active ingredient is nicotine. Any form of nicotine can be used. Nicotine can be formulated in a premix of the liquid suspension before being added to the bag matrix.

[0053] In a preferred embodiment, the nicotine is a nicotine salt or a resin complex of nicotine, wherein the nicotine is bound in an ion exchange resin (i.e., a nicotine / ion exchange resin complex). In another preferred embodiment, the nicotine salt is nicotine bitartrate, glutarate, aspartate, palmitate, or lactate, with nicotine bitartrate being most preferred. Combinations of these in any proportions are also possible and are disclosed in the context of this invention.

[0054] In yet another preferred embodiment, the nicotine may be in liquid form of encapsulated (e.g., encapsulated by means of cyclodextrin) nicotine (e.g., free nicotine base).

[0055] In a preferred embodiment, the nicotine is selected from nicotine tartrate, nicotine polycrylamide, nicotine beta-cyclodextrin, nicotine o-salicylate, nicotine gentianate, nicotine gallate, nicotine phthalate, nicotine isophthalate, nicotine acetylsupan H, nicotine benzoate, nicotine fumarate, nicotine R-mandelate, nicotine hydrochloride, nicotine L-lactate, nicotine levulinate, nicotine phosphate, nicotine ascorbate, nicotine ferulic acid, nicotine vanillate, nicotine picolinate, nicotine cumylate, nicotine nicotinate, nicotine pyruvate, and nicotine γ-m-dihydroxybenzoate. Combinations of these in any proportion are also possible and are disclosed in the context of this invention.

[0056] In a preferred embodiment, the active ingredient is nicotine and its content in the bag matrix is ​​about 0.5-20 mg, preferably about 0.5-15 mg, and most preferably about 0.5-10 mg.

[0057] In a preferred embodiment, the viscosity of methylcellulose at a concentration of 2% w / v at 20°C is about 200 to about 10,000 cP. More preferably, the viscosity of methylcellulose at a concentration of 2% w / v at 20°C is about 300 to about 5,000 cP. Viscosity is measured according to the method described in Ph. Eur. 11.0, pages 3379-3380.

[0058] In a preferred embodiment, the methylcellulose has a viscosity of about 300 to about 500 cP at a concentration of 2% w / v and a temperature of 20°C. An example of such methylcellulose is DuPont's Methocel™ 4AC.

[0059] In another preferred embodiment, the methylcellulose has a viscosity of about 2000 to about 5000 cP at 20°C at a concentration of 2% w / v, preferably 2500 to 5000 cP at a concentration of 2% w / v at 20°C. An example of such methylcellulose is DuPont's Methocel™ 4AM.

[0060] In another preferred embodiment, the methylcellulose contains about 27.5-31.5% by weight of methoxy groups. The methoxy group content can be determined by NMR spectroscopy.

[0061] In another preferred embodiment, methylcellulose is added in an amount of about 0.5% to 10% by weight based on the total weight of the bag matrix. More preferably, methylcellulose is added in an amount of about 1% to 8% by weight based on the total weight of the bag matrix, even more preferably about 1.2% to 6% by weight based on the total weight of the bag matrix, and most preferably about 1.3% to 5% by weight based on the total weight of the bag matrix.

[0062] In a preferred embodiment, the bag matrix also contains one or more flavorings.

[0063] In yet another preferred embodiment, the bag matrix comprises methylcellulose at a concentration of 2% w / v with a viscosity of about 300 to about 5000 cP at 20°C, one or more carriers, one or more active ingredients, and one or more flavoring agents, wherein the carrier is a water-insoluble fiber and the active ingredient is nicotine.

[0064] All of the preferred embodiments described above can be combined with each other, and such combinations are disclosed in the context of this invention.

[0065] Bag for oral use The present invention also provides a bag for oral use, comprising a bag matrix, wherein the bag matrix comprises one or more carriers, one or more active ingredients, and methylcellulose having a viscosity of about 200 to about 10,000 cP at a concentration of 2% w / v and at 20°C. The viscosity is measured according to the method described in Ph. Eur. 11.0, pages 3379-3380.

[0066] The bag substrate can be dry, semi-damp, or damp. In a preferred embodiment, the bag substrate is damp.

[0067] In yet another preferred embodiment, the bag substrate has a water content of about 13%-35% by weight, preferably about 15%-30% by weight, and more preferably about 17%-25% by weight.

[0068] In another preferred embodiment, the carrier comprises water-insoluble fibers and / or sugar alcohols. The carrier content in the bag matrix may be at least about 50% by weight, preferably about 50%-90% by weight, more preferably about 60%-85% by weight, and most preferably about 70%-80% by weight.

[0069] In a preferred embodiment, in combination with any of the above or below embodiments, the sugar alcohol is selected from xylitol, maltitol, mannitol, erythritol, isomaltitol, sorbitol, lactitol, and combinations thereof.

[0070] In another preferred embodiment, in combination with any of the above or below embodiments, the water-insoluble fiber is selected from cellulose fibers (e.g., powdered cellulose), wheat fibers, pea fibers, rice fibers, corn fibers, oat fibers, tomato fibers, barley fibers, rye fibers, beet fibers, buckwheat fibers, potato fibers, apple fibers, cocoa fibers, bran fibers, bamboo fibers, and combinations thereof.

[0071] In a preferred embodiment, the active ingredient is nicotine. Any form of nicotine can be used. Nicotine can be formulated in a premix of the liquid suspension before being added to the bag matrix.

[0072] In a preferred embodiment, the nicotine is a nicotine salt or a resin complex of nicotine, wherein the nicotine is bound in an ion exchange resin (i.e., a nicotine / ion exchange resin complex). In another preferred embodiment, the nicotine salt is nicotine tartrate, glutarate, aspartate, palmitate, or lactate, with nicotine tartrate being the most preferred.

[0073] In yet another preferred embodiment, the nicotine may be in liquid form of encapsulated (e.g., encapsulated by means of cyclodextrin) nicotine (e.g., free nicotine base).

[0074] In a preferred embodiment, the nicotine is selected from nicotine tartrate, nicotine polycrylamide, nicotine beta-cyclodextrin, nicotine o-salicylate, nicotine gentianate, nicotine gallate, nicotine phthalate, nicotine isophthalate, nicotine acetylsupan H, nicotine benzoate, nicotine fumarate, nicotine R-mandelate, nicotine hydrochloride, nicotine L-lactate, nicotine levulinate, nicotine phosphate, nicotine ascorbate, nicotine ferulic acid, nicotine vanillate, nicotine picolinate, nicotine cumylate, nicotine nicotinate, nicotine pyruvate, and nicotine γ-m-dihydroxybenzoate. Combinations of these in any proportion are also possible and are disclosed in the context of this invention.

[0075] In a preferred embodiment, the active ingredient is nicotine and its content in the bag matrix is ​​about 0.5-20 mg, preferably about 0.5-15 mg, and most preferably about 0.5-10 mg.

[0076] In a preferred embodiment, the methylcellulose has a viscosity of about 300 to about 5000 cP at a concentration of 2% w / v and a temperature of 20°C.

[0077] In a preferred embodiment, the viscosity of methylcellulose at a concentration of 2% w / v at 20°C is about 300 to about 500 cP. In another preferred embodiment, the viscosity of methylcellulose at a concentration of 2% w / v at 20°C is about 2000 to about 5000 cP, preferably about 2500 to about 5000 cP.

[0078] In another preferred embodiment, the methylcellulose contains about 27.5-31.5% by weight of methoxy groups. The methoxy group content can be determined by NMR spectroscopy.

[0079] In another preferred embodiment, methylcellulose is added in an amount of about 0.5% to 10% by weight based on the total weight of the bag matrix. More preferably, methylcellulose is added in an amount of about 1% to 8% by weight based on the total weight of the bag matrix, even more preferably about 1.2% to 6% by weight based on the total weight of the bag matrix, and most preferably about 1.3% to 5% by weight based on the total weight of the bag matrix.

[0080] In a preferred embodiment, the bag matrix also contains one or more flavorings.

[0081] In yet another preferred embodiment, the bag matrix comprises methylcellulose at a concentration of 2% w / v with a viscosity of about 300 to about 5000 cP at 20°C, one or more carriers, one or more active ingredients, and one or more flavoring agents, wherein the carrier is a water-insoluble fiber and the active ingredient is nicotine.

[0082] All of the preferred embodiments described above can be combined with each other, and such combinations are disclosed in the context of this invention.

[0083] The bag matrix 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, pentapotassium 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 salts, nitrates, nitrites, acetic acid and its salts, lactic acid and its salts, malic acid and its salts, and combinations thereof. One 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-intensity sweeteners such as sucralose, aspartame, acesulfame potassium (e.g., acesulfame potassium), alicon, saccharin and its salts, cyclohexane and its salts, glycyrrhizin, dihydrochalcone, sematrandezidine, monellin, stevioside, and combinations thereof.

[0084] Example The bag matrix having the composition given in Table 1 was prepared and filled into the bag according to the method of Example 3A of WO 2020 / 244721 A1. The nicotine direct premix was prepared according to the method of Example 2B of WO 2020 / 244721 A1.

[0085] Table 1:

[0086] Nicotine release test: The changes in nicotine release over time from the bags of Examples 1 and 2, and Comparative Example 1, were measured using the following method: A chewing buffer was prepared by dissolving 2.72 g potassium dihydrogen phosphate in 950 ml of purified water, and the pH of the solution was adjusted to 7.4 with 2 NKOH solution. Purified water was then added to obtain a final buffer volume of 1000 ml.

[0087] Degas 10 liters of the chewing buffer solution prepared as described above and heat to 38°C to prepare a solution (chewing buffer solution).

[0088] Transfer 900 ml of the obtained chewing buffer to each container in the USP dissolution apparatus 1 (e.g., Agilent 708-DS dissolution apparatus). Inside the container, adjust the chewing buffer (pH 7.4) to 37°C.

[0089] Transfer the weighed bag to the basket and start the dissolution device. Set the buffer sampling time to 2, 6, 12, 20, and 30 minutes. Set the rotation speed to 100 rpm. Manually collect release samples after 2 minutes using the cannula. Automatically collect release samples after 6, 12, 20, and 30 minutes using the dissolution device.

[0090] Filter all samples and prepare them for HPLC analysis.

[0091] As from Figure 1 As can be seen, compared with Comparative Example 1 (solid line) which contains sodium alginate as a humectant, Examples 1 (dotted line) and 2 (dashed line) which contain methylcellulose as a humectant exhibited improved (faster) nicotine release.

[0092] The present invention also relates to the following embodiments.

[0093] Example 1: Use of methylcellulose as a humectant in bag matrix.

[0094] Example 2: According to the use described in Example 1, the bag matrix further comprises one or more carriers and one or more active ingredients.

[0095] Example 3: The use according to Example 1 or 2, wherein the active ingredient is nicotine.

[0096] Example 4: The use according to any one of Examples 1-3, wherein the methylcellulose has a viscosity of about 200 to about 10,000 cP at 20°C with a concentration of 2% w / v.

[0097] Example 5: The use according to any one of Examples 1-4, wherein the methylcellulose contains about 27.5-31.5% by weight of methoxy groups.

[0098] Example 6: According to any one of Examples 1-5, the methylcellulose has a viscosity of about 300 to about 5000 cP at 20°C with a concentration of 2% w / v.

[0099] Example 7: The use according to any one of Examples 1-6, wherein the methylcellulose is added in an amount of about 0.5% to 10% by weight based on the total weight of the bag matrix.

[0100] Example 8: According to any one of Examples 1-7, the bag matrix further comprises one or more flavoring agents.

[0101] Example 9: A bag for oral use comprising a bag matrix, wherein the bag matrix 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 with a concentration of 2% w / v.

[0102] Example 10: A pouch for oral use according to Example 9, wherein the active ingredient is nicotine.

[0103] Example 11: A bag for oral use according to Example 9 or 10, wherein the methylcellulose contains about 27.5-31.5% by weight of methoxy groups.

[0104] Example 12: A bag for oral use according to any one of Examples 9-11, wherein the methylcellulose has a viscosity of about 300 to about 5000 cP at 20°C with a concentration of 2% w / v.

[0105] Example 13: A bag for oral use according to any one of Examples 9-12, wherein the amount of methylcellulose in the bag matrix is ​​about 0.5%-10% by weight based on the total weight of the bag matrix.

[0106] Example 14: The oral pouch according to any one of Examples 9-13 further comprises one or more flavorings.

Claims

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

2. The use according to claim 1, wherein the bag matrix 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 1-3, wherein the methylcellulose contains about 27.5-31.5% by weight of methoxy groups.

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

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

7. A bag for oral use, comprising a bag matrix, wherein the bag matrix 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 as measured as described in the specification at a concentration of 2% w / v, wherein the methylcellulose is added in an amount of about 0.5% to 6% by weight based on the total weight of the bag matrix.

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

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

10. A bag for oral use according to any one of claims 7-9, wherein the methylcellulose has a viscosity of about 300 to about 5000 cP at 20°C as measured as described in the specification at a concentration of 2% w / v.

11. The bag for oral use according to any one of claims 7-10, further comprising one or more flavorings.

Images