Nicotine Composition

Abstract

The present invention describes a composition, e.g., a tobacco-free or low tobacco nicotine-containing composition, comprising: a. nicotine in free base form in an amount of about 0.2% to about 2% by weight; b. natural cellulosic material in an amount of about 35% to about 60% by weight; c. water in an amount of at least 35% by weight; d. one or more pH controlling salts in an amount of about 0.5% to about 3% by weight; e. a release controlling agent comprising agar and / or agar derivatives in an amount of about 0.1% to about 2% by weight; and f. any additional ingredients in an amount preferably up to about 12% by weight. The composition may be provided in a pouch for oral delivery to a user.

Description

[Technical field]

[0001] The present invention relates to tobacco-free or low-tobacco nicotine compositions. The compositions are preferably for human consumption and can be delivered orally, for example, by placing a permeable pouch filled with the composition in the mouth of the user. [Background technology]

[0002] Tobacco-free or low-tobacco pouches with nicotine are alternative products that can help reduce the cravings associated with smoking cigarettes, cigars, or other nicotine delivery products. When smoking a cigarette or using an inhalation-based nicotine delivery system, i.e., so-called vaping, nicotine vapor is rapidly absorbed into the bloodstream through the lungs and reaches the brain within 10 seconds after inhalation. The brain produces an almost instantaneous feeling of gratification that lasts for some time after smoking / inhaling.

[0003] Tobacco-free or low-tobacco pouches with nicotine are intended to be used in the mouth by placing the pouch under the lips, thereby allowing the release and absorption of nicotine through the oral mucosa. The pouches typically comprise a saliva-permeable membrane material and contain particulate filler, nicotine or a nicotine derivative, and other ingredients such as flavorings. The particulate material may comprise polysaccharide or cellulosic materials, among others.

[0004] Nicotine is an alkaloid that was traditionally derived from tobacco leaves, but is now also available in a fully synthetic form. It is available both as free base nicotine and in the form of a variety of nicotine salts, which are produced from the interaction of nicotine with acids. Common nicotine salts include chloride, sulfate, benzoate, and tartrate.

[0005] It is known to provide tobacco-free or low-tobacco pouches in which nicotine is provided in a salt form in a powder formulation. Providing nicotine salts in such formulations has been developed in part due to the high stability of the system against chemical degradation and / or evaporation.

[0006] To release free base nicotine from formulations containing nicotine salts, the formulations contain significant amounts of buffer salts to increase the alkalinity of the formulation. Increasing alkalinity alters the dissociation constant of nicotine, resulting in the production of the free base form in solution (such as in the user's mouth) from the ionic form of nicotine in the salt. Uncharged free base nicotine has a higher permeability across the oral mucosa into the bloodstream than its ionic form, which is important for consumer use.

[0007] Notably, the pH of tobacco-free pouches with nicotine typically ranges from 6.9 to 10.1, resulting in undissociated free base nicotine levels of 7.7 to 99.2%, respectively (Stanfil et al. Nicotine & Tobacco Research, 2021, 1590-1596).

[0008] It follows that nicotine salt formulations tend to be characterized by a low moisture content, i.e., less than 10% by weight (e.g., 1-8% by weight). This is because a high moisture content promotes the formation of free base nicotine in situ, which reduces the stability of the product since free base nicotine is volatile and unstable to oxidative degradation. When nicotine oxidizes, it turns yellow-brown, which is often unattractive to consumers and also produces an unpleasant taste. In fact, some formulations contain large amounts of sweeteners (e.g., maltitol) to stimulate salivation. However, when saliva is excessively produced, the user tends to spit or swallow, which affects the uptake of nicotine. Furthermore, the degradation of the product indicates reactivity in the system, which can lead to the presence of undesirable (and potentially toxic) compounds.

[0009] These requirements pose problems for the user: formulations with low moisture content can feel hard and harsh when used, while high alkalinity (especially pH above about 9) can irritate the user's gums. In contrast, moist nicotine products have improved palatability when used in the mouth, i.e. soft and pleasant to the touch.

[0010] Nicotine pouches containing free base nicotine products are available with moisture levels of greater than 35% by weight. However, this type of formulation requires stabilization to prevent nicotine degradation and also requires ingredients to prevent moisture loss during storage. Thus, wet free base nicotine products tend to require the use of a greater number and amount of additives than products containing nicotine salts.

[0011] WO 2010 / 104464 and WO 2010 / 0114445 disclose compositions of free base nicotine that can be stabilized using salts of alginic acid such as sodium alginate (e.g., Protanal LFR 5 / 60). The amount of sodium alginate used as a stabilizer is substantial, usually corresponding to a nicotine:Protanal ratio of 1:2 (by weight). WO 2020244721 discloses compositions of free base nicotine, in which the free base nicotine is stabilized using an ion exchange resin, e.g., a polacrilex resin such as Amberlite IRP64 (a methacrylic acid polymer with divinylbenzene, or the potassium salt of divinylbenzene). The amount of polacrilex resin used as a nicotine stabilizer is a nicotine to resin ratio that can vary between 1:1.19 and 1:4. It is understood that to stabilize free base nicotine, typically a polymer with several carboxylate groups is used.

[0012] To prevent moisture loss during storage of free base nicotine formulations, humectants such as sugar alcohols are commonly used. US Patent Application Publication No. 2020 / 0383372 discloses several compositions of free base nicotine and polacrilex resin with moisture content greater than 15%, most commonly about 30%. Selected humectants include sugar alcohols from glycerol, propylene glycol, polyethylene glycol, alginates, pectin, xanthan gum, modified starch, hydroxypropyl cellulose, and triacetin.

[0013] However, moisture present in the product poses a significant challenge to formulation. Moisture not only acts as a nicotine solvent that facilitates diffusion transport from the formulation to the oral mucosa, but also acts as a medium for chemical reactions that can significantly accelerate the rate of chemical degradation and spoilage of the product. Indeed, nicotine formulations with high moisture content may still be unstable, especially if the moisture content is greater than 30% by weight. As mentioned above, nicotine degradation leads to discoloration of the product. Furthermore, it is important to avoid nicotine degradation and prevent moisture evaporation during storage. Nicotine degradation and moisture evaporation can lead to discrepancies between the actual nicotine content and the stated nicotine content (mg nicotine per gram). This reduces the shelf life of the product.

[0014] Physical instability is also a common problem for wet products. Physical instability can include discoloration, stickiness, clumping, phase changes (such as dissolution-recrystallization and evaporation). Discoloration and chemical decomposition can be related to each other. Powder clumping may require additional sieving to control particle size after compounding, resulting in additional costs during processing.

[0015] Physical and chemical instability can lead to the accumulation of toxic by-products of nicotine degradation, as well as poor usability of the product due to color changes (white product turning yellow, brown, or pink), dusting due to drying, leakage from the pouch, hardening of the product, poor mouthfeel, and changes in the nicotine release profile.

[0016] There is therefore a need to provide a tobacco-free or low-tobacco nicotine composition which is suitable for use in a pouch, where the nicotine has a high degree of chemical stability, where the composition has a high degree of physical stability, where the pH is at a level which is comfortable for the user, and where the composition contains a relatively high amount of moisture.

[0017] Furthermore, there is a need to provide tobacco-free or low-tobacco nicotine moist compositions to achieve both a rapid release of nicotine (and therefore rapid absorption into the bloodstream) and an improved overall sensory experience for the user.

[0018] Further, there is a need to provide such a product that can be manufactured in a simple, reliable and cost-effective manner. Summary of the Invention

[0019] In a first aspect, the present invention provides a method for producing a composition comprising the steps of: a. about 0.2% to about 5% by weight of nicotine in its free base form; b. a natural cellulosic material in an amount of about 35% to about 60% by weight; c. water in an amount of at least 35% by weight; d. one or more pH controlling salts in an amount of about 0.5% to about 3% by weight; e. a release control agent comprising agar and / or agar derivatives in an amount of about 0.1% by weight to about 2% by weight; f. any additional ingredients, preferably in an amount up to about 12% by weight; A composition is provided. All weight percentages are expressed as a percentage of the total weight of the composition.

[0020] In a second aspect, the present invention provides the use of agar as a nicotine release controlling agent in a composition comprising: a. about 0.2% to about 5% by weight of nicotine in its free base form; b. a natural cellulosic material in an amount of about 35% to about 60% by weight; c. water in an amount of at least 35% by weight; d. one or more pH controlling salts in an amount of about 0.5% to about 3% by weight; e. a release control agent comprising agar in an amount of about 0.1% by weight to about 2% by weight; f. any additional ingredients, preferably in an amount of up to about 12% by weight; Includes.

[0021] In a third aspect, the present invention provides the use of agar as a nicotine stabilizer in a composition comprising: a. about 0.2% to about 5% by weight of nicotine in its free base form; b. a natural cellulosic material in an amount of about 35% to about 60% by weight; c. water in an amount of at least 35% by weight; d. one or more pH controlling salts in an amount of about 0.5% to about 3% by weight; e. a release control agent comprising agar in an amount of about 0.1% by weight to about 2% by weight; and f. any additional ingredients, preferably in an amount up to about 12% by weight.

[0022] Preferably, the composition further comprises additional ingredients in an amount of about 1% to about 10% by weight, or more preferably in an amount of about 1% to about 8% by weight. The additional ingredients may include one or more additives selected from flavorants, flavor enhancers, sweeteners, and preservatives.

[0023] The sweetener is preferably present in an amount of about 1% to about 3% by weight. The sweetener may comprise a compound selected from sugars (sucrose, fructose, glucose, dextrose, maltose, lactose, galactose), sugar alcohols (such as xylitol, maltitol, sorbitol, erythritol) and / or sugar substitutes (such as aspartame, saccharin, sucralose, allulose, acesulfame K, cyclamate or steviol glycosides).

[0024] Preferably, the sweetener comprises a sugar alcohol in an amount of less than 3% by weight, preferably less than 2% by weight, for example 1% to 2% by weight. Additionally or alternatively, the sweetener may comprise a sugar substitute in an amount of less than 1% by weight, preferably less than 0.5% by weight, for example 0.05% to 0.3% by weight. Preferred sweeteners include xylitol and / or acesulfame K.

[0025] The preservative may comprise one or more preservatives selected from calcium chloride, salts of sorbic acid (such as potassium sorbate), salts of benzoic acid (such as sodium benzoate), nitrates, nitrites, sulfates, sulfites and propionates. Preferably, the preservative is present in an amount of less than about 1% by weight, preferably 0.1% to 0.5% by weight, for example about 0.25% to about 0.35% by weight.

[0026] The pH control salts may include buffer salts such as carbonates or sesquicarbonates; acetates, glycinates, acetates, glycinates, gluconates, borates, glycerophosphates or citrates; phosphates. A combination of ammonium chloride and sodium bicarbonate is preferred. When ammonium chloride is present, its amount may be 0.05% to 1% by weight, preferably 0.1% to 0.5% by weight, for example 0.15% to 0.25% by weight. When sodium bicarbonate is present, its amount may be less than 1% by weight, preferably 0.1% to 0.5% by weight, for example 0.2% to 0.3% by weight.

[0027] Preferably, the composition comprises more than 40% water by weight, for example 40% to 50% water by weight, preferably about 44% to about 48% water by weight.

[0028] Preferably, the natural cellulose material comprises powdered cellulose and / or microcrystalline cellulose (MCC), with MCC being preferred.

[0029] The release control agent preferably comprises agar in an amount of less than about 1% by weight of the composition, preferably less than 0.7% by weight. In practice, the release control agent may comprise agar in an amount of about 0.2% to about 0.7% by weight, preferably about 0.2% to about 0.5% by weight.

[0030] The ratio of agar to nicotine is preferably less than about 1.3: 1. In a further preferred embodiment, the ratio of agar to nicotine is from about 0.1:1 to about 1.2:1, preferably from about 0.1:1 to about 1:1, more preferably from about 0.1:1 to about 0.8:1.

[0031] Some embodiments may include tobacco leaf in an amount of less than 5% by weight, preferably about 1% to 3% by weight.

[0032] The pH of the composition, measured by CORESTA method No. 69 (2017), is preferably 6 to 9, more preferably 7 to 9, and even more preferably 7 to 8.5.

[0033] Preferably, any flavour enhancer present is selected from the group comprising sodium chloride, glutamate, glycine salt, inosinate and 5'-ribonucleotide salt, If sodium chloride is present, it is preferred that its amount is less than 8% by weight of the composition, preferably between 1% and 7%.

[0034] The compositions preferably comprise flavour compounds in an amount of less than about 5% by weight of the total composition, such as less than 3% by weight of the composition, or between 0.5% and 3% by weight of the composition.

[0035] A preferred amount of nicotine in the composition is from 0.2% to 3% by weight, or from 0.2% to 2% by weight.

[0036] In some embodiments, the composition may consist essentially of the above components.

[0037] In another aspect, the invention provides a water or saliva permeable pouch comprising the above-described composition. In yet another aspect, the invention provides a package comprising a plurality of these pouches.

[0038] In a further aspect, the present invention provides a process for forming a nicotine-containing composition as described above, the process comprising: a. mixing natural cellulose material in an amount of 40% to 60% by weight of the target composition with agar powder in an amount of 0.2% to 2% by weight of the target composition in a mixer, thereby forming a precursor composition; b. adding water to the precursor composition and mixing at a temperature above 50° C.; c. adding nicotine in free base form to the precursor composition in an amount of 0.2% to about 2% by weight of the desired final composition while the temperature is above 50°C; d. cooling the mixture; Additional water may be added between steps (c) and (d).

[0039] In a preferred embodiment, in steps (b) and (c), the mixing of the precursors is carried out at a temperature above about 60°C, preferably above about 70°C, preferably above 80°C.

[0040] In step (b), water may be provided to the precursor at a temperature above about 70° C., preferably above about 80° C. Indeed, in step (b), water may be provided to the precursor in the form of water vapor or steam.

[0041] If additional water is added between steps (c) and (d), its temperature may be greater than about 70° C., preferably greater than about 80° C. Indeed, the additional water may be in the form of steam or vapor.

[0042] In some embodiments, the precursor mixture is heated while in the mixer, for example during steps (b) and / or (c), and / or during or after the optional addition of water following step (c).

[0043] In some embodiments, additional water is added to the composition after step (d).

[0044] In a preferred embodiment, any of the following components may be added to the precursor mixture prior to step (b): e. one or more pH controlling salts in an amount of about 0.5% to about 3% by weight of the subject composition; f. Additional ingredients, preferably in amounts up to about 12% by weight of the subject composition.

[0045] Agar is a dry, hydrophilic, colloidal polysaccharide complex extracted from red algae (Rhodophyceae). Its structure is believed to be a variety of complex polysaccharide chains with alternating α-(1→3) and β-(1→4) bonds. Agar can be separated into a natural gelling fraction, agarose, and a sulfated, non-gelling fraction, agaropectin. Agar dissolves in hot water to form a viscous solution, but is sparingly soluble in cold water and ethanol (95%). A 1% w / v solution in water forms a firm jelly on cooling.

[0046] When the term "tobacco" is used, it means any part of any member of the Nicotiana genus, including leaves, stems, and stalks. Tobacco may be whole, shredded, threshed, cut, ground, cured, aged, fermented, or otherwise processed (e.g., granulated or encapsulated).

[0047] Embodiments of the present invention will now be described with reference to the following drawings. [Brief description of the drawings]

[0048] [Figure 1] FIG. 2 shows plots of nicotine release profiles of compositions according to the invention and comparative examples. [Diagram 2] FIG. 2 shows plots of nicotine release profiles of compositions according to the invention and comparative examples. [Diagram 3] FIG. 1 shows photographs of pouches and compositions according to the present invention and comparative examples. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0049] In a first embodiment of the present invention, a tobacco-free (or optionally low-tobacco) nicotine formulation for use in an oral pouch is provided. The formulation has a high moisture content and contains nicotine in its free base form. The composition includes a cellulosic filler and uses agar as a nicotine release agent to facilitate the release of nicotine from the composition when the composition is placed in the oral cavity of a user (e.g., in a pouch).

[0050] In one embodiment, the composition has the general formulation as set forth below. a. about 0.2% to about 5% by weight of nicotine in its free base form; b. a natural cellulose material, e.g., microcrystalline cellulose, in an amount of about 35% to about 60% by weight; c. water in an amount of at least 35% by weight; d. one or more pH controlling salts in an amount of about 1% to about 6% by weight, such as a combination of ammonium chloride and sodium bicarbonate; e. a controlled release agent comprising agar or a derivative thereof in an amount of about 0.1% by weight to about 2% by weight; f. Optional additional ingredients, such as flavors, flavor enhancers, sweeteners and preservatives, preferably in amounts up to about 12% by weight.

[0051] All weight percentages are based on the total weight of the composition.

[0052] The amount of nicotine in the composition varies depending on the desired strength of the product, in some embodiments, the amount of nicotine is between 0.2% and 3% by weight, or between 0.2% and 2% by weight.

[0053] The natural cellulose useful in the present invention can include powdered cellulose and / or microcrystalline cellulose.Examples of powdered cellulose that can be used in the present invention include Arbocel (RTM) supplied by J.Rettenmaier&Soehne GmbH, KC Flock (RTM) supplied by Elcema, Nippon Paper Industries Co.Ltd., Microcel 3E-150 supplied by Roquette Freres, Sanacel (RTM) supplied by CFF GmbH, Sanacel Pharma (RTM) supplied by CFF GmbH, Sancel-W supplied by NB Entrepreneurs Company, or Solka-Floc (RTM) supplied by J.Rettenmaier USA LP.

[0054] Examples of microcrystalline cellulose that can be used in the present invention include Avicel (RTM) PH supplied by Dupont Nutrition and Biosciences, Inc., Cellets (RTM) supplied by Pharmatrans Sanaq AG, Celphere (TM) supplied by Asahi Kasei Corporation, Ceolus (TM) KG supplied by Asahi Kasei Corporation, Emcocel (RTM) supplied by JRS Pharma GmbH, MCC Sanaq (RTM) supplied by Pharmatrans Sanaq AG, Pharmacel (RTM) supplied by DFE Pharma GmbH, Tabulose (RTM) supplied by Roquette Freres, Vivapur (RTM) supplied by JRS Pharma GmbH.

[0055] The water content of the composition should be at least 35% by weight, although it is preferred that the composition contains a greater proportion of water. A water content of the composition greater than 40% by weight tends to improve the palatability of the composition for the user, such as increasing softness. A preferred composition has a water content of greater than 42% by weight, for example 44% to 48% by weight of water.

[0056] The composition includes a pH controlling salt to provide an optimal pH of the composition during use in the mouth of the user. The pH of the composition is preferably 6-9, preferably 7-9, more preferably 7-8.5, when measured according to CORESTA Method No. 69 (2017). This can be achieved by providing a pH adjusting agent such as sodium bicarbonate, or a buffer salt such as a combination of ammonium chloride and sodium bicarbonate. Typical amounts of pH controlling salts are 0.2% to 2% by weight, preferably 0.2% to 1% by weight. Alternative buffer salts may be selected from, for example, carbonates or sesquicarbonates; acetates, glycinates, acetates, glycinates, gluconates, borates, glycerophosphates or citrates; phosphates.

[0057] The flavorings included in the composition are not limited, but preferably include flavonoid compounds that stimulate the user's olfactory system, typically in an amount of less than about 3% by weight of the total composition. Such compounds are commercially available and are well known to those skilled in the art.

[0058] Sweeteners or flavor enhancers can be included to improve the flavor of the composition.

[0059] Sweeteners may include sugar-based sweeteners such as sucrose, fructose, glucose, dextrose, maltose, lactose, galactose, etc.; sugar alcohols such as xylitol, maltitol, sorbitol, erythritol, etc.; or other sugar substitutes such as aspartame, saccharin, sucralose, allulose, acesulfame K, cyclamate, or steviol glycosides. Sweeteners may be present alone, but are preferably used in combination (e.g., sugar alcohols and sugar substitutes). A preferred combination is xylitol and acesulfame K. The amount of sweetener present in the composition will depend on the characteristics of the sweetener selected, as will be appreciated by those skilled in the art, but typically ranges from 1% to 3% by weight in total.

[0060] Flavor enhancers may include sodium chloride, salts of glutamic acid (such as monosodium glutamate), glycine salts, inosinate salts, and 5'-ribonucleotide salts (such as one or more disodium ribonucleotides). The amount of flavor enhancer present in the composition will depend on the characteristics of the flavor enhancer selected, as will be appreciated by those skilled in the art, but will typically range from 1% to 8% by weight in total.

[0061] Preservatives may include antimicrobial preservatives such as sorbates (such as sodium sorbate or potassium sorbate), benzoates, nitrates, nitrites, sulfates, sulfites, and propionates. Salts such as calcium chloride can also be used as preservatives.

[0062] All compositions may contain small amounts of tobacco, such as 1% to 5% by weight, particularly if contained in a pouch.

[0063] The inventors have surprisingly found that the presence of agar in the composition acts as an effective nicotine stabilizer and release control agent.Without wishing to be bound by any particular theory, it is hypothesized that nicotine may be partially bound in the agar gel that may be formed during manufacture.This appears to provide a highly stable nicotine composition that can be stored for a long time, despite the use of free base nicotine and high levels of moisture.Furthermore, the nicotine release profile of the composition is fast and consistent, providing excellent product performance.

[0064] This performance is achieved even though only a relatively small amount of agar is provided in the composition. The agar is preferably present in an amount of from 0.1% to about 1.2% by weight. It is preferably present in an agar to nicotine ratio of from about 0.1:1 to about 1.2:1, preferably from about 0.1:1 to about 1:1, more preferably from about 0.1:1 to about 0.8:1. This is a significantly lower ratio than is required for prior art stabilizers.

[0065] Any food or pharmaceutical grade agar can be used in the present invention, specific examples include Rokoagar (RTM) RGM 600 and RGM 800 supplied by Industrias Roko, SA.

[0066] In a preferred embodiment, the composition may have the following general composition: a. about 0.2% to about 3% by weight of nicotine in its free base form; b. microcrystalline cellulose in an amount of about 35% to about 60% by weight; c. water in an amount of at least 35% by weight, preferably greater than 40% by weight; d. buffer salts of ammonium chloride in amounts of 0.05% and 1% by weight and sodium bicarbonate in amounts of about 0.1% to about 1% by weight; e. a controlled release agent comprising agar in an amount of about 0.1% by weight to about 2% by weight; f. any additional ingredients, e.g. a. a flavoring in an amount of 0.5% to about 3% by weight; b. a flavor enhancer, such as sodium chloride, in an amount of 2% to 8% by weight; c. a sweetener such as xylitol in an amount of about 1% to 2% by weight and / or acesulfame K in an amount of 0.05% to 1% by weight; d. a preservative, such as potassium sorbate, in an amount of about 0.25% to about 1% by weight; e. Tobacco in an amount between 0% and 3% by weight.

[0067] In a further embodiment, a process for producing a tobacco-free or low-tobacco nicotine composition is provided. The process includes mixing in a vessel (such as an autoclave) natural cellulose in an amount of 30% to 60% by weight of the desired final composition and agar in an amount of 0.1% to 2% by weight of the final composition, each in powder or granular form. One or more of the other solid components of the composition (e.g., pH control salts, flavor enhancers, sweeteners, or preservatives) can also be added at this stage of the process, although any tobacco to be included in the final composition should ideally be retained until the remainder of the composition is completed.

[0068] At least a portion of the water (preferably at least 10% by weight of the desired final composition) is then added to the composition and the composition is heated. Heating can be accomplished in a variety of ways. The mixing vessel may be heated, for example, using a heated manifold. Alternatively or additionally, the water may be heated prior to being introduced into the mixing vessel, or some or all of the water may be added as steam.

[0069] The temperature of the resulting precursor mixture should be at least 50° C., preferably at least 60° C., and more preferably at least 70° C. The precursor is heated such that the agar at least partially dissolves in the water. Without wishing to be bound by any theory, it is hypothesized that the low concentration of agar, coupled with the shear forces applied during mixing, may be sufficient to dissolve the agar at such temperatures.

[0070] While the heated precursor mixture is being mixed, nicotine is added to the precursor in an amount of 0.2% to 2% by weight of the final composition. At this stage, other liquid components of the composition, such as flavorings, may also be added.

[0071] Optionally, a second portion of water (preferably at least 10% by weight of the desired final composition) is then added to the composition and the composition is again heated to at least 50°C, preferably at least 60°C, more preferably at least 70°C.

[0072] The precursor is then cooled, preferably with continued mixing. The resulting composition may be set aside. Without wishing to be bound by any particular theory, it is believed that the agar forms a gel that at least partially encapsulates the nicotine present, stabilizing the nicotine and providing superior release characteristics.

[0073] In an optional finishing step, more water may be added to the resulting composition (preferably at room temperature). This step is to give the composition more content, if necessary. In some embodiments, flavor enhancers, sweeteners or preservatives can be added at this stage in addition to or instead of being added at an earlier stage in the process.

[0074] The finished composition can optionally be mixed with tobacco in an amount up to 5% by weight of the final composition. The composition is soft to the touch, substantially dust-free, and does not form lumps. The product is white in color. In a preferred embodiment, it is packaged in a saliva-permeable pouch for oral delivery. EXAMPLES

[0075] Various compositions were prepared according to the method described above. [Table 1]

[0076] A 0.7 g portion of each of the finished compositions was packaged in saliva-permeable pouches and tested according to the following release test.

[0077] One subject will refrain from nicotine intake for 10 hours before the start of the experiment and from food and drink intake for 1 hour before the start of the experiment. Before the procedure, the test subject will rinse their mouth with water and wait for 10 minutes.

[0078] The pouch is taken, weighed and placed under the lips of the test subject. The pouch is left in place for 5 minutes without moving it. The pouch is then removed and held 50cm apart. 3 of distilled water and stirred or shaken for 30 minutes. Samples are taken and analyzed for nicotine content using HPLC.

[0079] The tester then waits at least one hour and repeats the experiment, holding the pouch in place for 10, 20, 30, and 40 minutes in successive repeats.

[0080] The results of the release test are shown in Figure 1. As can be seen, the inclusion of 20% by weight of agar is seen to slightly increase the release rate and total amount of nicotine released over 40 minutes. However, surprisingly, a relatively small percentage of agar in the composition (0.3% by weight, 0.6% by weight of nicotine) is seen to significantly increase both the release rate and the total amount released over 40 minutes.

[0081] Further compositions identical to that of Example 1, but containing different stabilizers instead of agar, were prepared and tested according to the same methodology. The stabilizers used in these examples are shown in the table below. [Table 2]

[0082] The results of the release test are shown in the graph of Figure 2, overlaid with the plot of Example 1. It is clear from the plot that agar provides the greatest total release of nicotine over a 40 minute period, with a significantly faster release of nicotine in the first 10 minutes of use, which is of great advantage to users who are trying to quit smoking.

[0083] pH Test - CORESTA Method No. 69 (2017) Calibrate the pH electrode using at least two pH buffer solutions (4.00 and 7.00 or 7.00 and 10.00) to perform a two-point calibration covering the pH range of the product being tested. The calibration is performed at 23°C along with the measurement of the sample. The calibration slope must be within 95%-105% before the electrode can be used for sample measurements. The electrode should be rinsed with water before and after each measurement.

[0084] The test sample is allowed to reach room temperature before preparation. The sample is then mixed with water at a concentration of 5% by weight and shaken or stirred for 30 minutes. The pH of the water in the sample mixture is then measured using a pH electrode.

[0085] Comparative Examples 10 to 12 Comparative Examples 10-12 list commercial products based on nicotine salts and characterized by a low moisture content, i.e. less than 10% by weight. These products are generally characterized by a long shelf life of at least 12 months. However, increasing moisture content leads to increased discoloration and clumping. Very dry products may become powdery during storage and be difficult to handle when packaged. Low moisture products are usually characterized by poor palatability (dry mouthfeel) and delayed nicotine release. The appearance of the samples is shown in Figure 3. [Table 3] [Table 4] [Table 5]

[0086] Comparative Examples 13 to 17 Comparative Examples 13-17 list commercial products based on nicotine free base and characterized by a high moisture content, i.e., more than 40% by weight. Almost all products are characterized by clumping and discoloration to various degrees. Comparative Examples 13-16 are variants of the same product from the same manufacturer, differing mainly with respect to the flavors, release modifiers, and sweeteners used. The products in these examples contain calcium chloride. Calcium chloride is usually used as an excipient with water-binding properties and as an antimicrobial preservative. The appearance of the samples is shown in Figure 3. [Table 6] [Table 7] [Table 8] [Table 9] [Table 10]

[0087] Comparative Examples 18 and 19 Comparative Examples 18 and 19 list commercial products based on free base nicotine and characterized by a moderate moisture content, i.e., less than 10-30% by weight. These products are characterized by a shelf life of approximately 6-12 months. Both products show signs of discoloration and clumping. Comparative Example 16, which contains a high amount of sugar alcohol, is particularly prone to clumping and hardening over time, which significantly reduces the palatability of the product. The appearance of the samples is shown in Figure 3. [Table 11] [Table 12]

[0088] Example 2 Example 2 represents an example of a formulation according to the invention. This product is characterized by high moisture content and high nicotine stability during storage for at least 12 months. No signs of discoloration, clumping, or dusting are observed after storage. [Table 13]

[0089] The examples show that the compositions of the present invention provide a soft, white product that avoids clumping and is therefore palatable upon use, easy to package and manufacture, has a long shelf life, and delivers nicotine quickly and consistently to the user.

[0090] The invention is as defined in the following claims.

Claims

1. 1. A composition comprising: a. about 0.2% to about 5% by weight of nicotine in its free base form; b. a natural cellulosic material in an amount of about 35% to about 60% by weight; c. water in an amount of at least 35% by weight; d. one or more pH controlling salts in an amount from about 0.5% to about 3% by weight; e. a release control agent comprising agar and / or agar derivatives in an amount of about 0.1% to about 2% by weight; f. any additional ingredients, preferably in an amount of up to about 12% by weight; A composition comprising:

2. 10. The composition of claim 1 further comprising additional components, preferably in an amount of about 1% to about 10% by weight, or more preferably in an amount of about 1% to about 8% by weight.

3. 3. The composition of claim 1 or claim 2, wherein the additional ingredients comprise one or more additives selected from flavorants, flavor enhancers, sweeteners and preservatives.

4. A composition according to claim 2 or claim 3, wherein the additional ingredient comprises a sweetener, preferably in an amount of from about 1% to about 3% by weight.

5. 5. The composition of claim 4, wherein the sweetener comprises a compound selected from sugars (sucrose, fructose, glucose, dextrose, maltose, lactose, galactose), sugar alcohols (such as xylitol, maltitol, sorbitol, erythritol) and / or sugar substitutes (such as aspartame, saccharin, sucralose, allulose, acesulfame K, cyclamate or steviol glycosides).

6. A composition according to claim 4 or claim 5, comprising sugar alcohol in an amount of less than 3% by weight, preferably less than 2% by weight, for example 1% to 2% by weight.

7. A composition according to any one of claims 4 to 6, comprising sugar substitute in an amount of less than 1% by weight, preferably less than 0.5% by weight, for example 0.05% to 0.3% by weight.

8. 8. A composition according to claim 6 or claim 7, wherein the sugar alcohol comprises xylitol and / or the sugar substitute comprises acesulfame K.

9. The composition according to any one of claims 2 to 8, further comprising one or more preservatives selected from calcium chloride, salts of sorbic acid (such as potassium sorbate), salts of benzoic acid (such as sodium benzoate), nitrates, nitrites, sulfates, sulfites and propionates.

10. 10. The composition of claim 9, wherein potassium sorbate is present in an amount of less than about 1% by weight, preferably from 0.1% to 0.5% by weight, for example from about 0.25% to about 0.35% by weight.

11. The composition of any one of claims 1 to 9, wherein the pH controlling salt comprises a buffer salt, such as a combination of ammonium chloride and sodium bicarbonate.

12. A composition according to claim 11, wherein the ammonium chloride is present in an amount of from 0.05% to 1% by weight, preferably from 0.1% to 0.5% by weight, for example from 0.15% to 0.25% by weight.

13. A composition according to any preceding claim, wherein sodium bicarbonate is present in an amount of less than 1% by weight, preferably from 0.1% to 0.5% by weight, for example from 0.2% to 0.3% by weight.

14. A composition according to any one of the preceding claims, comprising more than 40% water, such as from 40% to 50% water, preferably from about 44% to about 48% water.

15. The composition according to any one of claims 1 to 14, wherein the filler comprises powdered cellulose and / or microcrystalline cellulose (MCC).

16. A composition according to any one of claims 1 to 15, wherein the release controlling agent comprises agar in an amount of less than about 1% by weight, preferably less than 0.7% by weight.

17. 17. The composition of claim 16, wherein the release controlling agent comprises agar in an amount of about 0.2% to about 0.7% by weight, preferably about 0.2% to about 0.5% by weight.

18. 18. The composition of any one of claims 1 to 17, wherein the ratio of agar to nicotine is less than about 1.3:

1.

19. 19. The composition according to any one of claims 1 to 18, wherein the ratio of agar to nicotine is from about 0.1:1 to about 1.2:1, preferably from about 0.1:1 to about 1:1, more preferably from about 0.1:1 to about 0.8:

1.

20. The composition according to any one of claims 1 to 19, further comprising tobacco leaf in an amount of less than 5% by weight, preferably between about 1% and 3% by weight.

21. The composition according to any one of claims 1 to 20, having a pH of 6 to 9, preferably 7 to 9, more preferably 7 to 8.5, as measured by CORESTA method No. 69 (2017).

22. A composition according to any one of claims 3 to 21, wherein the flavour enhancer is selected from the group comprising sodium chloride, glutamate, glycine salts, inosinate and 5'-ribonucleotide salts.

23. 23. A composition according to claim 22, comprising sodium chloride in an amount of less than 8% by weight, preferably between 1% and 7% by weight.

24. 24. The composition according to any one of claims 3 to 23, comprising flavour compounds in an amount of less than about 5% by weight of the total composition, such as less than 3% by weight of the composition, or from 0.5% to 3% by weight of the composition.

25. 25. A composition according to any one of the preceding claims, wherein the amount of nicotine is from 0.2% to 3% by weight, or from 0.2% to 2% by weight.

26. A composition according to any one of claims 1 to 25 consisting essentially of the components as claimed.

27. A water or saliva permeable pouch comprising a composition according to any one of claims 1 to 26.

28. 28. A package comprising a plurality of the pouches of claim 27.

29. A process for forming a nicotine-containing composition according to any one of claims 1 to 26. a. mixing natural cellulose material in an amount of 40% to 60% by weight of the target composition with agar (and / or agar derivatives) powder in an amount of 0.2% to 2% by weight of the target composition in a mixer, thereby forming a precursor composition; b. adding water to the precursor composition and mixing at a temperature above 50° C.; c. adding nicotine in free base form to the precursor composition in an amount of 0.2% to about 2% by weight of the desired final composition while the temperature is above 50° C.; d. Cooling the mixture; The process includes:

30. 30. The process of claim 29, wherein additional water is added between steps (c) and (d).

31. 31. The process according to claim 29 or 30, wherein in steps (b) and (c), the mixing of the precursors is carried out at a temperature above about 60°C, preferably above about 70°C, preferably above 80°C.

32. The process according to any one of claims 29 to 31, wherein in step (b) the water is provided to the precursor at a temperature above about 70°C, preferably above about 80°C.

33. 33. The process of claim 32, wherein in step (b), the water is provided to the precursor in the form of water vapor or steam.

34. The process of any one of claims 30 to 33, wherein the temperature of the additional water added between step (c) and step (d) is greater than about 70°C, preferably greater than about 80°C.

35. 35. The process of claim 34, wherein the additional water added between steps (c) and (d) is in the form of steam or vapor.

36. 36. The process of any one of claims 29 to 35, wherein the precursor mixture is heated whilst in the mixer, for example during steps (b) and / or (c), and / or during or after the optional addition of water following step (c).

37. The process of any one of claims 29 to 36, wherein additional water is added to the composition after step (d).

38. Prior to step (b), the following components: a. one or more pH controlling salts in an amount of about 0.5% to about 3% by weight of the subject composition; b. additional components, preferably in an amount of up to about 12% by weight of the subject composition; The process of any one of claims 29 to 37, wherein any of the following is added to the precursor mixture.

39. The process according to any one of claims 29 to 38, wherein the target composition is a composition according to any one of claims 1 to 26.

40. a. about 0.2% to about 5% by weight of nicotine in its free base form; b. a natural cellulosic material in an amount of about 35% to about 60% by weight; c. water in an amount of at least 35% by weight; d. one or more pH controlling salts in an amount from about 0.5% to about 3% by weight; e. a release control agent comprising agar and / or agar derivatives in an amount of about 0.1% to about 2% by weight; f. any additional ingredients, preferably in an amount of up to about 12% by weight; 23. Use of agar as a nicotine release controlling agent in a composition comprising:

41. a. about 0.2% to about 5% by weight of nicotine in its free base form; b. a natural cellulosic material in an amount of about 35% to about 60% by weight; c. water in an amount of at least 35% by weight; d. one or more pH controlling salts in an amount from about 0.5% to about 3% by weight; e. a release control agent comprising agar and / or agar derivatives in an amount of about 0.1% to about 2% by weight; f. any additional ingredients, preferably in an amount of up to about 12% by weight; 13. Use of agar as a nicotine stabilizer in a composition comprising:

42. 40. The use according to claim 38 or claim 39, wherein the composition further comprises additional components, preferably in an amount of from about 1% to about 10% by weight, or more preferably in an amount of from about 1% to about 8% by weight.

43. The use according to any one of claims 40 to 42, wherein the additional ingredients in the composition comprise one or more additives selected from flavourings, flavour enhancers, sweeteners and preservatives.

44. 44. Use according to claim 42 or claim 43, wherein the additional ingredient comprises a sweetener, preferably in an amount of from about 1% to about 3% by weight.

45. 45. Use according to claim 44, wherein the sweetener comprises a compound selected from sugars (sucrose, fructose, glucose, dextrose, maltose, lactose, galactose), sugar alcohols (such as xylitol, maltitol, sorbitol, erythritol) and / or sugar substitutes (such as aspartame, saccharin, sucralose, allulose, acesulfame K, cyclamate or steviol glycosides).

46. 46. ​​Use according to claim 44 or claim 45, comprising sugar alcohol in an amount of less than 3% by weight, preferably less than 2% by weight, for example 1% to 2% by weight.

47. 47. Use according to claim 46, comprising sugar substitute in an amount of less than 1% by weight, preferably less than 0.5% by weight, for example between 0.05% and 0.3% by weight.

48. 48. Use according to claim 46 or claim 47, wherein the sugar alcohol comprises xylitol and / or the sugar substitute comprises acesulfame K.

49. 49. The use according to any one of claims 42 to 48, further comprising one or more preservatives selected from calcium chloride, salts of sorbic acid (such as potassium sorbate), salts of benzoic acid (such as sodium benzoate), nitrates, nitrites, sulfates, sulfites and propionates.

50. 50. The use according to claim 49, wherein potassium sorbate is present in an amount of less than about 1% by weight, preferably from 0.1% to 0.5% by weight, for example from about 0.25% to about 0.35% by weight.

51. 50. The use of any one of claims 40 to 49, wherein the pH controlling salt comprises a buffer salt, such as a combination of ammonium chloride and sodium bicarbonate.

52. 52. Use according to claim 51, wherein ammonium chloride is present in an amount of 0.05% to 1% by weight, preferably 0.1% to 0.5% by weight, for example 0.15% to 0.25% by weight.

53. Use according to any one of claims 40 to 52, wherein sodium bicarbonate is present in an amount of less than 1% by weight, preferably from 0.1% to 0.5% by weight, for example from 0.2% to 0.3% by weight.

54. 54. Use according to any one of claims 40 to 53, comprising more than 40% by weight of water, such as 40% to 50% by weight of water, preferably from about 44% to about 48% by weight of water.

55. 55. The use according to any one of claims 40 to 54, wherein the filler comprises powdered cellulose and / or microcrystalline cellulose (MCC).

56. 56. The use according to any one of claims 40 to 55, wherein the release controlling agent comprises agar in an amount of less than about 1% by weight, preferably less than 0.7% by weight.

57. 57. The use of claim 56, wherein the release controlling agent comprises agar in an amount of about 0.2% to about 0.7% by weight, preferably about 0.2% to about 0.5% by weight.

58. 58. The use of any one of claims 40 to 57, wherein the ratio of agar to nicotine is less than about 1.3:

1.

59. 59. Use according to any one of claims 40 to 58, wherein the ratio of agar to nicotine is from about 0.1:1 to about 1.2:1, preferably from about 0.1:1 to about 1:1, more preferably from about 0.1:1 to about 0.8:

1.

60. 60. The use according to any one of claims 40 to 59, further comprising tobacco leaf in an amount of less than 5% by weight, preferably between about 1% and 3% by weight.

61. 61. Use according to any one of claims 40 to 60, having a pH of 6 to 9, preferably 7 to 9, more preferably 7 to 8.5, measured by CORESTA method No. 69 (2017).

62. Use according to any one of claims 43 to 61, wherein the flavour enhancer is selected from the group comprising sodium chloride, glutamate, glycine salts, inosinate and 5'-ribonucleotide salts.

63. 63. Use according to claim 62, comprising sodium chloride in an amount of less than 8% by weight, preferably between 1% and 7% by weight.

64. 64. The use according to any one of claims 43 to 63, comprising flavour compounds in an amount of less than about 5% by weight of the total composition, such as less than 3% by weight of the composition, or from 0.5% to 3% by weight of the composition.

65. 65. Use according to any one of claims 40 to 64, wherein the amount of nicotine is from 0.2% to 3% by weight, or from 0.2% to 2% by weight.

66. Use according to any one of claims 40 to 65, wherein the composition consists essentially of the components according to the claims.

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