A nicotine composition and a snus

Abstract

The present application relates to a nicotine composition, which comprises nicotine-releasable particles, the particles comprising at least one of particles P1, particles P2 or particles P3, each of the particles P1, particles P2 or particles P3 independently comprising: (A) 0.1-10% of nicotine or a salt thereof; (B) 0.1-20% of a cyclodextrin compound or a salt thereof; and, (C) 20-80% of a binder; wherein the volume average particle size D1 of the particles P1 is 200 μm≤D1≤280 μm; the volume average particle size D2 of the particles P2 is 280 μm<D2≤320 μm; and the volume average particle size D3 of the particles P3 is 320 μm<D3≤450 μm. The present application can obtain oral tobacco with different nicotine release rates by adjusting the formula of raw materials and controlling the particle size of the particles in the nicotine composition, so as to release nicotine smoothly and meet the needs of different users.

Description

Technical Field

[0001] This invention relates to the field of tobacco products, and more specifically to a mouthwash with a controllable nicotine release rate. Background Technology

[0002] Nicotine, commonly known as tobacco alkaloid, is a substitute for regular cigarettes in oral cigarette products. The rate and evenness of nicotine release significantly impact the user experience. Current research on oral cigarettes largely focuses on slow-release nicotine. However, different user groups have varying preferences for nicotine release rates; some prefer a longer, sustained release, while others prefer a rapid release and quick onset of nicotine. Therefore, determining how to adjust process parameters to produce oral cigarettes with different nicotine release rates is a pressing issue. Summary of the Invention

[0003] In view of this, the present invention obtains oral cigarettes with different nicotine release rates by adjusting the raw material formula and controlling the particle size of the nicotine composition, which can release nicotine steadily and meet the needs of different users.

[0004] In a first aspect, the present invention provides a nicotine composition comprising particles capable of releasing nicotine salts, the particles comprising at least one of particles P1, P2, or P3, each of particles P1, P2, or P3 independently comprising:

[0005] (A) Nicotine or its salts, 0.1-10%;

[0006] (B) Cyclodextrin compounds or their salts, 0.1-20%; and,

[0007] (C) Adhesive 20-80%;

[0008] Wherein, the volume average particle size D1 of particle P1 is 200μm≤D1≤280μm; the volume average particle size D2 of particle P2 is 280μm<D2≤320μm; and the volume average particle size D3 of particle P3 is 320μm<D3≤450μm.

[0009] Preferably, in the nicotine composition, the volume average particle size D1 of particle P1 is 250μm≤D1≤280μm; the volume average particle size D2 of particle P2 is 285μm≤D2≤320μm; and the volume average particle size D3 of particle P3 is 335μm≤D3≤400μm.

[0010] Preferably, in the nicotine composition, the particles comprise any one of particles P1, particles P2, and particles P3.

[0011] Preferably, in the nicotine composition, each of particles P1, P2, and P3 independently comprises:

[0012] (A) Nicotine or its salts, 0.5-5%;

[0013] (B) 0.5-10% of cyclodextrin compounds or their salts; and,

[0014] (C) Adhesive 30-60%.

[0015] Preferably, in the nicotine composition, the particles are P1 particles, and the P1 particles comprise:

[0016] (A) Nicotine or its salts, 0.5-5%;

[0017] (B) 0.5-10% of cyclodextrin compounds or their salts; and,

[0018] (C) Adhesive 30-39.9%.

[0019] Preferably, in the nicotine composition, the particles are P2 particles, and the P2 particles comprise:

[0020] (A) Nicotine or its salts, 0.5-5%;

[0021] (B) 0.5-10% of cyclodextrin compounds or their salts; and,

[0022] (C) Adhesive 40-49.9%;

[0023] Preferably, in the nicotine composition, the particles are P3 particles, and the P3 particles comprise:

[0024] (A) Nicotine or its salts, 0.5-5%;

[0025] (B) 0.5-10% of cyclodextrin compounds or their salts; and,

[0026] (C) Adhesive 50-60%.

[0027] Preferably, in the nicotine composition, at least one of the particles P1, P2 and P3 further comprises: (D) 0.1-70% other excipients; the other excipients are selected from at least one of sweeteners, flavorings, pH adjusters, alcohol solvents, inorganic salts or water.

[0028] Preferably, in the nicotine composition, the nicotine salt is selected from at least one of nicotine malate, nicotine benzoate, or nicotine lactate.

[0029] Preferably, in the nicotine composition, the cyclodextrin compound or its salt is sodium sulfobutyl ether β-cyclodextrin.

[0030] Preferably, in the nicotine composition, the binder is microcrystalline cellulose.

[0031] Preferably, in the nicotine composition, the D10 of particles P1, P2 and P3 is 5-170 μm and the D90 is 480-600 μm.

[0032] In a second aspect, the present invention provides a mouthwash comprising the nicotine composition described in any of the preceding claims.

[0033] Preferably, the oral cigarette also includes a water-permeable pouch for packaging the nicotine composition.

[0034] Preferably, the oral tobacco satisfies any one of the following (1) to (3):

[0035] (1) Immediate-release oral cigarette, wherein the immediate-release oral cigarette releases Q1% of the nicotine or its salt in the human oral cavity after 5 minutes, wherein Q1 satisfies 50% ≤ Q1% ≤ 70%; and / or, the immediate-release oral cigarette releases more than 95% of the nicotine in the human oral cavity after time t1, wherein t1 satisfies 10 minutes ≤ t1 ≤ 25 minutes;

[0036] (2) The intermediate-release oral cigarette releases Q2% of the nicotine or its salt in the human oral cavity after 5 minutes, wherein Q2 satisfies 30% ≤ Q2% < 50%; and / or, the immediate-release oral cigarette releases more than 95% of the nicotine in the human oral cavity after time t2, wherein t2 satisfies 25 minutes < t2 ≤ 35 minutes;

[0037] (3) Slow-release oral cigarette, wherein the slow-release oral cigarette releases Q3% of the nicotine or its salt in the human oral cavity after 5 minutes, wherein Q3 satisfies 5% ≤ Q3% < 30%; and / or, the fast-release oral cigarette releases more than 95% of the nicotine in the human oral cavity after t3 time, wherein t3 satisfies 35min < t3 ≤ 50min.

[0038] Thirdly, the present invention provides a method for preparing the oral cigarette described in any of the preceding claims, comprising the following steps:

[0039] (S1) Prepare granules that release nicotine; and,

[0040] (S2) Fill water-permeable pouches with nicotine-releasing particles to obtain the oral cigarette;

[0041] The method for preparing particles includes the following steps:

[0042] (S1-1) Mix, stir and cut the raw materials simultaneously or in stages;

[0043] (S1-2) The mixture is wet granulated to obtain at least one of P1, P2 or P3 particles with a specific volume average particle size.

[0044] Preferably, in the method:

[0045] During the preparation of the particles P1, the stirring speed of the raw materials is 500-650 rpm, and the cutting speed is 250-400 rpm;

[0046] During the preparation of the P2 particles, the stirring speed of the raw materials is 400-550 rpm, and the cutting speed is 180-240 rpm.

[0047] During the preparation of the particles 3, the stirring speed of the raw materials is 250-450 rpm, and the cutting speed is 100-170 rpm.

[0048] Preferably, in the method, the cutting time is 5-20 minutes. Attached Figure Description

[0049] Figure 1 Examples 1-3 of this invention: in vitro dissolution curves of nicotine containing smoke from the oral cavity.

[0050] Figure 2 The in vitro dissolution curves of nicotine containing smoke released from the mouth in Examples 4-6 of this invention.

[0051] Figure 3 Examples 7-9 of this invention: in vitro dissolution curves of sustained-release oral nicotine. Detailed Implementation

[0052] In the following description, numerous specific details are set forth in order to provide a more thorough understanding of the invention. However, it will be apparent to those skilled in the art that the invention can be practiced without one or more of these details. In other instances, certain technical features well-known in the art have not been described in order to avoid obscuring the invention.

[0053] The implementation of this invention is described in detail below with reference to the definitions of terms:

[0054] Unless otherwise specified, "%" in this invention refers to mass percentage.

[0055] Nicotine Composition

[0056] The nicotine composition of the present invention includes nicotine-releasing particles, said particles including at least one of particles P1, particles P2, or particles P3, each of said particles P1, particles P2, or particles P3 independently comprising:

[0057] (A) Nicotine or its salts, 0.1-10%;

[0058] (B) Cyclodextrin compounds or their salts, 0.1-20%; and,

[0059] (C) Adhesive 20-80%.

[0060] In some embodiments, each of the particles P1, P2, or P3 independently comprises:

[0061] (A) Nicotine or its salts, 0.5-5%;

[0062] (B) 0.5-10% of cyclodextrin compounds or their salts; and,

[0063] (C) Adhesive 30-60%.

[0064] In some embodiments, each of the particles P1, P2, or P3 independently comprises

[0065] (A) Nicotine or its salts, 1-3%;

[0066] (B) 1-7% of cyclodextrins or their salts; and,

[0067] (C) Adhesive 30-60%.

[0068] In some embodiments, at least one of the particles P1, P2, or P3 further includes: (D) other excipients; said other excipients are selected from at least one of sweeteners, flavorings, pH adjusters, alcohol solvents, inorganic salts, or water.

[0069] (A) Nicotine or its salts

[0070] The nicotine or its salts of the present invention are derived from natural tobacco or can be obtained through artificial synthesis. For example, nicotine compounds can be extracted from tobacco materials through conventional grinding and other steps, and nicotine salts can be obtained further through conventional methods.

[0071] The nicotine or its salts of the present invention are orally acceptable, and may be selected from at least one of nicotine, nicotine hydrochloride, nicotine dihydrochloride, nicotine mononitrate, nicotine bitartrate, nicotine sulfate, nicotine zinc chloride monohydrate, nicotine pyruvate, nicotine phosphate, nicotine salicylate, nicotine malate, nicotine carbonate, nicotine bicarbonate, nicotine acetate, nicotine citrate, nicotine folic acid, nicotine fumarate, nicotine lactate, and nicotine benzoate. In some embodiments, the salts of the nicotine of the present invention are preferably selected from at least one of nicotine malate, nicotine benzoate, or nicotine lactate.

[0072] In some embodiments, the content of nicotine or its salt in the granules is 0.1-10%, for example, it can be 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9% or 10%.

[0073] (B) Cyclodextrins or their salts

[0074] The addition of cyclodextrin compounds or their salts to the nicotine composition of the present invention can regulate the release rate of nicotine in the nicotine composition, mask unpleasant odors such as ammonia, and improve the taste of the product.

[0075] The cyclodextrin compounds or their salts of the present invention are selected from at least one of natural cyclodextrins, branched cyclodextrins, alkyl cyclodextrins, hydroxyalkyl cyclodextrins, or sulfoalkyl cyclodextrins.

[0076] The natural cyclodextrin of the present invention is selected from at least one of α-cyclodextrin, β-cyclodextrin or γ-cyclodextrin.

[0077] The term "branched cyclodextrin" as used in this invention refers to a natural cyclodextrin ring with a branch containing a glycosyl group (e.g., glucose, maltose, cellobiose, lactose, sucrose, galactose, glucosamine, etc.). Branched cyclodextrins are formed by amylopectin enzymes binding glycosyl groups to the ring of natural cyclodextrin. For example, a branched cyclodextrin can be obtained by linking one, two, or three or more glucose molecules from a natural cyclodextrin to a glucose glycosyl group via an α,1→6 bond at the 6-position.

[0078] The term "alkyl cyclodextrin" as used in this invention refers to a product in which the hydrogen atom of the hydroxyl group in a natural cyclodextrin is replaced by an alkyl group. For example, the alkyl group can be C10 ... 1-8 Alkyl groups. Specifically, the alkyl group can be methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, or octyl, etc.

[0079] The term "hydroxyalkyl cyclodextrin" as used in this invention refers to a product in which the hydrogen atom of the hydroxyl group in natural cyclodextrin is replaced by a hydroxyalkyl group. For example, the hydroxyalkyl group can be C10-2000. 1-8 The hydroxyalkyl group can be hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl, hydroxyheptyl, or hydroxyoctyl, etc., having 1-6 hydroxyl groups.

[0080] The term "sulfonyl alkyl cyclodextrin" as used in this invention refers to a product in which the hydrogen atom of the hydroxyl group in a natural cyclodextrin is replaced by a sulfonyl alkyl group. For example, the alkyl group can be C10. 1-8 Alkyl groups. Specifically, sulfonyl groups can be sulfomethyl, sulfoethyl, sulfopropyl, sulfobutyl, sulfopentyl, sulfohexyl, sulfohepyl, or hydroxyoctyl, etc.

[0081] In some embodiments, the salt of the cyclodextrin compound of the present invention is selected from at least one of sodium, calcium, magnesium, iron, chromium, copper, zinc, lysine, arginine, or histidine salts. In some embodiments, the cyclodextrin salt is preferably sodium cyclodextrin, and most preferably sodium sulfobutyl ether β-cyclodextrin.

[0082] In some embodiments, the content of cyclodextrin compounds or their salts in the particles is 0.1-20%, for example, it can be 0.5%, 1%, 2%, 4%, 6%, 8%, 10%, 12%, 15%, 18% or 20%.

[0083] (C) Adhesive

[0084] The adhesive of the present invention is a carrier of nicotine or its salt, and plays a role in shaping and other functions.

[0085] In some embodiments, the adhesive of the present invention can be a variety of natural polymers, such as at least one selected from polysaccharides, polyols, natural fibers, or cellulose. In some embodiments, the preferred adhesive is microcrystalline cellulose.

[0086] In some embodiments, the adhesive content in the particles is 20-80%, for example, it can be 20%, 30%, 40%, 50%, 60%, 70% or 80%.

[0087] The binder in the nicotine composition of the present invention can regulate the rate of nicotine release in the composition. The inventors have found that, within a certain range, as the amount of binder increases, the rate of nicotine release from the nicotine salt in the composition slows down.

[0088] In some embodiments, the binder content in the P1 particles is 30-39.9%, for example, it can be 30%, 32%, 34%, 36%, 38% or 39%.

[0089] In some embodiments, the binder content in the P2 particles is 40-49.9%, for example, it can be 40%, 42%, 44%, 46%, 48% or 49%.

[0090] In some embodiments, the binder content in the P3 particles is 50-60%, for example, it can be 50%, 52%, 54%, 56%, 58% or 60%.

[0091] (D) Other excipients

[0092] In some embodiments, at least one of the particles P1, P2, or P3 further comprises 0.1-70% other excipients, preferably 5-65% other excipients, more preferably 20-60% other excipients; the other excipients are selected from at least one of sweeteners, flavorings, pH adjusters, alcohol solvents, inorganic salts, or water.

[0093] In some embodiments, the sweetener in the granules is selected from one or more of sorbitol, xylitol, mannitol, aspartame, acesulfame potassium, sucralose, saccharin, sodium saccharin, cyclamate, neotame, erythritol, trehalose, raffinose, cellobiose, tagatose, allulose, and inulin, preferably xylitol.

[0094] In some embodiments, the sweetener content in the granules is 1-20% or 2-10%.

[0095] In some embodiments, the flavoring in the granules is selected from one or more of the following: peppermint essence, wintergreen, peppermint, spearmint, coffee, cinnamon, apple, orange, watermelon, grape, lychee, berry, or coffee.

[0096] In some embodiments, the flavor content in the granules is 1-10% or 5-9%.

[0097] In some embodiments, the pH adjuster in the particles is selected from one or more of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, potassium hydroxide, sodium hydroxide, sodium phosphate, sodium dihydrogen phosphate, sodium phosphate, or disodium hydrogen phosphate.

[0098] In some embodiments, the pH adjuster content in the particles is 0.1-10% or 1-5%.

[0099] In some embodiments, the alcohol solvent in the particles is selected from propylene glycol.

[0100] In some embodiments, the content of alcohol solvent in the particles is 0.1-10 or 1-7%.

[0101] In some embodiments, the inorganic salt in the particles is selected from one or more of sodium chloride, calcium chloride, potassium chloride, ammonium chloride, sodium sulfate, calcium sulfate, ammonium sulfate, or potassium sulfate.

[0102] In some embodiments, the inorganic salt content in the particles is 0.1-5% or 1-2%.

[0103] Particles

[0104] The nicotine composition of the present invention contains nicotine-releasing particles having a specific particle size. The inventors have discovered that particles of different sizes release nicotine at different rates.

[0105] In some embodiments, the nicotine composition of the present invention comprises at least one of particles P1, particles P2, and particles P3, wherein the volume average particle size D1 of particle P1 is 200 μm ≤ D1 ≤ 280 μm; the volume average particle size D2 of particle P2 is 280 μm < D2 ≤ 320 μm; and the volume average particle size D3 of particle P3 is 320 μm < D3 ≤ 450 μm.

[0106] In some embodiments, the nicotine composition of the present invention comprises at least one of particles P1, particles P2 and particles P3, wherein the volume average particle size D1 of particle P1 is 250 μm ≤ D1 ≤ 280 μm; the volume average particle size D2 of particle P2 is 285 μm ≤ D2 ≤ 320 μm; and the volume average particle size D3 of particle P3 is 335 μm ≤ D3 ≤ 400 μm.

[0107] The volume average particle size (or average particle size) of this invention is D50, also known as the median volume particle size, which refers to the particle size value corresponding to a cumulative volume distribution percentage of 50%. D90: refers to the particle size value corresponding to a cumulative volume distribution percentage of 90% from smallest to largest in the particle size distribution. D10: refers to the particle size value corresponding to a cumulative volume distribution percentage of 10% from smallest to largest in the particle size distribution.

[0108] In some embodiments, the volume average particle size of the particle P1 may be, for example, 200 μm, 210 μm, 220 μm, 230 μm, 240 μm, 250 μm, 260 μm, 270 μm or 280 μm.

[0109] In some embodiments, the volume average particle size of the particle P2 may be, for example, 281 μm, 285 μm, 290 μm, 295 μm, 300 μm, 305 μm, 310 μm, 315 μm or 320 μm.

[0110] In some embodiments, the average particle size of the particles P3 may be, for example, 321 μm, 325 μm, 330 μm, 340 μm, 350 μm, 360 μm, 370 μm, 380 μm, 390 μm, 400 μm, 410 μm, 420 μm, 430 μm, 440 μm or 450 μm.

[0111] In some embodiments, the D10 of particles P1, P2 and P3 is 5-170 μm and the D90 is 480-600 μm.

[0112] The nicotine composition of the present invention can be used to prepare products with different nicotine release rates by including particles of the specific particle size mentioned above, or by combining particles of different particle sizes.

[0113] In some embodiments, the particles of the present invention comprise any one of particles P1, P2, and P3. In some embodiments, the particles of the present invention are particles P1, P2, or P3.

[0114] In some embodiments, the nicotine composition of the present invention comprises at least one of particles P1, P2, and P3.

[0115] In some embodiments, the nicotine composition of the present invention comprises any one of particles P1, particles P2, or particles P3.

[0116] In some embodiments, the nicotine composition of the present invention comprises particles P1.

[0117] In some embodiments, the nicotine composition of the present invention comprises particles P2.

[0118] In some embodiments, the nicotine composition of the present invention comprises particles P3.

[0119] In some embodiments, the nicotine composition of the present invention comprises particles P1 and particles P2.

[0120] In some embodiments, the nicotine composition of the present invention comprises particles P2 and particles P3.

[0121] In some embodiments, the nicotine composition of the present invention comprises particles P1 and particles P3.

[0122] In some embodiments, the nicotine composition of the present invention comprises particles P1, particles P2 and particles P3.

[0123] II. Holding a cigarette in the mouth

[0124] The nicotine composition of the present invention is suitable for making oral cigarettes.

[0125] In some embodiments, the nicotine composition of the present invention can be filled into a water-permeable pouch to obtain the oral cigarette of the present invention.

[0126] The aforementioned permeable pouches are made of materials known in the art, and are water-insoluble, for example, they may be made of woven materials.

[0127] The oral cigarette of the present invention has a nicotine release rate of 10-45 minutes in the human oral cavity (calculated based on the completion of nicotine release of more than 95%).

[0128] In some embodiments, the oral cigarette of the present invention is a fast-release oral cigarette, wherein the fast-release oral cigarette releases Q1% of the nicotine or its salt in the human oral cavity after 5 minutes, wherein Q1 satisfies 50% ≤ Q1% ≤ 70%; and / or, the fast-release oral cigarette releases more than 95% of the nicotine in the human oral cavity after time t1, wherein t1 satisfies 10 minutes ≤ t1 ≤ 25 minutes.

[0129] In some implementations, Q1% can be, for example, 50%, 55%, 60%, 65%, or 70%.

[0130] In some implementations, t1 can be, for example, 12 min, 14 min, 16 min, 18 min, 20 min, 22 min, or 25 min.

[0131] In some embodiments, the oral cigarette of the present invention is a mid-release oral cigarette, wherein the mid-release oral cigarette releases Q2% of the nicotine or its salt in the human oral cavity after 5 minutes, wherein Q2 satisfies 30% ≤ Q2% < 50%; and / or, the fast-release oral cigarette releases more than 95% of the nicotine in the human oral cavity after time t2, wherein t2 satisfies 25 minutes < t2 ≤ 35 minutes.

[0132] In some implementations, Q2% can be, for example, 30%, 35%, 40%, 45%, or 49%.

[0133] In some implementations, t2 can be, for example, 26 min, 28 min, 30 min, 32 min, 34 min, or 35 min.

[0134] In some embodiments, the oral cigarette of the present invention is a slow-release oral cigarette, wherein the slow-release oral cigarette releases Q3% of the nicotine or its salt in the human oral cavity after 5 minutes, wherein Q3 satisfies 5% ≤ Q3% < 30%; and / or, the fast-release oral cigarette releases more than 95% of the nicotine in the human oral cavity after time t3, wherein t3 satisfies 35min < t3 ≤ 50min.

[0135] In some implementations, Q3% can be, for example, 5%, 10%, 15%, 20%, 25%, or 29%.

[0136] In some implementations, t3 can be, for example, 36 min, 38 min, 40 min, 42 min, 45 min, 48 min, or 50 min.

[0137] The method for preparing the oral cigarette of the present invention includes the following steps:

[0138] (S1) Prepare granules that release nicotine; and,

[0139] (S2) Fill water-permeable pouches with nicotine-releasing particles to obtain the oral cigarette;

[0140] The method for preparing particles includes the following steps:

[0141] (S1-1) Mix, stir and cut the raw materials simultaneously or in stages;

[0142] (S1-2) The mixture is wet-granulated to obtain at least one of P1, P2 or P3 particles with a specific average particle size.

[0143] Different particle preparation process parameters can yield particles with different sizes. For example, the inventors discovered that by controlling the stirring speed and cutting speed after mixing the raw materials, and / or the cutting time, the particle size can be adjusted. A faster stirring speed results in larger particle sizes, and a longer cutting time results in larger particle sizes.

[0144] In some embodiments, during the preparation of particles P1, the raw material stirring speed is 500-650 rpm, and the cutting speed is 250-400 rpm; wherein the stirring speed can be, for example, 510 rpm, 530 rpm, 550 rpm, 580 rpm, 600 rpm, 620 rpm, or 650 rpm; and the cutting speed can be, for example, 250 rpm, 270 rpm, 300 rpm, 320 rpm, or 350 rpm. In some embodiments, during the preparation of particles P1, the cutting time is 10-15 min, for example, 10 min, 12 min, or 15 min.

[0145] In some embodiments, during the preparation of particles P2, the raw material stirring speed is 400-550 rpm, and the cutting speed is 180-240 rpm; wherein the stirring speed can be, for example, 410 rpm, 430 rpm, 450 rpm, 470 rpm, 500 rpm, 520 rpm, or 540 rpm, etc.; and the cutting speed can be, for example, 190 rpm, 200 rpm, 220 rpm, or 230 rpm, etc. In some embodiments, during the preparation of particles P2, the cutting time is 5-10 min, for example, 7 min, 8 min, or 9 min, etc.

[0146] In some embodiments, during the preparation of particles P3, the raw material stirring speed is 250-450 rpm, and the cutting speed is 100-170 rpm. The stirring speed can be, for example, 260 rpm, 280 rpm, 300 rpm, 320 rpm, 340 rpm, 360 rpm, 380 rpm, 400 rpm, or 420 rpm; the cutting speed can be, for example, 120 rpm, 130 rpm, 140 rpm, or 160 rpm. In some embodiments, the cutting time during the preparation of particles P3 is 5-10 minutes, for example, 7 minutes, 8 minutes, or 9 minutes.

[0147] The present invention will be further described below through specific embodiments.

[0148] raw material

[0149] Nicotine malate, nicotinic benzoate and nicotinic lactate: purchased from Huanggang Zhongyou Biotechnology.

[0150] Sodium cyclodextrin: Homemade sodium sulfobutyl ether β-cyclodextrin.

[0151] Microcrystalline cellulose: Hunan Jiudian Hongyang.

[0152] All other reagents are made from food-grade raw materials and can be used directly.

[0153] Particle size testing methods:

[0154] Instrument: Laser particle size analyzer.

[0155] Sample Analysis: Before testing, set the corresponding parameters according to the instrument parameters and save the method. Before testing, call the saved method and click "Start" to automatically align the system. The readings should be less than 100 for detector 1 and less than 50 for detector 20. After the system stabilizes, click the "Clean" button to clean the system. After cleaning, open the autosampler cover, add an appropriate amount of sample (500-1000 mg is recommended; shake the sample thoroughly before adding), close the cover, and click the "Start" button on the testing interface. The system will automatically detect and save the data according to the set parameters. For the final product, take 5 samples and perform 5 parallel measurements, then take the average value. For intermediate control, take 1 sample and perform one measurement.

[0156] Examples 1-3: Immediate-release oral tobacco

[0157] Example 1

[0158] All raw materials are calculated in 100 parts by weight. 34 parts microcrystalline cellulose, 9 parts xylitol, 6 parts sodium cyclodextrin, 2 parts potassium carbonate, and 1 part potassium chloride are mixed using a wet granulation machine. The dry materials are poured into the mixture, and stirring is started at 550 rpm. Cutting is then started at 300 rpm, and the mixture is stirred and cut for 5 minutes. 2 parts nicotine lactate and 35 parts purified water are mixed and sprayed into the wet granulation machine for 3 minutes, followed by cutting for another 3 minutes. Finally, 8 parts watermelon flavoring and 3 parts propylene glycol are mixed and sprayed into the wet granulation machine for 1 minute, followed by cutting for another 2 minutes to obtain granules. The granules are then discharged into small bags to obtain oral tobacco. The average particle size of the granules is 274 μm.

[0159] Example 2

[0160] All raw materials are calculated in 100 parts by weight. 33 parts microcrystalline cellulose, 10 parts xylitol, 7 parts sodium cyclodextrin, 2 parts potassium carbonate, and 2 parts potassium chloride are mixed using a wet granulator. The dry materials are poured into the mixture, and stirring is started at 550 rpm. Cutting is then started at 300 rpm, and the mixture is stirred and cut for 5 minutes. 2 parts nicotine lactate and 35 parts purified water are mixed and sprayed into the wet granulator for 3 minutes, followed by cutting for another 3 minutes. Finally, 7 parts watermelon flavoring and 2 parts propylene glycol are mixed and sprayed into the wet granulator for 1 minute, followed by cutting for another 2.5 minutes to obtain granules. The granules are then discharged into small bags to obtain oral tobacco. The average particle size of the granules is 262 μm.

[0161] Example 3

[0162] All raw materials are calculated in 100 parts by weight. 38 parts microcrystalline cellulose, 8 parts xylitol, 5 parts sodium cyclodextrin, 2 parts potassium carbonate, and 1 part potassium chloride are mixed using a wet granulation machine. The dry materials are poured into the mixture, and stirring is started at 550 rpm. Cutting is then started at 300 rpm, and the mixture is stirred and cut for 5 minutes. 2 parts nicotine lactate and 35 parts purified water are mixed and sprayed into the wet granulation machine for 3 minutes, followed by cutting for another 3 minutes. Finally, 7 parts watermelon flavoring and 2 parts propylene glycol are mixed and sprayed into the wet granulation machine for 1 minute, followed by cutting for another 2.0 minutes to obtain granules. The granules are then discharged into small bags to obtain oral tobacco. The average particle size of the granules is 280 μm.

[0163] Oral tobacco release in Examples 4-6

[0164] Example 4

[0165] All raw materials are calculated in 100 parts by weight. 43 parts microcrystalline cellulose, 5 parts xylitol, 3 parts sodium cyclodextrin, 2 parts sodium carbonate, and 2 parts calcium chloride are mixed in a wet granulator with stirring at 500 rpm; then cutting is initiated at 200 rpm for 5 minutes of mixing and cutting. 2 parts nicotine malate and 28 parts purified water are mixed and sprayed into the wet granulator for 3 minutes, followed by 2 minutes of cutting. Finally, 8 parts peppermint flavoring and 7 parts propylene glycol are mixed and sprayed into the wet granulator for 1 minute, followed by 1 minute of granulation. The granules are then discharged into small bags to obtain oral tobacco. The average particle size is 301 μm.

[0166] Example 5

[0167] All raw materials are calculated in units of 100 parts. 40 parts microcrystalline cellulose, 7 parts xylitol, 4 parts sodium cyclodextrin, 2 parts sodium carbonate, and 2 parts calcium chloride are mixed in a wet granulator with stirring at 500 rpm; then cutting is initiated at 200 rpm for 5 minutes. 2 parts nicotine malate and 28 parts purified water are mixed and sprayed into the wet granulator for 3 minutes, followed by cutting for another 2 minutes. Finally, 8 parts peppermint flavoring and 7 parts propylene glycol are mixed and sprayed into the wet granulator for 1 minute, followed by cutting for 75 seconds to obtain granules. The granules are then packaged into small bags to obtain oral tobacco. The average particle size is 287 μm.

[0168] Example 6

[0169] All raw materials are calculated in units of 100 parts. 41 parts microcrystalline cellulose, 6 parts xylitol, 4 parts sodium cyclodextrin, 2 parts sodium carbonate, and 2 parts calcium chloride are mixed using a wet granulator. Stirring is started at 500 rpm; cutting is then started at 200 rpm, and the mixture is stirred and cut for 5 minutes. 2 parts nicotine malate and 28 parts purified water are mixed and sprayed into the wet granulator for 3 minutes, followed by cutting for another 2 minutes. Finally, 8 parts peppermint flavoring and 7 parts propylene glycol are mixed and sprayed into the wet granulator for 1 minute, followed by cutting for another 50 seconds to obtain granules. The granules are then discharged into small bags to obtain oral tobacco. The average particle size of the granules is 316 μm.

[0170] Examples 7-9: Slow-release oral tobacco

[0171] Example 7

[0172] All raw materials are calculated in units of 100 parts. 55 parts microcrystalline cellulose, 2 parts xylitol, 1 part sodium cyclodextrin, 2 parts sodium bicarbonate, and 1 part sodium chloride are mixed in a wet granulator. Stirring is started at 400 rpm; cutting is then started at 150 rpm, and the mixture is stirred and cut for 5 minutes. 2 parts nicotine benzoate and 25 parts purified water are mixed and sprayed into the wet granulator for 3 minutes, followed by cutting for another 2 minutes. Finally, 8 parts strawberry flavoring and 4 parts propylene glycol are mixed and sprayed into the wet granulator for 1 minute, followed by cutting for another 1 minute to obtain granules. The granules are then discharged into small bags to obtain oral tobacco. The average particle size of the granules is 358 μm.

[0173] Example 8

[0174] All raw materials are calculated in units of 100 parts. 50 parts microcrystalline cellulose, 4 parts xylitol, 3 parts sodium cyclodextrin, 2 parts sodium bicarbonate, and 2 parts sodium chloride are mixed in a wet granulator with stirring at 400 rpm; then cutting is initiated at 150 rpm for 5 minutes. 2 parts nicotine benzoate and 25 parts purified water are mixed and sprayed into the wet granulator for 3 minutes, followed by cutting for another 2 minutes. Finally, 8 parts strawberry flavoring and 4 parts propylene glycol are mixed and sprayed into the wet granulator for 1 minute, followed by cutting for 1.5 minutes to obtain granules. The granules are then packaged into small bags to obtain oral tobacco. The average particle size is 335 μm.

[0175] Example 9

[0176] All raw materials are calculated in 100 parts by weight. 55 parts microcrystalline cellulose, 2 parts xylitol, 1 part sodium cyclodextrin, 2 parts sodium bicarbonate, and 2 parts sodium chloride are mixed in a wet granulator with stirring at 400 rpm; then cutting is initiated at 150 rpm for 5 minutes. 2 parts nicotine benzoate and 24 parts purified water are mixed and sprayed into the wet granulator for 3 minutes, followed by cutting for another 2 minutes. Finally, 8 parts strawberry flavoring and 4 parts propylene glycol are mixed and sprayed into the wet granulator for 1 minute, followed by cutting for 50 seconds to obtain granules. The granules are then packaged into small bags to obtain oral tobacco. The average particle size is 381 μm.

[0177] Comparative Example 1

[0178] All raw materials are calculated in units of 100 parts. 40 parts microcrystalline cellulose, 10 parts xylitol, 0 parts sodium cyclodextrin, 2 parts potassium carbonate, and 2 parts potassium chloride are mixed using a wet granulation machine. All dry materials are poured into the mixture, and stirring is started at 550 rpm. Cutting is then started at 300 rpm, and the mixture is stirred and cut for 5 minutes. 2 parts nicotine lactate and 35 parts purified water are mixed and sprayed into the wet granulation machine for 3 minutes, followed by cutting for another 3 minutes. Finally, 7 parts watermelon flavoring and 2 parts propylene glycol are mixed and sprayed into the wet granulation machine for 1 minute, followed by cutting for another 2 minutes to obtain granules. The granules are then discharged into small bags to obtain oral tobacco. The average particle size of the granules is 270 μm.

[0179] Test case

[0180] Test Example 1

[0181] The products from Examples 1-9 were subjected to in vitro nicotine dissolution tests.

[0182] Test method: 30 mL of prepared artificial saliva (composition: purified water (95%), electrolytes (sodium chloride, sodium dihydrogen phosphate, 1%), mucin (2%), amylase (2%)) was added to 50 mL of the solution in a storage bottle and placed in a constant temperature water bath at 37°C. The machine was turned on, the temperature was set to 37°C, and the parameters of the simulated dissolution device were set. Driven by the motor, the chewing manipulator and the left-right opening and closing rotating components in the simulated oral cavity began to work. After reaching the set number of chewing cycles, the motor stopped, and the solution was immediately dispensed. A peristaltic pump extracted the extract from the solution dish, and the nicotine content in the extract was measured.

[0183] The results are as follows Figure 1-3 As shown, this invention can prepare oral cigarettes with different in vitro nicotine dissolution rates by controlling the material ratios such as the content of microcrystalline cellulose and sodium cyclodextrin, as well as adjusting the speed and time of stirring and cutting. This allows for diversified control of the nicotine release from oral cigarettes, meeting the needs of different users. Specifically, in Examples 1-3, the immediate-release nicotine dissolves more than 50% within 5 minutes of oral inhalation, more than 70% within 10 minutes, and completely dissolves within about 20 minutes. Users experience a noticeable nicotine rush and throat hit during the first 5 minutes of oral inhalation. In Examples 4-6, the intermediate-release nicotine dissolves between 30-50% within 5 minutes of oral inhalation, between 50-70% within 10 minutes, and completely dissolves within about 30 minutes, with a stable overall release and a continuous taste. In Examples 7-9, the slow-release nicotine dissolves less than 30% within 5 minutes of oral inhalation, less than 50% within 10 minutes, and completely dissolves within about 40 minutes. Users experience a milder nicotine rush and throat hit during the first 10 minutes of oral inhalation.

[0184] Test Example 2

[0185] Test users' experience with the oral cigarettes of Examples 1-9 and Comparative Example 1 was conducted. The test sample for each example consisted of 5-7 people. They were asked to put the products of Examples 1-9 and Comparative Example 1 in their mouths and describe their experience after use. The average results were recorded.

[0186] Table 1. Sample Test Results of Examples

[0187]

[0188] As shown in Table 1, the oral tobacco product of the present invention, after user evaluation, can provide different tastes and satisfactions, and has a good taste with low irritation to the digestive tract.

[0189] All technical solutions described above that fall within the scope of this invention's conceptual framework are protected by this invention. It should be noted that for those skilled in the art, any improvements and modifications made without departing from the principles of this invention should also be considered within the scope of protection of this invention.

Claims

1. A nicotine composition comprising nicotine-releasing particles, said particles comprising at least one of particles P1, P2, or P3, each of said particles P1, P2, or P3 independently comprising: (A) Nicotine or its salts, 0.1-10%; (B) Cyclodextrin compounds or their salts, 0.1-20%; and, (C) Adhesive 20-80%; Wherein, the volume average particle size D1 of particle P1 is 200μm≤D1≤280μm; the volume average particle size D2 of particle P2 is 280μm<D2≤320μm; and the volume average particle size D3 of particle P3 is 320μm<D3≤450μm.

2. The nicotine composition according to claim 1, wherein the volume average particle size D1 of particle P1 is 250 μm ≤ D1 ≤ 280 μm; the volume average particle size D2 of particle P2 is 285 μm ≤ D2 ≤ 320 μm; and the volume average particle size D3 of particle P3 is 335 μm ≤ D3 ≤ 400 μm; preferably, the particles comprise any one of particles P1, P2, and P3.

3. The nicotine composition according to claim 1, wherein each of the particles P1, P2, or P3 independently comprises: (A) Nicotine or its salts, 0.5-5%; (B) Cyclodextrin compounds or their salts, 0.5-10%; and, (C) Adhesive 30-60%; Preferably, the particles are P1 particles, and the P1 particles comprise: (A) Nicotine or its salts, 0.5-5%; (B) 0.5-10% of cyclodextrin compounds or their salts; and, (C) Adhesive 30-39.9%; Preferably, the particles are P2 particles, and the P2 particles comprise: (A) Nicotine or its salts, 0.5-5%; (B) 0.5-10% of cyclodextrin compounds or their salts; and, (C) Adhesive 40-49.9%; Preferably, the particles are P3 particles, and the P3 particles comprise: (A) Nicotine or its salts, 0.5-5%; (B) 0.5-10% of cyclodextrin compounds or their salts; and, (C) Adhesive 50-60%.

4. The nicotine composition according to claim 1, wherein at least one of the particles P1, P2, or P3 further comprises: (D) Other excipients 0.1-70%; The other excipients are selected from at least one of sweeteners, flavorings, pH adjusters, alcohol solvents, inorganic salts, or water.

5. The nicotine composition according to claim 1, wherein the nicotine salt is selected from at least one of nicotine malate, nicotine benzoate, or nicotine lactate; Preferably, the cyclodextrin compound or its salt is sodium sulfobutyl ether β-cyclodextrin; Preferably, the adhesive is microcrystalline cellulose. Preferably, the D10 of particles P1, P2 and P3 is 5-170 μm and the D90 is 480-600 μm.

6. A mouthwash comprising the nicotine composition according to any one of claims 1-5.

7. The oral cigarette according to claim 6, further comprising a water-permeable pouch for packaging the nicotine composition.

8. The oral cigarette according to any one of claims 6-7, wherein the oral cigarette satisfies any one of the following (1) to (3): (1) Immediate-release oral cigarette, wherein the immediate-release oral cigarette releases Q1% of the nicotine or its salt in the human oral cavity after 5 minutes, wherein Q1 satisfies 50% ≤ Q1% ≤ 70%; and / or, the immediate-release oral cigarette releases more than 95% of the nicotine in the human oral cavity after time t1, wherein t1 satisfies 10 minutes ≤ t1 ≤ 25 minutes; (2) The intermediate-release oral cigarette releases Q2% of the nicotine or its salt in the human oral cavity after 5 minutes, wherein Q2 satisfies 30% ≤ Q2% < 50%; and / or, the immediate-release oral cigarette releases more than 95% of the nicotine in the human oral cavity after time t2, wherein t2 satisfies 25 minutes < t2 ≤ 35 minutes; (3) Slow-release oral cigarette, wherein the slow-release oral cigarette releases Q3% of the nicotine or its salt in the human oral cavity after 5 minutes, wherein Q3 satisfies 5% ≤ Q1% < 30%; and / or, the fast-release oral cigarette releases more than 95% of the nicotine in the human oral cavity after t3 time, wherein t3 satisfies 35min < t3 ≤ 50min.

9. A method for preparing the oral tobacco according to any one of claims 6-8, comprising the following steps: (S1) Prepare granules that release nicotine; and, (S2) Fill water-permeable pouches with nicotine-releasing particles to obtain the oral cigarette; in, The method for preparing particles includes the following steps: (S1-1) Mix, stir and cut the raw materials simultaneously or in stages; (S1-2) The mixture is wet granulated to obtain at least one of P1, P2 or P3 particles with a specific volume average particle size.

10. The method according to claim 9, wherein: During the preparation of the particles P1, the stirring speed of the raw materials is 500-650 rpm, and the cutting speed is 250-400 rpm; During the preparation of the P2 particles, the stirring speed of the raw materials is 400-550 rpm, and the cutting speed is 180-240 rpm. During the preparation of the particles 3, the stirring speed of the raw materials is 250-450 rpm, and the cutting speed is 100-170 rpm; Preferably, the cutting time is 5-20 minutes.

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