Nicotine sustained-release gel product and preparation method thereof

Abstract

The invention provides a nicotine sustained-release gel product and a preparation method thereof. The gel product comprises a gel matrix, and nicotine sustained-release microcapsules and ionic gel triggering particles embedded in the gel matrix, the components of the gel matrix comprise a polysaccharide material, a sweetening agent and water; the polysaccharide material comprises any one or a combination of at least two of high methoxyl pectin, carrageenan or curdlan; the ionic gel triggering particles comprise the following components: low-methoxyl pectin and calcium salt. According to the invention, the nicotine is subjected to lipid coating and gel coating, so that multi-layer nicotine release is realized. In the early stage of use, the nicotine abstinence reaction is relieved, and the immediate demand of nicotine is met; and the sustained supply of nicotine is ensured by slow release in the middle and later periods of use.

Description

Technical Field

[0001] This invention belongs to the field of smokeless tobacco products technology, specifically relating to a nicotine sustained-release gel product and its preparation method. Background Technology

[0002] Most existing nicotine products are in the form of nicotine pouches. Common nicotine pouch products generally use dry powder or granules as oral nicotine products, such as tobacco powder, cellulose granules, and microcrystalline cellulose. Dry powder or granules are highly fluid and easily leak from the nicotine pouch, leaving residue in the mouth and contaminating the packaging. Furthermore, rigid granules or powders require repeated ingestion to stimulate saliva production and dissolve, resulting in a rough, powdery texture that does not support chewing. Additionally, to maintain the stability of the carrier structure, additional binders are needed, which actually inhibits the release efficiency of nicotine.

[0003] CN113367375A discloses a fragrance-loaded supramolecular gel based on a racemic mandelic acid nicotine salt gelling agent with an iso-acid-base ratio. The gel comprises the racemic mandelic acid nicotine salt gelling agent and fragrance substances and solvents dispersed within it. The fragrance substances are stably immobilized within the gel network at room temperature, effectively increasing the storage stability of the aroma-producing components and achieving the co-immobilization and synergistic release of nicotine and aroma-producing components.

[0004] CN120694942A discloses a nicotine-containing gel and its preparation method. The components of the nicotine-containing gel include nicotine microcapsules, a penetrant, a gel matrix, a flavoring agent, and water. The combination of nicotine microcapsules and a gel matrix provides excellent biocompatibility and sustained-release properties. The addition of a penetrant enhances the skin permeability of nicotine, and the addition of a flavoring agent gives the gel the advantages of fresh breath and long-lasting fragrance, thus providing a new consumer option for smokers trying to quit and patients requiring nicotine medication.

[0005] Therefore, there is an urgent need to develop a gel-based sustained-release nicotine product to solve the problems of residue, contamination, low release efficiency, rough taste, and inability to chew existing oral nicotine products during use. Summary of the Invention

[0006] In view of the shortcomings of the prior art, the purpose of this invention is to provide a nicotine sustained-release gel product and its preparation method. The gel product of this invention releases nicotine rapidly in the initial stage of use to meet the immediate need for nicotine, and releases it slowly in the middle and later stages to ensure a continuous supply of nicotine.

[0007] To achieve this objective, the present invention adopts the following technical solution:

[0008] In a first aspect, the present invention provides a nicotine sustained-release gel product, the gel product comprising a gel matrix, and nicotine sustained-release microcapsules and ion gel triggering particles embedded in the gel matrix;

[0009] The components of the gel matrix include polysaccharide material, sweetener and water; the polysaccharide material includes any one or a combination of at least two of high-methoxyl pectin, carrageenan or guar gum;

[0010] The components of the ion gel triggering particles include low-methoxyl pectin and calcium salts.

[0011] This invention utilizes lipid and gel encapsulation to achieve multi-level nicotine release. Rapid release in the initial stage alleviates nicotine withdrawal symptoms and meets immediate nicotine needs; slow release in the middle and later stages ensures a continuous supply of nicotine.

[0012] As the gel product is chewed and broken down in the mouth, the nicotine sustained-release microcapsules are exposed, melting and releasing nicotine at oral temperatures, providing initial nicotine satisfaction. The calcium salts slowly dissolve in saliva, releasing calcium ions that cross-link with low-methoxyl pectin to form a secondary gel network, further encapsulating the nicotine and achieving a stable and sustained release of nicotine in the mouth during the later stages of use.

[0013] Preferably, the wall material of the nicotine sustained-release microcapsules comprises monoglycerides and / or beeswax, and the core material comprises nicotine or its salt.

[0014] Preferably, the mass ratio of the gel matrix, nicotine sustained-release microcapsules and ion gel triggering particles is (15-35):(5-15):(10-25).

[0015] The specific point values ​​in (15-35) can be 15, 16, 17, 18, 19, 20, 22, 25, 27, 30, 33 or 35, etc.

[0016] The specific point values ​​in (5-15) can be 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15, etc.

[0017] The specific point values ​​in (10-25) can be 10, 11, 12, 15, 17, 20, 21, 22, 23, 24 or 25, etc.

[0018] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0019] Preferably, the components of the gel matrix include 30-45 parts of polysaccharide material, 55-70 parts of sweetener and 15-20 parts of water by weight.

[0020] The weight parts of the polysaccharide material can be 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 43 or 45 parts, etc.

[0021] The sweetener can be present in parts by weight of 55, 56, 57, 58, 59, 60, 62, 65, 68, or 70 parts, etc.

[0022] The weight percentage of the water can be 15, 15.5, 16, 16.5, 17, 17.5, 18, 18.5, 19, 19.5, or 20 parts, etc.

[0023] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0024] Preferably, the mass ratio of the wall material to the core material is (2-10):(0.1-1).

[0025] The specific point values ​​in (2-10) can be 2, 3, 4, 5, 6, 7, 8, 9 or 10, etc.

[0026] The specific point values ​​in (0.1-1) can be 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9 or 1, etc.

[0027] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0028] Preferably, the wall material comprises monoglycerides and beeswax.

[0029] Preferably, the mass ratio of the monoglyceride to beeswax is (1-10):(1-10).

[0030] The specific point values ​​in the first (1-10) can be 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, etc.

[0031] The specific point values ​​in the second (1-10) can be 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, etc.

[0032] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0033] Preferably, the mass ratio of the low-methoxyl pectin to calcium salt is (3-7):1.

[0034] The specific point values ​​in (3-7) can be 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5 or 7, etc.

[0035] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0036] Preferably, the low-methoxyl pectin is prepared by a method comprising the following steps:

[0037] High-methoxyl pectin and ammonium salt react in water, the pH is adjusted, the resulting reaction solution is mixed with ethanol, solid-liquid separation is performed, the precipitate is collected, and the low-methoxyl pectin is obtained.

[0038] Ammonium groups exchange with pectin methyl ester groups, followed by molecular rearrangement of some amino groups to generate amide groups, thus preparing partially amidated low-methoxyl pectin. This pectin further forms a secondary gel network with calcium ions, providing moderate nicotine encapsulation and achieving a stable and sustained release of nicotine in the oral cavity during the later stages of use.

[0039] Preferably, the degree of esterification of the high-methoxyl pectin is not less than 50%, for example, it can be 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95%, etc.

[0040] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0041] Preferably, the concentration of high-methoxyl pectin in the reaction system is 18-48 g / L, for example, it can be 18 g / L, 19 g / L, 20 g / L, 22 g / L, 25 g / L, 27 g / L, 30 g / L, 33 g / L, 35 g / L, 38 g / L, 40 g / L, 45 g / L or 48 g / L, etc.; the concentration of ammonium salt is 0.5-3 g / L, for example, it can be 0.5 g / L, 0.6 g / L, 0.7 g / L, 0.8 g / L, 0.9 g / L, 1 g / L, 1.5 g / L, 2 g / L, 2.5 g / L or 3 g / L, etc.

[0042] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0043] Preferably, the ammonium salt includes any one or a combination of at least two of ammonium formate, ammonium carbonate, or ammonium bicarbonate.

[0044] Preferably, the ammonium salt includes ammonium formate, ammonium carbonate, and ammonium bicarbonate.

[0045] The combination of ammonium formate, ammonium carbonate and ammonium bicarbonate is preferred for the preparation of low-methoxyl pectin. The three ammonium salts have a synergistic effect, and the resulting polymer network and calcium ions have a better gelation effect, which can better regulate the sustained release of nicotine.

[0046] Preferably, the mass ratio of ammonium formate, ammonium carbonate and ammonium bicarbonate is (1-10):(1-10):(1-10).

[0047] The specific point values ​​in the first (1-10) can be 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, etc.

[0048] The specific point values ​​in the second (1-10) can be 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, etc.

[0049] The specific point values ​​in the third (1-10) can be 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, etc.

[0050] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0051] Preferably, the reaction temperature is 30-50℃, for example, 30℃, 32℃, 35℃, 37℃, 40℃, 43℃, 45℃, 48℃ or 50℃, etc.; the time is 20-30 h, for example, 20 h, 21 h, 22 h, 23 h, 24 h, 25 h, 26 h, 27 h, 28 h, 29 h or 30 h, etc.

[0052] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0053] Preferably, the reaction is carried out under stirring.

[0054] Preferably, the pH value is 2-2.5, for example, it can be 2, 2.05, 2.1, 2.15, 2.2, 2.25, 2.3, 2.35, 2.4, 2.45 or 2.5.

[0055] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0056] Preferably, the volume ratio of the reaction solution to ethanol is 1:(2-3).

[0057] The specific point values ​​in (2-3) can be 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9 or 3, etc.

[0058] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0059] Preferably, the mixing method is stirring.

[0060] Preferably, the process of collecting the precipitate further includes a drying step.

[0061] Preferably, the calcium salt comprises any one or a combination of at least two of calcium citrate, calcium tartrate, or calcium malate.

[0062] Preferably, the calcium salt includes calcium citrate, calcium tartrate, and calcium malate.

[0063] The optimal combination of calcium citrate, calcium tartrate, and calcium malate is selected. The three calcium salts have a synergistic effect and have a better gelation effect when combined with low-methoxyl pectin, which can better regulate the sustained release of nicotine.

[0064] Preferably, the mass ratio of calcium citrate, calcium tartrate and calcium malate is (1-3):(1-2):(1-3).

[0065] The specific point values ​​in the first (1-3) can be 1, 1.2, 1.5, 1.7, 2, 2.3, 2.5, 2.8 or 3, etc.

[0066] The specific point values ​​in (1-2) can be 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9 or 2, etc.

[0067] The specific point values ​​in the second (1-3) can be 1, 1.2, 1.5, 1.7, 2, 2.3, 2.5, 2.8 or 3, etc.

[0068] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0069] Preferably, the polysaccharide material includes high-methoxyl pectin, carrageenan, and guar gum.

[0070] A combination of high-methoxyl pectin, carrageenan, and curdlan gum was selected for nicotine gel matrix coating. These three polysaccharide materials exhibit a synergistic effect, resulting in better regulation of nicotine release. Furthermore, calcium ion release further influences carrageenan gelation. Simultaneously with secondary gelation by low-methoxyl pectin and calcium ions, ionogelation by carrageenan further strengthens the initial polysaccharide gelation network.

[0071] Preferably, the mass ratio of the high-methoxyl pectin, carrageenan, and guar gum is (1-3):(1-3):(0.1-0.5).

[0072] The specific point values ​​in the first (1-3) can be 1, 1.2, 1.5, 1.7, 2, 2.3, 2.5, 2.8 or 3, etc.

[0073] The specific point values ​​in the second (1-3) can be 1, 1.2, 1.5, 1.7, 2, 2.3, 2.5, 2.8 or 3, etc.

[0074] The specific point values ​​in (0.1-0.5) can be 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45 or 0.5, etc.

[0075] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0076] Preferably, the degree of esterification of the high-methoxyl pectin is not less than 50%, for example, it can be 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95%, etc.

[0077] Preferably, the sweetener includes any one or a combination of at least two of sorbitol, xylitol, maltitol, isomaltitol, monk fruit syrup, starch syrup, or sucrose.

[0078] Sweeteners can be selected as either artificial sweeteners or non-artificial sweeteners, depending on the user's needs.

[0079] Preferably, the components of the gel matrix further include a plasticizer.

[0080] Preferably, the components of the gel matrix further include 3-8 parts by weight of plasticizer.

[0081] The plasticizer can be present in parts by weight of 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, or 8 parts, etc.

[0082] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0083] Preferably, the plasticizer includes any one or a combination of at least two of glycerol, sorbitol, or polyethylene glycol.

[0084] Preferably, the components of the gel matrix further include an acidulant.

[0085] Preferably, the components of the gel matrix further include 0.5-1 parts by weight of acidulant.

[0086] The acidulant can be present in weight parts of 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, or 1 part, etc.

[0087] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0088] Preferably, the acidulant comprises any one or a combination of at least two of sodium citrate, potassium citrate, potassium lactate, or sodium lactate.

[0089] Preferably, the components of the gel matrix further include a cooling agent.

[0090] Preferably, the components of the gel matrix further include 0.1-0.5 parts by weight of a cooling agent.

[0091] The cooling agent can be present in parts by weight of 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, or 0.5 parts, etc.

[0092] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0093] Preferably, the cooling agent comprises any one or a combination of at least two of peppermint oil, menthol, menthone, ethyl menthane formamide, menthyl acetate, or limonene.

[0094] Preferably, the particle size of the nicotine sustained-release microcapsules is 50-300 μm, for example, it can be 50 μm, 60 μm, 70 μm, 80 μm, 90 μm, 100 μm, 150 μm, 200 μm, 250 μm or 300 μm.

[0095] Preferably, the particle size of the ion gel triggering particles is 100-300 μm, for example, it can be 100 μm, 120 μm, 150 μm, 170 μm, 200 μm, 230 μm, 250 μm, 280 μm or 300 μm, etc.

[0096] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0097] In a second aspect, the present invention provides a method for preparing a gel article as described in the first aspect, the method comprising:

[0098] The aqueous solution of the core material and the wall material are mixed, emulsified, and spray-dried to obtain the nicotine sustained-release microcapsules; low-methoxyl pectin and calcium salt are mixed and dry-granulated to obtain the ion gel trigger particles.

[0099] The polysaccharide material is mixed with water and heated to dissolve it. Then it is mixed with a sweetener to obtain a matrix solution. After the matrix solution is cooled, it is mixed with nicotine sustained-release microcapsules and ion gel triggering particles to gel and obtain the gel product.

[0100] Preferably, the emulsification temperature is 60-70℃, for example, it can be 60℃, 61℃, 62℃, 63℃, 64℃, 65℃, 66℃, 67℃, 68℃, 69℃ or 70℃, etc.; the time is 5-15 min, for example, it can be 5 min, 6 min, 7 min, 8 min, 9 min, 10 min, 11 min, 12 min, 13 min, 14 min or 15 min, etc.

[0101] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0102] Preferably, the emulsification is performed by stirring.

[0103] Preferably, the stirring speed is 9000-11000 rpm, for example, 9000 rpm, 9200 rpm, 9500 rpm, 9700 rpm, 10000 rpm, 10300 rpm, 10500 rpm, 10800 rpm or 11000 rpm.

[0104] Preferably, the heating includes raising the temperature to 80-90°C, for example, 80°C, 81°C, 82°C, 83°C, 84°C, 85°C, 86°C, 87°C, 88°C, 89°C, or 90°C.

[0105] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0106] Preferably, the process of mixing with the sweetener further includes adding any one or a combination of at least two of the following: plasticizer, acidulant, or cooling agent.

[0107] Preferably, the cooling includes reducing the temperature to 45-50°C, for example, 45°C, 45.5°C, 46°C, 46.5°C, 47°C, 47.5°C, 48°C, 48.5°C, 49°C, 49.5°C, or 50°C.

[0108] Preferably, the gelation temperature is 20-30℃, for example, 20℃, 21℃, 22℃, 23℃, 24℃, 25℃, 26℃, 27℃, 28℃, 29℃ or 30℃, etc.; the time is 20-40 min, for example, 20 min, 22 min, 25 min, 27 min, 30 min, 33 min, 35 min, 38 min or 40 min, etc.

[0109] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0110] Preferably, the gelation process further includes a drying step.

[0111] Preferably, the drying temperature is 35-45℃, for example, 35℃, 36℃, 37℃, 38℃, 39℃, 40℃, 41℃, 42℃, 43℃, 44℃ or 45℃, etc.; the time is 22-26 h, for example, 22 h, 22.5 h, 23 h, 23.5 h, 24 h, 24.5 h, 25 h, 25.5 h or 26 h, etc.

[0112] Preferably, the water content of the gel product is 15-25 wt%, for example, it can be 15 wt%, 16 wt%, 17 wt%, 18 wt%, 19 wt%, 20 wt%, 21 wt%, 22 wt%, 23 wt%, 24 wt%, or 25 wt%.

[0113] Other specific point values ​​within the range of the above values ​​can be selected, and will not be elaborated on here.

[0114] Compared with the prior art, the present invention has the following beneficial effects:

[0115] As the gel product is chewed and broken down in the mouth, the nicotine sustained-release microcapsules are exposed, melting and releasing nicotine at oral temperatures, providing initial nicotine satisfaction. Calcium salts slowly dissolve in saliva, releasing calcium ions which cross-link with low-methoxyl pectin to form a secondary gel network, further encapsulating the nicotine and achieving a stable and sustained release of nicotine in the mouth during the later stages of use. This invention achieves multi-layered nicotine release through lipid and gel encapsulation. Rapid release in the initial stage alleviates nicotine withdrawal symptoms and meets immediate nicotine needs; slow release in the later stages ensures a continuous supply of nicotine. Detailed Implementation

[0116] To further illustrate the technical means and effects of the present invention, the following describes the technical solution of the present invention in conjunction with preferred embodiments of the present invention. However, the present invention is not limited to the scope of the embodiments.

[0117] Where specific techniques or conditions are not specified in the examples, they shall be performed in accordance with the techniques or conditions described in the literature in this field, or in accordance with the product instructions. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased through legitimate channels.

[0118] The sources of materials used in the following specific embodiments are as follows:

[0119] The beeswax is sourced from Yihengjian Bee Industry Co., Ltd.; the high-methoxyl pectin, carrageenan, and guar gum are all sourced from Zhongyan Food Trading Co., Ltd.

[0120] Preparation Example 1

[0121] This preparation example provides a low-methoxyl pectin, which is prepared by a method comprising the following steps:

[0122] 3 g of high-methoxyl pectin, 0.1 g of ammonium formate, 0.06 g of ammonium carbonate, and 0.04 g of ammonium bicarbonate were mixed in 100 mL of water and stirred at 40 °C for 25 h. The pH was adjusted to 2.3 to obtain a reaction solution. The obtained reaction solution was mixed with ethanol at a volume ratio of 1:2.5, stirred, filtered, the precipitate was collected, and dried to obtain the low-methoxyl pectin.

[0123] Preparation Example 2

[0124] This preparation example provides a low-methoxyl pectin, which is prepared by a method comprising the following steps:

[0125] 4.8 g of high-methoxyl pectin, 0.1 g of ammonium formate, 0.1 g of ammonium carbonate, and 0.1 g of ammonium bicarbonate were mixed in 100 mL of water and stirred at 50 °C for 20 h. The pH was adjusted to 2.5 to obtain a reaction solution. The obtained reaction solution was mixed with ethanol at a volume ratio of 1:3, stirred, filtered, the precipitate was collected, and dried to obtain the low-methoxyl pectin.

[0126] Preparation Example 3

[0127] This preparation example provides a low-methoxyl pectin, which is prepared by a method comprising the following steps:

[0128] 1.8 g of high-methoxyl pectin, 0.05 g of ammonium formate, 0.03 g of ammonium carbonate, and 0.02 g of ammonium bicarbonate were mixed in 100 mL of water and stirred at 30 °C for 30 h. The pH was adjusted to 2 to obtain a reaction solution. The obtained reaction solution was mixed with ethanol at a volume ratio of 1:2 and stirred. The mixture was filtered, the precipitate was collected, and dried to obtain the low-methoxyl pectin.

[0129] Preparation Example 4

[0130] This preparation example provides a low-methoxyl pectin, which differs from Preparation Example 1 only in that: ammonium formate is not added, and its reduction is proportionally allocated to ammonium carbonate and ammonium bicarbonate, while the remaining steps and raw materials remain unchanged.

[0131] Preparation Example 5

[0132] This preparation example provides a low-methoxyl pectin, which differs from Preparation Example 1 only in that: no ammonium carbonate is added, and the reduction is proportionally allocated to ammonium formate and ammonium bicarbonate, while the remaining steps and raw materials remain unchanged.

[0133] Preparation Example 6

[0134] This preparation example provides a low-methoxyl pectin, which differs from Preparation Example 1 only in that: ammonium bicarbonate is not added, and its reduction is proportionally allocated to ammonium formate and ammonium carbonate, while the remaining steps and raw materials remain unchanged.

[0135] Preparation Example 7

[0136] This preparation example provides a low-methoxyl pectin, which differs from Preparation Example 1 only in that "0.1 g ammonium formate, 0.06 g ammonium carbonate and 0.04 g ammonium bicarbonate" are replaced with "0.2 g ammonium acetate", while the other steps and raw materials remain unchanged.

[0137] Example 1

[0138] This embodiment provides a nicotine sustained-release gel product, which is prepared by a method including the following steps:

[0139] (1) 4 g of monoglyceride, 2 g of beeswax and an aqueous solution containing 0.5 g of nicotine tartrate were mixed and stirred at 10,000 rpm and 65°C for 10 min to carry out emulsification reaction. Then, the mixture was spray-dried to control the particle size to 50-300 μm to obtain nicotine sustained-release microcapsules.

[0140] (2) 0.25 g calcium citrate, 0.25 g calcium tartrate, 0.5 g calcium malate and 5 g low methoxyl pectin provided in Preparation Example 1 were mixed and dry granulated to control the particle size to 100-300 μm to obtain ion gel triggered particles.

[0141] (3) By weight, 18 parts of high methoxyl pectin, 17 parts of carrageenan, 5 parts of guar gum and 18 parts of water are mixed, heated to 85°C and stirred to dissolve. Then, 60 parts of sorbitol, 5 parts of glycerol, 0.8 parts of sodium citrate and 0.3 parts of peppermint oil are mixed evenly to obtain a matrix solution.

[0142] (4) After the matrix solution is cooled to 48°C, it is mixed with nicotine sustained-release microcapsules and ion gel triggering particles at a mass ratio of 25:10:17, and gelled by standing at 25°C for 30 min. The gel is then dried at 40°C for 24 h to obtain the gel product.

[0143] Example 2

[0144] This embodiment provides a nicotine sustained-release gel product, which is prepared by a method including the following steps:

[0145] (1) 3 g monoglyceride, 7 g beeswax and an aqueous solution containing 1 g nicotine tartrate were mixed and stirred at 11000 rpm and 70°C for 5 min to carry out emulsification reaction. Then spray dried to control the particle size to 50-300 μm to obtain nicotine sustained-release microcapsules.

[0146] (2) 0.4 g calcium citrate, 0.2 g calcium tartrate, 0.4 g calcium malate and 7 g low methoxyl pectin provided in Preparation Example 2 were mixed and dry granulated to control the particle size to 100-300 μm to obtain ion gel triggered particles.

[0147] (3) By weight, 25 parts of high methoxyl pectin, 15 parts of carrageenan, 5 parts of guar gum and 20 parts of water are mixed, heated to 90°C and stirred to dissolve. Then, 70 parts of xylitol, 8 parts of glycerol, 1 part of potassium citrate and 0.5 parts of menthol are mixed evenly to obtain a matrix solution.

[0148] (4) After the matrix solution is cooled to 50°C, it is mixed with nicotine sustained-release microcapsules and ion gel triggering particles at a mass ratio of 35:5:10, and gelled by standing at 20°C for 40 min. The gel is then dried at 45°C for 22 h to obtain the gel product.

[0149] Example 3

[0150] This embodiment provides a nicotine sustained-release gel product, which is prepared by a method including the following steps:

[0151] (1) 1 g of monoglyceride, 1 g of beeswax and an aqueous solution containing 0.1 g of nicotine tartrate were mixed and stirred at 9000 rpm and 60℃ for 15 min to carry out emulsification reaction. Then, the mixture was spray-dried to control the particle size to 50-300 μm to obtain nicotine sustained-release microcapsules.

[0152] (2) 0.4 g calcium citrate, 0.4 g calcium tartrate, 0.2 g calcium malate and 3 g low methoxyl pectin provided in Preparation Example 3 were mixed and dry granulated to control the particle size to 100-300 μm to obtain ion gel triggered particles.

[0153] (3) By weight, mix 16 parts of high methoxyl pectin, 13 parts of carrageenan, 1 part of guar gum and 15 parts of water, heat to 80°C, stir to dissolve, and then mix evenly with 55 parts of maltitol, 3 parts of glycerol, 0.5 parts of potassium lactate and 0.1 parts of menthone to obtain a matrix solution.

[0154] (4) After the matrix solution is cooled to 45°C, it is mixed with nicotine sustained-release microcapsules and ion gel triggering particles at a mass ratio of 15:15:25, and gelled by standing at 30°C for 20 min. The gel is then dried at 35°C for 26 h to obtain the gel product.

[0155] Examples 4-7

[0156] This embodiment provides a nicotine sustained-release gel product, which differs from Example 1 only in that: in step (2), "low methoxy pectin provided in Preparation Example 1" is replaced with an equal amount of "low methoxy pectin provided in Preparation Examples 4-7", while the other steps and raw materials remain unchanged.

[0157] Example 8

[0158] This embodiment provides a nicotine sustained-release gel product, which differs from Example 1 only in that: in step (2), calcium citrate is not added, and its reduction is proportionally allocated to calcium tartrate and calcium malate, while the remaining steps and raw materials remain unchanged.

[0159] Example 9

[0160] This embodiment provides a nicotine sustained-release gel product, which differs from Example 1 only in that: in step (2), calcium tartrate is not added, and its reduction is proportionally allocated to calcium citrate and calcium malate, while the remaining steps and raw materials remain unchanged.

[0161] Example 10

[0162] This embodiment provides a nicotine sustained-release gel product, which differs from Example 1 only in that: in step (2), calcium malate is not added, and its reduction is proportionally allocated to calcium citrate and calcium tartrate, while the remaining steps and raw materials remain unchanged.

[0163] Example 11

[0164] This embodiment provides a nicotine sustained-release gel product, which differs from Example 1 only in that: in step (2), “0.25 g calcium citrate, 0.25 g calcium tartrate, 0.5 g calcium malate” is replaced with “0.25 g calcium carbonate, 0.25 g calcium lactate, 0.5 g calcium acetate”, while the other steps and raw materials remain unchanged.

[0165] Example 12

[0166] This embodiment provides a nicotine sustained-release gel product, which differs from Example 1 only in that: in step (3), no high-methoxyl pectin is added, and its reduced amount is allocated to carrageenan and guar gum in proportion, while the remaining steps and raw materials remain unchanged.

[0167] Example 13

[0168] This embodiment provides a nicotine sustained-release gel product, which differs from Example 1 only in that: in step (3), carrageenan is not added, and its reduced amount is allocated to high methoxyl pectin and guar gum in proportion, while the remaining steps and raw materials remain unchanged.

[0169] Example 14

[0170] This embodiment provides a nicotine sustained-release gel product, which differs from Example 1 only in that: in step (3), no guar gum is added, and its reduced amount is allocated to high methoxyl pectin and carrageenan in proportion, while the remaining steps and raw materials remain unchanged.

[0171] Comparative Example 1

[0172] This comparative example provides a nicotine sustained-release gel product, which differs from Example 1 only in that: in step (2), "the low methoxyl pectin provided in Preparation Example 1" is replaced with an equal amount of "commercially available low methoxyl pectin (purchased from Shandong Yibaolai Biotechnology Co., Ltd.)", while the other steps and raw materials remain unchanged.

[0173] Comparative Example 2

[0174] This comparative example provides a nicotine sustained-release gel product, which differs from Example 1 only in that: in step (3), “18 parts high methoxyl pectin, 17 parts carrageenan, and 5 parts guar gum” are replaced with “18 parts xanthan gum, 17 parts gelatin, and 5 parts agar”, while the other steps and raw materials remain unchanged.

[0175] Comparative Example 3

[0176] This comparative example provides a nicotine sustained-release gel product, which differs from Example 1 only in that: in step (4), no ion gel triggering particles are added, and the reduction is made up by the matrix solution, while the remaining steps and raw materials remain unchanged.

[0177] Test case

[0178] Nicotine in vitro dissolution tests were conducted on the nicotine gel products provided in Examples 1-14 and Comparative Examples 1-3 using an oral cavity simulation chewing device. Artificial saliva prepared according to Table 1 was added to a storage bottle and placed in a constant temperature water bath at 37°C. The device was turned on, the temperature was set to 37°C, and the parameters of the simulation dissolution device were set according to Table 2. Test samples were placed in a solution dish. Driven by a motor, the chewing manipulator and the left-right opening and rotating components in the simulated oral cavity began to work. After reaching the set number of chewing cycles, the motor stopped, and liquid was dispensed. A peristaltic pump extracted the extract from the solution dish, and the nicotine content in the extract was measured.

[0179] As shown in Table 3, Examples 1-3 demonstrate that the nicotine gel product provided by this invention releases rapidly in the initial stage of use, alleviating nicotine withdrawal symptoms and meeting immediate nicotine needs. In the later stages of use, it releases slowly, ensuring a continuous supply of nicotine. Comparative Example 3 shows that the secondary gelation triggered by ion-gel particles plays a decisive role in achieving the above-mentioned effects. Comparative Example 1 shows that the partially amidated low-methoxyl pectin formed by the exchange of ammonium groups with pectin methyl ester groups has better encapsulation properties for nicotine compared to conventionally available low-methoxyl pectin, forming a secondary gelation network with calcium ions. Examples 4-7 show that ammonium formate, ammonium carbonate, and ammonium bicarbonate have a synergistic effect, forming a polymer network with calcium ions that has a better gelation effect, allowing for better control of nicotine release. Example 11 shows that the type of calcium ions affects the secondary gelation effect of low-methoxyl pectin. Examples 8-10 show that calcium citrate, calcium tartrate, and calcium malate have a synergistic effect, exhibiting better gelation with low-methoxyl pectin and thus better regulating the sustained release of nicotine. Comparative Example 2 shows that the type of polysaccharide material affects the encapsulation of nicotine in the gel matrix. Examples 12-14 show that high-methoxyl pectin, carrageenan, and gellan gum have a synergistic effect, constructing a superior gel matrix framework and regulating nicotine release.

[0180]

[0181]

[0182]

[0183] This invention illustrates a nicotine sustained-release gel product and its preparation method through the above embodiments. However, this invention is not limited to the above embodiments, meaning that this invention does not necessarily rely on the above embodiments for implementation. Those skilled in the art should understand that any improvements to this invention, equivalent substitutions of the raw materials in the product, addition of auxiliary components, and selection of specific methods, all fall within the protection and disclosure scope of this invention.

[0184] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the protection scope of the present invention.

[0185] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not describe the various possible combinations separately.

Claims

1. A nicotine sustained-release gel product, characterized in that, The gel product includes a gel matrix, and nicotine sustained-release microcapsules and ion gel triggering particles embedded in the gel matrix; The components of the gel matrix include polysaccharide material, sweetener and water; the polysaccharide material includes any one or a combination of at least two of high-methoxyl pectin, carrageenan or guar gum; The components of the ion gel triggering particles include low-methoxyl pectin and calcium salts.

2. The gel product according to claim 1, characterized in that, The wall material of the nicotine sustained-release microcapsules includes monoglycerides and / or beeswax, and the core material includes nicotine or its salts. Preferably, the mass ratio of the gel matrix, nicotine sustained-release microcapsules, and ion gel triggering particles is (15-35):(5-15):(10-25); Preferably, the components of the gel matrix include, by weight, 30-45 parts of polysaccharide material, 55-70 parts of sweetener and 15-20 parts of water; Preferably, the mass ratio of the wall material to the core material is (2-10):(0.1-1); Preferably, the mass ratio of the low-methoxyl pectin to calcium salt is (3-7):

1.

3. The gel product according to claim 1 or 2, characterized in that, The low-methoxyl pectin is prepared by a method comprising the following steps: High-methoxyl pectin and ammonium salt react in water, the pH is adjusted, the resulting reaction solution is mixed with ethanol, solid-liquid separation is performed, the precipitate is collected, and the low-methoxyl pectin is obtained.

4. The gel product according to claim 3, characterized in that, The concentration of high-methoxyl pectin in the reaction system is 18-48 g / L, and the concentration of ammonium salt is 0.5-3 g / L; Preferably, the ammonium salt includes any one or a combination of at least two of ammonium formate, ammonium carbonate, or ammonium bicarbonate; Preferably, the ammonium salt includes ammonium formate, ammonium carbonate, and ammonium bicarbonate; Preferably, the mass ratio of ammonium formate, ammonium carbonate and ammonium bicarbonate is (1-10):(1-10):(1-10); Preferably, the reaction temperature is 30-50℃ and the time is 20-30 h; Preferably, the reaction is carried out under stirring. Preferably, the pH value is 2-2.5; Preferably, the volume ratio of the reaction solution to ethanol is 1:(2-3); Preferably, the mixing method is stirring; Preferably, the process of collecting the precipitate further includes a drying step.

5. The gel product according to any one of claims 1-4, characterized in that, The calcium salt includes any one or a combination of at least two of calcium citrate, calcium tartrate, or calcium malate. Preferably, the calcium salt includes calcium citrate, calcium tartrate, and calcium malate; Preferably, the mass ratio of calcium citrate, calcium tartrate and calcium malate is (1-3):(1-2):(1-3).

6. The gel article according to any one of claims 1-5, characterized in that, The polysaccharide materials include high-methoxyl pectin, carrageenan, and guar gum; Preferably, the mass ratio of the high-methoxyl pectin, carrageenan, and guar gum is (1-3):(1-3):(0.1-0.5).

7. The gel article according to any one of claims 1-6, characterized in that, The sweetener includes any one or a combination of at least two of the following: sorbitol, xylitol, maltitol, isomaltitol, monk fruit syrup, starch syrup, or sucrose; Preferably, the components of the gel matrix further include a plasticizer; Preferably, the components of the gel matrix further include 3-8 parts by weight of plasticizer; Preferably, the plasticizer includes any one or a combination of at least two of glycerol, sorbitol, or polyethylene glycol; Preferably, the components of the gel matrix further include an acidulant; Preferably, the components of the gel matrix further include 0.5-1 parts by weight of an acidulant; Preferably, the acidulant comprises any one or a combination of at least two of sodium citrate, potassium citrate, potassium lactate, or sodium lactate; Preferably, the components of the gel matrix further include a cooling agent; Preferably, the components of the gel matrix further include 0.1-0.5 parts by weight of a cooling agent; Preferably, the cooling agent comprises any one or a combination of at least two of peppermint oil, menthol, menthone, ethyl menthane formamide, menthyl acetate, or limonene.

8. The gel article according to any one of claims 1-7, characterized in that, The nicotine sustained-release microcapsules have a particle size of 50-300 μm; Preferably, the particle size of the ion gel triggering particles is 100-300 μm.

9. The method for preparing the gel product according to any one of claims 1-8, characterized in that, The method includes: The aqueous solution of the core material and the wall material are mixed, emulsified, and spray-dried to obtain the nicotine sustained-release microcapsules; low-methoxyl pectin and calcium salt are mixed and dry-granulated to obtain the ion gel trigger particles. The polysaccharide material is mixed with water and heated to dissolve it. Then it is mixed with a sweetener to obtain a matrix solution. After the matrix solution is cooled, it is mixed with nicotine sustained-release microcapsules and ion gel triggering particles to gel and obtain the gel product.

10. The method according to claim 9, characterized in that, The emulsification temperature is 60-70℃, and the time is 5-15 minutes; Preferably, the emulsification is performed by stirring; Preferably, the stirring speed is 9000-11000 rpm; Preferably, the heating includes raising the temperature to 80-90°C; Preferably, the process of mixing with the sweetener further includes adding any one or a combination of at least two of the following: plasticizer, acidulant, or cooling agent; Preferably, the cooling includes reducing the temperature to 45-50°C; Preferably, the gelation temperature is 20-30℃ and the time is 20-40 min; Preferably, the gelation process further includes a drying step; Preferably, the drying temperature is 35-45℃ and the drying time is 22-26 h; Preferably, the water content of the gel product is 15-25 wt%.

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