An oral nicotine delivery article and a method of making the same

Abstract

The present application provides an oral nicotine delivery product and a preparation method thereof, the oral nicotine delivery product comprising a deformable carrier matrix and a first nicotine reservoir and a second nicotine reservoir dispersed inside the deformable carrier matrix; the first nicotine reservoir and the second nicotine reservoir comprise a nicotine component and a reservoir wall material wrapping the nicotine component, and the reservoir wall material thickness of the first nicotine reservoir is lower than that of the second nicotine reservoir. The oral nicotine delivery product provided by the present application can actively adjust the release of nicotine according to the needs of consumers, realize on-demand satisfaction, and at the same time can realize the instantaneous release of nicotine, the onset time is fast, and the consumer demand can be immediately satisfied.

Description

Technical Field

[0001] This invention belongs to the field of oral products technology, specifically relating to an oral nicotine delivery product and its preparation method. Background Technology

[0002] The nicotine release rate of existing oral nicotine products (such as nicotine sachets, lozenges, and patches) is mainly determined by the formulation and structure, and users cannot adjust the nicotine release rate in real time according to their own needs. This leads to the following problems: (1) Individual differences cannot be met: Different users have different nicotine needs, and the same user's needs also differ in different scenarios. Sometimes they need to absorb and relieve quickly, and sometimes they need to release it smoothly. Existing products cannot achieve "on-demand adjustment".

[0003] (2) Lack of ritualistic behavior: Smokers are used to regulating nicotine intake through actions such as "inhaling". The ritualistic nature of this behavior is an important part of the pleasure. Existing smokeless products lack this interactivity.

[0004] (3) Insufficient initial burst power: Existing nicotine bags take effect slowly, usually requiring several minutes to reach peak blood drug concentration, making it difficult to meet the need for immediate relief.

[0005] Some studies have attempted to adjust the release rate through formulation optimization, such as controlling the moisture content (30% moisture content can increase the release rate by 40% within 2 minutes) and particle size (the release rate of 180μm particles is 3 times that of 1700μm particles). However, these methods are all passive adjustments and cannot achieve active control during use (Tian Yongfeng, Li Peng, Liu Ze, et al. Study on the influencing factors of nicotine release in the mouth using an artificial oral cavity simulation extrusion device [J]. Tobacco Science and Technology, 2019, 52(10): 68-74).

[0006] CN119185163A discloses a nicotine pouch for oral mucosal absorption and its preparation method. The nicotine pouch includes nicotine particles, at least one liquid-containing capsule, and a non-woven fabric pouch. The nicotine particles and capsule are encapsulated in the non-woven fabric pouch, with each pouch containing 1 to 3 capsules. When the nicotine particles are dry, the particle size is 1-1000 micrometers, and the moisture content ranges from 1% to 10% (w / w); when they are wet, the particle size is 1-1000 micrometers, and the moisture content ranges from 5% to 15% (w / w); when they are oily, the particle size is 1-1000 micrometers, and the moisture content ranges from 1% to 10% (w / w); when they are microgranules, the particle size is 30-2500 micrometers, and the moisture content ranges from 1% to 10% (w / w).

[0007] CN120346185A discloses a nicotine microcapsule composition, a nicotine microcapsule oral bag, and a method for preparing the same. The nicotine microcapsule composition includes nicotine, a blank capsule core, a binder, a sweetener, a pH adjuster, cellulose and cellulose derivatives, a polymeric coating material, a lubricant, a flavoring, and a solvent. The blank capsule core is loaded with the nicotine, and the polymeric coating material forms a single or multiple layer of drug-loaded material or coating on the blank capsule core. When the polymeric coating material forms multiple layers of drug-loaded material or coating, it sequentially includes, from the inside out, an isolation layer, a drug-containing layer, a protective layer, and a drug-loaded layer.

[0008] However, the aforementioned patented methods still cannot meet consumers' needs for real-time adjustment based on their own requirements. Therefore, how to provide an oral nicotine product that can actively adjust the nicotine release rate has become an urgent problem to be solved. Summary of the Invention

[0009] To address the shortcomings of existing technologies, the present invention aims to provide an oral nicotine delivery product and its preparation method. The oral nicotine delivery product provided by the present invention can actively adjust the release of nicotine according to the consumer's needs, achieving on-demand satisfaction. Simultaneously, it can achieve instantaneous nicotine release with rapid onset of action, immediately meeting the consumer's needs.

[0010] To achieve this objective, the present invention adopts the following technical solution: On one hand, the present invention provides an oral nicotine delivery article, the oral nicotine delivery article comprising a deformable carrier matrix and a first nicotine reservoir and a second nicotine reservoir dispersed within the deformable carrier matrix; The first nicotine reservoir and the second nicotine reservoir each include a nicotine component and a reservoir wall material that encapsulates the nicotine component, and the thickness of the reservoir wall material of the first nicotine reservoir is less than the thickness of the reservoir wall material of the second nicotine reservoir.

[0011] The aforementioned specific oral nicotine delivery products can actively adjust the release of nicotine according to the consumer's needs, achieving on-demand satisfaction. At the same time, they can achieve instant nicotine release, with a fast onset time, and can immediately meet the consumer's needs.

[0012] When a user applies external pressure to the product with their tongue or lips, the carrier matrix deforms, transmitting the pressure to the dispersed nicotine reservoirs. The reservoir walls rupture due to stress concentration, releasing the nicotine cores. The released nicotine quickly dissolves in saliva, accelerating absorption and achieving the function of regulating the release rate by the pressure applied.

[0013] Preferably, the first nicotine reservoir is dispersed in the shallow region of the deformable carrier matrix, the shallow region being the area within 0-1 mm of the outer surface of the oral nicotine delivery article.

[0014] Preferably, the second nicotine reservoir is dispersed in a deep region of the deformable carrier matrix, the deep region being an area more than 1 mm away from the outer surface of the oral nicotine delivery article.

[0015] The aforementioned specific nicotine reservoir distribution allows for a greater difference in nicotine release rates when consumers apply different levels of force, thus more effectively meeting consumers' needs for different nicotine release profiles.

[0016] Preferably, the deformable carrier matrix comprises any one or a combination of at least two of gelatin, agar, carrageenan, xanthan gum, hydroxypropyl methylcellulose, or polyethylene oxide.

[0017] Preferably, the deformable carrier matrix further includes any one or a combination of at least two of the following: fragrance, flavoring, or nicotine components.

[0018] Preferably, the nicotine components in the first and second nicotine reservoirs independently include any one or a combination of at least two of nicotine free base, nicotine salt, or nicotine-resin complex.

[0019] Preferably, the wall material of the first and second nicotine reservoirs independently comprises any one or a combination of at least two of gelatin, gum arabic, calcium alginate, or chitosan, and is not entirely the same as the deformable carrier matrix.

[0020] Preferably, the wall material of the first nicotine storage tank is 5-15 μm thick and cracks under a force of 0.5-2 N.

[0021] Preferably, the wall material of the second nicotine storage tank is 15-50 μm thick and cracks under a force of 2-5 N.

[0022] On the other hand, the present invention also provides a method for preparing the oral nicotine delivery article as described above, characterized in that the preparation method includes the following steps: (1) The nicotine component and the reservoir wall material are mixed with water to obtain the core material solution and the wall material solution, and then the first nicotine reservoir and the second nicotine reservoir are prepared by the complex coagulation method. (2) The deformable carrier matrix is ​​mixed with water to obtain a matrix sol; (3) The second nicotine reservoir is mixed with a portion of the matrix sol and cooled to a semi-solid state to form a deep matrix; the first nicotine reservoir is mixed with the remaining matrix sol and then poured onto the surface of the deep matrix. After cooling and drying, the oral nicotine delivery product is obtained. Steps (1) and (2) are not in any particular order.

[0023] Compared with the prior art, the present invention has the following beneficial effects: This invention provides an oral nicotine delivery product that can actively adjust the release of nicotine according to the consumer's needs, achieving on-demand satisfaction. It also enables instantaneous nicotine release with rapid onset of action, immediately meeting the consumer's needs. Specifically, it includes: (1) Active release control: Users can accelerate the release of nicotine in real time by squeezing according to their own needs, so as to achieve "on-demand satisfaction".

[0024] (2) Instant burst power: After compression, the storage tank ruptures, and nicotine is released instantly, with a fast onset time, which can meet the needs immediately.

[0025] (3) Ritualistic behavior: The squeezing action increases the interactivity and ritualistic nature of the product, enhancing psychological satisfaction.

[0026] (4) Dosage control: The amount of nicotine released in a single extrusion can be controlled by designing the number of reservoirs and the thickness of the wall material.

[0027] (5) Anti-abuse design: The rupture of the reservoir is an irreversible process, and the dose released by a single squeeze is limited, preventing excessive instantaneous intake of nicotine. Attached Figure Description

[0028] Figure 1 These are schematic cross-sectional views of the oral nicotine delivery articles provided in Examples 1-3; Figure 2 This is a schematic cross-sectional view of the oral nicotine delivery article provided in Example 4; Figure 3 This is a schematic cross-sectional view of the oral nicotine delivery article provided in Example 5; Wherein 1-deformable carrier matrix, 2-first nicotine reservoir, 21-nicotine component of the first nicotine reservoir, 22-reservoir wall material of the first nicotine reservoir, 3-second nicotine reservoir, 31-nicotine component of the second nicotine reservoir, 32-reservoir wall material of the second nicotine reservoir. Detailed Implementation

[0029] The technical solution of the present invention will be further illustrated below through specific embodiments. Those skilled in the art should understand that the embodiments described are merely illustrative of the present invention and should not be construed as limiting the invention in any way.

[0030] Example 1 This embodiment provides an oral nicotine delivery article with the following cross-sectional structure: Figure 1As shown, 1 is a deformable carrier matrix, 2 is the first nicotine reservoir, 21 is the nicotine component of the first nicotine reservoir, 22 is the reservoir wall material of the first nicotine reservoir, 3 is the second nicotine reservoir, 31 is the nicotine component of the second nicotine reservoir, and 32 is the reservoir wall material of the second nicotine reservoir.

[0031] The preparation method is as follows: 1. Preparation of the first nicotine reservoir: 2.1 g of nicotine tartrate (containing 1.05 g of nicotine) was dissolved in 10 mL of deionized water to obtain a core material solution; 1 g of gelatin and 1 g of gum arabic were mixed and added to 20 mL of deionized water, and stirred at 65 °C to dissolve, obtaining a wall material solution with a mass fraction of 10%; the core material solution was slowly added dropwise to the wall material solution, and emulsified by stirring at 45 °C for 15 min; the pH was adjusted to 4.2 with 10% acetic acid solution, and stirring was continued for 30 min for re-coagulation; 0.8 mL of 25% glutaraldehyde solution was added, and the mixture was cured at 4 °C for 2 h; the mixture was filtered, washed three times with deionized water, and vacuum dried at 40 °C to obtain the first nicotine reservoir with a wall thickness of 7-12 μm, a particle size of 80-120 μm, a bursting pressure of 0.8-1.5 N, a nicotine content of approximately 0.05 mg per reservoir, and a drug loading of 30%.

[0032] 2. Preparation of the second nicotine reservoir: 6.3 g of nicotine tartrate (containing 3.15 g of nicotine) was dissolved in 10 mL of deionized water to obtain a core material solution; 1.7 g of gelatin and 1.7 g of gum arabic were mixed and added to 20 mL of deionized water, and stirred at 65 °C to dissolve, obtaining a wall material solution with a mass fraction of 17%; the core material solution was slowly added dropwise to the wall material solution, and emulsified by stirring at 45 °C for 15 min; the pH was adjusted to 4.2 with 10% acetic acid solution, and stirring was continued for 50 min for re-coagulation; 0.8 mL of 25% glutaraldehyde solution was added, and the mixture was cured at 4 °C for 2 h; the mixture was filtered, washed three times with deionized water, and vacuum dried at 40 °C to obtain a second nicotine reservoir with a wall thickness of 20-40 μm, a particle size of 120-180 μm, a bursting pressure of 2.5-4.0 N, a nicotine content of approximately 0.15 mg per reservoir, and a drug loading of 30%.

[0033] 3. Preparation of matrix sol: Add 7.5g of gelatin and 0.5g of carrageenan to 80mL of deionized water, stir at 85℃ until completely dissolved, cool to 55℃, add 1.2g of peppermint flavoring, 0.6g of steviol glycosides and 0.2g of glycerol, stir evenly to obtain matrix sol (containing no free nicotine components).

[0034] 4. Layered casting and molding: ① Take 40mL of matrix sol, add 3g of second nicotine reservoir, stir at 30r / min for 4min to disperse evenly, pour into a mold with a size of 10mm×5mm×2mm, cool at 4℃ for 8min to semi-solidify, forming a deep matrix; ② Take the remaining 40mL of matrix sol, add 7g of the first nicotine reservoir, stir and disperse evenly under the same conditions, and slowly pour it onto the surface of the semi-cured deep matrix. ③ Continue cooling at 4℃ for 30 minutes until fully formed. After demolding, dry at 20℃ and 40% relative humidity until the moisture content is 12% to obtain the finished product.

[0035] Example 2 This embodiment provides an oral nicotine delivery article with the following cross-sectional structure: Figure 1 As shown.

[0036] The only difference between this embodiment and Embodiment 1 is the storage preparation process parameters: 1. Preparation of the first nicotine reservoir: The wall material solution concentration was 8%, the re-coagulation reaction time was 20 min, the core material / wall material mass ratio was 2.1:1.6, and the curing agent was added 15 min after the start of re-coagulation; a first nicotine reservoir with a wall thickness of 5-7 μm, a bursting force of 0.5-1 N, a single nicotine content of 0.05 mg, and a drug loading of 30% was obtained.

[0037] 2. Preparation of the second nicotine reservoir: The wall material solution concentration was 15%, the re-coagulation reaction time was 40 min, the core material / wall material mass ratio was 6.3:3.0, and the curing agent was added 25 min after the start of re-coagulation; a second nicotine reservoir with a wall thickness of 15-20 μm, a bursting force of 2-3 N, a single nicotine content of 0.15 mg, and a drug loading of 30% was obtained.

[0038] 3. The layered casting process and other parameters are exactly the same as in Example 1.

[0039] Example 3 This embodiment provides an oral nicotine delivery article with the following cross-sectional structure: Figure 1 As shown.

[0040] The only difference between this embodiment and Embodiment 1 is the storage preparation process parameters: 1. Preparation of the first nicotine reservoir: The wall material solution concentration was 12%, the re-coagulation reaction time was 45 min, the core material / wall material mass ratio was 2.1:2.4, and after the re-coagulation was completed, it was allowed to stand for 10 min before adding the curing agent; a first nicotine reservoir with a wall thickness of 12-15 μm, a bursting force of 1.5-2 N, a single nicotine content of 0.05 mg, and a drug loading of 30% was obtained.

[0041] 2. Preparation of the second nicotine reservoir: The wall material solution concentration was 20%, the re-coagulation reaction time was 65 min, the core material / wall material mass ratio was 6.3:4.0, and after the re-coagulation was completed, it was allowed to stand for 15 min before adding the curing agent; a second nicotine reservoir with a wall thickness of 40-50 μm, a bursting force of 4-5 N, a single nicotine content of 0.15 mg, and a drug loading of 30% was obtained.

[0042] 3. The layered casting process and other parameters are exactly the same as in Example 1.

[0043] Example 4 This embodiment provides an oral nicotine delivery article with the following cross-sectional structure: Figure 2 As shown, 1 is a deformable carrier matrix, 2 is the first nicotine reservoir, 21 is the nicotine component of the first nicotine reservoir, 22 is the reservoir wall material of the first nicotine reservoir, 3 is the second nicotine reservoir, 31 is the nicotine component of the second nicotine reservoir, and 32 is the reservoir wall material of the second nicotine reservoir.

[0044] The preparation method is as follows: This embodiment uses a non-layered mixing process: 7g of the first nicotine reservoir and 3g of the second nicotine reservoir are added simultaneously to all 80mL of matrix sol, stirred at 30r / min for 4min to disperse evenly, and then poured into a mold to cool and solidify; the remaining formula and parameters are exactly the same as in Example 1.

[0045] Example 5 This embodiment provides an oral nicotine delivery article with the following cross-sectional structure: Figure 3 As shown, 1 is a deformable carrier matrix, 2 is the first nicotine reservoir, 21 is the nicotine component of the first nicotine reservoir, 22 is the reservoir wall material of the first nicotine reservoir, 3 is the second nicotine reservoir, 31 is the nicotine component of the second nicotine reservoir, and 32 is the reservoir wall material of the second nicotine reservoir.

[0046] The preparation method is as follows: This embodiment uses a reverse-layer casting process for preparation: 1. Deep casting: Add 3g of first nicotine reservoir to 40mL of matrix sol, stir to disperse evenly, pour into the mold and cool to a semi-solid state.

[0047] 2. Shallow casting: Add 7g of the second nicotine reservoir to the remaining 40mL of matrix sol, stir to disperse evenly, and cast onto the surface of the deep matrix.

[0048] 3. The remaining formulas and parameters are exactly the same as in Example 1.

[0049] Comparative Example 1 This comparative example provides an oral nicotine delivery product, the preparation method of which is as follows: This comparative example provides an oral nicotine delivery article containing only a first nicotine reservoir (wall thickness 7-12 μm) without adding a second nicotine reservoir. The total amount of reservoirs added is the same as in Example 1; the remaining formulation and preparation method are the same as in Example 1.

[0050] Comparative Example 2 This comparative example provides an oral nicotine delivery product, the preparation method of which is as follows: This comparative example provides an oral nicotine delivery product containing only a second nicotine reservoir (wall thickness 20-40 μm) without adding a first nicotine reservoir. The total amount of reservoirs added is the same as in Example 1; the remaining formulation and preparation method are the same as in Example 1.

[0051] Effect test: The oral nicotine delivery products provided in Examples 1-5 and Comparative Examples 1-2 were immersed in artificial saliva (purchased from Sinopharm Chemical Reagent Co., Ltd.), and the nicotine release rate under different external forces was tested using a simulated extrusion device. The test conditions were: temperature 37°C, artificial saliva flow rate 1 mL / min, and constant extrusion forces of 0 N (no extrusion), 1 N (light pressure), and 3 N (heavy pressure) were applied respectively. The amount of nicotine released within 10 minutes was determined by high performance liquid chromatography (method steps refer to Example 1 of CN102156178B), and the peak release rate was calculated. The results are shown in the table below: The results are as follows: The data above shows that by employing two specific nicotine reservoir schemes and designing a specific structural distribution, this invention can effectively generate nicotine release patterns under different external force conditions, enabling the product to better meet consumers' needs for different nicotine release patterns.

[0052] The applicant declares that the present invention is illustrated by the above embodiments to illustrate the oral nicotine delivery article and its preparation method, but the present invention is not limited to the above embodiments, that is, it does not mean that the present invention must rely on the above embodiments to be implemented. Those skilled in the art should understand that any improvements to the present invention, equivalent substitutions of the raw materials of the product of the present invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

[0053] 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.

[0054] 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. An oral nicotine delivery article, characterized in that, The oral nicotine delivery article includes a deformable carrier matrix and a first nicotine reservoir and a second nicotine reservoir dispersed within the deformable carrier matrix; The first nicotine reservoir and the second nicotine reservoir each include a nicotine component and a reservoir wall material that encapsulates the nicotine component, and the thickness of the reservoir wall material of the first nicotine reservoir is less than the thickness of the reservoir wall material of the second nicotine reservoir.

2. The oral nicotine delivery article according to claim 1, characterized in that, The first nicotine reservoir is dispersed in the shallow region of the deformable carrier matrix, which is the area within 0-1 mm from the outer surface of the oral nicotine delivery article.

3. The oral nicotine delivery article according to claim 1 or 2, characterized in that, The second nicotine reservoir is dispersed in the deep region of the deformable carrier matrix, the deep region being an area more than 1 mm away from the outer surface of the oral nicotine delivery article.

4. The oral nicotine delivery article according to any one of claims 1-3, characterized in that, The deformable carrier matrix includes any one or a combination of at least two of gelatin, agar, carrageenan, xanthan gum, hydroxypropyl methylcellulose, or polyethylene oxide.

5. The oral nicotine delivery article according to claim 4, characterized in that, The deformable carrier matrix also includes any one or a combination of at least two of the following: fragrance, flavoring, or nicotine components.

6. The oral nicotine delivery article according to any one of claims 1-5, characterized in that, The nicotine components in the first and second nicotine reservoirs independently include any one or a combination of at least two of nicotine free base, nicotine salt, or nicotine-resin complex.

7. The oral nicotine delivery article according to any one of claims 1-6, characterized in that, The wall material of the first and second nicotine reservoirs independently comprises any one or a combination of at least two of gelatin, gum arabic, calcium alginate, or chitosan, and is not entirely identical to the deformable carrier matrix.

8. The oral nicotine delivery article according to any one of claims 1-7, characterized in that, The first nicotine storage tank has a wall thickness of 5-15 μm and is capable of cracking under a force of 0.5-2 N.

9. The oral nicotine delivery article according to any one of claims 1-8, characterized in that, The second nicotine storage tank has a wall thickness of 15-50 μm and is capable of cracking under a force of 2-5 N.

10. A method for preparing an oral nicotine delivery article according to any one of claims 1-9, characterized in that, The preparation method includes the following steps: (1) The nicotine component and the reservoir wall material are mixed with water to obtain the core material solution and the wall material solution, and then the first nicotine reservoir and the second nicotine reservoir are prepared by the complex coagulation method. (2) The deformable carrier matrix is ​​mixed with water to obtain a matrix sol; (3) The second nicotine reservoir is mixed with a portion of the matrix sol and cooled to a semi-solid state to form a deep matrix; the first nicotine reservoir is mixed with the remaining matrix sol and then poured onto the surface of the deep matrix. After cooling and drying, the oral nicotine delivery product is obtained. Steps (1) and (2) are not in any particular order.

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