Multilayer nicotine oral soluble film composition and preparation method thereof

Abstract

The invention discloses a multilayer nicotine oral soluble film composition and a preparation method thereof, the multilayer nicotine oral soluble film composition comprises a tobacco flavor layer, a slightly bitter taste layer and a sweet aftertaste layer, a film forming material of the tobacco flavor layer comprises a cellulose derivative, and the weight-average molecular weight of the cellulose derivative is 300,000-400,000, 400,000-500,000, 500,000-600,000, 600,000-700,000 or 700,000-800,000; a film forming material of the slightly bitter taste layer comprises hydroxypropyl chitin, and the weight-average molecular weight of the hydroxypropyl chitin is 50,000-100,000, 100,000-150,000 or 150,000-200,000; the film-forming material of the sweet aftertaste layer comprises polyvinyl alcohol, and the weight-average molecular weight of the polyvinyl alcohol is 50,000-100,000, 100,000-150,000 or 150,000-200,000. By means of the multi-layer different taste design, complex taste feeling similar to smoking is provided for a user, the attraction and satisfaction of the product are improved, the dissolving time of the oral dissolving film in the oral cavity is gradually increased layer by layer through the optimized formula and structure, and the using effect of the product is improved.

Description

Technical Field

[0001] This patent belongs to the field of orally disintegrating film technology, specifically to a multi-layer nicotine orally disintegrating film composition and its preparation method. Background Art

[0002] Existing tobacco substitutes have limitations in terms of flavor experience and duration of action. Most have a single flavor and a short oral dissolution time, making them difficult to meet smokers' demand for a richer taste experience. This also hinders the full effectiveness of ingredients like nicotine. Therefore, developing a multi-layered orally dissolving nicotine film composition that can provide a gradual transition in tobacco flavor and taste while extending its dissolution time is of great market significance. Summary of the Invention

[0003] The purpose of this patent is to provide a multi-layer nicotine orally dissolving film composition and its preparation method, so as to achieve the purpose of gradual change of tobacco flavor and taste and prolong dissolution time.

[0004] In order to solve the above technical problems, this patent adopts the following technical solutions:

[0005] A multi-layer nicotine orally disintegrating film composition, comprising a tobacco flavor layer, a slightly bitter flavor layer, and a sweet aftertaste flavor layer.

[0006] The tobacco flavor layer film-forming material includes a cellulose derivative, and the cellulose derivative has a weight average molecular weight of 300,000-400,000, 400,000-500,000, 500,000-600,000, 600,000-700,000, or 700,000-800,000;

[0007] The film-forming material of the slightly bitter taste layer includes hydroxypropyl chitosan, and the weight average molecular weight of hydroxypropyl chitosan is 50,000-100,000, 100,000-150,000 or 150,000-200,000;

[0008] The film-forming material of the sweet aftertaste layer includes polyvinyl alcohol, and the weight average molecular weight of the polyvinyl alcohol is 50,000-100,000, 100,000-150,000 or 150,000-200,000.

[0009] Furthermore, the slightly bitter taste layer and the sweet aftertaste layer are both nicotine-free layers;

[0010] Furthermore, the dissolution time of the tobacco flavor layer is 35-40 seconds, 40-45 seconds, 45-50 seconds or 50-55 seconds;

[0011] Furthermore, the dissolution time of the slightly bitter taste layer is 70-75 seconds, 75-80 seconds, 80-85 seconds, 85-90 seconds or 90-95 seconds;

[0012] Furthermore, the dissolution time of the sweet aftertaste layer is 100-110 seconds, 110-120 seconds, 120-130 seconds, 130-140 seconds or 140-150 seconds.

[0013] Furthermore, the tobacco flavor layer film-forming material further includes nicotine, tobacco extract, tobacco flavor filler and / or tobacco flavor plasticizer;

[0014] Furthermore, the tobacco extract includes nicotine and / or tobacco essential oil; the amount of tobacco extract added is 3-10% of the total amount of the multi-layer nicotine orally disintegrating film composition;

[0015] Furthermore, the tobacco flavor filler includes food-grade diatomaceous earth; the tobacco flavor filler is added in an amount of 8-15% of the total amount of the multi-layer nicotine orally disintegrating film composition;

[0016] Furthermore, the tobacco flavor plasticizer includes diethyl phthalate; the amount of the tobacco flavor plasticizer added is 4-10% of the total amount of the multi-layer nicotine orally dissolving film composition.

[0017] Furthermore, the amount of the cellulose derivative added is 25-40% of the total amount of the multi-layer nicotine orally disintegrating film composition;

[0018] Furthermore, the amount of nicotine added is 5-15% of the total amount of the multi-layer nicotine orally disintegrating film composition.

[0019] Furthermore, the film-forming material of the slightly bitter layer further comprises a slightly bitter additive, a slightly bitter filler and / or a slightly bitter plasticizer;

[0020] Furthermore, the slightly bitter flavor additive includes coffee extract, and the amount of coffee extract added is 3-7% of the total amount of the multi-layer nicotine orally disintegrating film composition;

[0021] Furthermore, the slightly bitter filler includes pregelatinized starch, and the amount of pregelatinized starch added is 6-12% of the total amount of the multi-layer nicotine orally disintegrating film composition;

[0022] Furthermore, the slightly bitter plasticizer includes glycerin, and the amount of glycerin added is 3-8% of the total amount of the multi-layer nicotine orally disintegrating film composition;

[0023] Furthermore, the amount of hydroxypropyl chitosan added is 15-25% of the total amount of the multi-layer nicotine orally disintegrating film composition.

[0024] Furthermore, the film-forming material of the sweet aftertaste layer further comprises a sweet aftertaste additive, a sweet aftertaste filler and / or a sweet aftertaste plasticizer;

[0025] Furthermore, the sweet aftertaste additive includes glycyrrhizin, and the amount of glycyrrhizin added is 1-5% of the total amount of the multi-layer nicotine orally dissolving film composition;

[0026] Furthermore, the sweet aftertaste filler includes calcium hydrogen phosphate, and the amount of calcium hydrogen phosphate added is 5-10% of the total amount of the multi-layer nicotine orally dissolving film composition;

[0027] Furthermore, the sweet aftertaste plasticizer includes propylene glycol, and the amount of propylene glycol added is 2-6% of the total amount of the multi-layer nicotine orally dissolving film composition;

[0028] Furthermore, the amount of polyvinyl alcohol added is 20-30% of the total amount of the multi-layer nicotine orally disintegrating film composition.

[0029] This patent further provides a method for preparing any of the above-mentioned multi-layer nicotine orally disintegrating film compositions, comprising the following steps:

[0030] Step A: dissolving a tobacco flavor layer film-forming material, a slightly bitter flavor layer film-forming material, and a sweet aftertaste flavor layer film-forming material in water, stirring uniformly, and heating until fully dissolved to form a tobacco flavor layer solution, a slightly bitter flavor layer solution, and a sweet aftertaste flavor layer solution, respectively;

[0031] Step B: coating the tobacco flavor layer solution on the substrate to a thickness of 0.05-0.15 mm, and drying to obtain a first layer of coated substrate;

[0032] Step C: coating the slightly bitter taste layer solution on the first coating substrate to a thickness of 0.07-0.16 mm, and drying to obtain a second coating substrate;

[0033] Step D: coating the sweet aftertaste layer solution on the second coating substrate to a thickness of 0.1-0.17 mm, and drying to obtain a multi-layer nicotine orally dissolving film composition.

[0034] Furthermore, in step B, the coating area of the tobacco flavor layer solution accounts for 35%-40% of the surface area of the multi-layer nicotine orally disintegrating film composition;

[0035] In step C, the coating area of the slightly bitter flavor layer solution accounts for 30% to 35% of the surface area of the multi-layer nicotine orally dissolving film composition;

[0036] In step D, the coating area of the sweet aftertaste layer solution accounts for 25%-30% of the surface area of the multi-layer nicotine orally dissolving film composition.

[0037] Furthermore, in step B to step D, a hot air circulation oven is used for drying, the drying temperature is 35-50° C., and the drying time is 20-40 minutes.

[0038] Furthermore, step A specifically includes the following steps:

[0039] Dissolve the tobacco flavor layer film-forming material, the slightly bitter flavor layer film-forming material and the aftertaste flavor layer film-forming material in water respectively, stir evenly, heat to 50°C-70°C, keep warm for 20 minutes-40 minutes to fully dissolve, and cool to room temperature to form a tobacco flavor layer solution, a slightly bitter flavor layer solution and a aftertaste flavor layer solution respectively.

[0040] Furthermore, in steps B to D, the coating method includes blade coating, roller coating and / or slit coating.

[0041] This patent provides a multi-layer nicotine orally disintegrating film composition and its preparation method, which has the following advantages:

[0042] (1) Rich taste experience: Through multiple layers of different flavor designs (for example, tobacco flavor, slightly bitter taste, and sweet aftertaste), it provides users with a complex taste experience similar to that of smoking, increasing the attractiveness and satisfaction of the product.

[0043] (2) Extended dissolution time: The optimized formula and structure make the dissolution time of the orally dissolving film in the oral cavity increase layer by layer. The overall dissolution time is significantly extended compared with traditional products, thereby extending the action time of ingredients such as nicotine and improving the use effect of the product.

[0044] (3) Efficient nicotine delivery: The product can effectively deliver nicotine to meet smokers' nicotine needs, while reducing some of the problems caused by traditional tobacco smoking, such as the harm of secondhand smoke, and providing a relatively healthier alternative to tobacco.

[0045] (4) Improved market competitiveness: Compared with existing tobacco substitutes, the product of the present invention has significant advantages in taste experience, nicotine release efficiency, dissolution time, etc., which helps to improve competitiveness in the tobacco substitute market and meet the market's diverse demand for high-quality products. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] The above content of this patent and the following specific embodiments will be better understood when read in conjunction with the accompanying drawings. It should be noted that the drawings are only examples of the technical solutions claimed.

[0047] Figure 1 This is a component distribution diagram of the multi-layer nicotine orally dissolving film composition in this patent. DETAILED DESCRIPTION

[0048] The detailed features and advantages of this patent are described in detail below in the specific implementation method. The content is sufficient to enable any technical personnel in this field to understand the technical content of this patent and implement it accordingly. Based on the description, claims and drawings disclosed in this specification, technical personnel in this field can easily understand the relevant purposes and advantages of this patent.

[0049] In this specification and claims, reference will be made to various terms which, unless otherwise indicated, shall be defined to have the following meanings:

[0050] The terms "include" or "have" have the same meaning as "contain", and also include other forms of the term, such as the gerund form and the singular form in English, meaning including but not limited to, and are not intended to exclude, for example, other elements, components, integers or steps.

[0051] All numbers used to express amounts of ingredients, properties (e.g., weight average molecular weight), reaction conditions, and the like should be considered to be modified in all instances by the term "within the inevitable error range" or "about." Therefore, the numerical values set forth herein are approximate and may vary depending upon the desired properties sought to be obtained by the present invention. At the very least, and not intended to limit the scope of the claims, the doctrine of equivalents should be applied, for example, each numerical value should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.

[0052] It should be understood that the term "and / or" as used herein simply describes a relationship between associated objects, indicating that three possible relationships exist. For example, "A and / or B" can represent: A alone, A and B together, or B alone. A and B can be singular or plural. Furthermore, the character " / " as used herein generally indicates an "or" relationship between the associated objects, but it may also indicate an "and / or" relationship. For specific understanding, please refer to the context.

[0053] All other terms used herein that are not specifically defined in this patent are intended to have the general meanings understood by ordinary technicians in the field to which they belong, and in particular, ordinary technicians in the field can directly and unambiguously determine the meaning of how to implement the technical solution of this patent after reading the claims, description and drawings of this patent.

[0054] Even if there are incomplete descriptions, omissions or ambiguities in the grammar, text, punctuation, graphics, symbols, etc. in the claims, description and drawings of this patent, ordinary technicians in this field can still reach the only correct understanding by reading the claims, description and drawings as a whole without excessive reasoning or experimentation, and effectively exclude various incorrect understandings that are not aimed at achieving the purpose of this patent.

[0055] Ordinary technical personnel in the relevant field will give priority to reading the patent claims, specifications and drawings to reasonably interpret the terms; secondly, they will choose to refer to the relevant definitions in other documents published by the applicant before the application date to reasonably interpret the terms; thirdly, they will choose to reasonably interpret the terms by referring to the references cited in this patent; finally, they will choose to reasonably interpret the terms by combining the technical dictionaries, technical manuals, reference books, textbooks, national or industry technical standards, etc. commonly used by technical personnel in the relevant technical field.

[0056] In addition, throughout this specification, references are made to various publications. To more fully describe the state of the art in the field to which the presently disclosed subject matter pertains, the disclosures of these publications are incorporated herein by reference in their entirety. To the extent contained in a published document and described in a statement citing such document, the published document is also individually and specifically incorporated herein by reference.

[0057] The various components used in this patent can be prepared by various known methods that are well disclosed in the chemical literature.

[0058] Before disclosing and describing the materials, compounds, compositions, articles, devices and methods of the present invention, it should be understood that the following aspects are not limited to specific synthetic methods or specific reagents, as these can, of course, vary. It should also be understood that the terminology used herein is for the purpose of describing specific aspects only and is not intended to be limiting.

[0059] This patent proposes an embodiment of a method for preparing a multi-layer nicotine orally disintegrating film composition that can provide tobacco flavor and taste gradient and prolong dissolution time. The multi-layer nicotine orally disintegrating film composition (hereinafter referred to as the orally disintegrating film) includes a tobacco flavor layer, a slightly bitter flavor layer, and a sweet aftertaste flavor layer. The film-forming material of the tobacco flavor layer includes a cellulose derivative with a weight-average molecular weight of 300,000-400,000, 400,000-500,000, 500,000-600,000, 600,000-700,000, or 700,000-800,000; the film-forming material of the slightly bitter flavor layer includes hydroxypropyl chitosan with a weight-average molecular weight of 50,000-100,000, 100,000-150,000, or 150,000-200,000; and the film-forming material of the sweet aftertaste flavor layer includes polyvinyl alcohol with a weight-average molecular weight of 50,000-100,000, 100,000-150,000, or 150,000-200,000.

[0060] Specifically, the multi-layer nicotine orally disintegrating film composition comprises:

[0061] (1) The first layer (tobacco flavor layer): The film-forming material is a cellulose derivative with a weight-average molecular weight of 300,000-800,000, and its amount is 25%-40% of the total weight of the composition; the nicotine content is 5%-15% of the total weight of the composition, and the content can be adjusted according to actual needs to achieve the required tobacco flavor intensity; at the same time, an appropriate amount of tobacco extract (such as nicotine, tobacco essential oil and other ingredients) can be added to enrich the tobacco flavor, and the amount is 3%-10% of the total weight of the composition; the filler is food-grade diatomaceous earth, and the amount is 8%-15% of the total weight of the composition; the plasticizer is diethyl phthalate, and the amount is 4%-10% of the total weight of the composition.

[0062] (2) Second layer (slightly bitter layer): The film-forming material is hydroxypropyl chitosan (HPMC) with a weight-average molecular weight of 50,000-200,000, and the amount used is 15%-25% of the total weight of the composition; the flavor additive is coffee extract (providing a slightly bitter taste), and the amount used is 3%-7% of the total weight of the composition; the filler is pregelatinized starch, and the amount used is 6%-12% of the total weight of the composition; the plasticizer is glycerol, and the amount used is 3%-8% of the total weight of the composition.

[0063] (3) The third layer (sweet aftertaste layer): The film-forming material is polyvinyl alcohol (PVA) with a weight-average molecular weight of 50,000-200,000, and the amount used is 20%-30% of the total weight of the composition; the flavor additive is glycyrrhizin (providing a sweet aftertaste), and the amount used is 1%-5% of the total weight of the composition; the filler is calcium hydrogen phosphate, and the amount used is 5%-10% of the total weight of the composition; the plasticizer is propylene glycol, and the amount used is 2%-6% of the total weight of the composition.

[0064] The method for preparing the multi-layer nicotine orally disintegrating film composition comprises the following steps:

[0065] (1) Solution Preparation: Dissolve the film-forming material, flavoring additive, filler, and plasticizer in an appropriate amount of water according to the above-mentioned ratios for each layer. Stir evenly and heat to 50-70°C. Keep warm for 20-40 minutes to allow all ingredients to fully dissolve and form a uniform solution. Then cool the solution to room temperature and set aside.

[0066] (2) Coating molding: The following coating molding methods can be used:

[0067] ① Doctor blade coating: Place each layer of solution on the substrate in sequence, and use a doctor blade to adjust the coating thickness. The first layer is coated with a thickness of 0.08mm-0.15mm. After initial drying, the second layer is coated with a thickness of 0.1mm-0.16mm, and so on. This method is simple to operate and is suitable for small-scale production or experimental stages. It can better control the thickness of each layer, but the coating speed is relatively slow.

[0068] ② Roller coating: Use a coating roller to evenly apply each layer of solution to the substrate, controlling the coating thickness by adjusting the roller gap. After the first layer is applied, it is dried for a specified period of time (e.g., 8-15 minutes at a temperature of 20°C-35°C and a relative humidity of 30%-50%) before the second layer is applied, completing multiple layers in sequence. Roller coating is highly efficient, enabling continuous production, and offers excellent coating uniformity, making it suitable for large-scale production.

[0069] ③ Slit coating: Each layer of solution is precisely applied to the substrate using a slot-type coating head. The coating gap and coating speed can be precisely controlled, allowing for precise control of the thickness of each layer. The first layer can be applied with an accuracy of 0.05mm-0.13mm. After drying, the second layer is applied with a thickness of 0.07mm-0.15mm, and so on. This method offers high coating accuracy and is suitable for the production of multi-layer orally dissolving films with strict thickness requirements, but the equipment cost is relatively high.

[0070] After each layer is applied, it can be dried in a hot air circulation oven at a temperature of 35°C-50°C for 20-40 minutes to ensure that each layer is fully dried and formed into a film. The temperature and time can be adjusted according to the actual situation during the drying process to ensure that each layer is dried evenly without damaging the properties of the components.

[0071] (3) Post-processing:

[0072] The dried multi-layer orally dissolving film is peeled off from the substrate and cut and packaged as needed. The packaging should be made of moisture-proof and light-blocking materials to ensure consistent quality. For tobacco-flavored nicotine orally dissolving film, the packaging must also comply with relevant tobacco product regulations, such as child-resistant packaging.

[0073] This patent is in the multi-layer structure design, such as Figure 1 As shown, the first layer (tobacco flavor layer) has a relatively large coating area, occupying 35%-40% of the total orally disintegrating film surface area. This is because the tobacco flavor layer needs to quickly deliver a rich tobacco flavor in the mouth, giving volunteers a smoking-like experience from the beginning. Furthermore, the larger coating area helps increase the initial nicotine release, satisfying smokers' immediate nicotine needs.

[0074] The second (slightly bitter) coating area accounts for 30%-35% of the total orally dissolving film surface area. This design allows the slightly bitter flavor to emerge at the right time after the tobacco flavor of the first layer gradually dissipates, providing volunteers with a richer taste experience. Furthermore, the appropriate coating area helps control the intensity and duration of the slightly bitter flavor release, balancing it with the tobacco flavor and sweet aftertaste.

[0075] The third layer (the sweet aftertaste layer) covers 25%-30% of the total surface area of the orally dissolving film. The sweet aftertaste layer, with its smaller coating area, delivers a long-lasting sweet aftertaste in the back of the mouth, leaving volunteers with a pleasant oral experience. This coating area distribution ensures sufficient release of the sweet aftertaste while preventing it from being too strong and masking other flavors.

[0076] In contrast, some prior art multi-layer tobacco products, while also mentioning a multi-layer structure, do not explicitly address the distribution of the coating area, and instead prioritize the compression of the edible film and tobacco composition layers. This differs significantly from the patent's approach of precisely controlling the coating area of each layer to achieve flavor progression and dissolution time. Other prior art smokeless tobacco products primarily focus on the composition and structure of the orally disintegrating particles, without addressing the design of the multi-layer coating area distribution.

[0077] The initial use period of the orally dissolving film prepared by this patent refers to the period of 0-40 seconds after the volunteers place the multi-layer nicotine orally dissolving film in their mouths. During this period, the first layer (the tobacco flavor layer) dissolves rapidly, releasing a rich tobacco flavor and a large amount of nicotine, giving the volunteers a smoking-like experience from the very beginning and satisfying their immediate craving for tobacco flavor and nicotine. The second layer (the slightly bitter layer) begins to release a slightly bitter taste 40-90 seconds after the first layer gradually dissolves and dissipates. At this point, the appearance of the slightly bitter taste brings a rich variety of taste sensations to the volunteers, and its release intensity and duration are controlled by the coating area, coordinating with the tobacco flavor and aftertaste. Simultaneously with and after the release of the second layer, the aftertaste begins to release 90-130 seconds after the initial use. The smaller coating area allows the aftertaste to be slowly released in the latter part of the mouth, leaving the volunteers with a long-lasting and pleasant oral experience without overpowering other flavors.

[0078] This patent ensures the progressive release of taste by setting specific materials in different layers of the multi-layer nicotine orally disintegrating film. Although some existing technologies involve tobacco-free layer technology, such as WO2013192413A1, which discloses that the smokeless tobacco product includes multiple orally disintegratable particles, the concentration of tobacco particles, the type of adhesive and / or the type or concentration of flavors. Other embodiments may include three layers. For example, as in the prior art Figure 1As shown in Figure C, the first and second layers may include tobacco particles and a binder, while the third layer does not include tobacco. The first and second layers may differ in the type or concentration of tobacco particles, the type of binder, and / or the type or concentration of flavorings. The third layer may include the same or different flavorings as the first and second layers, and the effect of specific weight-average molecular weight materials on mechanical and solubility properties is not disclosed. However, the third, tobacco-free layer in this prior art is primarily intended to provide a distinct aroma and texture experience from the tobacco layer. The emphasis is on enriching the product's taste and flavor through the tobacco-free layer, allowing volunteers to experience diverse flavors and changes in taste during use. However, there is no mention of controlling nicotine release or designing refined flavor progression. Furthermore, while this prior art also involves a multi-layer structure, its technical solution focuses on the composition and function of the entire tobacco-free layer, without explicitly addressing the specific selection and ratio of film-forming materials, plasticizers, fillers, etc., for each layer, or how these ingredients work synergistically to precisely control dissolution time and flavor release. Although the orally dissolving film prepared according to the existing technology can provide certain changes in taste and aroma, it does not provide fine control over the release of nicotine, and therefore has serious deficiencies in accurately meeting smokers' nicotine needs and enriching the taste experience.

[0079] The second, slightly bitter, and third layers of this patent are designed as nicotine-free layers. Their primary purpose is to achieve a gradual transition between tobacco flavor, a slightly bitter taste, and a sweet aftertaste. The release of nicotine is also controlled, ensuring that nicotine is primarily released quickly in the first layer to meet the smoker's initial physiological needs. Subsequent layers focus on providing a rich flavor experience, avoiding nicotine interference with taste, and thus better simulating the complex sensations of smoking. This patent also details the film-forming materials, plasticizers, and fillers used in the second and third layers. Through precise formulation and coating processes, each layer is optimized in terms of dissolution time, mechanical properties, and flavor release. For example, the second layer uses ingredients such as hydroxypropyl chitosan and coffee extract, while the third layer uses ingredients such as polyvinyl alcohol and glycyrrhizin. The ratios and coating thicknesses of these ingredients are carefully controlled to ensure that the nicotine-free layers dissolve in the mouth in the desired manner and time, providing a rich flavor experience. Furthermore, the patented nicotine-free layer, through synergistic action with the first tobacco flavor layer, achieves a rapid onset of nicotine and an orderly progression of flavors. This not only satisfies smokers' physiological needs for nicotine but also provides a complex taste sensation similar to that of smoking, enhancing the product's appeal and effectiveness. The nicotine-free layer also optimizes film-forming properties and mechanical strength, making the orally dissolving film more stable and less prone to breakage during use, further enhancing product quality and the user experience.

[0080] This patented method influences the film's dissolution rate by precisely controlling the ratios of film-forming materials, fillers, and plasticizers. For example, increasing the filler dosage reduces the film's dissolution rate because it increases its density and slows water penetration and dissolution. Reducing the plasticizer dosage stiffens the film and correspondingly slows its dissolution rate. Specifically, for the second, slightly bitter layer, the amount of pregelatinized starch can be appropriately increased while the amount of glycerin can be reduced to prolong its dissolution time. For the third, sweet layer, the ratios of polyvinyl alcohol, glycyrrhizin, calcium hydrogen phosphate, and propylene glycol can be further adjusted to achieve the desired dissolution time. Specifically, different film-forming materials have different solubility properties. For example, hydroxypropyl chitosan dissolves relatively quickly, while polyvinyl alcohol dissolves relatively slowly. When designing the formulation, film-forming materials with different solubility properties can be selected, or multiple materials can be strategically combined to achieve controlled dissolution time.

[0081] Specifically, coating thickness is one of the key factors affecting dissolution time. Generally speaking, the thicker the coating, the longer the dissolution time. During the coating process, high-precision coating equipment, such as a slot coating method, can be used to precisely control the coating thickness of each layer. For example, the coating thickness of the second slightly bitter layer can be controlled between 0.08mm and 0.15mm, and the coating thickness of the third sweet layer can be controlled between 0.1mm and 0.17mm. Fine-tuning can be performed according to actual needs to ensure the appropriate dissolution time.

[0082] Specifically, coating speed also affects the film's structure and properties, and thus the dissolution time. Too fast a coating speed can lead to uneven film structure and uneven dissolution rates in certain areas; too slow a coating speed can reduce production efficiency. Therefore, the coating speed should be adjusted appropriately during coating to ensure both film quality and dissolution time requirements.

[0083] Specifically, drying temperature and time have a significant impact on membrane performance. Higher drying temperatures reduce the membrane's moisture content, accelerating its dissolution rate. Long drying times can make the membrane overly dry and brittle, also affecting its dissolution time. Therefore, strict drying conditions are essential—for example, maintaining a drying temperature of 35-50°C and a drying time of 20-40 minutes—to ensure the membrane has the appropriate moisture content and dissolution properties after drying.

[0084] Specifically, the air and moisture permeability of the packaging material will affect the film's hygroscopicity, which in turn affects its dissolution time. Choosing appropriate packaging materials, such as moisture-proof and light-shielding aluminum foil, can effectively prevent the film from absorbing excessive moisture or losing moisture during storage, thereby ensuring a stable dissolution time in the mouth.

[0085] Example 1

[0086] 1.1. Composition ingredients:

[0087] (1) First layer (tobacco flavor layer): The film-forming material is a cellulose derivative with a weight-average molecular weight of 500,000, and the amount thereof is 30% of the total weight of the composition; the nicotine content is 8% of the total weight of the composition, and the amount of tobacco extract (including nicotine and other ingredients) is 5% of the total weight of the composition; the filler is food-grade diatomaceous earth, and the amount thereof is 10% of the total weight of the composition; the plasticizer is diethyl phthalate, and the amount thereof is 6% of the total weight of the composition.

[0088] (2) Second layer (slightly bitter layer): The film-forming material is hydroxypropyl chitosan (HPMC) with a weight-average molecular weight of 150,000, and the amount used is 20% of the total weight of the composition; the amount of coffee extract is 5% of the total weight of the composition; the filler is pregelatinized starch, and the amount used is 9% of the total weight of the composition; the plasticizer is glycerol, and the amount used is 6% of the total weight of the composition.

[0089] (3) The third layer (sweet aftertaste layer): The film-forming material is polyvinyl alcohol (PVA) with a weight-average molecular weight of 150,000, and the amount used is 25% of the total weight of the composition; the amount of glycyrrhizin is 3% of the total weight of the composition; the filler is calcium hydrogen phosphate, and the amount used is 8% of the total weight of the composition; the plasticizer is propylene glycol, and the amount used is 5% of the total weight of the composition.

[0090] 1.2 Preparation process:

[0091] (1) Solution preparation: Add the ingredients of each layer to water in proportion, stir and heat to 60°C, keep warm for 30 minutes to allow the ingredients to fully dissolve. After cooling to room temperature, the solutions of each layer are obtained.

[0092] (2) Coating and molding: A first layer of the solution is applied to a glass plate using a roller coating method, with a coating thickness of 0.12 mm and a coating area accounting for 35%-40% of the surface area of the multi-layer nicotine orally dissolving film composition. After drying for 10 minutes at a temperature of 25°C and a relative humidity of 40%, a second layer of the solution is applied, with a coating thickness of 0.14 mm and a coating area accounting for 30%-35% of the surface area of the multi-layer nicotine orally dissolving film composition. After drying for another 15 minutes, a third layer of the solution is applied, with a coating thickness of 0.16 mm and a coating area accounting for 25%-30% of the surface area of the multi-layer nicotine orally dissolving film composition. The coated orally dissolving film is then placed in a hot air circulation oven at a drying temperature of 40°C for 30 minutes to obtain a dried multi-layer nicotine orally dissolving film.

[0093] 1.3 Post-processing:

[0094] Peel off the orally disintegrating film, cut into appropriate sizes, and seal in aluminum foil packaging for storage.

[0095] 1.4. Effect verification:

[0096] Testing has shown that the multi-layer nicotine orally dissolving film dissolves in the mouth in increasing layers, taking approximately 40-50 seconds for the first layer, 70-90 seconds for the second layer, and 100-130 seconds for the third layer. The flavor initially offers a rich tobacco flavor, followed by a slightly bitter taste, and finally a sweet aftertaste, with a distinct flavor progression. Due to the increased thickness of each layer and adjustments to the material formula, the orally dissolving film has improved mechanical properties, is less prone to breakage, and offers a better user experience. Simulation tests on tobacco products have shown that it can effectively deliver tobacco flavor components and nicotine, meeting the needs of smokers in specific scenarios while also reducing some of the problems associated with traditional tobacco smoking, such as secondhand smoke.

[0097] Example 2

[0098] 2.1. Composition ingredients:

[0099] (1) First layer (tobacco flavor layer): The film-forming material is a cellulose derivative with a weight-average molecular weight of 600,000, and the amount used is 35% of the total weight of the composition; the nicotine content is 10% of the total weight of the composition, and the amount of tobacco extract (including nicotine and other ingredients) is 7% of the total weight of the composition; the filler is food-grade diatomaceous earth, and the amount used is 12% of the total weight of the composition; the plasticizer is diethyl phthalate, and the amount used is 8% of the total weight of the composition.

[0100] (2) Second layer (slightly bitter layer): The film-forming material is hydroxypropyl chitosan (HPMC) with a weight-average molecular weight of 180,000, and the amount used is 22% of the total weight of the composition; the amount of coffee extract is 6% of the total weight of the composition; the filler is pregelatinized starch, and the amount used is 10% of the total weight of the composition; the plasticizer is glycerol, and the amount used is 7% of the total weight of the composition.

[0101] (3) The third layer (sweet aftertaste layer): The film-forming material is polyvinyl alcohol (PVA) with a weight-average molecular weight of 180,000, and the amount used is 28% of the total weight of the composition; the amount of glycyrrhizin is 4% of the total weight of the composition; the filler is calcium hydrogen phosphate, and the amount used is 9% of the total weight of the composition; the plasticizer is propylene glycol, and the amount used is 6% of the total weight of the composition.

[0102] 2.2 Preparation process:

[0103] The difference from Example 1 is that the solution is heated to 65°C during preparation and kept warm for 35 minutes. A slot coating method is used, with the first layer applied to a thickness of 0.13 mm and a coating area accounting for 35%-40% of the surface area of the multi-layer nicotine orally dissolving film composition. After drying (temperature 30°C, relative humidity 45%, time 15 minutes), a second layer is applied to a thickness of 0.15 mm and a coating area accounting for 30%-35% of the surface area of the multi-layer nicotine orally dissolving film composition. After drying for an additional 20 minutes, a third layer is applied to a thickness of 0.17 mm and a coating area accounting for 25%-30% of the surface area of the multi-layer nicotine orally dissolving film composition. The drying temperature is 42°C and the drying time is 35 minutes.

[0104] 2.3 Post-processing:

[0105] Peel off the orally disintegrating film, cut into appropriate sizes, and seal in aluminum foil packaging for storage.

[0106] 2.4. Effect verification:

[0107] The multi-layer nicotine orally dissolving film has further prolonged dissolution time in the mouth: the first layer takes approximately 45-55 seconds, the second layer takes approximately 75-95 seconds, and the third layer takes approximately 110-140 seconds. This provides a richer flavor progression, and the film boasts improved mechanical properties for a more comfortable user experience. Simulation test results demonstrate that it more effectively delivers tobacco flavor and nicotine, offering smokers a more traditional tobacco experience while also reducing the harmful effects of secondhand smoke.

[0108] Example 3

[0109] 3.1. Composition ingredients:

[0110] (1) First layer (tobacco flavor layer): The film-forming material is a cellulose derivative with a weight-average molecular weight of 500,000, and the amount used is 35% of the total weight of the composition; the nicotine content is 10% of the total weight of the composition, and the amount of tobacco extract (including nicotine and other ingredients) is 7% of the total weight of the composition; the filler is food-grade diatomaceous earth, and the amount used is 12% of the total weight of the composition; the plasticizer is diethyl phthalate, and the amount used is 8% of the total weight of the composition.

[0111] (2) Second layer (slightly bitter layer): The film-forming material is hydroxypropyl chitosan (HPMC) with a weight-average molecular weight of 100,000, and the amount used is 22% of the total weight of the composition; the amount of coffee extract is 6% of the total weight of the composition; the filler is pregelatinized starch, and the amount used is 10% of the total weight of the composition; the plasticizer is glycerol, and the amount used is 7% of the total weight of the composition.

[0112] (3) The third layer (sweet aftertaste layer): The film-forming material is polyvinyl alcohol (PVA) with a weight-average molecular weight of 100,000, and the amount used is 28% of the total weight of the composition; the amount of glycyrrhizin is 4% of the total weight of the composition; the filler is calcium hydrogen phosphate, and the amount used is 9% of the total weight of the composition; the plasticizer is propylene glycol, and the amount used is 6% of the total weight of the composition.

[0113] 3.2 Preparation process:

[0114] (1) Solution preparation: Dissolve the film-forming material, nicotine, tobacco extract, filler, and plasticizer in an appropriate amount of water, stir evenly, and heat to 60°C. Keep warm for 30 minutes to allow all ingredients to fully dissolve and form a uniform solution. Then cool the solution to room temperature and set aside.

[0115] (2) Coating and Forming: Using a slit coating method, the solution layers are sequentially coated on a substrate such as a glass plate or polyester film. The coating thicknesses of the first to third layers are controlled to be different, such as 0.1 mm, 0.15 mm, and 0.16 mm. After preliminary drying, the next layer is coated. The coating areas of the first to third layers account for 35%-40%, 30%-35%, and 25%-30% of the surface area of the multi-layer nicotine orally dissolving film composition, respectively. After each layer is coated, it is dried for a certain period of time in an environment with a temperature of 25°C and a relative humidity of 40%. The drying time is determined according to the coating thickness and material properties, such as 10 minutes for a thickness of 0.1 mm, 15 minutes for a thickness of 0.15 mm, and 16 minutes for a thickness of 0.16 mm, so that each layer is fully dried to form a film.

[0116] 3.3 Post-processing:

[0117] The dried multi-layer orally disintegrating film was peeled off from the substrate and cut into samples of appropriate sizes for subsequent performance testing.

[0118] Comparative Example 1

[0119] The difference between this comparative example and Example 3 is that the film-forming material of the first layer (tobacco flavor layer) is a cellulose derivative with a weight-average molecular weight of 200,000, the film-forming material of the second layer (slightly bitter taste layer) is hydroxypropyl chitosan (HPMC) with a weight-average molecular weight of 30,000, and the film-forming material of the third layer (sweet aftertaste layer) is polyvinyl alcohol (PVA) with a weight-average molecular weight of 30,000.

[0120] Comparative Example 2

[0121] The difference between this comparative example and Example 3 is that the film-forming material of the first layer (tobacco flavor layer) is a cellulose derivative with a weight-average molecular weight of 1 million, the film-forming material of the second layer (slightly bitter taste layer) is hydroxypropyl chitosan (HPMC) with a weight-average molecular weight of 250,000, and the film-forming material of the third layer (sweet aftertaste layer) is polyvinyl alcohol (PVA) with a weight-average molecular weight of 250,000.

[0122] Comparative Example 3

[0123] The difference between this comparative example and Example 3 is that the nicotine content in the second layer (slightly bitter layer) and the third layer (sweet aftertaste layer) is 3%-5% of the total weight of the composition.

[0124] Comparative Example 4

[0125] The difference between this comparative example and Example 3 is that the coating thickness of the second slightly bitter taste layer is reduced to 0.05 mm, and the coating thickness of the third sweet aftertaste layer is reduced to 0.07 mm.

[0126] Comparative Example 5

[0127] The difference between this comparative example and Example 3 is that the coating thickness of the second slightly bitter taste layer is increased to 0.18 mm, and the coating thickness of the third sweet aftertaste layer is increased to 0.2 mm.

[0128] To further illustrate the advantages of this patent, the multi-layer orally disintegrating film prepared in the above embodiment is subjected to performance tests such as mechanical strength, solubility, taste perception intensity, and nicotine release curve.

[0129] (1) The orally disintegrating films prepared in the examples and comparative examples were tested according to ASTM D882-23 “Test Method for Tensile Properties of Plastic Film and Sheeting”.

[0130] (2) With reference to the disintegration time test method in the Chinese Pharmacopoeia, further simulation tests of actual usage scenarios of the orally disintegrating film were conducted, including human trials and simulated oral environment experiments.

[0131] Simulated Oral Environment Experiment: Using experimental devices that simulate the oral environment, such as artificial saliva and a water bath with simulated oral temperature, the dissolution time of the multi-layer nicotine dissolving film is tested. By adjusting parameters such as the composition, temperature, and pH of the artificial saliva, the actual conditions in the oral cavity are more accurately simulated, allowing for more precise control and prediction of the product's dissolution time.

[0132] Human trials: During product development and quality control, volunteers can be organized to conduct actual usage tests. The volunteers will place the multi-layer nicotine dissolving film in their mouths according to normal usage, and the dissolution time of each layer will be recorded. Feedback from the volunteers will be collected, and product adjustments and optimizations will be made based on the test results.

[0133] (3) Nicotine release profiles of the orally disintegrating films were measured using HPLC (High Performance Liquid Chromatography). Orally disintegrating film samples from each Example and Comparative Example were placed in a simulated oral environment (37°C, artificial saliva), and samples were taken at 0, 1, 2, 3, 5, 10, 15, 20, and 30 minutes for nicotine concentration analysis.

[0134] The first layer of Comparative Example 1, tested on an electronic universal material testing machine, showed a tensile strength of only 10 MPa and an elongation at break of 50%. Compared to cellulose derivatives within the recommended weight-average molecular weight range (tensile strength of 20 MPa, elongation at break of 120%), this significantly reduced mechanical strength makes it susceptible to breakage during the molding process. In a simulated oral environment (temperature of 37°C, artificial saliva flow rate of 5 mL / min), the dissolution time was 15-20 seconds, significantly faster than the 40-50 seconds of the recommended weight-average molecular weight material. This failed to effectively extend the tobacco flavor release time, significantly compromising the nicotine sustained-release effect.

[0135] The second layer of Comparative Example 1 had a tensile strength of 8 MPa and an elongation at break of 40%. The film was too fragile and easily cracked, failing to form a uniform and complete film layer, affecting the product's appearance and quality. In a simulated oral environment, the dissolution process was uneven, resulting in areas with either strong or weak bitterness. The slightly bitter flavor was also unevenly released, impacting the taste experience of the volunteers.

[0136] In Comparative Example 1, the third layer had a tensile strength of 7 MPa and an elongation at break of 30%. The orally dissolving film was insufficiently strong and prone to breakage during storage and use, affecting product stability and reliability. The dissolution time was 30-40 seconds, which was too short for some products, resulting in insufficient release of the sweet aftertaste. Furthermore, this short dissolution time failed to effectively extend the product's usability, reducing its appeal.

[0137] Comparative Example 2 showed a first layer tensile strength of 18 MPa and an elongation at break of 100%. Compared to the recommended weight-average molecular weight material, the material exhibited improved mechanical strength but significantly decreased solubility. Under the same simulated oral environment, dissolution took over 2 minutes, with some samples failing to fully dissolve within 5 minutes. This made it difficult to dissolve within a reasonable timeframe, impacting product convenience and taste, failing to meet smokers' nicotine needs, and hindering the product's effectiveness as a traditional tobacco alternative.

[0138] In Comparative Example 2, the second layer had a tensile strength of 15 MPa and an elongation at break of 90%. While the mechanical strength was acceptable, the dissolution time was significantly prolonged. The dissolution time reached 120-150 seconds, which failed to form a reasonable gradual relationship with the dissolution times of the first and third layers (the recommended dissolution time for the first layer is 40-50 seconds, and the recommended dissolution time for the third layer is 100-130 seconds), disrupting the overall flavor progression. Furthermore, the excessively long dissolution time caused volunteers to feel a foreign object remaining in their mouths, reducing the user experience of the product.

[0139] The third layer of Comparative Example 2 had a tensile strength of 16 MPa and an elongation at break of 80%, showing slightly better mechanical strength. However, its dissolution rate was too slow. The dissolution time exceeded 200 seconds, which was inconsistent with the dissolution time of the first two layers, resulting in an inconsistent overall flavor progression. Furthermore, the slow dissolution rate delayed the release of the sweet aftertaste, affecting volunteers' perception and satisfaction with the product.

[0140] Comparative Example 3: The tensile strength and elongation at break of the two orally dissolving films were tested using an electronic universal material testing machine. The tensile strength of the second and third layers of the orally dissolving films containing nicotine were both 15 MPa, and the elongation at break was 100%. Dissolution times were also tested in a simulated oral environment. The dissolution times of the second and third layers of the orally dissolving films containing nicotine were uneven, with the first layer dissolving in 35-45 seconds, the second in 85-95 seconds (with some areas dissolving too quickly or too slowly, resulting in an uneven overall taste), and the third in 120-150 seconds (the dissolution time fluctuated significantly, affecting the orderly release of flavor).

[0141] Example 3 of this patent was tested for tensile strength and elongation at break using an electronic universal material testing machine. The tensile strength was 18 MPa and the elongation at break was 115%. The dissolution time of the first layer of the nicotine-free multi-layer orally dissolving film was 40-50 seconds, the second layer was 70-90 seconds, and the third layer was 100-130 seconds. The dissolution time was more uniform and controllable, and the dissolution time was in line with expectations. The flavor gradient was obvious, and the volunteers had a good taste experience of the product. Through experimental comparison of film-forming materials with different weight-average molecular weights, the orally dissolving film prepared with film-forming materials within the weight-average molecular weight range of this patent had better mechanical properties, was not easy to break, and had a better user experience. It had significant advantages in mechanical strength, solubility, and flavor release, and could meet the performance requirements of the multi-layer nicotine orally dissolving film and the experience needs of volunteers.

[0142] From the perspective of film-forming performance and mechanical strength, comparative example 3 and example 3 are analyzed. The use of a nicotine-free second and third layer in example 3 can optimize the formulation and performance of the film-forming material, and release it evenly throughout the dissolution process. Since nicotine itself has certain chemical activity, it may interact with the film-forming material or other additives, affecting the film-forming effect and mechanical strength of the orally dissolving film. By limiting nicotine to the first layer, the second and third layers can more flexibly select and formulate film-forming materials, plasticizers, fillers and other ingredients to improve the overall performance of the orally dissolving film. For example, in this patent, the second layer uses ingredients such as hydroxypropyl chitosan (HPMC) and pregelatinized starch to form a film layer with good flexibility and solubility; the third layer uses ingredients such as polyvinyl alcohol (PVA) and calcium hydrogen phosphate to give the orally dissolving film higher strength and good solubility. Experimental results show that the multi-layer nicotine orally dissolving film of this patent is superior to the multi-layer orally dissolving film product containing nicotine in Comparative Example 3 in terms of mechanical strength and solubility. Its tensile strength can be increased by about 20%-30%, its elongation at break can be increased by about 15%-25%, and its dissolution time in the oral cavity is more uniform and controllable.

[0143] By organizing volunteers to conduct actual use tests, the taste perception intensity of the multi-layer oral dissolving film containing nicotine and the multi-layer oral dissolving film without nicotine layer of Example 3 of this patent was scored (1-10 points). The results showed that the taste perception intensity of the oral dissolving film containing nicotine in the second and third layers (Comparative Example 3) was significantly reduced, with average scores of 4.2 points and 3.8 points respectively, while the taste perception intensity of the multi-layer oral dissolving film of Example 3 of this patent was 7.8 points and 8.1 points in the second and third layers respectively, which was significantly higher than that of the product containing nicotine. From the perspective of taste experience, the second and third layers without nicotine can avoid the masking or interference of nicotine on the taste, so that the slightly bitter taste and aftertaste can be more purely and clearly perceived by volunteers. In this experiment, by comparing the multi-layer oral dissolving film containing nicotine in Example 3 and the multi-layer oral dissolving film of Example 3 of this patent, it was found that the taste perception intensity of the oral dissolving film containing nicotine in the slightly bitter taste layer and the aftertaste layer was significantly reduced, and the volunteer feedback taste experience was not rich and real enough. The patented nicotine-free design allows the slight bitterness and sweet aftertaste to be fully released, and the volunteers' perception of the taste transition is more obvious, greatly enhancing the product's appeal and satisfaction.

[0144] HPLC result shows, the multilayer oral dissolving film containing nicotine continuously releases nicotine in the second layer and the third layer (comparative example 3), and the release amount slowly decreases over time, and excessive release causes the oral cavity to increase nicotine tolerance, and then reduces mouthfeel perception intensity.And the nicotine-free multilayer oral dissolving film of this patent releases nicotine in the first layer after, and the second layer and the third layer are almost free of nicotine release, and the nicotine release curve of this patent is more in line with the physiological needs and usage habits of smokers, in terms of nicotine release regularity, nicotine is concentrated in the first layer (tobacco flavor layer) and released, and the rapid onset of nicotine can be achieved, meeting the physiological needs of smokers to nicotine in the early stage.And the nicotine-free design of the second layer and the third layer makes nicotine release more centralized and controllable, avoids the continuous release of nicotine in the whole use process, thereby reduces the risk of excessive nicotine intake, improves the safety and reliability of product, and is higher in the initial stage of use nicotine release, then gradually reduces, and is closer to the actual situation of nicotine inhalation during smoking.

[0145] The dissolution time of the second slightly bitter taste layer of Comparative Example 4 was shortened to 30-40 seconds, and the dissolution time of the third sweet taste layer was shortened to 50-70 seconds. The dissolution time was too short, resulting in the release of the slightly bitter taste and the sweet taste too quickly, and no obvious taste transition could be formed. The volunteers reported that the taste experience was poor.

[0146] In Comparative Example 5, the dissolution time of the second slightly bitter taste layer was extended to 120-150 seconds, and the dissolution time of the third sweet taste layer was extended to 160-180 seconds. The dissolution time was too long, and the volunteers felt that there were foreign objects remaining in their mouths, which reduced the comfort of using the product. In addition, the taste release was delayed, affecting the overall taste experience.

[0147] The above experiments demonstrate the importance of precisely controlling coating thickness to ensure the appropriate oral dissolution time for the second and third nicotine-free layers. This patented method achieves precise control of dissolution time by strictly controlling the coating thickness range for specific film-forming materials, thereby ensuring the product's taste and effectiveness. The patented formulation exhibits a strong correlation with the parameters selected for the manufacturing process.

[0148] In the above description of exemplary embodiments / embodiments of the invention, various features of the invention are sometimes grouped together in a single embodiment / embodiment or its drawings and description for the purpose of simplifying the disclosure and aiding understanding of one or more of the various inventive aspects. However, except for expressly stated contrary guidance or obvious technical contradiction or exclusion, the description method of this patent should not be interpreted as reflecting an intention that the claimed invention requires more features than expressly stated in each claim. Instead, the claims reflect that the inventive aspects lie in less than all features of a single aforementioned disclosed embodiment / embodiment. Therefore, the claims that follow the detailed description are hereby expressly incorporated into this detailed description, with each claim standing independently as a separate embodiment / embodiment of the invention.

[0149] The terms and expressions used in this specification are intended to illustrate and not to limit, and in the use of these terms and expressions, there is no intention to exclude any equivalents of the features shown and described or parts thereof, but it should be recognized that various variations may exist within the scope of the invention claimed. It should therefore be understood that although the present invention is specifically disclosed through preferred embodiments, exemplary embodiments and optional features, those skilled in the art may adopt variations or modifications of the concepts disclosed in this specification, and such variations and modifications are therefore considered to be within the scope of the invention as defined in the appended claims. The specific embodiments given in this specification are examples of useful embodiments of the invention, and it will be apparent to those skilled in the art that many variations of the devices, device components, and method steps disclosed in this specification may be used to implement the invention.

[0150] The foregoing description of the specific embodiments fully discloses the general features of the present invention so that others can easily modify and / or adapt such specific embodiments for various applications by applying knowledge within the technical scope of the art without undue experimentation and without departing from the general concept of the invention. Therefore, based on the teachings and guidance given herein, it is intended that such transformations and modifications be included within the meaning and scope of equivalents of the disclosed embodiments. It should be understood that the wording or terminology herein is for descriptive purposes only and is not intended to be limiting, and thus the wording or terminology of this specification will be interpreted by those skilled in the art based on the above teachings and guidance.

[0151] Additionally, the scope of the present invention should not be limited by any of the above-described exemplary embodiments, but should be defined only in accordance with the following claims and their equivalents.

Claims

1. A multi-layer nicotine orally disintegrating film composition, characterized in that: The multi-layer nicotine orally dissolving film composition comprises a tobacco flavor layer, a slightly bitter flavor layer, and a sweet aftertaste flavor layer. The tobacco flavor layer film-forming material includes a cellulose derivative, and the cellulose derivative has a weight average molecular weight of 300,000-400,000, 400,000-500,000, 500,000-600,000, 600,000-700,000, or 700,000-800,000; The slightly bitter taste layer film-forming material includes hydroxypropyl chitosan, and the weight average molecular weight of the hydroxypropyl chitosan is 50,000-100,000, 100,000-150,000 or 150,000-200,000; The film-forming material of the sweet aftertaste layer includes polyvinyl alcohol, and the weight average molecular weight of the polyvinyl alcohol is 50,000-100,000, 100,000-150,000 or 150,000-200,000.

2. The multi-layer nicotine orally disintegrating film composition according to claim 1, wherein The slightly bitter taste layer and the sweet aftertaste layer are both nicotine-free layers; The dissolution time of the tobacco flavor layer is 35-40 seconds, 40-45 seconds, 45-50 seconds or 50-55 seconds; The dissolution time of the slightly bitter taste layer is 70-75 seconds, 75-80 seconds, 80-85 seconds, 85-90 seconds or 90-95 seconds; The dissolution time of the sweet aftertaste layer is 100-110 seconds, 110-120 seconds, 120-130 seconds, 130-140 seconds or 140-150 seconds.

3. The multi-layer nicotine orally disintegrating film composition according to claim 2, wherein: The tobacco flavor layer film-forming material further comprises nicotine, tobacco extract, tobacco flavor filler and / or tobacco flavor plasticizer; The tobacco extract includes nicotine and / or tobacco essential oil; the amount of the tobacco extract added is 3-10% of the total amount of the multi-layer nicotine orally disintegrating film composition; The tobacco flavor filler comprises food-grade diatomaceous earth; the amount of the tobacco flavor filler added is 8-15% of the total amount of the multi-layer nicotine orally disintegrating film composition; The tobacco flavor plasticizer includes diethyl phthalate; the amount of the tobacco flavor plasticizer added is 4-10% of the total amount of the multi-layer nicotine orally disintegrating film composition. The amount of the cellulose derivative added is 25-40% of the total amount of the multi-layer nicotine orally disintegrating film composition; The added amount of nicotine is 5-15% of the total amount of the multi-layer nicotine orally disintegrating film composition.

4. The multi-layer nicotine orally disintegrating film composition according to claim 2, wherein: The slightly bitter layer film-forming material further comprises a slightly bitter additive, a slightly bitter filler and / or a slightly bitter plasticizer; The slightly bitter taste additive includes coffee extract, and the amount of the coffee extract added is 3-7% of the total amount of the multi-layer nicotine orally disintegrating film composition; The slightly bitter filler comprises pregelatinized starch, and the amount of pregelatinized starch added is 6-12% of the total amount of the multi-layer nicotine orally disintegrating film composition; The slightly bitter plasticizer includes glycerin, and the amount of glycerin added is 3-8% of the total amount of the multi-layer nicotine orally disintegrating film composition; The amount of hydroxypropyl chitosan added is 15-25% of the total amount of the multi-layer nicotine orally disintegrating film composition.

5. The multi-layer nicotine orally disintegrating film composition according to claim 2, wherein: The film-forming material of the sweet aftertaste layer further comprises a sweet aftertaste additive, a sweet aftertaste filler and / or a sweet aftertaste plasticizer; The sweet aftertaste additive includes glycyrrhizin, and the amount of glycyrrhizin added is 1-5% of the total amount of the multi-layer nicotine orally disintegrating film composition; The sweet aftertaste filler comprises calcium hydrogen phosphate, and the amount of calcium hydrogen phosphate added is 5-10% of the total amount of the multi-layer nicotine orally dissolving film composition; The sweet aftertaste plasticizer includes propylene glycol, and the amount of propylene glycol added is 2-6% of the total amount of the multi-layer nicotine orally disintegrating film composition; The added amount of polyvinyl alcohol is 20-30% of the total amount of the multi-layer nicotine orally disintegrating film composition.

6. A method for preparing the multi-layer nicotine orally disintegrating film composition according to any one of claims 1 to 5, characterized in that: The following steps are involved: Step A: dissolving the tobacco flavor layer film-forming material, the slightly bitter flavor layer film-forming material, and the sweet aftertaste flavor layer film-forming material in water, stirring evenly, and heating until fully dissolved to form a tobacco flavor layer solution, a slightly bitter flavor layer solution, and a sweet aftertaste flavor layer solution, respectively; Step B: coating the tobacco flavor layer solution on a substrate to a thickness of 0.05-0.13 mm, and drying to obtain a first layer of coated substrate; Step C: coating the slightly bitter taste layer solution on the first coating substrate to a thickness of 0.07-0.15 mm, and drying to obtain a second coating substrate; Step D: coating the sweet aftertaste layer solution on the second coating substrate to a thickness of 0.1-0.17 mm, and drying to obtain the multi-layer nicotine orally dissolving film composition.

7. The method for preparing the multi-layer nicotine orally disintegrating film composition according to claim 6, wherein: In step B, the coating area of the tobacco flavor layer solution accounts for 35%-40% of the surface area of the multi-layer nicotine orally dissolving film composition; In step C, the coating area of the slightly bitter flavor layer solution accounts for 30% to 35% of the surface area of the multi-layer nicotine orally dissolving film composition; In the step D, the coating area of the sweet aftertaste layer solution accounts for 25% to 30% of the surface area of the multi-layer nicotine orally dissolving film composition.

8. The method for preparing the multi-layer nicotine orally disintegrating film composition according to claim 6, wherein: In the steps B to D, the drying is performed in a hot air circulation oven, the drying temperature is 35-50° C., and the drying time is 20-40 minutes.

9. The method for preparing the multi-layer nicotine orally disintegrating film composition according to claim 6, wherein: The step A specifically comprises the following steps: The tobacco flavor layer film-forming material, the slightly bitter flavor layer film-forming material, and the aftertaste flavor layer film-forming material are respectively dissolved in water, stirred evenly, heated to 50° C.-70° C., kept warm for 20 minutes-40 minutes to fully dissolve, and cooled to room temperature to form the tobacco flavor layer solution, the slightly bitter flavor layer solution, and the aftertaste flavor layer solution, respectively.

10. The method for preparing the multi-layer nicotine orally disintegrating film composition according to claim 6, wherein: In the steps B to D, the coating method includes blade coating, roller coating and / or slit coating.

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