Nicotine oral soluble film with multi-layer structure

Abstract

The invention provides a nicotine oral soluble film with a multi-layer structure, and belongs to the technical field of tobacco products. The nicotine oral soluble film with the multi-layer structure comprises a first film layer and a second film layer, wherein the first film layer comprises a first water-soluble polymer material and a nicotine release substance; the second film layer comprises a second water-soluble polymer material; wherein the first film layer and the second film layer are dissolved under the condition of being in contact with saliva, and the dissolving speed of the first film layer is higher than that of the second film layer.

Description

Technical Field

[0001] The present disclosure relates to the technical field of tobacco products, and particularly to a nicotine oromucosal film with a multi-layer structure. Background Art

[0002] With the improvement of people's health awareness, the market demand for traditional tobacco products such as combustible cigarettes has gradually declined. As a new form of tobacco product, oral tobacco has the advantages of convenient use, no need for combustion, and no second-hand smoke pollution, and has gradually become a research hotspot in the tobacco industry.

[0003] However, in related technologies, it is difficult for oral tobacco to meet the needs of users in terms of the smoking experience. Summary of the Invention

[0004] In view of this, in order to at least partially solve at least one of the above-mentioned technical problems, the present disclosure provides a nicotine oromucosal film with a multi-layer structure.

[0005] According to an embodiment of one aspect of the present disclosure, there is provided a nicotine oromucosal film with a multi-layer structure. The nicotine oromucosal film with a multi-layer structure includes: a first film layer, including a first water-soluble polymer material and a nicotine releaser; a second film layer, including a second water-soluble polymer material; wherein, the first film layer and the second film layer dissolve when contacting saliva, and the dissolution rate of the first film layer is greater than that of the second film layer.

[0006] According to an embodiment of the present disclosure, the first film layer and the second film layer can dissolve when contacting saliva. The first water-soluble polymer material and the nicotine releaser in the first film layer can rapidly release nicotine when contacting saliva to provide an initial nicotine stimulus; the second film layer includes a second water-soluble polymer material, and the dissolution rate of the second film layer is less than that of the first film layer. The second film layer can regulate the release rate of nicotine in the first film layer and prevent the nicotine releaser in the first film layer from directly contacting the external environment, thereby enhancing the stability of the first film layer. In addition, a nicotine releaser can be added to the second film layer to continuously and slowly release nicotine, prolonging the use time of the nicotine oromucosal film; the second film layer may also not include a nicotine releaser, preventing the nicotine releaser in the first film layer from entering the digestive tract through oral swallowing and reducing the irritation of the nicotine releaser to the throat and stomach. Description of the Drawings

[0007] Through the following description of the embodiments of the present disclosure with reference to the drawings, the above and other objects, features, and advantages of the present disclosure will become clearer. In the drawings:

[0008] Figure 1 A schematic diagram of a nicotine oromucosal film with a multi-layer structure according to an embodiment of the present disclosure is shown;

[0009] Figure 2 Shows a schematic diagram of a nicotine orally dissolving film with a multi-layer structure according to another embodiment of the present disclosure;

[0010] Figure 3 Shows a schematic diagram of a nicotine orally dissolving film with a multi-layer structure according to another embodiment of the present disclosure;

[0011] Figure 4 Shows a schematic diagram of a nicotine orally dissolving film with a multi-layer structure according to another embodiment of the present disclosure;

[0012] In the above-mentioned drawings, the meanings of the reference numerals are specifically as follows:

[0013] 1 - First film layer;

[0014] 2 - Second film layer;

[0015] 3 - Isolation layer;

[0016] 4 - Taste optimization layer. Detailed implementation manners

[0017] Hereinafter, embodiments of the present disclosure will be described with reference to the drawings. However, it should be understood that these descriptions are merely exemplary and are not intended to limit the scope of the present disclosure. In the following detailed description, for the sake of explanation, many specific details are set forth to provide a comprehensive understanding of the embodiments of the present disclosure. However, obviously, one or more embodiments can also be implemented without these specific details. In addition, in the following description, descriptions of well-known structures and technologies are omitted to avoid unnecessarily confusing the concepts of the present disclosure.

[0018] The terms used herein are merely for describing specific embodiments and are not intended to limit the present disclosure. The term "including" used herein indicates the presence of features, steps, operations, but does not exclude the presence or addition of one or more other features.

[0019] In the case of using expressions such as "at least one of A, B, and C, etc.", generally, it should be interpreted according to the meaning that those skilled in the art usually understand this expression (for example, "a system having at least one of A, B, and C" should include, but is not limited to, a system having only A, only B, only C, having A and B, having A and C, having B and C, and / or having A, B, and C, etc.). In the case of using expressions such as "at least one of A, B, or C, etc.", generally, it should be interpreted according to the meaning that those skilled in the art usually understand this expression (for example, "a system having at least one of A, B, or C" should include, but is not limited to, a system having only A, only B, only C, having A and B, having A and C, having B and C, and / or having A, B, and C, etc.).

[0020] It should also be noted that the directional terms mentioned in the embodiments, such as "upper", "lower", "front", "rear", "left", "right", etc., are only references to the directions in the accompanying drawings and are not used to limit the protection scope of the present disclosure. Throughout the drawings, the same elements are denoted by the same or similar reference numerals. When it may cause confusion in the understanding of the present disclosure, the conventional structures or configurations will be omitted.

[0021] A nicotine pouch is a tobacco product. They are small fiber bags containing nicotine. During use, these bags are usually placed between the gums and the upper lip, and the nicotine is absorbed by the human body through the palatal mucosa. The nicotine pouch does not require heating or burning. Compared with traditional tobacco, e-cigarettes, and heated tobacco, the nicotine pouch is more harm-reducing in terms of its composition. Secondly, the nicotine pouch can absorb nicotine through the oral mucosa, providing a smokeless and tar-free smoking experience. The smoking method is more private and convenient, not restricted by the environment, and applicable to any place. However, the inventors found that nicotine pouches have many deficiencies in terms of nicotine release rate, stability, etc., and nicotine pouches are easily swallowed into the digestive tract through the mouth, causing irritation to the throat and stomach, which is difficult to meet the needs of users. Moreover, after using the nicotine pouch, the remaining contents need to be discarded, causing environmental pollution.

[0022] In the process of implementing the present disclosure, it was found that a nicotine orally dissolving film can be developed by adding nicotine releaser to the orally dissolving film and solving at least one of the problems such as nicotine release rate, stability, and irritation to the throat and stomach in the nicotine orally dissolving film through the multi-layer structure design of the nicotine orally dissolving film.

[0023] In view of this, the present disclosure provides a nicotine orally dissolving film with a multi-layer structure, as Figure 1 shown. The nicotine orally dissolving film with a multi-layer structure includes a first film layer 1 and a second film layer 2. Among them, the first film layer 1 includes a water-soluble polymer material and a nicotine releaser; the second film layer 2 includes a second water-soluble polymer material. Among them, the first film layer 1 and the second film layer 2 dissolve when in contact with saliva, and the dissolution rate of the first film layer 1 is greater than that of the second film layer 2.

[0024] According to an embodiment of the present disclosure, the first film layer 1 and the second film layer 2 can be dissolved when contacting saliva. The first water-soluble polymer material and the nicotine releaser in the first film layer 1 can rapidly release nicotine when contacting saliva, providing an initial nicotine stimulation; the second film layer 2 includes a second water-soluble polymer material, and the dissolution rate of the second film layer 2 is less than that of the first film layer 1. The second film layer 2 can regulate the release rate of nicotine in the first film layer 1 and prevent the nicotine releaser in the first film layer 1 from directly contacting the external environment, improving the stability of the first film layer 1. In addition, a nicotine releaser can be added to the second film layer 2 to continuously and slowly release nicotine, prolonging the usage time of the nicotine orally disintegrating film; the second film layer 2 may not include a nicotine releaser, preventing the nicotine releaser in the first film layer 1 from entering the digestive tract through oral swallowing, reducing the irritation of the nicotine releaser to the throat and stomach.

[0025] It should be noted that the dissolution rate of the first film layer 1 can represent the time required for the first film layer 1 to be completely dissolved. The dissolution rate of the second film layer 2 can represent the time required for the second film layer 2 to be completely dissolved. That the dissolution rate of the first film layer 1 is greater than that of the second film layer 2 means that the time required for the first film layer 1 to be completely dissolved is greater than that of the second film layer 2.

[0026] It should be noted that the present disclosure does not limit the sucking position of the nicotine orally disintegrating film and the placement method of the nicotine orally disintegrating film, and users can choose the sucking method according to their own needs. Optionally, when sucking the nicotine orally disintegrating film with a multi-layer structure provided by the embodiment of the present disclosure, the side of the first film layer 1 of the nicotine orally disintegrating film can be contacted with parts such as the upper palate of the oral cavity, the center of the tongue surface, under the tongue, between the upper gum and the lip and cheek for sucking. Exemplarily, the user can contact the side of the first film layer 1 of the nicotine orally disintegrating film with the upper palate of the oral cavity for sucking.

[0027] In some embodiments of the present disclosure, the first water-soluble polymer may include at least one of pullulan, hypromellose, povidone, polyethylene glycol, carboxymethyl cellulose, hydroxypropyl cellulose, polyethylene oxide, and polyvinyl alcohol. The first water-soluble polymer can enable the nicotine releaser in the first film layer 1 to be rapidly released, improving the user's sucking experience.

[0028] In some embodiments of the present disclosure, the nicotine releaser can be chemically synthesized or extracted from tobacco plants. The nicotine releaser can be nicotine or a pharmaceutically acceptable salt thereof. Exemplarily, the nicotine releaser may include at least one of nicotine, nicotine microcapsules, nicotine liposomes, nicotine citrate salt, nicotine malate salt, and nicotine tartrate salt.

[0029] According to an embodiment of the present disclosure, the first film layer 1 further includes an adhesive. The adhesive includes at least one of polyacrylic acid, sodium alginate, guar gum, sodium carboxymethyl cellulose, 5-methylpyrrolidone chitosan, polyglutamic acid, polycarbophil, dextran sulfate. Through the adhesive, the nicotine orally dissolving film can be effectively adhered to the sucking site (such as the upper palate mucosa, etc.), making the nicotine orally dissolving film not easy to move or fall off, providing good adhesion between the nicotine orally dissolving film and maximizing the efficacy of the nicotine orally dissolving film.

[0030] According to an embodiment of the present disclosure, the first film layer 1 may further include at least one of a nicotine release regulator and a plasticizer. The plasticizer can accelerate the dissolution and disintegration of the nicotine orally dissolving film in the oral environment while ensuring the physical properties of the nicotine orally dissolving film. Exemplarily, the plasticizer may include at least one of polyethylene glycol, glycerol, polysorbate, polyethylene glycol, propylene glycol, hexylene glycol, polypropylene glycol. The nicotine release regulator can accelerate the release rate of the nicotine release agent in the first film layer 1. Exemplarily, the nicotine release regulator may include at least one of sodium glycocholate, sodium citrate, disodium ethylenediaminetetraacetate.

[0031] According to an embodiment of the present disclosure, the thickness of the first film layer 1 may be 70~200μm. Exemplarily, the thickness of the first film layer 1 may be 70μm, 80μm, 100μm, 120μm, 150μm, 180μm, 200μm or the range between any two of the above values. The thickness of the first film layer 1 within the above range can enable the first film layer 1 to have both a suitable sucking time and a sucking rate.

[0032] According to an embodiment of the present disclosure, in the first film layer 1, the mass ratio of the first water-soluble polymer to the nicotine release agent may be (30~80):(1~20). Exemplarily. The mass ratio of the water-soluble polymer to the nicotine release agent may be 30:1, 30:5, 30:10, 30:15, 30:20, 50:1, 50:5, 50:10, 50:15, 50:20, 80:1, 80:5, 80:10, 80:15, 80:20 or the range between any two of the above values. The mass ratio of the water-soluble polymer to the nicotine release agent in the first film layer 1 within the above range can enable the first film layer 1 to have both a suitable sucking time and a sucking rate.

[0033] According to an embodiment of the present disclosure, in the first film layer 1, the mass ratio of the first water-soluble polymer material, nicotine releaser, adhesive, nicotine release regulator, and plasticizer may be (30-80):(1-20):(1-12):(1-10):(2-10). Exemplarily, in the first film layer 1, the mass ratio of the first water-soluble polymer material, nicotine releaser, adhesive, nicotine release regulator, and plasticizer may be 30:1:1:1:2, 30:10:6:5:5, 50:5:3:3:8, 50:10:6:5:5, 50:20:12:10:10, 80:10:6:5:5, 80:20:12:10:10, or any range between any two of the above values. The mass ratio of the water-soluble polymer, nicotine releaser, instant plasticizer, and acid regulator in the first film layer 1 within the above range can enable the first film layer 1 to have a suitable sucking time and sucking rate, and make the first film layer 1 have high stability.

[0034] According to an embodiment of the present disclosure, the first film layer 1 may further include at least one of fruit flavor essence, sweetener, disintegrant, and colorant. Those skilled in the art can select suitable fruit flavor essence, sweetener, disintegrant, colorant, etc. according to actual needs. Exemplarily, the fruit flavor essence may include at least one of citrus-type essence, fruit-type essence, and mint-type essence. The sweetener may include at least one of sucrose, glucose, sodium saccharin, fructose, xylitol, stevia, aspartame, sucralose, neotame, and acesulfame potassium. The disintegrant may include sodium bicarbonate, sodium dodecyl sulfate, etc. The colorant may include sunset yellow, lemon yellow, carmine, etc.

[0035] In some embodiments of the present disclosure, as Figure 2 shown, the second film layer 2 may further include a nicotine releaser, and the second film layer 2 can be used to continuously and slowly release nicotine. The nicotine releasers in the first film layer 1 and the second film layer 2 may be the same or different. The nicotine releaser in the second film layer 2 may include at least one of nicotine microcapsules, nicotine citrate salt, nicotine malate salt, and nicotine tartrate salt. At this time, when the nicotine orally disintegrating film contacts saliva, the first film layer 1 can quickly release nicotine, and the second film layer 2 can continuously and slowly release nicotine. Through the combined action of the first film layer 1 and the second film layer 2, the nicotine release rate and nicotine release time of the nicotine orally disintegrating film can be regulated.

[0036] In some embodiments of the present disclosure, the second water-soluble polymer material may include at least one of polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycol, carboxymethyl cellulose, hydroxypropyl cellulose, and maltodextrin. The second water-soluble polymer material can regulate the release rate of nicotine in the first film layer 1 and extend the sucking time of the nicotine orally disintegrating film.

[0037] In some embodiments of the present disclosure, as Figure 2As shown, in the second film layer 2, the mass ratio of the second water-soluble polymer material to the sustained-release nicotine salt can be (3 to 10):(1 to 6). Exemplarily, in the second film layer 2, the mass ratio of the second water-soluble polymer material to the sustained-release nicotine salt can be 3:1, 3:2, 3:3, 3:5, 5:1, 5:2, 5:3, 5:6, 7:1, 7:3, 7:6, 10:1, 10:3, 10:5, 10:6 or within the range between any two of the above ratios. When the mass ratio of the second water-soluble polymer material to the sustained-release nicotine salt is within the above range, the second film layer 2 can release nicotine continuously and stably.

[0038] According to an embodiment of the present disclosure, the second film layer 2 may further include a plasticizer, and the plasticizer may include at least one of polyethylene glycol, glycerol, polysorbate, polyethylene glycol, propylene glycol, hexylene glycol, and polypropylene glycol. The plasticizer can ensure the physical properties of the second film layer 2. Those skilled in the art can select the appropriate dosage of the plasticizer according to actual needs. Exemplarily, the mass ratio of the second water-soluble polymer material to the plasticizer can be (15 to 40):(1 to 5).

[0039] In some embodiments of the present disclosure, as Figure 1 and Figure 2 shown, the thickness of the second film layer 2 can be 50 to 100 μm. Exemplarily, the thickness of the second film layer 2 can be 50 μm, 55 μm, 60 μm, 65 μm, 70 μm, 75 μm, 80 μm, 85 μm, 90 μm, 95 μm, 100 μm or within the range between any two of the above values. When the thickness of the second film layer 2 is within the above range, the nicotine orally disintegrating film can have an appropriate nicotine release rate and nicotine release time.

[0040] According to an embodiment of the present disclosure, based on the mass of the nicotine release in the nicotine orally disintegrating film, when the nicotine orally disintegrating film contacts saliva, more than 60 wt% of the nicotine release in the nicotine orally disintegrating film is released within 60 seconds. Thereby, an instantaneous sense of satisfaction can be provided to the user.

[0041] According to an embodiment of the present disclosure, based on the mass of the nicotine release in the nicotine orally disintegrating film, when the nicotine orally disintegrating film contacts saliva, within 120 seconds, no more than 80 wt% of the nicotine release in the nicotine orally disintegrating film is released. Thereby, a continuous sense of satisfaction can be provided to the user, and the use time of the nicotine orally disintegrating film can be extended.

[0042] According to an embodiment of the present disclosure, the first film layer 1 is used to rapidly release nicotine in the case of contacting saliva, providing an instantaneous sense of satisfaction for the user; the second film layer 2 is mainly used to continuously and slowly release nicotine, providing a continuous sense of satisfaction for the user and prolonging the use time of the nicotine orally dissolving film. The dissolution rates of the first film layer 1 and the second film layer 2 can be regulated by selecting appropriate first and second water-soluble polymer materials, so that the dissolution rate of the first film layer 1 is greater than that of the second film layer 2. Exemplarily, for the same type of first and second water-soluble polymer materials, generally, the water-soluble polymer material with a lower relative molecular mass has a higher dissolution rate. Therefore, the relative molecular mass of the first water-soluble polymer material can be made greater than that of the second water-soluble polymer material, so that the dissolution rate of the first film layer 1 is greater than that of the second film layer 2.

[0043] In some embodiments of the present disclosure, as Figure 2 shown, the nicotine orally dissolving film with a multi-layer structure may further include a barrier layer 3. The barrier layer 3 may include a third water-soluble polymer material. The barrier layer 3 can prevent the nicotine release substances in the first film layer 1 and the second film layer 2 from entering the digestive tract through oral swallowing, reducing the irritation of the nicotine release substances to the throat and gastrointestinal tract. The nicotine orally dissolving film may include the first film layer 1, the second film layer 2 and the barrier layer 3. The first film layer 1 includes a first water-soluble polymer material and a nicotine release substance, and is used to rapidly release nicotine in the case of contacting saliva. The second film layer 2 includes a second water-soluble polymer material and a nicotine release substance, and is used to continuously and slowly release nicotine. The barrier layer 3 includes a third water-soluble polymer material, and is used to prevent the nicotine release substances in the first film layer 1 and the second film layer 2 from entering the digestive tract through oral swallowing, reducing the irritation of the nicotine release substances to the throat and gastrointestinal tract. The nicotine orally dissolving film provided by the embodiment of the present disclosure can avoid the first-pass effect brought by the absorption of the nicotine release substance through the digestive tract, improve the bioavailability of the nicotine release substance, and at the same time reduce the irritation of the nicotine release substance to the throat and gastrointestinal tract.

[0044] In some embodiments of the present disclosure, the third water-soluble polymer material may include at least one of hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropylated high amylose, polyvinylpyrrolidone, gelatin, pectin, polyvinyl alcohol, and chitosan composite film.

[0045] In some embodiments of the present disclosure, the barrier layer 3 may further include at least one of a plasticizer and a flavoring agent. The plasticizer can improve the folding resistance and manufacturability of the nicotine orally disintegrating film. The plasticizer includes at least one of polyethylene glycol, glycerol, polysorbate, propylene glycol, hexylene glycol, and polypropylene glycol. The flavoring agent includes at least one of fruit flavor essence and sweetener. Among them, the fruit flavor essence may include at least one of citrus flavor essence, fruit flavor essence, and mint flavor essence, and the sweetener may include at least one of sucrose, glucose, sodium saccharin, fructose, xylitol, stevia, aspartame, sucralose, neotame, and acesulfame potassium.

[0046] In some embodiments of the present disclosure, the thickness of the barrier layer 3 may be 50 to 150 μm. Exemplarily, the thickness of the barrier layer 3 may be 50 μm, 55 μm, 60 μm, 65 μm, 70 μm, 75 μm, 80 μm, 85 μm, 90 μm, 95 μm, 100 μm, 110 μm, 120 μm, 130 μm, 140 μm, 150 μm or a range between any two of the above values.

[0047] In some embodiments of the present disclosure, as Figure 3 and Figure 4 shown, the nicotine orally disintegrating film having a multi-layer structure may further include a taste optimization layer 4.

[0048] As Figure 3 shown, the nicotine orally disintegrating film may include a first film layer 1, a second film layer 2, a barrier layer 3, and a taste optimization layer 4. The first film layer 1 includes a first water-soluble polymer material and a nicotine releasate, and is used to rapidly release nicotine when in contact with saliva. The second film layer 2 includes a second water-soluble polymer material and a nicotine releasate, and is used to continuously and slowly release nicotine. The barrier layer 3 includes a third water-soluble polymer material, and is used to prevent the nicotine releasate in the first film layer 1 and the second film layer 2 from entering the digestive tract through oral swallowing, and reduce the irritation of the nicotine releasate to the throat and stomach. The taste optimization layer 4 is used to release flavoring components to enhance the user experience. The nicotine orally disintegrating film having a multi-layer structure provided by the embodiments of the present disclosure is a nicotine orally disintegrating film with good taste, rapid nicotine release, and high stability.

[0049] As Figure 4As shown, the nicotine orally dissolving film may include a first film layer 1, a second film layer 2, and a taste optimization layer 4. The first film layer 1 includes a first water-soluble polymer material and a nicotine releaser, and is used to rapidly release nicotine when contacting saliva. The second film layer 2 may include a second water-soluble polymer material and may not include a nicotine releaser. In this case, the second film layer 2 can be used to prevent the nicotine releaser in the first film layer 1 from entering the digestive tract through oral swallowing, and reduce the irritation of the nicotine releaser to the throat and gastrointestinal tract. The taste optimization layer 4 is used to release flavoring components to enhance the user experience. The nicotine orally dissolving film with a multi-layer structure provided by the embodiments of the present disclosure is a nicotine orally dissolving film with good taste, rapid nicotine release, and high stability.

[0050] In some embodiments of the present disclosure, the thickness of the taste optimization layer 4 is 50-100 μm. Exemplarily, the thickness of the taste optimization layer 4 can be 50 μm, 55 μm, 60 μm, 65 μm, 70 μm, 75 μm, 80 μm, 85 μm, 90 μm, 95 μm, 100 μm, or within the range of any two of the above values.

[0051] In some embodiments of the present disclosure, the taste optimization layer 4 may include a low-viscosity film-forming material, and the low-viscosity film-forming material may include at least one of sodium alginate, methylcellulose, and whey protein. The taste optimization layer 4 may also include at least one of a flavoring agent and a sweetening agent. The present disclosure does not limit the specific types of the flavoring agent and the sweetening agent, and relevant personnel can select according to actual needs. The flavoring agent may include one or more of mint, fruit essence, plant extracts, etc. The sweetening agent may include one or more of sucralose, aspartame, steviol glycoside, etc. In the taste optimization layer 4, the mass ratio of the low-viscosity film-forming material, the flavoring agent, and the sweetening agent may be (2-10):(1-4):(1-2). Exemplarily, in the taste optimization layer 4, the mass ratio of the low-viscosity film-forming material, the flavoring agent, and the sweetening agent may be 2:1:1, 2:2:1, 1:1:1, 5:1:1, 5:1:2, 5:2:1, 5:5:2, 5:4:1, 5:4:2, 10:1:1, 10:1:2, 10:2:1, 10:4:1, 10:3:2, or within the range of any two of the above values.

[0052] According to the embodiments of the present disclosure, the thickness of the nicotine orally dissolving film with a multi-layer structure may be 130-500 μm. Exemplarily, the thickness of the nicotine orally dissolving film with a multi-layer structure can be 130 μm, 150 μm, 180 μm, 200 μm, 250 μm, 300 μm, 350 μm, 400 μm, 450 μm, 500 μm, or within the range of any two of the above values.

[0053] According to an embodiment of the present disclosure, the mass ratio of the first film layer 1 and the second film layer 2 can be (3 - 8):(2 - 4). Exemplarily, the mass ratio of the first film layer 1 and the second film layer 2 is 3:2, 3:3, 3:4, 5:2, 5:3, 5:4, 7:2, 7:3, 7:4, 8:2, 8:3, 8:4 or the range between any two of the above values.

[0054] According to an embodiment of the present disclosure, the nicotine orally dissolving film having a multi-layer structure may include a first film layer 1, a second film layer 2, and a taste optimization layer 4. The first film layer 1 may include a water-soluble polymer material and a nicotine releaser, and is used to rapidly release nicotine when contacting saliva. The second film layer 2 may include a second water-soluble polymer material and a nicotine releaser, and is used to continuously and slowly release nicotine. The taste optimization layer 4 is used to release flavoring components.

[0055] It should be noted that the number of film layers of the nicotine orally dissolving film having a multi-layer structure provided by the embodiments of the present disclosure can be 2 - 10 layers. Those skilled in the art can design multiple first film layers 1, multiple second film layers 2, multiple isolation layers 3, or multiple taste optimization layers 4, etc. according to actual needs.

[0056] The present disclosure also provides a preparation method of a nicotine orally dissolving film having a multi-layer structure, including: preparing a nicotine orally dissolving film having a multi-layer structure by a layer-by-layer coating method or a co-extrusion molding method, and the nicotine orally dissolving film having a multi-layer structure includes: a first film layer, including a first water-soluble polymer material and a nicotine releaser; a second film layer, including a second water-soluble polymer material; wherein, the first film layer and the second film layer dissolve when contacting saliva, and the dissolution rate of the first film layer is greater than that of the second film layer.

[0057] Among them, preparing a nicotine orally dissolving film having a multi-layer structure by a layer-by-layer coating method may include: coating a first solution on a substrate, and drying to obtain a first film layer; coating a second solution on the surface of the first film layer, and converting the second solution into a second film layer to obtain a nicotine orally dissolving film having a multi-layer structure. In the above drying, the drying temperature can be 40°C - 90°C, and the drying time can be 1 - 4 hours. The solvents in the first solution and the second solution can be independently selected from water, ethanol, etc.

[0058] Preparing a nicotine orally dissolving film having a multi-layer structure by a co-extrusion molding method may include: co-extruding a first melt and a second melt into a film through a multi-channel extruder, converting the first melt into a first film layer, and converting the second melt into a second film layer to obtain a nicotine orally dissolving film having a multi-layer structure.

[0059] The following will specifically illustrate the present disclosure with specific embodiments. It should be noted that, without conflict, the embodiments in the present disclosure and the features in the embodiments can be combined with each other.

[0060] Example 1

[0061] This example provides a nicotine orally dissolving film with a multi-layer structure, including a first film layer and a second film layer. The components and the content of each component of the first film layer and the second film layer are shown in Table 1 for details.

[0062] Table 1

[0063]

[0064] The preparation method of the nicotine orally dissolving film with a multi-layer structure provided in this example is as follows:

[0065] (1) Completely dissolve nicotine tartrate in water, then add the other components in Table 1, and stir until completely dissolved to obtain a first solution. After evacuating the first solution to remove air bubbles, uniformly coat it on a substrate and dry it at 65 °C to obtain a first film layer, and the thickness of the first film layer is 80 μm.

[0066] (2) Add the components of the second film layer in Table 1 to water, and stir until completely dissolved to obtain a second solution. After evacuating the second solution to remove air bubbles, uniformly coat it on the surface of the first film layer and dry it at 65 °C to obtain a second film layer, and the thickness of the second film layer is 50 μm. After film formation, cut it into appropriate sizes and shapes, and package it to obtain the nicotine orally dissolving film.

[0067] The nicotine orally dissolving film provided in this example has good film-forming property, smooth appearance, uniform color. The second film layer is white, and the first film layer is orange. The second film layer can prevent nicotine tartrate in the first film layer from entering the digestive tract through oral swallowing, and reduce the irritation of nicotine release to the larynx and gastrointestinal tract.

[0068] Example 2

[0069] This example provides a nicotine orally dissolving film with a multi-layer structure, including a first film layer, a second film layer and a separation layer. The components and the content of each component of the first film layer, the second film layer and the separation layer are shown in Table 2 for details.

[0070] Table 2

[0071]

[0072] The preparation method of the nicotine orally dissolving film with a multi-layer structure provided in this example is as follows:

[0073] (1) Completely dissolve nicotine tartrate in water, then add the other components in Table 2, and stir until completely dissolved to obtain a first solution. After evacuating the first solution to remove air bubbles, uniformly coat it on a substrate and dry it at 65 °C to obtain a first film layer, and the thickness of the first film layer is 0.1 mm.

[0074] (2) Add the components of the second film layer in Table 2 into water, stir until completely dissolved to obtain a second solution. After evacuating the second solution to remove air bubbles, uniformly coat it on the surface of the first film layer and dry it at 65 °C to obtain the second film layer with a thickness of 80 μm.

[0075] (3) Add the components of the barrier layer in Table 2 into water, stir until completely dissolved to obtain a third solution. After evacuating the third solution to remove air bubbles, uniformly coat it on the surface of the second film layer and dry it at 65 °C to obtain the barrier layer with a thickness of 80 μm. After film formation, cut it into suitable sizes and shapes and package it to obtain the nicotine orally dissolving film.

[0076] Example 3

[0077] This example provides a nicotine orally dissolving film with a multi-layer structure, including a first film layer, a second film layer, and a barrier layer. For the components and the content of each component in the first film layer, the second film layer, and the barrier layer, please refer to Table 3.

[0078] Table 3

[0079]

[0080] The preparation method of the nicotine orally dissolving film with a multi-layer structure provided in this example is as follows:

[0081] (1) Completely dissolve nicotine tartrate in water, then add the other components in Table 3 and stir until completely dissolved to obtain a first solution. After evacuating the first solution to remove air bubbles, uniformly coat it on a substrate and dry it at 65 °C to obtain the first film layer with a thickness of 100 μm.

[0082] (2) Add the components of the second film layer in Table 3 into water, stir until completely dissolved to obtain a second solution. After evacuating the second solution to remove air bubbles, uniformly coat it on the surface of the first film layer and dry it at 65 °C to obtain the second film layer with a thickness of 80 μm.

[0083] (3) Add the components of the barrier layer in Table 3 into water, stir until completely dissolved to obtain a third solution. After evacuating the third solution to remove air bubbles, uniformly coat it on the surface of the second film layer and dry it at 65 °C to obtain the barrier layer with a thickness of 80 μm. After film formation, cut it into suitable sizes and shapes and package it to obtain the nicotine orally dissolving film.

[0084] Comparative Example 1

[0085] This comparative example provides a nicotine orally dissolving film and its preparation method. Referring to Example 1, the difference is that the second film layer in the nicotine orally dissolving film is replaced with a first film layer of the same thickness.

[0086] Comparative Example 2

[0087] This comparative example provides a nicotine orally dissolving film with a multi-layer structure and its preparation method. The difference from Example 1 is that the first film layer in the nicotine orally dissolving film is replaced with a second film layer of the same thickness.

[0088] The nicotine orally dissolving films with multi-layer structures provided in Example 3, Comparative Example 1, and Comparative Example 2 were placed in a nicotine extraction solution (artificial saliva) for detection of the cumulative dissolution amount of nicotine. The detection results are shown in Table 4 in detail.

[0089] Table 4

[0090]

[0091] It can be analyzed from Table 4 that the nicotine orally dissolving film with a multi-layer structure provided in the embodiments of the present disclosure can continuously and stably release nicotine release substances. Nicotine can be rapidly released within 1 minute of contact with the nicotine extraction solution, and the nicotine release time can last for 5 minutes.

[0092] The nicotine orally dissolving films with multi-layer structures provided in Example 3 and Comparative Example 1 were placed in an open state in a simulated extreme environment (40°C, 75% RH) for stability detection. The nicotine tartrate content is shown in Table 5 in detail.

[0093] Table 5

[0094]

[0095] The nicotine orally dissolving film with a multi-layer structure provided in the embodiments of the present disclosure has good stability.

[0096] The specific embodiments described above further illustrate the purpose, technical solutions, and beneficial effects of the present disclosure. It should be understood that the above are only specific embodiments of the present disclosure and are not used to limit the present disclosure. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present disclosure shall be included within the protection scope of the present disclosure.

Claims

1. A nicotine orally disintegrating film having a multi-layer structure, characterized in that, The nicotine orally disintegrating film with a multi-layer structure comprises: A first film layer, comprising a first water-soluble polymer material and a nicotine releasate; A second film layer, comprising a second water-soluble polymer material; Wherein, the first film layer and the second film layer dissolve when contacting saliva, and the dissolution rate of the first film layer is greater than that of the second film layer.

2. The nicotine orally disintegrating film having a multi-layer structure according to claim 1, wherein, Based on the mass of the nicotine releasate in the nicotine orally disintegrating film, when the nicotine orally disintegrating film contacts saliva, more than 60 wt% of the nicotine releasate in the nicotine orally disintegrating film is released within 60 seconds.

3. The nicotine orally disintegrating film having a multi-layer structure according to claim 2, wherein The second film layer further comprises a nicotine releasate; Based on the mass of the nicotine releasate in the nicotine orally disintegrating film, when the nicotine orally disintegrating film contacts saliva, within 120 seconds, no more than 80 wt% of the nicotine releasate in the nicotine orally disintegrating film is released.

4. The nicotine orally dissolving film with a multi-layer structure according to claim 3, wherein, The nicotine orally disintegrating film with a multi-layer structure further comprises a barrier layer, and the barrier layer comprises a third water-soluble polymer material; The third water-soluble polymer material comprises at least one of hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropylated high amylose, polyvinylpyrrolidone, gelatin, pectin, polyvinyl alcohol, and chitosan composite film; The thickness of the barrier layer is 50 - 150 μm.

5. The nicotine orally dissolving film having a multi-layer structure according to claim 4, wherein, The barrier layer further comprises at least one of a plasticizer and a flavoring agent; The plasticizer comprises at least one of polyethylene glycol, glycerol, polysorbate, propylene glycol, hexylene glycol, and polypropylene glycol; The flavoring agent comprises at least one of fruit flavor essence and sweetening agent.

6. The nicotine orally disintegrating film with a multi-layer structure according to any one of claims 1 to 5, characterized in that, The first water-soluble polymer material comprises at least one of pullulan, hydroxypropyl methylcellulose, polyvinylpyrrolidone, polyethylene glycol, carboxymethyl cellulose, hydroxypropyl cellulose, polyethylene oxide, and polyvinyl alcohol; The second water-soluble polymer material comprises at least one of polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycol, carboxymethyl cellulose, hydroxypropyl cellulose, and maltodextrin; The nicotine releasate comprises at least one of nicotine, nicotine microcapsules, nicotine liposomes, nicotine citrate, nicotine malate, and nicotine tartrate; The thickness of the first film layer is 50 - 100 μm; The thickness of the second film layer is 50 - 100 μm.

7. The nicotine orally dissolving film with a multi-layer structure according to any one of claims 1 to 5, characterized in that, The nicotine orally disintegrating film with a multi-layer structure further comprises a taste optimization layer; The taste optimization layer is used for releasing flavoring components; The thickness of the taste optimization layer is 50 - 100 μm.

8. The nicotine orally dissolving film with a multi-layer structure according to any one of claims 1 to 5, wherein The first film layer further comprises an adhesive; The adhesive comprises at least one of polyacrylic acid, sodium alginate, guar gum, sodium carboxymethyl cellulose, 5-methylpyrrolidone chitosan, polyglutamic acid, polycarbophil, and dextran sulfate.

9. The nicotine orally disintegrating film with a multi-layer structure according to any one of claims 1 to 5, characterized in that, The first film layer further comprises at least one of a nicotine release regulator and a plasticizer; The nicotine release regulator may comprise at least one of sodium glycocholate, sodium citrate, and disodium ethylenediaminetetraacetate; The plasticizer comprises at least one of polyethylene glycol, glycerol, polysorbate, polyethylene glycol, propylene glycol, hexylene glycol, and polypropylene glycol.

10. The nicotine orally disintegrating film having a multi-layer structure according to any one of claims 1 to 5, characterized in that, In the first film layer, the mass ratio of the water-soluble polymer to the nicotine releasate is (30 - 80):(1 - 20); The mass ratio of the first film layer to the second film layer is (3 - 8):(2 - 4).

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