Nicotine oral membrane and preparation method thereof

Abstract

The invention discloses a nicotine oral film agent and a preparation method thereof. The nicotine oral film agent comprises the following components in parts by weight: 2-10 parts of nicotine, 40-80 parts of a film-forming material and 1-5 parts of nano silicon oxide. The nano silicon oxide is added into the oral film agent, so that the tensile strength, stiffness, folding resistance and wear resistance of the nicotine oral film agent are improved, and the oral film agent is convenient to use in gingival mucosa and buccal mucosa.

Description

Technical Field

[0001] The invention belongs to the technical field of oral products, and particularly relates to a nicotine oral film and a preparation method thereof. Background Art

[0002] Nicotine oral film is a new type of nicotine product that replaces snus and nicotine bags. While ensuring the satisfaction of nicotine, nicotine oral film has the advantages of small thickness, can be completely disintegrated, and does not need to be spit out. When using nicotine oral film, it needs to be attached between the upper lip and upper gum mucosa and cheek mucosa of the mouth, and is absorbed into the blood circulation through epithelial cells, reducing the irritation of nicotine (also known as nicotine) to the stomach, causing vomiting and stomach cramps.

[0003] Existing oral dissolving films disintegrate directly in the oral cavity, are placed on the tongue surface when used, and are directly dissolved in the oral saliva. They are rectangular in shape, soft in texture, and thin in thickness. When using nicotine oral films, the product needs to be placed between the upper lip of the oral cavity and the upper gum mucosa and the buccal mucosa. This special use position puts forward new requirements for the stiffness of nicotine oral films: films that are too soft are difficult to operate when attached, and folds or wrinkles will occur if you are not careful, and even damage the oral films. If they are too hard, the oral mucosa will be scratched, and during the cutting process of the oral dissolving film, when the oral film is too hard, the oral film is easy to crack during the cutting process. When the oral film is too soft, the oral film is easy to stick to the knife during the cutting process and burrs are easy to appear on the edge. Therefore, it is urgent to design an oral film that is suitable for use with the gum mucosa and the buccal mucosa and is easy to process. Summary of the invention

[0004] In view of the problem that the existing oral films are not suitable for use on gingival mucosa and buccal mucosa and are not convenient for processing, the present invention provides a nicotine oral film and a preparation method thereof.

[0005] The technical solution adopted by the present invention to solve the above technical problems is as follows: In a first aspect, an embodiment of the present invention provides a nicotine oral film, comprising the following components by weight: 2 to 10 parts of nicotine, 40 to 80 parts of film-forming material, and 1 to 5 parts of nano-silicon oxide. Optionally, the average particle size Dv50 of the nano-silicon oxide is 10-100 nm. Optionally, the average particle size Dv50 of the nano-silicon oxide is 10~50nm.

[0006] In a second aspect, the present invention further provides a method for preparing a nicotine oral film, comprising the following steps: The nicotine, film-forming material and nano silicon oxide are added to a mixed solvent and mixed, and then subjected to vacuum degassing treatment to obtain a coating solution; the mixed solvent is water, ethanol and a plasticizer; The coating solution is applied, dried, and then cut to obtain a nicotine oral film.

[0007] Optionally, the mass ratio of the mixed solvent to the film-forming material is (40-120): (40-80). Optionally, the volume ratio of the water and ethanol solvents is (3-6):1, and the mass content of the plasticizer in the mixed solvent is 1%~5%.

[0008] Optionally, the plasticizer is selected from one or more of propylene glycol, glycerol, polyethylene glycol, and sorbitol.

[0009] Optionally, the film-forming material includes one or more of polyvinyl alcohol, hydroxypropyl methylcellulose, hydroxymethyl starch, hydroxypropyl starch, acetate starch, phosphate starch, gum arabic, guar gum, pectin, gelatin, hydroxypropyl cellulose, sodium carboxymethyl cellulose, microcrystalline cellulose, ethyl cellulose, pullulan, polyvinyl pyrrolidone, sodium alginate and polyethylene oxide; And / or, the nicotine is free nicotine and / or nicotine salt; the nicotine salt includes one or more of nicotine benzoate salt, nicotine tartaric acid salt, nicotine malate salt, nicotine resinate salt, nicotine citrate salt, and nicotine lactate salt. Optionally, the nicotine oral film further comprises 0 to 8 parts of a flavoring agent, wherein the flavoring agent comprises at least one of a sweetener, a fragrance and a cooling agent. Optionally, the nicotine oral film meets at least one of the following conditions: The nicotine oral film has a thickness of 80 to 150 μm and a water content of 4% to 10%; The edge smoothness of the nicotine oral film is greater than 98%; The tensile strength of the nicotine oral film is >10Mpa; The stiffness of the nicotine oral film is 6-11N.

[0010] In the present invention, on the one hand, nano-silicon oxide is added to the oral film to improve the tensile strength, stiffness, folding resistance and wear resistance of the nicotine oral film, so that the oral film is easy to use on the gingival mucosa and buccal mucosa. By adding a specific amount of nano-silicon oxide, the toughness and tensile strength of the oral film are improved, so as to ensure the smoothness of the edge of the oral film during the cutting process of the oral film. At the same time, the addition of nano-silicon oxide can prevent the oral film from being overly softened in a high temperature environment; in a high humidity environment, it can prevent the oral film from becoming sticky or losing its shape due to absorbing too much water.

[0011] On the other hand, in the preparation method, water, ethanol and plasticizer are used as a mixed solvent to prepare the oral film. By controlling the volatilization degree of the mixed solvent, the flexibility and hardness of the oral film formed by the film-forming material are adjusted, so that the oral film is suitable for use on the gingival mucosa and buccal mucosa. The preparation method is simple and has good application prospects. DETAILED DESCRIPTION In order to make the technical problems, technical solutions and beneficial effects solved by the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0012] An embodiment of the present invention discloses a nicotine oral film, comprising the following components by weight: 2-10 parts of nicotine, 40-80 parts of film-forming material and 1-5 parts of nano silicon oxide. In the present embodiment, the addition of nano silicon oxide significantly improves the physical properties of nicotine oral film, such as tensile strength, stiffness, folding resistance and wear resistance, thanks to its high specific surface area and active surface, it can be evenly dispersed in the polymer matrix of the film-forming material, and form a stable network structure, as well as the ability to act as a stress transmission medium, so that nicotine oral film is more stable when used in gingival mucosa and buccal mucosa. At the same time, the chemical inertness and thermal stability of nano silicon oxide enhance the stability of the film under high temperature and high humidity environments, prevent stickiness or deformation caused by excessive softening and water absorption, and ensure the consistency and reliability of nicotine oral film in different environments. In addition, by accurately controlling the amount of nano silicon oxide added, the processing performance of nicotine oral film can be further improved, the smoothness of the cutting edge can be ensured, and the beauty and consistency of the product can be improved. This improvement significantly enhances the user experience.

[0013] The weight of nicotine includes but is not limited to 2 parts, 3 parts, 4 parts, 5 parts, 6 parts, 7 parts, 8 parts, 9 parts or 10 parts. The weight of film-forming material includes but is not limited to 40 parts, 43 parts, 46 parts, 49 parts, 52 parts, 55 parts, 58 parts, 61 parts, 64 parts, 67 parts, 70 parts, 73 parts, 76 parts or 80 parts. The weight of nano silicon oxide includes but is not limited to 1 part, 2 parts, 3 parts, 4 parts or 5 parts. In some embodiments, the average particle size Dv50 of the nano-silicon oxide is 10-100 nm. By selecting nano-silicon oxide within the above particle size range, it can be evenly distributed in the oral film, effectively enhancing the mechanical properties of the oral film and preventing the oral film from breaking or cracking.

[0014] Specifically, the average particle size Dv50 of nano silicon oxide includes but is not limited to 10nm, 15nm, 20nm, 25nm, 30nm, 35nm, 40nm, 45nm, 50nm, 55nm, 60nm, 65nm, 70nm, 75nm, 80nm, 85nm, 90nm, 95nm or 100nm. In some embodiments, the average particle size Dv50 of the nano-silicon oxide is 10-50 nm.

[0015] An embodiment of the present invention further provides a method for preparing a nicotine oral film, comprising the following steps: The nicotine, film-forming material and nano silicon oxide are added to a mixed solvent and mixed, and then subjected to vacuum degassing treatment to obtain a coating solution; the mixed solvent is water, ethanol and a plasticizer; The coating solution is applied, dried, and then cut to obtain a nicotine oral film.

[0016] Specifically, the nicotine oral film is in the shape of a long strip with rounded corners, or the nicotine oral film is in the shape of a circle or an ellipse. By adding nano silicon oxide, the rounded corners are smooth and burr-free after cutting, thereby improving the comfort of use.

[0017] In the preparation method, water, ethanol and a plasticizer are used as a mixed solvent to prepare an oral film. By controlling the volatilization degree of the mixed solvent, the flexibility and hardness of the oral film formed by the film-forming material are adjusted, so that the oral film is suitable for use on the gingival mucosa and the buccal mucosa. The preparation method is simple and has good application prospects.

[0018] In some embodiments, the mass ratio of the mixed solvent to the film-forming material is (40-120): (40-80). The hardness and flexibility of the formed oral film can be improved by adjusting the mass ratio of the mixed solvent to the film-forming material. In some embodiments, the volume ratio of the water to the ethanol solvent is (3-6):1, and the mass content of the plasticizer in the mixed solvent is 1% to 5%. By limiting the volume ratio or mass content of each component in the mixed solvent, the volatility of each component in the mixed solvent is controlled, thereby improving the flexibility and hardness of the oral film, making the oral film suitable for use on the gingival mucosa and buccal mucosa.

[0019] In some embodiments, the plasticizer is selected from one or more of propylene glycol, glycerol, polyethylene glycol, and sorbitol.

[0020] In some embodiments, the film-forming material includes one or more of polyvinyl alcohol, hydroxypropyl methylcellulose, hydroxymethyl starch, hydroxypropyl starch, acetate starch, phosphate starch, gum arabic, guar gum, pectin, gelatin, hydroxypropyl cellulose, sodium carboxymethyl cellulose, microcrystalline cellulose, ethyl cellulose, pullulan, polyvinyl pyrrolidone, sodium alginate and polyethylene oxide. By selecting the above film-forming materials, the mechanical properties of the oral film can be adjusted.

[0021] And / or, the nicotine is free nicotine and / or nicotine salt; the nicotine salt includes one or more of nicotine benzoate salt, nicotine tartaric acid salt, nicotine malate salt, nicotine resinate salt, nicotine citrate salt, and nicotine lactate salt. In some embodiments, the nicotine oral film further comprises 0 to 8 parts of a flavoring agent, wherein the flavoring agent comprises at least one of a sweetener, a fragrance, and a cooling agent. By adding a flavoring agent, the mouthfeel of the oral film is improved. In some embodiments, the nicotine oral film meets at least one of the following conditions: The thickness of the nicotine oral film is 80-150 μm, and the water content is 4%-10%. The viscosity and flexibility of the oral film can be adjusted by controlling the water content of the oral film.

[0022] The edge smoothness of the nicotine oral film is greater than 98%. The addition of nano silicon oxide makes the edge smoothness of the oral film greater than 98%, thereby avoiding burrs after cutting and improving the comfort of use.

[0023] The tensile strength of the nicotine oral film is >10Mpa; The stiffness of the nicotine oral film is 6-11 N. By making the tensile strength and stiffness of the oral film meet the above requirements, the oral film can be used on the gingival mucosa and buccal mucosa, thereby improving the comfort of use. The present invention is further described below by way of examples.

[0024] Example 1 This example is used to illustrate the nicotine oral film disclosed in the present invention and its preparation method.

[0025] The raw materials of nicotine oral film include 5 parts of nicotine benzoate salt, 60 parts of film-forming material, 3 parts of nano silicon oxide, and 105 parts of mixed solvent (80 parts of water, 20 parts of ethanol, and 5 parts of propylene glycol). The volume ratio of water to ethanol in the mixed solvent is 3:1.

[0026] The film-forming material is composed of 20 parts of hydroxypropyl methylcellulose, 35 parts of carboxymethyl cellulose and 5 parts of sodium alginate. The Dv50 of nano silicon oxide is 50 nm.

[0027] The film-forming material and nano silicon oxide are added to ethanol and propylene glycol, stirred and dissolved to obtain a film-forming material solution; nicotine benzoate salt is added to water, stirred and dissolved to obtain a nicotine benzoate salt solution, which is then added to the film-forming material solution and mixed, and vacuum degassing is performed to obtain a coating solution.

[0028] The coating solution is applied, dried, and then cut to obtain a nicotine oral film.

[0029] Example 2 This example is used to illustrate the nicotine oral film disclosed in the present invention and the preparation method thereof. The difference from Example 1 is that the amount of nano-silicon oxide is 1 part.

[0030] Example 3 This example is used to illustrate the nicotine oral film and the preparation method thereof disclosed in the present invention. The difference from Example 1 is that the amount of nano-silicon oxide is 5 parts.

[0031] Example 4 This example is used to illustrate the nicotine oral film and the preparation method thereof disclosed in the present invention. The difference from Example 1 is that the Dv50 of nano-silicon oxide is 10 nm.

[0032] Example 5 This example is used to illustrate the nicotine oral film and the preparation method thereof disclosed in the present invention. The difference from Example 1 is that the Dv50 of the nano-silicon oxide is 100 nm.

[0033] Example 6 This example is used to illustrate the nicotine oral film and the preparation method thereof disclosed in the present invention. The difference from Example 1 is that the Dv50 of nano-silicon oxide is 200 nm.

[0034] Example 7 This example is used to illustrate the nicotine oral film and the preparation method thereof disclosed in the present invention. The difference from Example 1 is that the volume ratio of water to ethanol in the mixed solvent is 2:1, and the mixed solvent includes 72 parts of water, 28 parts of ethanol, and 5 parts of propylene glycol.

[0035] Example 8 This example is used to illustrate the nicotine oral film and the preparation method thereof disclosed in the present invention. The difference from Example 1 is that the volume ratio of water to ethanol in the mixed solvent is 6:1, and the mixed solvent includes 88.5 parts of water, 11.5 parts of ethanol, and 5 parts of propylene glycol.

[0036] Example 9 This example is used to illustrate the nicotine oral film and the preparation method thereof disclosed in the present invention. The difference from Example 1 is that the volume ratio of water to ethanol in the mixed solvent is 7:1, and the mixed solvent includes 90 parts of water, 10 parts of ethanol, and 5 parts of propylene glycol.

[0037] Example 10 This example is used to illustrate the nicotine oral film and the preparation method thereof disclosed in the present invention. The difference from Example 1 is that the raw materials of the nicotine oral film include 6 parts of nicotine citrate salt, 80 parts of film-forming materials (10 parts of gelatin, 60 parts of hydroxypropyl starch, 10 parts of carboxymethyl cellulose), 3 parts of nano silicon oxide, and 86 parts of a mixed solvent (60 parts of water, 20 parts of ethanol, 1 part of sorbitol, and 5 parts of glycerol).

[0038] Embodiment 11 This example is used to illustrate the nicotine oral film and the preparation method thereof disclosed in the present invention. The difference from Example 1 is that the raw materials of the nicotine oral film include 2 parts of nicotine tartrate salt, 75 parts of film-forming materials (5 parts of polyvinyl pyrrolidone, 60 parts of carboxymethyl cellulose, 5 parts of microcrystalline cellulose, 5 parts of pullulan), 3 parts of nano silicon oxide, and 108.5 parts of a mixed solvent (70 parts of water, 35 parts of ethanol, and 3.5 parts of glycerol).

[0039] Example 12 This example is used to illustrate the nicotine oral film and the preparation method thereof disclosed in the present invention. The difference from Example 1 is that the raw materials of the nicotine oral film include 10 parts of nicotine tartrate salt, 40 parts of film-forming materials (5 parts of polyvinyl pyrrolidone, 30 parts of carboxymethyl cellulose, 5 parts of microcrystalline cellulose), 1 part of nano-silicon oxide, and 40 parts of a mixed solvent (32 parts of water, 7 parts of ethanol, and 1 part of glycerol).

[0040] Comparative Example 1 This comparative example is used to illustrate the nicotine oral film and the preparation method thereof disclosed in the present invention, and is different from Example 1 in that no nano-silicon oxide is added.

[0041] Comparative Example 2 This comparative example is used to illustrate the nicotine oral film disclosed in the present invention and the preparation method thereof, and is different from Example 1 in that the amount of nano-silicon oxide is 7 parts.

[0042] Comparative Example 3 This comparative example is used to illustrate the nicotine oral film and the preparation method thereof disclosed in the present invention, and is different from Example 1 in that water is used instead of the mixed solvent.

[0043] Comparative Example 4 This comparative example is used to illustrate the nicotine oral film and the preparation method thereof disclosed in the present invention, and is different from Example 1 in that the mixed solvent includes 80 parts of water and 25 parts of ethanol.

[0044] Comparative Example 5 This comparative example is used to illustrate the nicotine oral film and the preparation method thereof disclosed in the present invention. The difference from Example 1 is that the mixed solvent includes 100 parts of water and 5 parts of propylene glycol.

[0045] Performance Testing Tensile strength test: Use a tensile testing machine to select an undamaged and wrinkle-free nicotine oral film, cut the film into nicotine oral film samples with a size of 1.5*2cm, place the sample vertically fixed on the fixture of the testing machine, stretch it at a constant tensile speed of 90mm / min until the sample breaks, and record the maximum tensile force at this time. Calculate the tensile strength based on the size of the sample. Test 5 samples and take the average of the test results as the indicator of the sample tensile strength.

[0046] Stiffness test: The above-mentioned nicotine oral film was cut into strips of a certain size of 5cm×1cm and a thickness of 100μm, and fixed on the texture analyzer platform. The sample was subjected to a downward pressure puncture test using a probe with a diameter of 2mm, and the maximum force generated during the puncture process was recorded. Each sample was tested 5 times, and the average value of the test results was taken as the stiffness index of the sample.

[0047] Folding resistance test: The nicotine oral film was cut into a square of 5 cm × 5 cm, and folded 180° repeatedly at the same position until cracks or breaks appeared on the surface of the nicotine oral film. The number of folds when the sample reached the damage state was recorded each time, and the test was repeated for 3 samples, and the average number of folds was finally calculated to determine the folding resistance of the nicotine oral film.

[0048] Edge smoothness test: The nicotine oral film was cut into strips with a size of 5 cm×1 cm and a thickness of 100 μm. The edges of the nicotine oral film were observed using an optical microscope with a magnification of 10 to 100 times, and the Sobel edge detection algorithm in the ImageJ image processing platform was used to analyze and quantify the smoothness of the edges.

[0049] The specific test results are shown in Table 1.

[0050] Table 1 From the data of Examples 1-3 and Comparative Examples 1-2, it can be seen that adding an appropriate amount of nano-silicon oxide can improve the performance of the film. Adding an appropriate amount of nano-silicon oxide can optimize the comprehensive performance of the film and help maintain the stiffness between 6-11N. Adding too much nano-silicon oxide will affect the folding resistance.

[0051] From the test results of Examples 4-6, it can be seen that nano silicon oxide with a particle size range of 10-100 nm can improve the performance of the film to a certain extent, and the effect of 10-50 nm is better.

[0052] By comparing the test results of Examples 1, 7-9 with Comparative Examples 3-5, it can be seen that changing the composition of the mixed solvent affects the performance of the film. The appropriate solvent ratio can adjust the flexibility and hardness of the film, thereby affecting its performance and ensuring that the stiffness is between 6-11N. In Example 1, the volume ratio of water to ethanol is 3:1, and in Comparative Example 3, only water is used as a solvent. The tensile strength (7.8MPa), stiffness (4.6N), folding resistance (25 times) and edge smoothness (96.5%) of the film are significantly reduced, proving that ethanol plays an important role in the performance of the film in the solvent system, and has a significant effect on stiffness. When ethanol is not added, the stiffness is far below the reasonable range. In Comparative Example 4, the volume ratio of water to ethanol is 2:1, and various performance indicators are lower than those in Example 1, with a stiffness of 5.7N; Comparative Example 5 has no ethanol and the ratio of water to propylene glycol is changed, and the performance is also poor. In Examples 10-12, the type of film-forming material was changed. From the test results, it can be seen that the type of film-forming material affects the performance of the film agent. The film-forming material selected in the present invention can meet the demand. Different ratios and types can make the performance of the film agent vary within a certain range, and the stiffness can also be maintained in a reasonable range of 6-11N.

[0053] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A nicotine oral film, characterized in that: The invention comprises the following components by weight: 2-10 parts of nicotine, 40-80 parts of film-forming materials and 1-5 parts of nano silicon oxide.

2. The nicotine oral film according to claim 1, characterized in that The average particle size Dv50 of the nano silicon oxide is 10-100 nm.

3. The nicotine oral film according to claim 2, characterized in that The average particle size Dv50 of the nano silicon oxide is 10-50 nm.

4. A method for preparing the nicotine oral film according to any one of claims 1 to 3, characterized in that: The following steps are involved: The nicotine, film-forming material and nano silicon oxide are added to a mixed solvent and mixed, and then subjected to vacuum degassing treatment to obtain a coating solution; the mixed solvent is water, ethanol and a plasticizer; The coating solution is applied, dried, and then cut to obtain a nicotine oral film.

5. The method for preparing the nicotine oral film according to claim 4, characterized in that: The mass ratio of the mixed solvent to the film-forming material is (40-120): (40-80).

6. The method for preparing the nicotine oral film according to claim 4, characterized in that: The volume ratio of the water and ethanol solvents is (3-6):1, and the mass content of the plasticizer in the mixed solvent is 1% to 5%.

7. The method for preparing the nicotine oral film according to claim 4, characterized in that: The plasticizer is selected from one or more of propylene glycol, glycerol, polyethylene glycol, and sorbitol.

8. The method for preparing the nicotine oral film according to claim 4, characterized in that: The film-forming material includes one or more of polyvinyl alcohol, hydroxypropyl methylcellulose, hydroxymethyl starch, hydroxypropyl starch, acetate starch, phosphate starch, gum arabic, guar gum, pectin, gelatin, hydroxypropyl cellulose, sodium carboxymethyl cellulose, microcrystalline cellulose, ethyl cellulose, pullulan, polyvinyl pyrrolidone, sodium alginate and polyethylene oxide; And / or, the nicotine is free nicotine and / or nicotine salt; the nicotine salt includes one or more of nicotine benzoate salt, nicotine tartaric acid salt, nicotine malate salt, nicotine resinate salt, nicotine citrate salt, and nicotine lactate salt.

9. The method for preparing the nicotine oral film according to claim 4, characterized in that: The nicotine oral film further comprises 0 to 8 parts of a flavoring agent, wherein the flavoring agent comprises at least one of a sweetener, a fragrance and a cooling agent.

10. The method for preparing the nicotine oral film according to claim 4, characterized in that: The nicotine oral film meets at least one of the following conditions: The nicotine oral film has a thickness of 80 to 150 μm and a water content of 4% to 10%; The edge smoothness of the nicotine oral film is greater than 98%; The tensile strength of the nicotine oral film is >10Mpa; The stiffness of the nicotine oral film is 6-11N.

Images