Membrane liquid for preparing buccal product, preparation method of membrane liquid and buccal product

Abstract

The invention discloses a film liquid for preparing a buccal product, a preparation method of the film liquid and the buccal product. The preparation method of the film liquid comprises the steps that materials to be mixed are obtained, and the materials to be mixed comprise a fluid material and a solid material; the material to be mixed is placed in a material chamber of a centrifugal device, the material chamber comprises a first chamber body and a second chamber body, the first chamber body is used for feeding solid materials, and the second chamber body is used for feeding fluid materials and mixing the fluid materials and the solid materials; a centrifugation step: enabling the material chamber to rotate and revolve, and dispersing the to-be-mixed material in the material chamber to obtain a membrane liquid; wherein a dihedral angle between a plane formed by autorotation of the material chamber and a plane formed by revolution of the material chamber is 5-45 degrees; the solid content of the membrane liquid is 40-70%, and the viscosity of the membrane liquid is 5000-50000 cp. According to the preparation method, the high-quality membrane liquid with good uniformity and less caking can be prepared, the steps are simple and convenient, and the efficiency is high.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of oral products, in particular to a film liquid for preparing an oral product, a preparation method of the film liquid and the oral product. BACKGROUND

[0002] An oral product, such as an oral nicotine product, is a product containing a nicotine active ingredient (nicotine or its derivative), usually in the form of powder, tablet, sachet, film, etc., which is placed in the oral cavity, then dissolves and releases the nicotine active ingredient, and is absorbed through the oral mucosa, thereby relieving the nicotine withdrawal symptoms during smoking cessation. A nicotine oral film usually comprises a film-forming base material, an active ingredient, a flavoring agent, etc. These materials are mixed with water to prepare a film liquid, and then coated and dried to obtain an oral film. The film-forming base material (such as hydroxypropyl methyl cellulose, pullulan, polyvinyl alcohol, sodium alginate, etc.) usually has high viscosity, and the solid content of the film liquid is high (usually higher than 30%). At present, the film liquid is prepared by mixing and preparing through magnetic or mechanical stirring. However, for high-viscosity and high-solid-content film liquids, the mixing efficiency of the traditional magnetic or mechanical stirring method is low, the dissolution and swelling speed is slow, and the preparation process takes several hours. In addition, under conventional stirring, the powder material is easily wrapped to form "fish eye" agglomerates. The inside of these agglomerates is dry powder, and the outside is wrapped by gel. It is difficult to disperse and dissolve again, resulting in poor uniformity of the film liquid system and affecting the quality of the final oral film. SUMMARY

[0003] The present application provides a film liquid for preparing an oral product and a preparation method thereof, and an oral product, to solve the problems of poor uniformity and low efficiency of high-viscosity film liquids prepared by the existing method.

[0004] The present application discloses a preparation method of a film liquid for preparing an oral product, comprising: obtaining a material to be mixed, wherein the material to be mixed comprises a fluid material and a solid material; a feeding step: placing the material to be mixed in a material chamber of a centrifugal device, wherein the material chamber comprises a first chamber and a second chamber, the first chamber is used for feeding the solid material, and the second chamber is used for feeding the fluid material and mixing the fluid material and the solid material; a centrifugation step: making the material chamber rotate and revolve, and dispersing the material to be mixed in the material chamber to obtain the film liquid; wherein the dihedral angle of the plane formed by the rotation of the material chamber and the plane formed by the revolution of the material chamber is 5°-45°; the solid content of the film liquid is 40%-70%, and the viscosity of the film liquid is 5000 cp-50000 cp.

[0005] In an implementation form of the application, the centrifugal device further comprises a screen member for separating the material chamber into the first chamber and the second chamber and for communicating the first chamber and the second chamber.

[0006] In an implementation form of the application, the centrifuging step comprises a first stage, a second stage and a third stage; wherein the centrifuging step satisfies at least one of the following conditions: I. in the first stage, the revolution speed is 1000 rpm-1500 rpm, the rotation speed is 500 rpm-700 rpm, and the centrifuging time is 60 seconds-120 seconds; II. in the second stage, the revolution speed is 2000 rpm-2500 rpm, the rotation speed is 2200 rpm-2750 rpm, and the centrifuging time is 180 seconds-250 seconds; III. in the third stage, the revolution speed is 1000 rpm-2000 rpm, the rotation speed is 1000 rpm-2000 rpm, and the centrifuging time is 30 seconds-50 seconds; IV. in the first stage, the ratio of the revolution speed to the rotation speed is 1:0.4-0.6; V. in the second stage, the ratio of the revolution speed to the rotation speed is 1:1.05-1.2; VI. in the third stage, the ratio of the revolution speed to the rotation speed is 1:0.9-1.1.

[0007] In an implementation form of the application, the material chamber is subjected to vacuumizing treatment; wherein the vacuumizing treatment satisfies at least one of the following conditions: I. in the first stage, the vacuum degree is 80 kPa-100 kPa; II. in the second stage, the vacuum degree is 8 kPa-12 kPa; III. in the third stage, the vacuum degree is 20 kPa-30 kPa.

[0008] In an implementation form of the application, the screen member has a mesh number of 60 mesh-80 mesh; and / or, the particle size of the solid material is not greater than 250 μm.

[0009] In an implementation form of the application, the material chamber has dispersing teeth and / or dispersing beads therein, the dispersing teeth and the dispersing beads being used for dispersing the material to be mixed.

[0010] The application further discloses a film liquid for preparing a buccal preparation, which is prepared by the preparation method.

[0011] In an implementation form of the application, the film liquid comprises at least one of a film-forming base material, an active ingredient, a plasticizer, a flavoring agent, a pH adjuster and an antioxidant.

[0012] In one implementation of the present application, the film-forming substrate comprises at least one of hydroxypropyl methyl cellulose, ethyl cellulose, polyethylene oxide, pullulan, sodium alginate, soluble starch, gelatin, gelatin-porous starch composite; the active ingredient comprises at least one of nicotine, nicotine derivative; the plasticizer comprises at least one of glycerol, sorbitol, propylene glycol, polyethylene glycol, xylitol; the flavoring agent comprises at least one of aromatic agent, sweetener, salty agent, cooling agent, sour agent; the pH regulator comprises at least one of citric acid, lactic acid, malic acid, tartaric acid, sodium citrate, sodium lactate, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate and magnesium carbonate; the antioxidant comprises at least one of propyl gallate, calcium propionate, tea polyphenol, chitosan, ascorbic acid, vitamin E, dibutylhydroxytoluene and butylhydroxyanisole.

[0013] The present application also discloses a mouth piece, comprising a functional layer, wherein the functional layer is formed by the film liquid prepared by the preparation method or is formed by the film liquid.

[0014] The present application has the following advantages: The preparation method of the film liquid for preparing the mouth piece of the present application utilizes the forced dispersion principle of centrifugal force, and the dry and wet materials are thrown to the cavity wall due to the centrifugal force of high-speed rotation in the material cavity. In this process, the shear force and impact force received can instantaneously break up the powder lumps and fully and quickly contact with the liquid, reducing the generation of "lumping" phenomenon, which is beneficial to ensure the uniformity of the film liquid. The high-speed rotation forms a negative pressure zone in the center region of the material cavity, which can automatically extract the gas entrained in the material, realize synchronous defoaming, and can save the independent standing or vacuum defoaming process. Compared with the traditional stirring method, the mixing of high-viscosity and high-solid-content materials has better mixing performance, and the steps are simple and efficient. BRIEF DESCRIPTION OF DRAWINGS

[0015] Figure 1 A structural schematic diagram of a centrifugal device of a specific embodiment is shown.

[0016] Figure 2 A structural schematic diagram of a material cavity of a centrifugal device of a specific embodiment is shown.

[0017] Figure 3 Pictures of the film liquids prepared by Example 1, Example 2 and Control Example 1 involved in the present application are shown. DETAILED DESCRIPTION

[0018] The present invention will now be described in further detail with reference to specific embodiments and accompanying drawings. In the following embodiments, many details are described to facilitate a better understanding of the present application. However, those skilled in the art will readily recognize that some features may be omitted in different situations, or may be replaced by other materials or methods. In some cases, certain operations related to the present application are not shown or described in the specification. This is to avoid obscuring the core parts of the present application with excessive description. For those skilled in the art, detailed description of these related operations is not necessary; they can fully understand the related operations based on the description in the specification and general technical knowledge in the art.

[0019] Furthermore, the features, operations, or characteristics described in the specification can be combined in any suitable manner to form various embodiments. At the same time, the steps or actions in the method description can be rearranged or adjusted in a manner obvious to those skilled in the art. Therefore, the various orders in the specification and drawings are only for the clear description of a particular embodiment and do not imply a necessary order, unless otherwise stated that a particular order must be followed.

[0020] The serial numbers assigned to components in this article, such as "first" and "second", are used only to distinguish the objects being described and have no sequential or technical meaning.

[0021] The membrane solution for oral nicotine products has high viscosity and solid content. Traditional magnetic or mechanical stirring methods have low mixing efficiency for high-viscosity, high-solids membrane solutions, slow dissolution and swelling rates, and the entire batching process can take several hours, severely restricting production efficiency. Moreover, traditional magnetic or mechanical stirring methods often result in uneven mixing and agglomeration. High-viscosity material powders are prone to forming "fish-eye" clumps. These clumps are dry powder inside and coated with gel on the outside, making them difficult to redisperse and dissolve. This leads to poor uniformity of the membrane solution system, affecting the quality of the final oral nicotine product. In addition, traditional magnetic or mechanical stirring methods introduce a large number of air bubbles into the membrane solution, requiring a lengthy settling and degassing process or an independent vacuum degassing process. The added process steps not only extend the production cycle but also easily introduce impurities and contaminants during the transfer of the solution.

[0022] In view of this, this application proposes a membrane liquid for preparing oral products and its preparation method, and oral products, which subverts the traditional step-by-step operation mode of "stirring-dissolving-degassing". It creatively uses a centrifuge device as the core reactor for one-time, integrated preparation of membrane liquid. By utilizing the strong centrifugal force, shear force and negative pressure environment generated by the high-speed rotation of the centrifuge device, the entire process of mixing, dispersing, dissolving and degassing of materials is completed simultaneously. This application has at least one of the following advantages: (1) Simple process: The multiple unit operations of "feeding, mixing, high-speed shear dispersion, dissolving and degassing" are integrated into a centrifuge device and a single step, which simplifies the process flow, eliminates material transfer between processes, and reduces the intensity of manual operation and error rate. (2) Good uniformity of membrane liquid: Utilizing the principle of forced dispersion by centrifugal force, dry and wet materials are thrown towards the cavity wall by the centrifugal force of high-speed rotation in the rotor cavity. During this process, they are subjected to huge shear force and impact force, which can instantly break up the powder clumps and make full and rapid contact with the liquid, fundamentally eliminating the generation of "clumping" phenomenon and ensuring the ultimate uniformity of membrane liquid. (3) High-efficiency degassing: High-speed rotation creates a negative pressure zone in the center of the material chamber, which can automatically extract the gas entrained in the material, eliminating the need for separate settling or vacuum degassing processes, and the degassing effect is more thorough. (4) Improved efficiency: The membrane solution preparation process, which originally required several hours, is shortened to 3 to 5 minutes, and a high-quality membrane solution that can be directly coated can be obtained. With the preparation method of this application, 2 kg of qualified membrane solution can be stably produced every 5 minutes, and the production efficiency is improved by orders of magnitude, which is very suitable for industrial continuous production.

[0023] This specific embodiment provides a method for preparing a film liquid for preparing oral products (sometimes simply referred to as "preparation method" or "method").

[0024] In one specific embodiment, the preparation method includes: obtaining the materials to be mixed, a feeding step, and a centrifugation step.

[0025] In one specific embodiment, the materials to be mixed include fluid materials and solid materials. It should be noted that fluid materials can refer to substances that are free-flowing and have no fixed shape at room temperature, such as liquids and slurries. Solid materials can refer to substances that have a fixed shape and volume at room temperature, i.e., solid substances, such as powders.

[0026] In one specific embodiment, the materials to be mixed may include at least one of the following: a film-forming substrate, an active ingredient, a plasticizer, a flavoring agent, a pH adjuster, an antioxidant, and a solvent. It should be noted that the film solution of this application contains a film-forming substrate, has a high viscosity, and the materials are prone to agglomeration. The preparation method of the film solution of this application exhibits good mixing performance for materials with high viscosity.

[0027] In one specific embodiment, the film-forming substrate may include at least one of the following: hydroxypropyl methylcellulose, ethyl cellulose, polyoxyethylene, pullulan, sodium alginate, soluble starch, gelatin, or a gelatin-porous starch composite. The film-forming substrate may be a solid material. In the step of obtaining the mixture to be prepared, the solid material mainly includes the film-forming substrate.

[0028] In one specific embodiment, the active ingredient may include at least one of the following: nicotine and nicotine derivatives. Nicotine may include natural nicotine and synthetic nicotine. Nicotine derivatives may include one or more of the following: nicotine salts, nicotine in a matrix such as a glycobase or an organometallic complex, nicotine-resin combinations, nicotine inclusion complexes, and non-covalently bound nicotine. Non-covalently bound nicotine includes nicotine lactate, nicotine malate, nicotine salicylate, nicotine cyclodextrin-encapsulated complexes, nicotine hydrochloride, nicotine dihydrochloride, nicotine tartrate, nicotine tartrate dihydrate, nicotine sulfate, nicotine zinc chloride, and nicotine benzoate. Nicotine derivatives also include nicotine with substituents, such as one or more mixtures of hexamethylnicotine, hexamethylnicotine lactate, hexamethylnicotine malate, hexamethylnicotine salicylate, hexamethylnicotine cyclodextrin encapsulated complex, hexamethylnicotine hydrochloride, hexamethylnicotine dihydrochloride, hexamethylnicotine tartrate, hexamethylnicotine tartrate dihydrate, hexamethylnicotine sulfate, hexamethylnicotine zinc chloride, and hexamethylnicotine benzoate. In one specific embodiment, the active ingredient may also be selected from other substances with medical or other specific uses, such as vitamins, capsaicin, caffeine, etc., to meet the needs of different users. In one specific embodiment, the active ingredient may also be selected from other alkaloids or amino acids, such as alkaloids from tobacco, coffee, tea, etc. The active ingredient may be a liquid material.

[0029] In one specific embodiment, the plasticizer may include at least one of the following: glycerol, sorbitol, propylene glycol, polyethylene glycol, and xylitol. The plasticizer may include solid materials or fluid materials.

[0030] In one specific embodiment, the flavoring agent may include at least one of the following: aromatizer, sweetener, saltiness agent, cooling agent, and acidifier. The aromatizer may include at least one of bergamot flavoring, eucalyptus flavoring, citrus flavoring, lemon flavoring, peppermint flavoring, peppermint flavoring, menthol, licorice flavoring, wintergreen flavoring, tobacco flavoring, coffee flavoring, vanilla flavoring, lime flavoring, apple flavoring, peach flavoring, mango flavoring, cherry flavoring, blueberry flavoring, strawberry flavoring, cola flavoring, cinnamon flavoring, vanilla flavoring, and watermelon flavoring. The sweetener may include at least one of xylitol, sorbitol, mannitol, yigol, lactitol, maltitol, isomaltitol, hydrogenated starch hydrolysate, erythritol, maltodextrin, aspartame, acesulfame potassium, sodium saccharin, sucralose, neotame, cyclamate, alitane, steviol glycosides, arabinitol, and monk fruit sweetener. Salting agents may include at least one of sodium chloride, potassium chloride, yeast extract, and seaweed extract. Cooling agents may include at least one of menthol, menthol derivatives, WS-3, and WS-23. Acidifying agents may include at least one of citric acid, acetic acid, lactic acid, malic acid, tartaric acid, and ascorbic acid. Sweeteners, cooling agents, salting agents, acidifying agents, and flavoring agents may also be other types of edible-grade substances, which will not be elaborated upon here. Flavoring agents may include solid materials or liquid materials.

[0031] In one specific embodiment, the pH adjuster includes at least one selected from citric acid, lactic acid, malic acid, tartaric acid, sodium citrate, sodium lactate, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, and magnesium carbonate. The pH adjuster may be a solid material.

[0032] In one specific embodiment, the antioxidant includes at least one selected from parabens, calcium propionate, tea polyphenols, chitosan, ascorbic acid, vitamin E, butylated hydroxytoluene, and butylated hydroxyanisole. The antioxidant may be a solid material.

[0033] Figure 1 A schematic diagram of the structure of a centrifuge device 10 according to a specific embodiment is shown.

[0034] In one specific embodiment, the feeding step includes: placing the materials to be mixed into the material chamber 11 of the centrifuge device 10.

[0035] In one specific embodiment, the number of material chambers 11 can be multiple. For example, there can be two, three, four, etc. The multiple material chambers 11 are arranged in a centrally symmetrical manner. For example, as... Figure 1 As shown, the two material chambers 11 are symmetrically arranged with a center of symmetry. It should be noted that setting up multiple material chambers can help improve work efficiency, and the central symmetry arrangement can ensure stability during centrifugation.

[0036] It should be noted that the material chamber 11 can be fixedly connected to the main body of the centrifuge device, or it can be detachably connected. For example, the material chamber 11 can be a detachable centrifuge tube.

[0037] Figure 2 A schematic diagram of the material chamber 11 of a centrifuge device 10 according to a specific embodiment is shown.

[0038] In one specific embodiment, the material chamber 11 may include a first chamber 111 and a second chamber 112. The second chamber 112 may be located below the first chamber 111. The first chamber 111 may be used for dispensing solid materials. The second chamber 112 may be used for dispensing fluid materials and for mixing fluid materials and solid materials.

[0039] In one specific embodiment, the centrifuge device 10 may further include a screen 12. The screen 12 can be used to sieve solid materials.

[0040] In one specific embodiment, the screen 12 may be disposed in the material chamber 11.

[0041] In one specific embodiment, the screen 12 divides the material chamber 11 into a first chamber 111 and a second chamber 112, and connects the first chamber 111 and the second chamber 112. It should be noted that, in this case, after solid material is added to the first chamber 111, solid material with a particle size smaller than the screen mesh size can pass through the screen 12 and enter the second chamber 112 to mix with the fluid material in the second chamber 112. Through sieving, the particle size uniformity of the solid material can be improved, and the screen 12 allows the solid material to enter the second chamber 112 through individual mesh openings and contact the fluid material. Compared to directly adding all the solid material into the fluid material at once, this further reduces agglomeration in the membrane solution.

[0042] In one specific embodiment, during the feeding step, the fluid material is fed into the second chamber 112, and the solid material is fed into the first chamber 111. Under the influence of gravity and / or centrifugal force, the solid material passes through the screen 12 into the second chamber 112. In this case, the screen 12 allows the solid material to enter the second chamber 112 through individual mesh openings and come into contact with the fluid material. Compared to directly feeding all the solid material into the fluid material at once, this further reduces clumping in the membrane solution.

[0043] In one specific embodiment, the mesh size of the screen 12 can be from 60 to 80 mesh. For example, the mesh size of the screen 12 can be 60, 70, or 80 mesh. It should be noted that this allows the solid material to have a smaller particle size, which is beneficial for forming a film liquid with good uniformity.

[0044] In one specific embodiment, the particle size of the solid material is no greater than 250 μm. For example, the particle size of the solid material can be 250 μm, 200 μm, 150 μm, or 100 μm.

[0045] In one specific embodiment, the centrifugation step includes: causing the material chamber 11 to rotate and revolve to disperse the materials to be mixed within the material chamber 11 to obtain a membrane solution. Rotation refers to the material chamber 11 rotating around its own axis, and revolve refers to the material chamber 11 rotating around the central axis of all material chambers 11 (usually also the central axis of the centrifuge device 10). It should be noted that in this case, the material chamber 11 generates centrifugal force through its revolve, propelling the materials outward. This causes the dry and wet materials within the material chamber to be thrown against the chamber wall due to the high-speed centrifugal force, instantly breaking up powder clumps and ensuring sufficient and rapid contact with the liquid, reducing the formation of "agglomerates" and helping to ensure the uniformity of the membrane solution. The rotation of the material chamber 11 also generates shear force, preventing materials from adhering to the walls, enhancing internal agitation, and further homogenizing the materials under the action of shear force. The rotation also promotes upward / downward circulation of materials in the central area of ​​the material chamber 11, forming a vortex, further promoting uniform mixing. In addition, centrifugal force causes bubbles (low density) to gather towards the center of rotation. The bubbles merge into larger bubbles at the center, which then rise rapidly and burst, enabling simultaneous mixing and degassing.

[0046] In one specific embodiment, the rotation and revolution directions of the material chamber 11 can be the same or different. For example, the rotation direction of the material chamber 11 can be clockwise or counterclockwise, and the revolution direction of the material chamber 11 can be clockwise or counterclockwise.

[0047] In one specific embodiment, the dihedral angle between the plane formed by the rotation of the material chamber 11 and the plane formed by the revolution of the material chamber 11 is 5° to 45°. For example, the dihedral angle between the plane formed by the rotation of the material chamber 11 and the plane formed by the revolution of the material chamber 11 can be 5°, 10°, 15°, 20°, 25°, 30°, 35°, 40°, or 45°. The dihedral angle between the plane formed by the rotation of the material chamber 11 and the plane formed by the revolution of the material chamber 11 can be as follows: Figure 2 As shown by angle α in the diagram. It should be noted that, in this case, avoiding inward tilting of the material chamber 11 can promote the overall flow of the material, prevent the material from depositing at the bottom, and also enhance the three-dimensional flow and folding mixing of the material, thereby improving the mixing efficiency.

[0048] In one specific embodiment, the centrifugation step includes a first stage, a second stage, and a third stage.

[0049] In one specific embodiment, in the first stage, the revolution speed can be 1000 rpm to 1500 rpm, and the rotation speed can be 500 rpm to 700 rpm. The centrifugation time is 60 seconds to 120 seconds. For example, in the first stage, the revolution speed can be 1000 rpm, 1100 rpm, 1200 rpm, 1300 rpm, 1400 rpm, or 1500 rpm, and the rotation speed can be 500 rpm, 550 rpm, 600 rpm, 650 rpm, or 700 rpm. The centrifugation time in the first stage can be 60 seconds, 70 seconds, 80 seconds, 90 seconds, 100 seconds, 110 seconds, or 120 seconds. It should be noted that in the first stage, the revolution speed is higher than the rotation speed, and the overall speed is not high, which is conducive to the mixing of materials, the removal of air bubbles, and the prevention of overflow.

[0050] In one specific embodiment, in the first stage, the ratio of the revolution speed to the rotation speed can be 1:0.4 to 0.6. For example, the revolution-rotation ratio in the first stage can be 1:0.4, 1:0.5, or 1:0.6. It should be noted that when the revolution speed is higher than the rotation speed, the centrifugal force is downward, resulting in stronger mixing ability.

[0051] In one specific embodiment, in the second stage, the revolution speed can be 2000 rpm to 2500 rpm, and the rotation speed can be 2200 rpm to 2750 rpm. The centrifugation time can be 180 seconds to 250 seconds. For example, in the second stage, the revolution speed can be 2000 rpm, 2100 rpm, 2200 rpm, 2300 rpm, 2400 rpm, or 2500 rpm, and the rotation speed can be 2200 rpm, 2300 rpm, 2400 rpm, 2500 rpm, 2600 rpm, 2700 rpm, or 2750 rpm. The centrifugation time in the second stage can be 180 seconds, 190 seconds, 200 seconds, 210 seconds, 220 seconds, 230 seconds, 240 seconds, or 250 seconds. It should be noted that in the second stage, both the revolution speed and the rotation speed are relatively high, which is beneficial to the rapid dispersion and dissolution of the material.

[0052] In one specific embodiment, in the second stage, the ratio of the revolution speed to the rotation speed can be 1:1.05 to 1.2. For example, the revolution-rotation ratio in the second stage can be 1:1.05, 1:1.1, or 1:1.2.

[0053] In one specific embodiment, in the third stage, the revolution speed can be 1000 rpm to 2000 rpm. The rotation speed can be 1000 rpm to 2000 rpm. The centrifugation time can be 30 seconds to 50 seconds. For example, in the third stage, the revolution speed can be 1000 rpm, 1200 rpm, 1400 rpm, 1600 rpm, 1800 rpm, or 2000 rpm, the rotation speed can be 1000 rpm, 1200 rpm, 1400 rpm, 1600 rpm, 1800 rpm, or 2000 rpm, and the centrifugation time in the third stage can be 30 seconds, 40 seconds, or 50 seconds.

[0054] In one specific embodiment, in the third stage, the ratio of the revolution speed to the rotation speed is 1:0.9 to 1.1. For example, the revolution-rotation ratio in the third stage can be 1:0.9, 1:1, or 1:1.1. It should be noted that in the third stage, both the revolution speed and the rotation speed are reduced, resulting in low-speed debubbling to ensure that the remaining bubbles are discharged.

[0055] In one specific embodiment, the total centrifugation time in the centrifugation step can be 200 seconds to 500 seconds. For example, the total centrifugation time can be 200 seconds, 300 seconds, 400 seconds, or 500 seconds.

[0056] In one specific embodiment, the centrifugation step includes evacuating the material chamber 11. It should be noted that evacuation facilitates the removal of air bubbles from the material.

[0057] In one specific embodiment, during the centrifugation step, the vacuum level in the material chamber 11 can be between 8 kPa and 100 kPa. Vacuum level refers to the degree below standard atmospheric pressure; a vacuum level of 50 kPa indicates a pressure value 50 kPa lower than standard atmospheric pressure. This helps to further reduce air bubbles in the membrane solution.

[0058] In one specific embodiment, the vacuum level in the first stage can be 80 kPa to 100 kPa. For example, the vacuum level in the first stage can be 80 kPa, 90 kPa, or 100 kPa.

[0059] In one specific embodiment, the vacuum level in the second stage can be 8 kPa to 12 kPa. For example, the vacuum level in the second stage can be 8 kPa, 9 kPa, 10 kPa, 11 kPa or 12 kPa.

[0060] In one specific embodiment, the vacuum level in the third stage can be 20 kPa to 30 kPa. For example, the vacuum level in the third stage can be 20 kPa, 22 kPa, 24 kPa, 26 kPa, 28 kPa, or 30 kPa.

[0061] In one specific embodiment, the frictional heat generated during the shearing process can further promote the swelling and dissolution of the material.

[0062] In one specific embodiment, the temperature in the material chamber during the centrifugation step can be 20°C to 35°C.

[0063] In one specific embodiment, the material chamber 11 may have dispersing teeth or dispersing beads. The dispersing teeth and dispersing beads are used to disperse the mixture. The dispersing teeth can be protrusions with a serrated structure disposed within the material chamber. The dispersing beads can be glass beads, zirconia beads, stainless steel beads, etc., and may also be called grinding beads or media beads. The number of dispersing teeth or dispersing beads can be one or more. It should be noted that under the action of centrifugal force and shear force, the material impacts the dispersing teeth, and is subjected to intense shearing and impact from the dispersing teeth or impact and grinding from the dispersing beads. This allows the powder particles to be instantly dispersed and refined, fully mixed with the liquid, and efficiently dissolved, further reducing agglomeration.

[0064] In one specific embodiment, the second chamber 112 may have dispersion teeth or dispersion beads.

[0065] In one specific embodiment, after the centrifugation step, the resulting mixture can be directly used as a membrane solution for coating and molding to obtain a mouthpiece or a functional layer of a mouthpiece. That is, the preparation of the membrane solution can be completed entirely within the centrifuge device 10, without the need for transfer to other devices for stirring or degassing. In another specific embodiment, after the centrifugation step, the membrane solution can be discharged through the outlet connected to the material chamber 11 for subsequent coating. This reduces contamination caused during the transfer process.

[0066] In one specific embodiment, based on a total mass of 100 parts, the mixture to be mixed includes: 40 to 70 parts of film-forming substrate, 2 to 20 parts of active ingredient, 3 to 10 parts of plasticizer, 0.5 to 10 parts of flavoring agent, and the balance being solvent. For example, based on a total mass of 100 parts, the mixture to be mixed may include: 40, 50, 60, or 70 parts of film-forming substrate, 2, 5, 10, 15, or 20 parts of active ingredient, 3, 5, 7, or 10 parts of plasticizer, 0.5, 1, 3, 5, 7, or 10 parts of flavoring agent, and the balance being solvent.

[0067] This specific embodiment also provides a membrane solution. The membrane solution can be prepared by the above-described preparation method.

[0068] In one specific embodiment, the solid content of the membrane solution is 40% to 70%. For example, the solid content of the membrane solution can be 40%, 50%, 60%, or 70%. It should be noted that the preparation method of this application can quickly and effectively mix membrane solutions with high solid content and reduce the generation of bubbles.

[0069] In one specific embodiment, the viscosity of the membrane solution is 5000 cp to 50000 cp. For example, the viscosity of the membrane solution can be 5000 cp, 10000 cp, 15000 cp, 20000 cp, 25000 cp, 30000 cp, 35000 cp, 40000 cp, 45000 cp, or 50000 cp. It should be noted that the preparation method of this application can quickly and effectively mix high-viscosity membrane solutions and reduce the generation of bubbles.

[0070] In one specific embodiment, based on a total mass of 100 parts, the film solution comprises: 40 to 70 parts of film-forming substrate, 2 to 20 parts of active ingredient, 3 to 10 parts of plasticizer, 0.5 to 10 parts of flavoring agent, and the balance being solvent. For example, based on a total mass of 100 parts, the film solution may include: 40, 50, 60, or 70 parts of film-forming substrate, 2, 5, 10, 15, or 20 parts of active ingredient, 3, 5, 7, or 10 parts of plasticizer, 0.5, 1, 3, 5, 7, or 10 parts of flavoring agent, and the balance being solvent.

[0071] This specific embodiment also provides a mouthpiece. The mouthpiece includes a functional layer, which is formed by coating and drying a film solution prepared by the above-described preparation method.

[0072] In one specific embodiment, the oral article may consist of only a functional layer. During use, the functional layer is placed in the oral cavity, where saliva comes into contact with the functional layer, releasing the active ingredients from the functional layer into the saliva.

[0073] In one specific embodiment, the oral article may have a multi-layered structure.

[0074] In one specific embodiment, the oral article may further include a support layer. There may be multiple support layers. The support layer may be located outside the functional layer and serves to support and protect the functional layer. The support layer is a water-permeable layer, allowing saliva to pass through it and enter the functional layer to release the active ingredient.

[0075] In one specific embodiment, the number of functional layers can be one or more.

[0076] In one specific embodiment, the oral article has two or more functional layers, and there may be an isolation layer between the different functional layers. The isolation layer is used to separate the different functional layers.

[0077] The present application will be further described in detail below through specific experimental procedures and experimental data examples. The following examples are for further illustration only and should not be construed as limiting the present application. In these examples, unless otherwise specified, all reagents and instruments used are commercially available, and all experimental operations are performed in accordance with product instructions and standard experimental procedures.

[0078] I. Preparation of membrane solution: Example 1:

[0079] Feeding: Weigh each raw material according to the formula. Load the fluid material into the customized centrifuge tube (i.e., material chamber) of the centrifuge (manufacturer: Simeda, model: TMV-4000TT). Then, insert a customized separator into the centrifuge bottle. The separator has multiple holes with a diameter of approximately 1mm (i.e., the separator divides the centrifuge tube into two chambers, namely the first chamber and the second chamber). Feed the solid material onto the separator, close and lock the feeding port. The dihedral angle between the plane of revolution and the plane of rotation of the material chamber is approximately 30°.

[0080] Centrifugation: Set the centrifuge operating parameters, start the equipment, and begin centrifugation at room temperature. Centrifugation consists of three stages: Stage 1: Low-speed, slow centrifugation to remove air bubbles and prevent overflow. Centrifugation parameters: revolution speed 1200 rpm, rotation speed 600 rpm, centrifugation time 90 seconds; vacuum degree in the material chamber 100 kPa. Stage 2: High-speed dissolving centrifugation for rapid and uniform dispersion and dissolution. Centrifugation parameters: revolution speed 2000 rpm, rotation speed 2200 rpm, centrifugation time 21 seconds; vacuum degree in the material chamber 10 kPa. Stage 3: Low-speed degassing to ensure the removal of remaining air bubbles. Revolution speed 1500 rpm, rotation speed 1500 rpm, centrifugation time 40 seconds; vacuum degree in the material chamber 25 kPa. During the centrifugation stage, under the powerful centrifugal force, the material is thrown against the mixing chamber wall, instantly dispersing and refining the powder particles, ensuring thorough mixing with the liquid, efficient dissolution, and reduced agglomeration. The material within the chamber generates strong shear forces and turbulence under the combined centrifugal force of revolution and rotation, which is beneficial for mixing high-viscosity materials. Furthermore, under the combined centrifugal force field and shearing action, tiny bubbles in the material are rapidly compressed, merged, and pushed towards low-pressure areas (such as the liquid surface or center). For example, the negative pressure zone formed at the center of the rotor continuously extracts air trapped in the liquid membrane, achieving online degassing. Simultaneously, the frictional heat and mechanical forces generated during shearing accelerate the swelling and dissolution process of the polymer material. In summary, this embodiment achieves an integrated operation of dispersion-dissolution-degassing through centrifugation, conducted within the material chamber, eliminating the need for separate stirring, dissolution, and degassing, as well as multiple material transfers. This method simplifies the process flow, eliminates material transfer between processes, and reduces manual operation intensity and error rate.

[0081] Discharge: After the centrifuge stops running, open the discharge valve located at the bottom of the material chamber. The uniform, bubble-free, and viscosity-compliant high-quality film liquid obtained after centrifugation and dispersion is discharged under gravity or slight positive pressure and can be directly transported to the downstream coating machine for the molding and production of lozenges. Example 2:

[0082] Compared to Example 1, Example 2 uses a sieve during material feeding. Specifically, the feeding steps in Example 2 are as follows: weigh each raw material according to the formula, load the fluid material into a custom-designed centrifuge tube (i.e., material chamber) of a centrifuge (manufacturer: Simeda, model: TMV-4000TT), then insert a custom-designed 60-mesh sieve into the centrifuge flask (i.e., the sieve divides the centrifuge tube into two chambers, namely the first chamber and the second chamber), feed the solid material onto the sieve, and close and lock the feeding port. The dihedral angle between the plane of revolution and the plane of rotation of the material chamber is approximately 30°.

[0083] The other steps in Example 2 are the same as in Example 1.

[0084] Compare with Example 1: Comparative Example 1 uses the traditional mixing method. Each material is weighed according to the formula and the following steps are performed at room temperature: the mixture is stirred at 200 rpm for 20 minutes in a mixer; it is then homogenized at 1000 rpm for 10 minutes in a homogenizer to disperse the mixture, and then allowed to stand for 1.5 hours to remove bubbles.

[0085] Regarding the formulation, four formulations were prepared: Formulation A, Formulation B, Formulation C, and Formulation D. Formulation D is a sustained-release formulation with higher viscosity. These four formulations were used to verify whether the membrane solutions with different formulations were suitable for the preparation method of this embodiment. The specific settings of each formulation are shown in the table below: Formula A:

[0086] Formula B:

[0087] Formula C:

[0088] Formula D:

[0089] II. Result Testing: (1) Observation of clumping phenomenon: Figure 3Images of the membrane solutions prepared in each example and control example are shown, all of which are membrane solutions of Formulation B. From left to right, the images show the membrane solutions of Control Example 1, Example 1, and Example 2, respectively. 50g of freshly prepared membrane solutions (all of which are membrane solutions of Formulation B) from Example 1, Example 2, and Control Example 1 were taken and sieved using a standard test sieve with a pore size of 150μm (100 mesh). The membrane solution was poured into the sieve, and the sieve was gently shaken above a beaker. Agglomerates that could not pass through the sieve were observed and collected. The mass of the agglomerates remaining on the sieve was weighed using a precision balance, and its percentage of the total sample mass (i.e., the agglomeration rate) was calculated. Simultaneously, the membrane solutions after sieving were photographed to visually compare the fineness and uniformity of the two groups of membrane solutions. The results are shown in the table below:

[0090] In summary, the membrane liquid preparation method of this application has an extremely low agglomeration rate (0.10%), which is more than 98% lower than that of the traditional method (4.70%), and can effectively solve the agglomeration problem in the preparation of high viscosity membrane liquids.

[0091] (2) Nicotine uniformity analysis: Three samples (approximately 1g each) were taken from three different locations (top, middle, and bottom) of the same batch of prepared membrane solution. The actual nicotine content in each sample was determined using high-performance liquid chromatography (HPLC). The mean (X̄), standard deviation (SD), and relative standard deviation (RSD) of the nicotine content in the three samples were calculated. RSD is a core indicator of uniformity; the smaller the RSD value, the more uniform the distribution. Typically, RSD ≤ 3.0% is required. The results are shown in the table below:

[0092] In summary, under all four formulations, the nicotine content RSD values ​​of the membrane solutions prepared by the method of this application are significantly lower than those of the traditional process (control example). In particular, formulation D shows a sharp deterioration in uniformity (RSD as high as 23.90%) when the traditional process is used to process high-viscosity sustained-release formulations, resulting in almost unqualified products. However, the process of this application still maintains an extremely high uniformity of 1.00%, fully demonstrating the disruptive advantage of centrifugal forced dispersion technology in processing high-viscosity, easily agglomerated materials, and solving the technical bottleneck that traditional stirring processes cannot overcome.

[0093] (3) Viscosity test: Samples (approximately 1g each) were taken from three different locations (top, middle, and bottom) of the same batch of prepared membrane solution, for a total of three samples. The twist of each sample was tested, and the average and range were calculated.

[0094]

[0095] In summary, under all four formulations, the membrane solution prepared by the method of this application exhibits a consistently low viscosity range of 100-200 cP across the upper, middle, and lower positions. This indicates that the membrane solution system is highly homogeneous throughout, without precipitation or stratification. In contrast, the viscosity range of the traditional process is as high as 1700-2000 cP, indicating internal inhomogeneity and a significant concentration gradient. In particular, for formulation D, the traditional process achieves a viscosity range as high as 7500 cP when processing this high-viscosity formulation, with the bottom viscosity being 1.5 times that of the upper part, indicating severe phase separation. The process of this application, however, produces a viscosity range of only 200 cP, making it suitable for processing ultra-high viscosity materials into a homogeneous and stable system, demonstrating its unparalleled mixing and dispersion capabilities.

[0096] The above description, in conjunction with specific embodiments, provides a further detailed explanation of this application and should not be construed as limiting the specific implementation of this application to these descriptions. For those skilled in the art, several simple deductions or substitutions can be made without departing from the concept of this application.

Claims

1. A method for preparing a film liquid for use in preparing oral products, characterized in that, include: Obtain the materials to be mixed, wherein the materials to be mixed include fluid materials and solid materials; Feeding step: The materials to be mixed are placed in the material chamber of the centrifuge, wherein the material chamber includes a first chamber and a second chamber, the first chamber is used to feed the solid material, and the second chamber is used to feed the fluid material and mix the fluid material and the solid material; Centrifugation step: The material chamber is rotated and revolved to disperse the mixture in the material chamber to obtain the membrane liquid; wherein, the dihedral angle between the plane formed by the rotation of the material chamber and the plane formed by the revolving of the material chamber is 5°~45°; the solid content of the membrane liquid is 40%~70%, and the viscosity of the membrane liquid is 5000cp~50000cp.

2. The preparation method according to claim 1, characterized in that, The centrifuge device further includes a screen, which is used to divide the material chamber into a first chamber and a second chamber, and to connect the first chamber and the second chamber.

3. The preparation method according to claim 1, characterized in that, The centrifugation step includes a first stage, a second stage, and a third stage; wherein the centrifugation step satisfies at least one of the following conditions: I. In the first stage, the revolution speed is 1000rpm~1500rpm, the rotation speed is 500rpm~700rpm, and the centrifugation time is 60 seconds~120 seconds; II. In the second stage, the revolution speed is 2000rpm~2500rpm, the rotation speed is 2200rpm~2750rpm, and the centrifugation time is 180 seconds~250 seconds; III. In the third stage, the revolution speed is 1000rpm~2000rpm, the rotation speed is 1000rpm~2000rpm, and the centrifugation time is 30 seconds~50 seconds; IV. In the first stage, the ratio of the revolution speed to the rotation speed is 1:0.4~0.6; V. In the second stage, the ratio of the revolution speed to the rotation speed is 1:1.05~1.2; VI. In the third stage, the ratio of the revolution speed to the rotation speed is 1:0.9~1.

1.

4. The preparation method according to claim 3, characterized in that, In the centrifugation step, the material chamber is evacuated; wherein the evacuation process satisfies at least one of the following conditions: I. In the first stage, the vacuum level is 80 kPa to 100 kPa; II. In the second stage, the vacuum level is 8 kPa to 12 kPa; III. In the third stage, the vacuum level is 20 kPa to 30 kPa.

5. The preparation method according to claim 2, characterized in that, The mesh size of the screen is 60 to 80 mesh; And / or, the particle size of the solid material is not greater than 250 μm.

6. The preparation method according to any one of claims 1 to 5, characterized in that, The material chamber has dispersing teeth and / or dispersing beads, which are used to disperse the material to be mixed.

7. A film solution for preparing oral products, characterized in that, The membrane is prepared by the preparation method according to any one of claims 1 to 6, wherein the solid content of the membrane liquid is 40% to 70%, and the viscosity of the membrane liquid is 5000 cp to 50000 cp.

8. The membrane solution according to claim 7, characterized in that, The film solution includes at least one of the following: film-forming substrate, active ingredient, plasticizer, flavoring agent, pH adjuster, and antioxidant.

9. The membrane solution according to claim 8, characterized in that, The film-forming substrate includes at least one of the following: hydroxypropyl methylcellulose, ethylcellulose, polyoxyethylene, pullulan, sodium alginate, soluble starch, gelatin, and gelatin-porous starch complex. The active ingredient includes at least one of the following: nicotine or nicotine derivatives; The plasticizer includes at least one of the following: glycerin, sorbitol, propylene glycol, polyethylene glycol, and xylitol; The flavoring agent includes at least one of the following: aroma agent, sweetener, saltiness agent, cooling agent, and acidifier; The pH adjuster includes at least one of citric acid, lactic acid, malic acid, tartaric acid, sodium citrate, sodium lactate, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, and magnesium carbonate. The antioxidants include at least one of parabens, calcium propionate, tea polyphenols, chitosan, ascorbic acid, vitamin E, butylated hydroxytoluene, and butylated hydroxyanisole.

10. A mouth-held product, characterized in that, It includes a functional layer, wherein the functional layer is obtained by membrane liquid forming according to any one of the preparation methods of claims 1 to 6, or by membrane liquid forming according to any one of claims 7 to 9.

Images