Preparation method of nicotine product and nicotine composite material

Abstract

The invention relates to a preparation method of a nicotine product and a nicotine composite material. The nicotine product comprises at least one particle cluster, each particle cluster independently comprises a plurality of nicotine composite particles, each nicotine composite particle comprises a pellet and a nicotine active material arranged on the surface layer of the pellet, and the aggregation index of each particle cluster is independently smaller than or equal to 1. By controlling the aggregation index of each particle cluster, the concentration release uniformity of the nicotine active material can be effectively controlled.

Description

Technical Field

[0001] The present application relates to the technical field of oral products, and in particular to a method for preparing a nicotine product and a nicotine composite material. Background Art

[0002] Nicotine pouches are small bag-shaped products that contain nicotine active ingredients and other auxiliary ingredients. They are easy to use and have rich flavors. The release of nicotine active ingredients in traditional nicotine pouches is poorly controllable, and the concentration of nicotine active ingredients released is prone to poor uniformity during use, resulting in a poor consumer experience.

[0003] Therefore, it is necessary to improve the traditional technology. Summary of the invention

[0004] Based on this, the present application provides a nicotine product with better controllable release of nicotine active ingredients and a method for preparing a nicotine composite material.

[0005] The technical solution of this application to solve the above technical problems is as follows.

[0006] On the one hand, the present application provides a nicotine product, comprising at least one particle cluster, each of the particle clusters independently comprising a plurality of nicotine composite particles, each of the nicotine composite particles comprising a micropill and a nicotine active material disposed on the surface of the micropill, and the aggregation index of each of the particle clusters independently being ≤1.

[0007] In some of the embodiments, in the nicotine product, the aggregation index of each particle cluster is independently ≤0.5.

[0008] In some of the embodiments, in the nicotine product, the particle size of the micropellets is independently 200 μm to 1500 μm.

[0009] In some embodiments, in the nicotine product, the micropellets include at least one of microcrystalline cellulose micropellets and sucrose micropellets.

[0010] In some embodiments, in the nicotine product, the nicotine active material includes at least one of nicotine and a nicotine derivative.

[0011] In some of the embodiments, in the nicotine product, the mass proportion of the nicotine active material is 1% to 10%.

[0012] In some of the embodiments, in the nicotine product, the mass proportion of the micropellets is 50% to 98%.

[0013] In some embodiments, in the nicotine product, each of the nicotine composite particles further comprises a coating layer, the coating layer is disposed on the surface of the pellet, and the nicotine active material is disposed in at least one of the following ways:

[0014] (1) The nicotine active material is disposed between the micropellets and the coating layer;

[0015] (2) The nicotine active material is disposed in the coating layer;

[0016] (3) The nicotine active material is disposed on a surface of the coating layer away from the micropill.

[0017] In some of the embodiments, in the nicotine product, the ratio of the thickness of the coating layer to the particle size of the micropellets is 0.02-0.1:1.

[0018] In some embodiments, in the nicotine product, the coating layer comprises a coating material, wherein:

[0019] The coating material comprises at least one of hydroxypropyl cellulose, hydroxypropyl methyl cellulose and ethyl cellulose; and / or,

[0020] In the nicotine product, the mass proportion of the coating material is 1% to 20%.

[0021] In some embodiments, in the nicotine product, the nicotine composite particles further include additives, wherein the additives include at least one of an anti-sticking agent, a sweetener, an edible flavor, and a pH adjuster.

[0022] On the one hand, the present application provides a method for preparing nicotine composite particles, comprising the following steps:

[0023] preparing a spray solution including a nicotine active material;

[0024] The spraying solution is sprayed on the surface of at least one micro-pellet raw material to obtain nicotine-containing micro-pellets, and the nicotine-containing micro-pellets are dried to prepare the nicotine composite particles; the aggregation index of each micro-pellet raw material is ≤1.

[0025] In some of the embodiments, in the method for preparing nicotine composite particles, the spraying solution also includes a coating material, the nicotine composite particles include pellets and a coating layer disposed on the surface of the pellets, and the nicotine active material is disposed in the coating layer.

[0026] In some embodiments, the method for preparing nicotine composite particles, before the drying step and after obtaining the nicotine-containing pellets, further comprises the following steps:

[0027] A coating solution including a coating material is sprayed on the surface of the nanoparticles to form a coating layer.

[0028] In some embodiments, the method for preparing nicotine composite particles further comprises the following steps before the drying step and after the coating layer is formed:

[0029] A spraying solution including a nicotine active material is sprayed on the surface of the coating layer away from the pellets.

[0030] Compared with the prior art, the nicotine product of the present application has the following beneficial effects:

[0031] The nicotine product of the present application includes at least one particle cluster, each particle cluster includes a plurality of nicotine composite particles, the nicotine composite particles include micropills and nicotine active materials disposed on the surface of the micropills, and the concentration release uniformity of the nicotine active materials can be effectively controlled by controlling the aggregation index of each particle cluster. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] In order to more clearly illustrate the technical solutions in the embodiments of the present application and to more completely understand the present application and its beneficial effects, the following is a brief introduction to the drawings required for use in the description of the embodiments. Obviously, the drawings described below are only some embodiments of the present application. For those skilled in the art, other drawings can be obtained based on these drawings without creative work. It should also be noted that the drawings are all drawn in a simplified form and are only used to conveniently and clearly assist in explaining the present application. The various sizes of each component shown in the drawings are arbitrarily shown and may be accurate or may not be drawn according to the actual scale. For example, in order to make the illustration clearer, the size of the components is appropriately exaggerated in some places in the drawings. Unless otherwise specified, the components in the figure are not drawn to scale. This application does not limit each size of each component.

[0033] Figure 1 This is an electron microscope image of the nicotine composite particles prepared in Example 1;

[0034] Figure 2 This is an electron microscope image of the microcrystalline cellulose pellets 350 used in Example 1;

[0035] Figure 3 This is an electron microscope image of the nicotine composite particles prepared in Example 3;

[0036] Figure 4 This is an electron microscope image of the microcrystalline cellulose pellets 500 used in Example 3;

[0037] Figure 5 This is a microscope image of microcrystalline cellulose 200 used in Comparative Example 2;

[0038] Figure 6 This is a microscope image of microcrystalline cellulose 102 used in Comparative Example 1;

[0039] Figure 7 The nicotine release curves of the nicotine bags prepared in Examples 1 to 3 are shown;

[0040] Figure 8 This is a nicotine release curve of the nicotine bag prepared in Example 4;

[0041] Fig. 9 The nicotine release curves of the nicotine bags prepared in Examples 1, 5 and 6 are shown. DETAILED DESCRIPTION

[0042] The present application will be further described in detail below in conjunction with the accompanying drawings, embodiments and examples. It should be understood that these embodiments and examples are only used to illustrate the present application and are not used to limit the scope of the present application. The purpose of providing these embodiments and examples is to make the understanding of the disclosure of the present application more thorough and comprehensive. It should also be understood that the present application can be implemented in many different forms and is not limited to the embodiments and examples described herein. Those skilled in the art can make various changes or modifications without violating the connotation of the present application, and the equivalent form obtained also falls within the protection scope of the present application. For example, the features described or described as part of an embodiment can be combined in another embodiment in a suitable manner to produce a new embodiment. In addition, in the description below, a large number of specific details are given in order to provide a more comprehensive understanding of the present application. It should be understood that the present application can be implemented without one or more of these details.

[0043] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which this application belongs. The terms used herein in the specification of this application are only for the purpose of describing implementation modes and embodiments and are not intended to limit this application.

[0044] Unless otherwise specified or incompatible herewith, the terms and phrases used herein shall have the following meanings:

[0045] In the present application, "plurality", "multiple", "multiple times", etc., unless otherwise specified, refer to a quantity greater than 2 or equal to 2. For example, "one or more" means one or greater than or equal to two.

[0046] As used herein, "combination thereof", "any combination thereof", "any combination thereof" etc. include all suitable combinations of any two or more of the listed items.

[0047] Herein, the “suitable” mentioned in “suitable combination”, “suitable method”, “any suitable method”, etc., shall be based on the ability to implement the technical solution of this application, solve the technical problems of this application, and achieve the expected technical effects of this application.

[0048] Herein, "preferred", "better", "more preferred", and "suitable" are only used to describe implementation methods or examples with better effects, and it should be understood that they do not constitute a limitation on the scope of protection of this application. If multiple "preferred" items appear in a technical solution, unless otherwise specified and there is no contradiction or mutual restriction, each "preferred" item is independent.

[0049] In the present application, "further", "further", "particularly" and the like are used for descriptive purposes to indicate differences in content, but should not be construed as limiting the scope of protection of the present application.

[0050] In this application, "optionally", "optional", and "optional" mean optional or dispensable, that is, any one of the two parallel schemes of "yes" or "no". If multiple "options" appear in a technical solution, unless otherwise specified and there is no contradiction or mutual restriction, each "optional" is independent.

[0051] In the present application, the terms "first", "second", "third", "fourth", etc. in "the first aspect", "the second aspect", "the third aspect", "the fourth aspect", etc. are used only for descriptive purposes and cannot be understood as indicating or implying relative importance or quantity, nor can they be understood as implicitly indicating the importance or quantity of the indicated technical features. Moreover, "first", "second", "third", "fourth", etc. only serve the purpose of non-exhaustive enumeration and description, and it should be understood that they do not constitute a closed limitation on quantity.

[0052] In the present application, the technical features described in an open manner include closed technical solutions composed of the listed features, and also include open technical solutions containing the listed features.

[0053] In the present application, when it comes to a numerical interval (i.e., a numerical range), unless otherwise specified, the distribution of the optional numerical values ​​in the numerical interval is considered to be continuous, and includes the two numerical endpoints (i.e., the minimum value and the maximum value) of the numerical interval, and each numerical value between the two numerical endpoints. Unless otherwise specified, when the numerical interval only refers to the integers in the numerical interval, it includes the two endpoint integers of the numerical range, and each integer between the two endpoints, which is equivalent to directly listing each integer. When multiple numerical ranges are provided to describe features or characteristics, these numerical ranges can be combined. In other words, unless otherwise specified, the numerical range disclosed herein should be understood to include any and all sub-ranges included therein. The "numerical value" in the numerical interval can be any quantitative value, such as a number, a percentage, a ratio, etc. "Numerical interval" allows broadly including numerical interval types such as percentage intervals, ratio intervals, and ratio intervals.

[0054] The temperature parameters in this application, unless otherwise specified, are allowed to be either constant temperature treatment or to vary within a certain temperature range. It should be understood that the constant temperature treatment allows the temperature to fluctuate within the accuracy range controlled by the instrument. Fluctuations within the range of ±5°C, ±4°C, ±3°C, ±2°C, and ±1°C are allowed.

[0055] In this application, the term "room temperature" or "normal temperature" generally refers to 4°C to 35°C, for example, 20°C ± 5°C. In some embodiments of this application, "room temperature" or "normal temperature" refers to 10°C to 30°C. In some embodiments of this application, "room temperature" or "normal temperature" refers to 20°C to 30°C.

[0056] In this application, when referring to the unit of a data range, if there is a unit only after the right endpoint, it means that the units of the left and right endpoints are the same. For example, 3~5 h means that the units of the left endpoint "3" and the right endpoint "5" are both h (hours).

[0057] All documents mentioned in this application are cited as references in this application, just as each document is cited as reference separately. Unless they conflict with the invention purpose and / or technical solution of this application, the cited documents involved in this application are cited with all contents and all purposes. When the cited documents are involved in this application, the definitions of relevant technical features, terms, nouns, phrases, etc. in the cited documents are also cited. When the cited documents are involved in this application, the examples and preferred methods of the cited relevant technical features can also be incorporated into this application as references, but are limited to the implementation of this application. It should be understood that when the cited content conflicts with the description in this application, the present application shall prevail or be modified adaptively according to the description of this application.

[0058] The mass or weight of the relevant components mentioned in the specification of the embodiments of the present application may not only refer to the specific content of each component, but also indicate the proportional relationship of the mass or weight between the components. Therefore, as long as the content of the relevant components is proportionally enlarged or reduced according to the specification of the embodiments of the present application, it is within the scope disclosed in the specification of the embodiments of the present application. Specifically, the mass or weight described in the specification of the embodiments of the present application may be units known in the chemical industry such as μg, mg, g, and kg.

[0059] Nicotine replacement therapy

[0060] For smokers who are addicted to smoking, nicotine pouches are a nicotine replacement product. It can alleviate smokers' physiological dependence on nicotine to a certain extent. When smokers try to quit smoking or reduce their smoking, using nicotine pouches can provide a certain amount of nicotine to alleviate withdrawal reactions, such as irritability, anxiety, and inattention. For example, some smokers find that their desire for cigarettes has decreased after they start using nicotine pouches because the body can still obtain nicotine, an addictive substance.

[0061] Reducing the harm of traditional tobacco

[0062] Compared with traditional cigarettes, nicotine pouches do not involve the tobacco combustion process. The combustion of traditional cigarettes will produce thousands of harmful chemicals, including tar, carbon monoxide, polycyclic aromatic hydrocarbons and other carcinogens. During the use of nicotine pouches, there is no combustion process, so these harmful components caused by combustion will not be produced. Therefore, from this perspective, it can help users reduce the health risks caused by inhaling tobacco combustion products to a certain extent.

[0063] Ease of use

[0064] Nicotine pouches are small and easy to carry. They can be used in many situations, such as in workplaces where smoking is prohibited or in public transportation. Users can use nicotine pouches to satisfy their nicotine needs without producing smoke like smoking, which can affect the health of others or violate smoking regulations.

[0065] Satisfy oral habits

[0066] For smokers who are used to having something in their mouth, nicotine bags can satisfy this habit to a certain extent. It is placed in the mouth, similar to chewing gum or lozenges, and can provide users with a similar oral touch and habitual action when smoking, helping them gradually change their smoking behavior patterns.

[0067] That is, nicotine pouches can be used as a drug to help people quit addiction.

[0068] Traditional nicotine bag products contain powder in the bag and adopt wet granulation or fluidized bed granulation process. They have poor sustained release effect, poor controllability and reproducibility, and there is a risk of powder leakage.

[0069] An embodiment of the present application provides a nicotine product, comprising at least one particle cluster, each particle cluster independently comprising a plurality of nicotine composite particles, each nicotine composite particle comprising a pellet and a nicotine active material disposed on the surface of the pellet, and the aggregation index of each particle cluster is independently ≤1.

[0070] The nicotine product of the present application includes at least one particle cluster, each particle cluster includes a plurality of nicotine composite particles, the nicotine composite particles include micropills and nicotine active materials disposed on the surface of the micropills, and the concentration release uniformity of the nicotine active materials can be effectively controlled by controlling the aggregation index of each particle cluster.

[0071] The nicotine product of the present application can effectively control the sustained-release rate of nicotine active materials, effectively reduce the problems of oral irritation, sore throat or stomach burning caused by excessive local concentration of nicotine when used, and the sustained-release time is relatively long.

[0072] It can be understood that the Polydispersity Index (PDI) is PDI = (D90 - D10) / D50, where D10 means that 10% of the particles in the sample have a particle size smaller than this value, D50 means that 50% of the particles in the sample have a particle size smaller than this value, and D50 means that 90% of the particles in the sample have a particle size smaller than this value. The smaller the PDI value, the more concentrated the particle size distribution is and the higher the particle uniformity is.

[0073] It can also be understood that the nicotine product includes at least one particle cluster, which can be one particle cluster or two or more particle clusters, each particle cluster independently includes a plurality of nicotine composite particles, and the aggregation index of each particle cluster is independently ≤1. Among them, the aggregation index of each particle cluster independently includes but is not limited to 0.1, 0.2, 0.3, 0.4, 0.42, 0.43, 0.5, 0.6, 0.7, 0.8, 0.9, 1. In some examples, any two of these point values ​​can be used as the range of end values, the same below.

[0074] In some of these examples, the aggregation index of each particle cluster is independently ≤ 0.75.

[0075] In some of these examples, the aggregation index of each particle cluster is independently ≤ 0.5.

[0076] In some of the examples, the nicotine composite particles contain two or more particle clusters, and the aggregation index of all nicotine composite particles in the nicotine product is ≤ 2. In this way, the rate at which the nicotine active material releases the active substance can be effectively controlled.

[0077] In some of these examples, the nicotine products contain one, two, or three particle clusters.

[0078] In some of the examples, the particle sizes of the micropellets in the nicotine products are independently 200 μm to 1500 μm.

[0079] It can be understood that the particle size of the micropellets in each nicotine composite particle in the nicotine product is in the range of 200 μm to 1500 μm; further, the particle size of the micropellets independently includes but is not limited to 200 μm, 220 μm, 250 μm, 280 μm, 300 μm, 320 μm, 350 μm, 380 μm, 400 μm, 420 μm, 450 μm, 480 μm, 500 μm, 520 μm, 550 μm, 580 μm, 600 μm, 620 μm, 650 μm, 680 μm, 700 μm, 720 μm, 750 μm, 780 μm, 800 μm, 820 μm, 850 μm, 880 μm, 900 μm, 920 μm, 950 μm, 980 μm, 1000 μm, μm, 1100 μm, 1200 μm, 1300 μm, 1400 μm, 1500 μm.

[0080] In some of these examples, the particle size of the micropellets in the nicotine products is independently 200 μm to 1000 μm.

[0081] Furthermore, the particle sizes of the micropellets in the nicotine product are independently 355 μm to 1000 μm.

[0082] On the basis of controlling the aggregation index of particle clusters in nicotine products, further controlling the particle size of the microcapsules can further improve the release concentration uniformity of the nicotine active material and further control the sustained release rate of the nicotine active material.

[0083] In some of these examples, the particle size distribution range of each pellet in the nicotine product includes, but is not limited to, one of the following:

[0084] (1) The particle size distribution range of each microparticle is 200 μm~600 μm;

[0085] (2) The particle size distribution range of each microparticle is 300 μm~900 μm;

[0086] (3) The particle size distribution range of each microparticle is 400 μm~1200 μm;

[0087] (4) The particle size distribution range of each micropellet is 500 μm~1500 μm.

[0088] Furthermore, the particle size distribution range of each micro-pellet in the nicotine product includes but is not limited to one of the following:

[0089] (1) The particle size distribution range of each microparticle is 200 μm~400 μm;

[0090] (2) The particle size distribution range of each microparticle is 300 μm~600 μm;

[0091] (3) The particle size distribution range of each microparticle is 400 μm~800 μm;

[0092] (4) The particle size distribution range of each micropellet is 500 μm~1000 μm.

[0093] Furthermore, the particle size distribution range of each micro-pellet in the nicotine product includes but is not limited to one of the following:

[0094] (1) The particle size distribution range of each microparticle is 200 μm~350 μm;

[0095] (2) The particle size distribution range of each microparticle is 355 μm~500 μm;

[0096] (3) The particle size distribution range of each micropellet is 500 μm~710 μm.

[0097] In some examples, in the nicotine product, the pellets include at least one of microcrystalline cellulose pellets and sucrose pellets.

[0098] Furthermore, microcrystalline cellulose microcapsules include but are not limited to microcrystalline cellulose 200 (particle size range is 200 μm~350 μm), microcrystalline cellulose 350 (particle size range is 355 μm~500 μm), and microcrystalline cellulose 500 (particle size range is 500 μm~710 μm).

[0099] It can be understood that the microcapsules used in the present application are spherical or quasi-spherical (such as prolate spheroids), which are formed by spherical granulation of microcrystalline cellulose, have a very tight particle size distribution, can better control and improve the consistency of release rate between batches, have good reproducibility, and ensure that the product properties between different batches are relatively stable; no secondary granulation is required.

[0100] In some of the examples, in the nicotine product, the nicotine active material includes at least one of nicotine and a nicotine derivative.

[0101] It is understood that nicotine derivatives include but are not limited to at least one of nicotine salts, nicotine substitutes, salts of nicotine substitutes, etc. Nicotine substitutes include but are not limited to 6-methyl nicotine, and salts of nicotine substitutes include but are not limited to 6-methyl nicotine salts.

[0102] In some of these examples, the mass proportion of nicotine active materials in nicotine products is 1% to 10%.

[0103] It will be understood that in nicotine products, the mass proportion of nicotine active materials includes but is not limited to 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, and 10%.

[0104] In some examples, pellets account for 50% to 98% of the mass of nicotine products.

[0105] It can be understood that in nicotine products, the mass proportion of micropellets includes but is not limited to 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, and 98%.

[0106] In some of the examples, in the nicotine products, each nicotine composite particle further includes a coating layer, the particle coating layer is disposed on the surface of the particle pellet, and the nicotine active material of the particle is disposed in at least one of the following ways:

[0107] (1) The nicotine active material is disposed between the particle pellet and the particle coating layer;

[0108] (2) the particulate nicotine active material is disposed in the particle coating layer;

[0109] (3) The nicotine active material is disposed on the surface of the particle coating layer away from the particle pellets.

[0110] It can be understood that in method (1), the nicotine active material forms a continuous or discontinuous nicotine active material layer between the micro-pellets and the coating layer; in method (2), the nicotine active material and the coating material in the coating layer are mixed with each other to form a coating layer.

[0111] Furthermore, the micropill surface layer includes the micropill surface and the interior of a portion of the pore structure of the micropill.

[0112] Furthermore, in method (3), the nicotine active material is disposed on the surface of the coating layer away from the micro-pills in the form of a coating. Furthermore, the coating layer is provided with a pore structure, and the nicotine active material is disposed on the surface of the coating layer away from the micro-pills and enters into the pore structure of the coating layer.

[0113] It is understandable that the nicotine active material can be arranged in one of the above-mentioned methods (1) to (3), or in two or three ways; for example, when two of them are selected, part of the nicotine active material is arranged in one way, and the remaining nicotine active material is arranged in another way.

[0114] For example, in some of the examples, in the nicotine products, part of the nicotine active material is disposed between the microcrystalline cellulose pellets and the coating layer, and part of the nicotine active material is disposed on the surface of the coating layer away from the pellets.

[0115] The microcrystalline cellulose pellets with a coating layer will not dissolve or disintegrate, effectively reducing the possibility of gelatinization and improving user experience.

[0116] It can also be understood that the nicotine product includes at least one particle cluster, and the arrangement of the nicotine active material in the nicotine composite particles in different particle clusters can be the same or different; the arrangement of the nicotine active material in multiple nicotine composite particles in the same particle cluster can be the same or different.

[0117] In some of these examples, in nicotine products, the ratio of the coating thickness to the particle size of the pellets is 0.02~0.1:1.

[0118] It is understood that the ratio of the thickness of the coating layer to the particle size of the micropellets includes but is not limited to 0.02:1, 0.03:1, 0.04:1, 0.05:1, 0.06:1, 0.07:1, 0.08:1, 0.09:1, and 0.1:1.

[0119] In some of these examples, in the nicotine article, the coating layer includes a coating material.

[0120] In some examples, in the nicotine product, the coating material includes at least one of hydroxypropyl cellulose, hypromellose and ethyl cellulose.

[0121] In some examples, the mass proportion of coating materials in nicotine products is 1% to 20%.

[0122] It will be appreciated that the mass proportion of coating materials includes but is not limited to 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, and 20%.

[0123] In some of these examples, in the nicotine products, the coating layer is provided with a porous structure.

[0124] It can be understood that the coating layer having a porous structure can increase the release rate of the nicotine active ingredient, increase the contact area of ​​saliva therewith, and further increase the release rate; it can be selected according to needs.

[0125] In some of the examples, in the nicotine product, the nicotine composite particles further include additives, and the additives include at least one of an anti-sticking agent, a sweetener, an edible flavor, and a pH adjuster.

[0126] The nicotine product provided by the present application can slow down the taste decay rate of flavors.

[0127] In some examples, the anti-adherent agent includes, but is not limited to, at least one of talc, magnesium stearate, and glyceryl monostearate.

[0128] In some examples, the mass of the anti-adherent agent is 10% to 50% of the mass of the coating material. It is understood that the mass of the anti-adherent agent is 10%, 20%, 30%, 40% or 50% of the mass of the coating material.

[0129] In some examples, the sweetener includes but is not limited to at least one of xylitol, sorbitol, mannitol, igltol, lactitol, maltitol, isomalt, hydrogenated starch hydrolysate, erythritol, maltotriitol, aspartame, acesulfame potassium, saccharin sodium, sucralose, neotame, cyclamate, alitame, steviol glycosides, arabitol and monk fruit sweetener.

[0130] In some examples, the pH adjuster includes, but is not limited to, at least one of citric acid, sodium carbonate, and sodium bicarbonate.

[0131] In some of the examples, the nicotine product includes an osmotic bag, and the nicotine composite particles in each particle cluster are loaded into the osmotic bag to form a nicotine bag.

[0132] When the nicotine composite particles in each particle cluster are loaded into the permeation bag, the loading amount fluctuates less and can be quantified more accurately.

[0133] It is understood that the permeable bag allows saliva to pass through and prevents or inhibits the passage of nicotine composite particles. The material of the permeable bag can be any suitable food-grade material, such as woven or non-woven fabrics (e.g., cotton, fleece fabrics, etc.), heat-sealable non-woven cellulose or other polymeric materials, such as synthetic, semi-synthetic or natural polymeric materials. Suitable materials are also those that have no significant effect on the release of nicotine from the bag.

[0134] The nicotine composite particles in each particle cluster are filled into an osmotic bag and retained in the osmotic bag by sealing. An ideal osmotic bag is chemically and physically stable, pharmaceutically acceptable, insoluble in water, and easy to fill with particles and seal.

[0135] The osmotic bag can be placed in the oral cavity by the user. Saliva then enters the osmotic bag, and the nicotine and other components soluble in the saliva begin to dissolve and are transported with the saliva out of the osmotic bag and into the oral cavity, where the nicotine can be absorbed.

[0136] In some of these examples, the permeate bag comprises a fiber bag.

[0137] In some of the examples, the nicotine product further includes an outer packaging, and the nicotine bag is disposed in the outer packaging and enclosed by the outer packaging.

[0138] An embodiment of the present application provides a method for preparing nicotine composite particles, comprising the following steps:

[0139] Step S10: preparing a spray solution including a nicotine active material;

[0140] Step S20: spraying the particle spraying solution on the surface of at least one pellet raw material to obtain nicotine-containing pellets, and drying the nicotine-containing pellets to prepare granular nicotine composite particles; the aggregation index of each granular pellet raw material is ≤1.

[0141] The preparation method of the nicotine composite particles of the present application has good fluidity of the micro-pills and good uniformity of the content of the nicotine active material on the surface of the micro-pills.

[0142] It can be understood that the spray solution including the nicotine active material is disposed on the surface of the pellet raw material, and the obtained nicotine-containing pellets can be dried to obtain the above-mentioned nicotine composite particles, and the nicotine composite particles include pellets and the nicotine active material disposed on the surface of the pellets. It should be noted that the nicotine-containing pellets refer to pellets containing nicotine active materials.

[0143] In some of the examples, in step S10, the spraying solution also includes a coating material, the granular nicotine composite particles include pellets and a coating layer disposed on the surface of the granular pellets, and the granular nicotine active material is disposed in the particle coating layer.

[0144] It can be understood that the coating material is mixed with nicotine active material and solvent and other substances to prepare a first spray solution; the first spray solution is then disposed on the surface of the micro-pellet raw material, and the nicotine active material in the obtained nicotine composite particles is disposed in the coating layer.

[0145] Further, the solvent includes an organic solvent and water; further, the organic solvent includes ethanol; it can be understood that the coating material and the nicotine active material can be mixed with an organic aqueous solution, such as an ethanol aqueous solution.

[0146] Furthermore, the coating material and the solvent are first mixed to obtain a coating solution, and then the coating solution is mixed with the nicotine active material.

[0147] In some other examples, in step S20, before the particle drying step, after obtaining the particles containing Ni micro pellets, the following step S30 is also included:

[0148] The coating solution including the coating material is sprayed on the surface of the granular nanoparticles to form a coating layer.

[0149] It can be understood that in step S30, the coating solution including the coating material is sprayed on the surface of the nicotine-containing micropellets for coating to form a coating layer. At this time, the nicotine active material in the prepared nicotine composite particles is arranged between the micropellets and the coating layer, and part of the nicotine active material will enter the pore structure of the micropellets.

[0150] In some examples, the coating process includes the following steps:

[0151] The coating solution was sprayed onto the surface of the pellets.

[0152] Furthermore, the mass concentration of the coating solution used in the coating treatment is 3% to 10%.

[0153] It will be appreciated that the coating solution comprises the coating material.

[0154] In some examples, in step S30, the coating solution further includes a porogen.

[0155] Furthermore, the pore-forming agent includes but is not limited to PEG400; further, the mass of the pore-forming agent is 0-5% of the mass of the coating material.

[0156] In some examples, in step S30, the coating solution further includes a sweetener.

[0157] In some examples, in step S30, the pH value of the coating solution is 4 to 9. Further, the pH adjuster includes but is not limited to at least one of citric acid, sodium carbonate and sodium bicarbonate.

[0158] It can be understood that the present application adopts a coating method commonly used in the art for coating, such as fluidized bed coating; further, the coating process parameters include at least one of the following:

[0159] (1) Inlet air temperature: 25℃~35℃;

[0160] (2) Atomization pressure: 0.5 bar~3.0 bar;

[0161] (3) Air volume: 50 m 3 / h~140 m 3 / h;

[0162] (4) Peristaltic pump speed: 3 g / min~15 g / min.

[0163] In some examples, step S30, after the coating process and before the particle drying step, further includes the following step S40:

[0164] A spraying solution including nicotine active material is sprayed onto the surface of the particle coating layer away from the particle pellets.

[0165] It can be understood that when the spray solution including the nicotine active material is sprayed on the surface of the coating layer away from the pellets, part of the nicotine active material in the obtained nicotine composite particles is disposed between the pellets and the coating layer, and part of the nicotine active material is disposed on the surface of the coating layer away from the pellets; further, part of the nicotine active material may be disposed in the pore structure of the coating layer.

[0166] In some of the examples, in the method for preparing nicotine composite particles, after the spraying solution prepared in step S10 is disposed on the surface of the micro-pellet raw material, the method further includes the step of spraying edible flavoring.

[0167] In some examples, the method for preparing the nicotine composite material comprises the following steps:

[0168] preparing a mixed solution including a coating material;

[0169] Preparing a first spray solution including a nicotine active material, a sweetener, a pore-forming agent and an anti-adhesive agent, wherein the pH value of the first spray solution is 4 to 9;

[0170] The first spraying solution and the edible flavor are sprayed onto the surface of the micro-pellets in sequence.

[0171] In some examples, the method for preparing the nicotine composite material comprises the following steps:

[0172] preparing a coating solution comprising a coating material, a sweetener, a pore-forming agent and an anti-adhesive agent, wherein the pH value of the coating solution is 4-9;

[0173] preparing a second spray solution including a nicotine active material;

[0174] The second spraying solution and the coating solution are sprayed onto the surface of the pellet raw material in sequence.

[0175] In some examples, the method for preparing the nicotine composite material comprises the following steps:

[0176] preparing a coating solution comprising a coating material, a sweetener, a pore-forming agent and an anti-adhesive agent, wherein the pH value of the coating solution is 4-9;

[0177] preparing a second spray solution including a nicotine active material;

[0178] Spraying a portion of the second spray solution on the surface of the micro-pellet raw material to obtain first micro-pellets;

[0179] Spraying the coating solution on the surface of the first micro-pellets to obtain second micro-pellets;

[0180] The remaining second spray solution is sprayed onto the surface of the second micropellets.

[0181] The present application is further described in detail below in conjunction with specific implementation methods, but the implementation methods of the present application are not limited thereto.

[0182] The coating process parameters of each embodiment and comparative example are the same, as follows:

[0183] (1) Inlet air temperature: 25℃~35℃;

[0184] (2) Atomization pressure: 0.5 bar~3.0 bar;

[0185] (3) Air volume: 50 m 3 / h~140 m 3 / h;

[0186] (4) Peristaltic pump speed: 3 g / min~15 g / min.

[0187] Example 1

[0188] (1) Add 90% ethanol aqueous solution into a beaker, start stirring (50 rpm~1000 rpm), slowly pour the coating material (hydroxypropyl methylcellulose) into the ethanol aqueous solution until it is completely dissolved to obtain a coating solution with a mass concentration of 5%;

[0189] (2) Add nicotine, sweetener (acesulfame potassium), and pore-forming agent (polyethylene glycol 400) to the coating solution, stir (50 rpm to 1000 rpm) until completely dissolved, then add anti-adhesive (talcum powder), stir and disperse, and adjust the pH value to 4 to 9 with citric acid and sodium bicarbonate to obtain a nicotine mixed solution;

[0190] (3) Spraying the nicotine mixed solution prepared in step (2) onto the surface of micropellet powder (model: microcrystalline cellulose pellet 350, particle size range: 355 μm-500 μm, ratio of maximum particle size to minimum particle size: about 1.43:1, aggregation index of particle clusters: <0.43), controlling the coating thickness to be 5% of the particle size of the micropellet, and controlling the water content to be ≤5%;

[0191] (4) Spraying the flavor solution on the surface of the coating layer of the particles prepared in step (3) to obtain nicotine composite particles, which are then placed in a fiber bag to obtain a nicotine bag.

[0192] Among them, the preparation raw materials are calculated by mass: 90 parts of microcapsules, 5 parts of nicotine, 3 parts of coating materials, 1 part of anti-adherent agents, 0.1 parts of sweeteners, 0.5 parts of flavors, and 0.4 parts of pH adjusters.

[0193] Example 2

[0194] It is basically the same as Example 1, except that the raw materials for preparation are calculated by weight: 85 parts of micropellets, 5 parts of nicotine, 8 parts of coating materials, 1 part of anti-adherent agent, 0.1 part of sweetener, 0.5 part of flavor, and 0.4 part of pH adjuster.

[0195] Example 3

[0196] The method is basically the same as Example 1, except that the pellet powder used in Example 3 is microcrystalline cellulose pellet 500, with a particle size range of 500 μm to 710 μm, a ratio of the maximum particle size to the minimum particle size of 1.42:1, and an aggregation index of particle clusters of <0.42.

[0197] Example 4

[0198] The method is basically the same as Example 1, except that the pellet powder used in Example 4 is microcrystalline cellulose pellet 200, the particle size range is 200 μm to 350 μm, the ratio of the maximum particle size to the minimum particle size is 1.75:1, and the aggregation index of the particle cluster is less than 0.75.

[0199] Example 5

[0200] (1) Add 90% ethanol aqueous solution into a beaker, start stirring (50 rpm~1000 rpm), slowly pour the coating material (hydroxypropyl methylcellulose), pore-forming agent (polyethylene glycol 400), sweetener (acesulfame potassium) and anti-adhesive agent (talc) into the ethanol aqueous solution until they are completely dissolved, and adjust the pH value to 4~9 with citric acid and sodium bicarbonate to obtain a coating solution. The mass concentration of the coating material in the coating solution is 5%;

[0201] (2) Mix nicotine and water and stir (50 rpm~1000 rpm) until completely dissolved to obtain a nicotine solution;

[0202] (3) spraying the nicotine solution prepared in step (2) onto the surface of micropellet powder (microcrystalline cellulose pellets 350, particle size range 355 μm~500 μm, maximum particle size to minimum particle size ratio of about 1.43:1, particle cluster aggregation index <0.43);

[0203] (4) Spraying the coating solution prepared in step (1) onto the surface of the particles prepared in step (3) to form a coating layer, controlling the coating thickness to be 5% of the particle size of the micropellets and controlling the water content to be ≤5%;

[0204] (5) Spraying the flavor solution on the surface of the coating layer of the particles prepared in step (4) to obtain nicotine composite particles, which are then placed in a fiber bag to obtain a nicotine bag.

[0205] Among them, the preparation raw materials are calculated by mass: 90 parts of microcapsules, 5 parts of nicotine, 3 parts of coating materials, 1 part of anti-adherent agents, 0.1 parts of sweeteners, 0.5 parts of flavors, and 0.4 parts of pH adjusters.

[0206] Example 6

[0207] (1) Add 90% ethanol aqueous solution into a beaker, start stirring (50 rpm~1000 rpm), slowly pour the coating material (hydroxypropyl methylcellulose), pore-forming agent (polyethylene glycol 400), sweetener (acesulfame potassium) and anti-adhesive agent (talc) into the ethanol aqueous solution until they are completely dissolved, and adjust the pH value to 4~9 with citric acid and sodium bicarbonate to obtain a coating solution. The mass concentration of the coating material in the coating solution is 5%;

[0208] (2) Mix nicotine and water and stir (50 rpm~1000 rpm) until completely dissolved to obtain a nicotine solution;

[0209] (3) spraying half of the nicotine solution prepared in step (2) onto the surface of micropellet powder (microcrystalline cellulose pellets 350, particle size range 355 μm~500 μm, ratio of maximum particle size to minimum particle size of about 1.43:1, aggregation index of particle clusters <0.43);

[0210] (4) spraying the coating solution prepared in step (1) onto the surface of the particles prepared in step (3);

[0211] (5) Spraying the remaining nicotine active material solution onto the surface of the particles obtained in step (4) to obtain nicotine composite particles, which are then placed in a fiber bag to obtain a nicotine bag.

[0212] Among them, the preparation raw materials are calculated by mass: 90 parts of microcapsules, 5 parts of nicotine, 3 parts of coating materials, 1 part of anti-adherent agents, 0.1 parts of sweeteners, 0.5 parts of flavors, and 0.4 parts of pH adjusters.

[0213] Comparative Example 1

[0214] The method is basically the same as Example 1, except that the microcrystalline cellulose 102 used in Example 1 is amorphous, has a particle size range of 50 μm to 200 μm, and an aggregation index of particle clusters exceeds 1.

[0215] Comparative Example 2

[0216] The method is basically the same as Example 1, except that the microcrystalline cellulose 200 used in Comparative Example 2 is amorphous, has a particle size range of 75 μm to 500 μm, and an aggregation index of particle clusters exceeds 1.

[0217] The electron microscope image of the nicotine composite particles prepared in Example 1 is as follows: Figure 1 As shown; the electron microscope image of the microcrystalline cellulose pellets 350 used in Example 1 is as shown Figure 2 The electron microscope image of the nicotine composite particles prepared in Example 3 is shown in Figure 3 As shown; the electron microscope image of the microcrystalline cellulose pellets 500 used in Example 3 is as shown Figure 4 As shown; the microscopic image of the microcrystalline cellulose 200 used in Comparative Example 2 is as shown Figure 5 As shown; the microscopic image of the microcrystalline cellulose 102 used in Comparative Example 1 is as shown Figure 6 shown.

[0218] Dissolution curve experiment:

[0219] Equipment: Dissolution apparatus-paddle method;

[0220] Sample: nicotine pouches prepared in various embodiments and comparative examples;

[0221] Dissolution medium: pH 6.8, 900 mL;

[0222] Sampling points: 0.5min, 1min, 2min, 3min, 5min, 10min, 15min, 20min, 30min;

[0223] Test conditions: heating temperature 37℃, speed 50r / min;

[0224] Analysis method: High performance liquid chromatography was used to detect nicotine content.

[0225] The results are shown in Table 1.

[0226] Table 1

[0227]

[0228] The nicotine release curves of the nicotine bags prepared in Examples 1 to 3 are as follows: Figure 7As shown; the nicotine release curves of the nicotine bags prepared in Example 1 and Example 4 are as shown Figure 8 As shown; the nicotine release curves of the nicotine bags prepared in Example 1, Example 5 and Example 6 are as shown Fig. 9 shown.

[0229] From Table 1 and Figure 7 It can be seen that when the particle size of the pellet powder is the same, as the coating thickness increases, the dissolution rate will slow down accordingly; as the particle size of the pellet powder increases, the dissolution rate will decrease under the same coating weight gain; from Table 1 and Figure 8 It can be seen that the dissolution rate of Example 4 is slow; from Table 1 and Fig. 9 It can be seen that in Example 1, nicotine is added to the coating layer, in Example 5, nicotine is disposed in the coating layer (i.e., between the micropellets and the coating layer), and in Example 6, half of the nicotine is disposed in the coating layer and the other half is disposed outside the coating layer (i.e., on the surface of the coating layer). Under the same coating weight gain, the nicotine release rate of Example 6>Example 1>Example 4.

[0230] In Comparative Examples 1 and 2, the amorphous microcrystalline cellulose powder used has a relatively large particle size between the maximum and minimum particle sizes, and the aggregation index of the particle clusters exceeds 1, resulting in agglomeration, and the small-sized particles are adhered to the surface of the large-sized particles by the coating liquid.

[0231] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0232] The above-described embodiments only express several implementation methods of the present application, which is convenient for understanding the technical solution of the present application in detail, but it cannot be understood as limiting the scope of protection of the invention patent. It should be pointed out that for ordinary technicians in this field, without departing from the concept of the present application, several modifications and improvements can be made, which all belong to the scope of protection of the present application. It should be understood that the technical solutions obtained by those skilled in the art through logical analysis, reasoning or limited experiments on the basis of the technical solutions provided in the present application are all within the scope of protection of the claims attached to the present application. Therefore, the scope of protection of the patent of this application shall be based on the contents of the attached claims, and the description and drawings can be used to explain the contents of the claims.

Claims

1. A nicotine product, characterized in that: It comprises at least one particle cluster, each of the particle clusters independently comprises a plurality of nicotine composite particles, each of the nicotine composite particles comprises a micropill and a nicotine active material disposed on the surface of the micropill, and the aggregation index of each of the particle clusters independently is ≤1.

2. The nicotine product according to claim 1, wherein The aggregation index of each particle cluster is independently ≤0.5; and / or, The particle size of the micropellets is 200 μm to 1500 μm.

3. The nicotine product according to claim 1, wherein The micropellets include at least one of microcrystalline cellulose micropellets and sucrose micropellets; and / or, The nicotine active material includes at least one of nicotine and nicotine derivatives; and / or, In the nicotine product, the mass proportion of the nicotine active material is 1% to 10%; and / or, In the nicotine product, the mass of the micropills accounts for 50% to 98%.

4. The nicotine product according to any one of claims 1 to 3, characterized in that Each of the nicotine composite particles further comprises a coating layer, which is disposed on the surface of the pellets, and the nicotine active material is disposed in at least one of the following ways: (1) The nicotine active material is disposed between the micropellets and the coating layer; (2) The nicotine active material is disposed in the coating layer; (3) The nicotine active material is disposed on a surface of the coating layer away from the micropill.

5. The nicotine product according to claim 4, characterized in that The ratio of the thickness of the coating layer to the particle size of the micropills is 0.02-0.1:

1.

6. The nicotine product according to claim 4, wherein: The coating layer comprises a coating material, wherein: The coating material comprises at least one of hydroxypropyl cellulose, hydroxypropyl methyl cellulose and ethyl cellulose; and / or, In the nicotine product, the mass proportion of the coating material is 1% to 20%.

7. A method for preparing nicotine composite particles, characterized in that: The following steps are involved: preparing a spray solution including a nicotine active material; The spraying solution is sprayed on the surface of at least one micro-pellet raw material to obtain nicotine-containing micro-pellets, and the nicotine-containing micro-pellets are dried to prepare the nicotine composite particles; the aggregation index of each micro-pellet raw material is ≤1.

8. The preparation method according to claim 7, characterized in that: The spraying solution also includes a coating material, the nicotine composite particles include micropills and a coating layer disposed on the surface of the micropills, and the nicotine active material is disposed in the coating layer.

9. The preparation method according to claim 7, characterized in that: Before the drying step, after obtaining the nephrite-containing pellets, the method further comprises the following steps: A coating solution including a coating material is sprayed on the surface of the nanoparticles to form a coating layer.

10. The preparation method according to claim 9, characterized in that: Before the drying step and after forming the coating layer, the method further comprises the following steps: A spraying solution including a nicotine active material is sprayed on the surface of the coating layer away from the pellets.

Images