Nicotine product and preparation method for nicotine composite particles

Abstract

The present application relates to a nicotine product and a preparation method for nicotine composite particles. 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 provided on the surface layer of the pellet. The polydispersity index of each particle cluster is independently less than and equal to 1.

Description

Preparation methods of nicotine products and nicotine compound particles

[0001] Related applications

[0002] This application claims priority to Chinese patent application filed on January 22, 2025, application number 202510105672.7, entitled "Preparation method of nicotine articles and nicotine composite materials", the entire contents of which are incorporated herein by reference. Technical Field

[0003] This application relates to the field of oral products technology, and in particular to a nicotine product and a method for preparing nicotine compound particles. Background Technology

[0004] Nicotine pouches are small, pouch-shaped products containing nicotine active ingredients and other auxiliary ingredients. They are convenient to use and offer a variety of flavors. However, traditional nicotine pouches have poor control over the release of nicotine active ingredients, resulting in inconsistent nicotine concentrations and a poor consumer experience.

[0005] Therefore, it is necessary to improve traditional technologies. Summary of the Invention

[0006] Based on this, this application provides a nicotine product with good controllability of nicotine active ingredient release and a method for preparing nicotine composite particles.

[0007] The technical solution to the above-mentioned technical problems in this application is as follows.

[0008] This application provides a nicotine product comprising at least one particle cluster, each particle cluster independently comprising multiple nicotine composite particles, each nicotine composite particle comprising microspheres and a nicotine active material disposed on the surface of the microspheres, and the aggregation degree index of each particle cluster independently ≤1.

[0009] In some embodiments, in the nicotine product, the aggregation index of each of the particle clusters is independently ≤0.5.

[0010] In some embodiments, the microspheres in the nicotine product have a particle size of 200 μm to 1500 μm, respectively.

[0011] In some embodiments, the microspheres in the nicotine product include at least one of microcrystalline cellulose microspheres and sucrose microspheres.

[0012] In some embodiments, the nicotine active material in the nicotine product includes at least one of nicotine and nicotine derivatives.

[0013] In some embodiments, the nicotine active material accounts for 1% to 10% of the mass of the nicotine product.

[0014] In some embodiments, the microspheres comprise 50% to 98% of the nicotine product by mass.

[0015] In some embodiments, the nicotine product further includes a coating layer on the surface of the microspheres, wherein the nicotine active material is disposed in at least one of the following ways:

[0016] (1) The nicotine active material is disposed between the microspheres and the coating layer;

[0017] (2) The nicotine active material is disposed in the coating layer;

[0018] (3) The nicotine active material is disposed on the surface of the coating layer away from the microparticles.

[0019] In some embodiments, in the nicotine product, the ratio of the thickness of the coating layer to the particle size of the microspheres is 0.02 to 0.1:1.

[0020] In some embodiments, the coating layer in a nicotine product comprises a coating material.

[0021] In some embodiments, the coating material in the nicotine product includes at least one of hydroxypropyl cellulose, hydroxypropyl methylcellulose, and ethyl cellulose.

[0022] In some embodiments, the coating material accounts for 1% to 20% of the mass of the nicotine product.

[0023] In some embodiments, the nicotine compound particles in the nicotine product further include additives, the additives including at least one of an anti-sticking agent, a sweetener, an edible flavoring, and a pH adjuster.

[0024] This application provides a method for preparing nicotine complex particles, comprising the following steps:

[0025] Preparation of a spraying solution containing nicotine-active materials;

[0026] The spraying solution is sprayed onto the surface of at least one micro-particle raw material to obtain nicotine-containing micro-particles, and the nicotine-containing micro-particles are dried to prepare the nicotine composite particles; the aggregation degree index of each micro-particle raw material is ≤1.

[0027] In some embodiments, in the method for preparing nicotine composite particles, the spraying solution further includes a coating material, the nicotine composite particles include microspheres and a coating layer disposed on the surface of the microspheres, and the nicotine active material is disposed in the coating layer.

[0028] In some embodiments, the method for preparing nicotine complex particles, before the drying step and after obtaining the nicotine-containing microspheres, further includes the following step:

[0029] A coating solution, including coating material, is sprayed onto the surface of the nitrocellulose-containing pellets to form a coating layer.

[0030] In some embodiments, the method for preparing nicotine complex particles, before the drying step and after forming the coating layer, further includes the following steps:

[0031] A spray solution containing nicotine active material is sprayed onto the surface of the coating layer away from the microparticles.

[0032] Compared with the prior art, the nicotine product of this application has the following beneficial effects:

[0033] The nicotine product of this application includes at least one particle cluster, each particle cluster including multiple nicotine composite particles, the nicotine composite particles including microspheres and nicotine active material disposed on the surface of the microspheres, and by controlling the aggregation index of each particle cluster, the uniformity of the concentration release of nicotine active material can be effectively controlled. Attached Figure Description

[0034] Figure 1 is an electron microscope image of the nicotine composite particles prepared in Example 1;

[0035] Figure 2 is an electron microscope image of the microcrystalline cellulose pellets 350 used in Example 1;

[0036] Figure 3 is an electron microscope image of the nicotine composite particles prepared in Example 3;

[0037] Figure 4 is an electron microscope image of the microcrystalline cellulose pellets 500 used in Example 3;

[0038] Figure 5 is a microscope image of the microcrystalline cellulose 200 used in Comparative Example 2;

[0039] Figure 6 is a microscope image of the microcrystalline cellulose 102 used in Comparative Example 1;

[0040] Figure 7 shows the nicotine release curves of the nicotine bags prepared in Examples 1 to 3;

[0041] Figure 8 is a nicotine release curve of the nicotine bag prepared in Example 4;

[0042] Figure 9 shows the nicotine release curves of the nicotine bags prepared in Examples 1, 5 and 6. Detailed Implementation

[0043] The present application will be further described in detail below with reference to the accompanying drawings, embodiments, and examples. It should be understood that these embodiments and examples are for illustrative purposes only and are not intended to limit the scope of the present application. The purpose of providing these embodiments and examples is to enable a more thorough and comprehensive understanding of the disclosure of the present application. 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 modifications or alterations without departing from the spirit of the present application, and the equivalent forms obtained also fall within the protection scope of the present application. For example, features described or described as part of one embodiment can be combined in a suitable manner in another embodiment to produce new embodiments. Furthermore, numerous specific details are set forth in the following description to provide a fuller understanding of the present application. It should be understood that the present application can be implemented without one or more of these details.

[0044] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used herein in the specification of this application is for descriptive purposes only and is not intended to be limiting of the application.

[0045] Unless otherwise stated or in case of contradiction, the terms or phrases used herein shall have the following meanings:

[0046] In this application, the terms "multiple", "various", "multiple times", etc., unless otherwise specified, refer to a quantity greater than or equal to 2. For example, "one or more" means one, or more than or equal to two.

[0047] The terms “combinations of,” “any combination of,” and “any combination of” used in this article include all suitable combinations of any two or more of the listed items.

[0048] In this document, the term "suitable" as used in "suitable combination", "suitable method", "any suitable method", etc., refers to the ability to implement the technical solution of this application, solve the technical problem of this application, and achieve the expected technical effect of this application.

[0049] In this document, terms such as "preferred," "better," "more suitable," and "ideal" are merely descriptions of more effective implementation methods or embodiments, and should be understood not to limit the scope of protection of this application. If multiple "preferred" terms appear in a technical solution, unless otherwise specified and there are no contradictions or mutual constraints, each "preferred" term shall be independent.

[0050] In this application, terms such as "further," "even further," and "particularly" are used to describe purposes and indicate differences in content, but should not be construed as limiting the scope of protection of this application.

[0051] In this application, "optionally," "optionally," and "optional" mean that something is optional, that is, it means that it is selected from either "with" or "without." If there are multiple "optional" entries in a technical solution, unless otherwise specified, and there are no contradictions or mutual constraints, each "optional" entry shall be independent.

[0052] In this application, the terms "first aspect," "second aspect," "third aspect," "fourth aspect," etc., are used for descriptive purposes only and should not be construed as indicating or implying relative importance or quantity, nor should they be construed as implicitly indicating the importance or quantity of the indicated technical features. Moreover, "first," "second," "third," "fourth," etc., serve only as a non-exhaustive enumeration and should be understood not to constitute a closed limitation on quantity.

[0053] In this application, the technical features described in an open-ended manner include both closed technical solutions consisting of the listed features and open technical solutions that include the listed features.

[0054] In this application, when numerical intervals (i.e., numerical ranges) are involved, unless otherwise specified, the distribution of selectable numerical values ​​within the numerical interval is considered continuous, and includes the two endpoints of the numerical interval (i.e., the minimum and maximum values), as well as every numerical value between these two endpoints. Unless otherwise specified, when a numerical interval refers only to integers within that numerical interval, it includes the two endpoint integers of the numerical range, as well as every integer between the two endpoints, which is equivalent to directly listing every integer. When multiple numerical ranges are provided to describe features or characteristics, these numerical ranges can be merged. In other words, unless otherwise specified, the numerical ranges disclosed herein should be understood to include any and all subranges included therein. The "numerical value" in the numerical interval can be any quantitative value, such as a number, percentage, ratio, etc. The term "numerical interval" can be broadly included to include numerical interval types such as percentage intervals, ratio intervals, and proportion intervals.

[0055] Unless otherwise specified, the temperature parameters in this application are permitted to be either constant-temperature treatment or variations within a certain temperature range. It should be understood that the constant-temperature treatment allows temperature fluctuations within the precision range of the instrument control, such as ±5℃, ±4℃, ±3℃, ±2℃, or ±1℃.

[0056] In this application, the terms "room temperature" or "normal temperature" generally refer to 4℃ to 35℃, for example, 20℃ ± 5℃. In some embodiments of this application, "room temperature" or "normal temperature" refers to 10℃ to 30℃. In some embodiments of this application, "room temperature" or "normal temperature" refers to 20℃ to 30℃.

[0057] In this application, if the unit of a data range is only followed by the right endpoint, it indicates that the units of the left and right endpoints are the same. For example, 3~5h means that the units of the left endpoint "3" and the right endpoint "5" are both h (hours).

[0058] The mass or weight of the relevant components mentioned in the embodiments of this application can refer not only to the specific content of each component, but also to the proportional relationship of mass or weight between the components. Therefore, any scaling up or down of the content of the relevant components according to the embodiments of this application is within the scope disclosed in the embodiments of this application. Specifically, the mass or weight mentioned in the embodiments of this application can be units known in the chemical industry, such as μg, mg, g, and kg.

[0059] Nicotine replacement

[0060] For smokers, nicotine pouches serve as a nicotine replacement product. They can alleviate a smoker's physiological dependence on nicotine to some extent. When smokers attempt to quit or reduce their smoking, using a nicotine pouch can provide a certain amount of nicotine to reduce withdrawal symptoms such as irritability, anxiety, and difficulty concentrating. For example, some smokers find their cravings for cigarettes decrease after starting to use nicotine pouches, even though their bodies can still obtain the addictive substance nicotine.

[0061] Reduce harm from traditional tobacco

[0062] Unlike traditional cigarettes, nicotine pouches do not involve the combustion of tobacco. The combustion of traditional cigarettes produces thousands of harmful chemicals, including tar, carbon monoxide, and carcinogens such as polycyclic aromatic hydrocarbons. Since nicotine pouches do not involve combustion, they do not produce these harmful byproducts of tobacco combustion. Therefore, from this perspective, they can help users reduce the health risks associated with inhaling tobacco combustion products to some extent.

[0063] Ease of use

[0064] Nicotine pouches are small and portable. They can be used in many situations, such as in workplaces where smoking is prohibited or on public transportation. Users can satisfy their nicotine cravings by using nicotine pouches without producing smoke like cigarettes, thus avoiding the health risks to others or violating smoking bans.

[0065] Satisfy oral habits

[0066] For smokers who are accustomed to having something in their mouth, nicotine pouches can satisfy this habit to some extent. Placed inside the mouth, similar to chewing gum or a lozenge, they provide a similar tactile sensation and habitual action to smoking, helping them gradually change their smoking behavior.

[0067] Nicotine bags can be used as a drug to help people overcome addiction.

[0068] Traditional nicotine pouch products contain powder and are produced using wet granulation or fluidized bed granulation processes. These processes result in poor sustained-release effects, poor controllability and reproducibility, and a risk of powder leakage.

[0069] One embodiment of this application provides a nicotine product comprising at least one particle cluster, each particle cluster independently comprising multiple nicotine composite particles, each nicotine composite particle comprising microspheres and nicotine active material disposed on the surface of the microspheres, and the aggregation degree index of each particle cluster independently ≤1.

[0070] The nicotine product of this application includes at least one particle cluster, each particle cluster including multiple nicotine composite particles, the nicotine composite particles including microspheres and nicotine active material disposed on the surface of the microspheres, and by controlling the aggregation index of each particle cluster, the uniformity of the concentration release of nicotine active material can be effectively controlled.

[0071] The nicotine product of this application can effectively control the sustained release rate of nicotine active materials, effectively reduce the problems of oral irritation, throat burning or stomach burning caused by excessive local concentration of nicotine during use, and has a long sustained release time.

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

[0073] It can also be understood that nicotine products include at least one particle cluster, which can be one particle cluster or two or more particle clusters. Each particle cluster independently includes multiple nicotine composite particles, and the aggregation index of each particle cluster is independently ≤1. The aggregation index of each particle cluster is independently, but 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, and 1. In some examples, it can be any two of these point values ​​forming a range.

[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 examples, nicotine products contain two or more types of particle clusters, and the aggregation index of all nicotine composite particles in the nicotine product is ≤2. This effectively controls the rate at which the nicotine active material releases its active substances.

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

[0078] In some of these examples, the particle size of the microspheres in the nicotine products ranges independently from 200 μm to 1500 μm.

[0079] It is understood that the particle size of the microspheres in each nicotine complex particle in nicotine products is in the range of 200μm to 1500μm; furthermore, the particle size of the microspheres is independently including but not limited to 200μm, 220μm, 250μm, 280μm, 300μm, 320μm, 350μm, 380μm, 400μm, 420μm, 450μm, 480μm, 500μm, 520μm, etc. 550μm, 580μm, 600μm, 620μm, 650μm, 680μm, 700μm, 720μm, 750μm, 780μm, 800μm, 820μm, 850μm, 880μm, 900μm, 920μm, 950μm, 980μm, 1000μm, 1100μm, 1200μm, 1300μm, 1400μm, 1500μm. In some examples, any two of these point values ​​can be used as endpoints within a range.

[0080] In some of these examples, the particle size of the microspheres in the nicotine product is independently between 200 μm and 1000 μm.

[0081] Furthermore, the particle size of the microspheres in the nicotine products is independently 355μm to 1000μm.

[0082] By controlling the aggregation index of particle clusters in nicotine products, further controlling the particle size of microspheres can further improve the uniformity of the release concentration of nicotine active materials and further control the sustained release rate of nicotine active materials.

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

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

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

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

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

[0088] Furthermore, the particle size distribution range of each microsphere in nicotine products includes, but is not limited to, one of the following:

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

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

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

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

[0093] Furthermore, the particle size distribution range of each microsphere in nicotine products includes, but is not limited to, one of the following:

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

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

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

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

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

[0099] It is understood that the microspheres used in this application are spherical or near-spherical (such as elongated spheres) and are formed by spheroidizing microcrystalline cellulose. They have a very dense particle size distribution, which can better control and improve the consistency of release rate between batches, have good reproducibility, and ensure that the product properties are relatively stable between different batches; no secondary granulation is required.

[0100] In some of these examples, the nicotine active material in nicotine products includes at least one of nicotine and nicotine derivatives.

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

[0102] In some of these examples, the nicotine active material accounts for 1% to 10% of the mass of the nicotine product.

[0103] It is understood that the mass percentage of nicotine active material in nicotine products includes, but is not limited to, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, and 10%. In some examples, any two of these point values ​​can be used as endpoints within a range.

[0104] In some of these examples, microcapsules comprise 50% to 98% of the mass of nicotine products.

[0105] It is understood that the mass percentage of microspheres in nicotine products 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%. In some examples, any two of these point values ​​can be used as endpoints within a range.

[0106] In some examples, the nicotine products further include a coating layer on each nicotine composite particle, the coating layer being disposed on the surface of the microparticles, and the arrangement of the nicotine active material is selected from at least one of the following methods:

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

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

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

[0110] It is understood that in method (1), the nicotine active material forms a continuous or discontinuous nicotine active material layer between the microparticle and the coating layer; in method (2), the nicotine active material and the coating material in the coating layer are mixed to form the coating layer.

[0111] Furthermore, the microsphere surface includes both the surface of the microsphere and the interior of some of its porous structures.

[0112] Furthermore, in method (3), the nicotine active material is disposed on the surface of the coating layer away from the microparticles in a coating form. Furthermore, the coating layer has a porous structure, and the nicotine active material is disposed on the surface of the coating layer away from the microparticles and enters the porous structure of the coating layer.

[0113] It is understandable that the nicotine active material can be set in one of the above methods (1) to (3), or two or three methods can be used; for example, when two of them are used, some of the nicotine active materials are set in one method, and the remaining nicotine active materials are set in another method.

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

[0115] Microcrystalline cellulose pellets with a coating layer prevent the microcrystalline cellulose from dissolving or disintegrating, effectively reducing the possibility of gelatinization and improving the user experience.

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

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

[0118] It is understood that the ratio of the coating thickness to the particle size of the microspheres 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, the coating layer in nicotine products includes a coating material.

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

[0121] In some of these examples, the coating material accounts for 1% to 20% of the mass of nicotine products.

[0122] It is understood that the mass percentage of the coating material 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%. In some examples, any two of these point values ​​can be used as endpoints within a range.

[0123] In some of these examples, the coating layer of nicotine products has a porous structure.

[0124] It is understandable that the porous structure of the coating layer can increase the release rate of the active ingredient in nicotine and increase the contact area between saliva and the coating, thereby increasing the release rate; this can be selected as needed.

[0125] In some of these examples, the nicotine compound particles in the nicotine product also include additives, including at least one of anti-sticking agents, sweeteners, flavorings, and pH adjusters.

[0126] The nicotine products provided in this application can slow down the rate at which the flavor of the flavor fades.

[0127] In some of these examples, the anti-adhesive 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-adhesive is 10% to 50% of the mass of the coating material. It can be understood that the mass of the anti-adhesive is 10%, 20%, 30%, 40%, or 50% of the mass of the coating material, etc. In some examples, it can be a range formed by any two of these point values ​​as endpoints.

[0129] In some of these examples, the sweeteners include, but are not limited to, at least one of xylitol, sorbitol, mannitol, yigerol, lactitol, maltitol, isomaltitol, hydrogenated starch hydrolysate, erythritol, maltotriol, aspartame, acesulfame potassium, sodium saccharin, sucralose, neotame, cyclamate, alitane, steviol glycosides, arabinitol, and monk fruit sweetener.

[0130] In some of these 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 these examples, nicotine products include permeation bags, in which nicotine composite particles from various particle clusters are filled to form nicotine bags.

[0132] When the nicotine compound particles in each particle cluster are loaded into the permeation bag, the filling volume fluctuates less, allowing for more precise quantification.

[0133] As understood, permeation bags allow saliva to pass through while preventing or inhibiting the passage of nicotine complex particles. The material of the permeation bag can be any suitable food-grade material, such as woven or nonwoven fabrics (e.g., cotton, fleece, etc.), heat-sealable nonwoven cellulose, or other polymeric materials, such as synthetic, semi-synthetic, or natural polymers. Suitable materials are also those that do not significantly affect the release of nicotine from the bag.

[0134] The nicotine complex particles from each particle cluster are filled into a permeation bag and held in place by sealing. Ideally, the permeation bag is chemically and physically stable, pharmaceutically acceptable, insoluble in water, and easy to fill with particles and seal.

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

[0136] In some of these examples, the permeable bag includes a fiber bag.

[0137] In some of these examples, the nicotine product also includes outer packaging, with the aforementioned nicotine bag located within and sealed by the outer packaging.

[0138] One embodiment of this application provides a method for preparing nicotine complex particles, comprising the following steps:

[0139] Step S10: Prepare a spraying solution containing nicotine active material;

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

[0141] The method for preparing nicotine composite particles in this application results in microspheres with good flowability and good uniformity of nicotine active material content on the surface of the microspheres.

[0142] It is understood that by applying a spray solution containing nicotine active materials to the surface of microsphere raw materials, the resulting nicotine-containing microspheres can be dried to obtain the aforementioned nicotine composite particles. These nicotine composite particles include microspheres and nicotine active materials disposed on the surface of the microspheres. It should be noted that "nicotine-containing microspheres" refers to microspheres containing nicotine active materials.

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

[0144] It is understandable that the coating material is mixed with nicotine active material and solvent to prepare the first spray solution; then the first spray solution is applied to the surface of the micro-particle raw material, and the nicotine active material in the nicotine composite particles obtained at this time is located in the coating layer.

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

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

[0147] In other examples, step S20, prior to the particle drying step and after obtaining the nitroglycerin-containing pellets, further includes the following step S30:

[0148] A coating solution, including coating materials, is sprayed onto the surface of granules containing microparticles to form a coating layer.

[0149] It is understood that in step S30, a coating solution including coating material is sprayed onto the surface of the nicotine-containing microspheres to form a coating layer. At this time, the nicotine active material in the nicotine composite particles is located between the microspheres and the coating layer, and some of the nicotine active material will enter the pore structure of the microspheres.

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

[0151] The coating solution is sprayed onto the surface of the microspheres.

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

[0153] It is understandable that coating solutions include coating materials.

[0154] In some of these examples, in step S30, the coating solution also includes a pore-forming agent.

[0155] Furthermore, the porogen includes, but is not limited to, PEG400; furthermore, the mass of the porogen is 0-5% of the mass of the coating material.

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

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

[0158] It is understood that this application employs coating methods commonly used in the art, such as fluidized bed coating; furthermore, 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 to 3.0 bar;

[0161] (3) Air volume: 50m³ 3 / h~140m 3 / h;

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

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

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

[0165] It is understood that when a spray solution containing nicotine active material is sprayed onto the surface of the coating layer away from the microparticles, some of the nicotine active material in the resulting nicotine composite particles is located between the microparticles and the coating layer, while some of the nicotine active material is located on the surface of the coating layer away from the microparticles; furthermore, some of the nicotine active material may be located in the pore structure of the coating layer.

[0166] In some examples, the method for preparing nicotine compound particles includes a step of spraying edible flavoring after the spraying solution prepared in step S10 is applied to the surface of the micro-particle raw material.

[0167] In some of these examples, the preparation method of nicotine complex particles includes the following steps:

[0168] Prepare a mixed solution including the coating material;

[0169] A first spray solution comprising nicotine active material, sweetener, pore-forming agent and anti-adhesion agent is prepared, wherein the pH value of the first spray solution is 4 to 9;

[0170] The first spraying solution and the food flavoring were sprayed onto the surface of the micro-pellets in sequence.

[0171] In some of these examples, the preparation method of nicotine complex particles includes the following steps:

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

[0173] Preparation of a second spraying solution comprising nicotine-active materials;

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

[0175] In some of these examples, the preparation method of nicotine complex particles includes the following steps:

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

[0177] Preparation of a second spraying solution comprising nicotine-active materials;

[0178] A portion of the second coating solution is sprayed onto the surface of the micro-pellet material to obtain the first micro-pellet.

[0179] The coating solution was sprayed onto the surface of the first microcapsule to obtain the second microcapsule;

[0180] The remaining second coating solution is sprayed onto the surface of the second micro-particles.

[0181] The present application will be described in further detail below with reference to specific embodiments, but the embodiments of the present application are not limited thereto.

[0182] The coating process parameters are the same for all embodiments and comparative examples, as follows:

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

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

[0185] (3) Air volume: 50m³ 3 / h~140m 3 / h;

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

[0187] Example 1

[0188] (1) Add a 90% ethanol aqueous solution to a beaker, turn on the stirrer (50 rpm to 1000 rpm), and 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 and stir (50 rpm to 1000 rpm) until completely dissolved. Then add anti-adhesion agent (talc), stir to disperse, and adjust the pH value to 4 to 9 with citric acid and sodium bicarbonate to obtain a nicotine mixed solution.

[0190] (3) Spray the nicotine mixed solution obtained in step (2) onto the surface of micro pellet powder (model is microcrystalline cellulose pellet 350, particle size range is 355μm~500μm, the ratio of the maximum particle size to the minimum particle size is about 1.43:1, and the aggregation index of the particle cluster is <0.43), control the coating thickness to be 5% of the micro pellet particle size, and control the water content to be ≤5%;

[0191] (4) Spray the fragrance solution onto the surface of the coating layer of the granules prepared in step (3) to obtain nicotine composite granules, and pack them into fiber bags to obtain nicotine bags.

[0192] The raw materials used in the preparation, by mass, consist of 90 parts microcapsules, 5 parts nicotine, 3 parts coating material, 1 part anti-sticking agent, 0.1 parts sweetener, 0.5 parts flavoring, and 0.4 parts pH adjuster.

[0193] Example 2

[0194] The preparation method is basically the same as Example 1, except that the raw materials are prepared in the following proportions by weight: 85 parts microcapsules, 5 parts nicotine, 8 parts coating material, 1 part anti-sticking agent, 0.1 parts sweetener, 0.5 parts flavoring, and 0.4 parts pH adjuster.

[0195] Example 3

[0196] The results are basically the same as in Example 1, except that the microparticles used in Example 3 are microcrystalline cellulose pellets 500 with a particle size range of 500 μm to 710 μm, a maximum particle size to minimum particle size ratio of 1.42:1, and a particle cluster aggregation index of <0.42.

[0197] Example 4

[0198] The results are basically the same as in Example 1, except that the microparticles used in Example 4 are microcrystalline cellulose pellets 200 with a particle size range of 200μm to 350μm, a maximum particle size to minimum particle size ratio of 1.75:1, and a particle cluster aggregation index of <0.75.

[0199] Example 5

[0200] (1) Add a 90% ethanol aqueous solution to a beaker and start stirring (50 rpm to 1000 rpm). Slowly pour the coating material (hydroxypropyl methylcellulose), pore-forming agent (polyethylene glycol 400), sweetener (acesulfame potassium), and anti-sticking agent (talc) into the ethanol aqueous solution until completely dissolved. Adjust the pH value to 4 to 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 to 1000 rpm) until completely dissolved to obtain a nicotine solution;

[0202] (3) Spray the nicotine solution obtained in step (2) onto the surface of micro pellet powder (microcrystalline cellulose pellets 350, with a particle size range of 355μm to 500μm, a ratio of the maximum particle size to the minimum particle size of about 1.43:1, and an aggregation index of particle clusters < 0.43).

[0203] (4) Spray the coating solution obtained in step (1) onto the surface of the particles obtained in step (3) to form a coating layer, control the coating thickness to be 5% of the micro-particle size, and control the water content to be ≤5%.

[0204] (5) Spray the fragrance solution onto the surface of the coating layer of the granules prepared in step (4) to obtain nicotine composite granules, and pack them into fiber bags to obtain nicotine bags.

[0205] The raw materials used in the preparation, by mass, consist of 90 parts microcapsules, 5 parts nicotine, 3 parts coating material, 1 part anti-sticking agent, 0.1 parts sweetener, 0.5 parts flavoring, and 0.4 parts pH adjuster.

[0206] Example 6

[0207] (1) Add a 90% ethanol aqueous solution to a beaker and start stirring (50 rpm to 1000 rpm). Slowly pour the coating material (hydroxypropyl methylcellulose), pore-forming agent (polyethylene glycol 400), sweetener (acesulfame potassium), and anti-sticking agent (talc) into the ethanol aqueous solution until completely dissolved. Adjust the pH value to 4 to 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 to 1000 rpm) until completely dissolved to obtain a nicotine solution;

[0209] (3) Spray half of the nicotine solution obtained in step (2) onto the surface of micro pellet powder (microcrystalline cellulose pellets 350, with a particle size range of 355μm to 500μm, a ratio of the maximum particle size to the minimum particle size of about 1.43:1, and an aggregation index of particle clusters < 0.43).

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

[0211] (5) Spray the remaining nicotine active material solution onto the surface of the particles obtained in step (4) to obtain nicotine composite particles, and put them into a fiber bag to obtain a nicotine bag.

[0212] The raw materials used in the preparation, by mass, consist of 90 parts microcapsules, 5 parts nicotine, 3 parts coating material, 1 part anti-sticking agent, 0.1 parts sweetener, 0.5 parts flavoring, and 0.4 parts pH adjuster.

[0213] Comparative Example 1

[0214] The results are basically the same as in Example 1, except that the microcrystalline cellulose 102 used in Comparative Example 1 is amorphous with a particle size range of 50 μm to 200 μm and an aggregation index of more than 1.

[0215] Comparative Example 2

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

[0217] The electron microscope (EM) images of the nicotine composite particles prepared in Example 1 are shown in Figure 1; the EEM image of the microcrystalline cellulose pellets 350 used in Example 1 is shown in Figure 2; the EEM image of the nicotine composite particles prepared in Example 3 is shown in Figure 3; the EEM image of the microcrystalline cellulose pellets 500 used in Example 3 is shown in Figure 4; the microscopic image of the microcrystalline cellulose 200 used in Comparative Example 2 is shown in Figure 5; and the microscopic image of the microcrystalline cellulose 102 used in Comparative Example 1 is shown in Figure 6.

[0218] Dissolution curve experiment:

[0219] Equipment: Dissolution apparatus - paddle method;

[0220] Samples: Nicotine bags prepared in each example and comparative example;

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

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

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

[0224] Analytical method: Nicotine content was determined by high performance liquid chromatography.

[0225] The results are shown in Table 1.

[0226] Table 1

[0227] The nicotine release curves of the nicotine bags prepared in Examples 1 to 3 are shown in Figure 7; the nicotine release curves of the nicotine bags prepared in Examples 1 and 4 are shown in Figure 8; and the nicotine release curves of the nicotine bags prepared in Examples 1, 5, and 6 are shown in Figure 9.

[0228] As shown in Table 1 and Figure 7, when the particle size of the microparticles used is the same, the dissolution rate will decrease accordingly as the coating thickness increases; as the particle size of the microparticles increases, the dissolution rate will decrease for the same coating weight gain; as shown in Table 1 and Figure 8, the dissolution rate of Example 4 is slower; as shown in Table 1 and Figure 9, when nicotine is added to the coating layer in Example 1, nicotine is placed inside the coating layer (i.e., between the microparticles and the coating layer) in Example 5, and half of the nicotine is placed inside the coating layer and the other half is placed outside the coating layer (i.e., on the surface of the coating layer) in Example 6, the nicotine release rate is Example 6 > Example 1 > Example 4 for the same coating weight gain.

[0229] In contrast, Comparative Examples 1 and 2 used amorphous microcrystalline cellulose powder with a large particle size ratio between the maximum and minimum particle sizes. The aggregation index of the particle clusters exceeded 1, resulting in agglomeration and clumping. Small-diameter particles were adhered to the surface of large-diameter particles by the coating liquid.

[0230] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above 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.

[0231] The embodiments described above are merely illustrative of several implementation methods of this application, intended to facilitate a detailed understanding of the technical solutions of this application, but should not be construed as limiting the scope of protection of the invention patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these all fall within the scope of protection of this application. It should be understood that technical solutions obtained by those skilled in the art based on the technical solutions provided in this application through logical analysis, reasoning, or limited experimentation are all within the scope of protection of the appended claims. Therefore, the scope of protection of this patent application should be determined by the content of the appended claims, and the specification and drawings can be used to interpret the content of the claims.

Claims

1. 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 microspheres and a nicotine active material disposed on the surface of the microspheres, and each particle cluster having an aggregation index ≤1.

2. The nicotine product as claimed in claim 1, wherein, The aggregation index of each particle cluster is independently ≤0.

5.

3. The nicotine product according to any one of claims 1 to 2, wherein, The nicotine product contains two or more of the aforementioned particle clusters, and the aggregation index of all nicotine composite particles in the nicotine product is ≤2.

4. The nicotine product according to any one of claims 1 to 3, wherein, The particle size of the microspheres is 200 μm to 1500 μm.

5. The nicotine article of any one of claims 1 to 4, wherein, The particle size of the microspheres is 355 μm to 1000 μm.

6. The nicotine article of any one of claims 1 to 5, wherein, The microspheres include at least one of microcrystalline cellulose microspheres and sucrose microspheres.

7. The nicotine article of any one of claims 1 to 6, wherein, The nicotine active material includes at least one of nicotine and nicotine derivatives.

8. The nicotine article according to any one of claims 1 to 7, wherein, In the nicotine product, the nicotine active material accounts for 1% to 10% of the total mass.

9. The nicotine article according to any one of claims 1 to 8, wherein, In the nicotine product, the microcapsules account for 50% to 98% of the total mass.

10. The nicotine article according to any one of claims 1 to 9, wherein, Each of the nicotine composite particles further includes a coating layer, which is disposed on the surface of the microparticles, and the nicotine active material is disposed in a manner selected from at least one of the following: (1) The nicotine active material is disposed between the microspheres and the coating layer; (2) The nicotine active material is disposed in the coating layer; (3) The nicotine active material is disposed on the surface of the coating layer away from the microparticles.

11. The nicotine article of claim 10, wherein, The ratio of the thickness of the coating layer to the particle size of the microspheres is 0.02 to 0.1:

1.

12. The nicotine article according to any one of claims 10-11, wherein, The coating layer includes a coating material.

13. The nicotine article as claimed in claim 12, wherein, The nicotine product satisfies at least one of the following characteristics: (1) The coating material includes at least one of hydroxypropyl cellulose, hydroxypropyl methylcellulose and ethyl cellulose; (2) In the nicotine product, the coating material accounts for 1% to 20% of the total mass.

14. The nicotine article according to any one of claims 10 to 13, wherein, The coating layer has a porous structure.

15. The nicotine article according to any one of claims 1 to 14, wherein, The nicotine compound particles also include additives, which include at least one of anti-sticking agents, sweeteners, flavorings, and pH adjusters.

16. The nicotine article according to any one of claims 1 to 15, wherein, The nicotine product includes a permeation bag, in which the nicotine composite particles in each of the particle clusters are filled to form a nicotine bag.

17. The nicotine article as claimed in any one of claims 16, wherein, The nicotine product also includes outer packaging, with the nicotine bag disposed inside the outer packaging.

18. A method for preparing nicotine complex particles, comprising the following steps: Preparation of a spraying solution containing nicotine-active materials; The spraying solution is sprayed onto the surface of at least one micro-particle raw material to obtain nicotine-containing micro-particles, and the nicotine-containing micro-particles are dried to prepare the nicotine composite particles; the aggregation degree index of each micro-particle raw material is ≤1.

19. The method for preparing nicotine composite particles as described in claim 18, wherein, The method for preparing the nicotine complex particles satisfies at least one of the following characteristics: (1) The spraying solution also includes a coating material, the nicotine composite particles include micro pellets and a coating layer disposed on the surface of the micro pellets, and the nicotine active material is disposed in the coating layer; (2) Before the drying step, and after obtaining the nitroglycerin-containing pellets, the following steps are also included: A coating solution, including coating material, is sprayed onto the surface of the nitrocellulose-containing pellets to form a coating layer.

20. The method for preparing nicotine composite particles as described in claim 19, wherein, Before the drying step, and after the coating layer is formed, the following steps are also included: A spray solution containing nicotine active material is sprayed onto the surface of the coating layer away from the microparticles.

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