Buccal product and preparation method thereof

Abstract

The invention discloses a buccal product and a preparation method thereof, the buccal product comprises a composition, the composition comprises a first adsorbent and a functional substance, the first adsorbent is electropositive as a whole, the functional substance is electronegative as a whole, and the functional substance is at least partially adsorbed on the first adsorbent. According to the buccal product, the first adsorbent and the functional substance have different electrical properties, the adsorption capacity of substances in the buccal product can be enhanced through the electrostatic adsorption effect, and the powder leakage phenomenon is reduced.

Description

Technical Field

[0001] The present application relates to the field of food or medical technology, and in particular to an oral product and a preparation method thereof. Background Art

[0002] Oral products, such as oral nicotine products, are products containing nicotine active ingredients (nicotine or its derivatives), which are usually placed in the oral cavity in the form of powder, film, pouch, etc., and then dissolve and release the nicotine active ingredient, and are absorbed through the oral mucosa. It has the advantages of accurate dosage, rapid onset, and portability. Oral nicotine products, such as nicotine pouches, are usually composed of a permeable bag and nicotine particles encapsulated in the permeable bag, wherein the nicotine particles usually include an adsorbent and a nicotine active substance. Nicotine particles are currently usually prepared by dry fluidized granulation technology. However, there are the following deficiencies: the adsorbents are usually only combined into granules by establishing crystal bridges with water, the adsorption force is insufficient, and after the water is dried and fluidized, the powder is easily leaked in the mouth during use by the user. Summary of the Invention

[0003] The present application provides an oral product and a preparation method thereof, which are used to detect and solve the problem that existing oral products are prone to powder leakage.

[0004] The present application discloses an oral product, comprising a composition, wherein the composition comprises a first adsorbent and a functional substance, wherein the first adsorbent is positively charged as a whole, the functional substance is negatively charged as a whole, and the functional substance is at least partially adsorbed on the first adsorbent.

[0005] In one implementation of the present application, the first adsorbent includes a first carrier and a cationic agent.

[0006] In one implementation of the present application, the first carrier includes at least one of microcrystalline cellulose and silicified microcrystalline cellulose; and / or, the cationic agent includes at least one of chitosan hydrochloride, ε-polylysine hydrochloride, chitosan oligosaccharide hydrochloride and amino starch; and / or, the first adsorbent includes microcrystalline cellulose modified with chitosan hydrochloride.

[0007] In one implementation of the present application, the composition further includes a second adsorbent, and the second adsorbent is used to adsorb at least a portion of the functional substance.

[0008] In one implementation of the present application, the second adsorbent includes a second carrier and a charge synergist, and the charge synergist is used to make the second adsorbent negatively charged as a whole.

[0009] In one implementation of the present application, the second carrier includes a sugar alcohol; and / or, the second carrier includes at least one of lactitol, erythritol, xylitol, isomalt, mannitol, sorbitol and maltitol; and / or, the second carrier is a porous material; and / or, the specific surface area of ​​the second carrier is ≥15m 2 / g; and / or, the charge synergist comprises at least one of sodium carboxymethyl cellulose, citrate, malate and tartrate.

[0010] In one implementation of the present application, the composition further comprises at least one of a binder, a sweetener, a fragrance, a cooling agent, a pH adjuster, a preservative, and a surface lubricant.

[0011] In one implementation of the present application, the functional substance includes nicotine salt; and / or, the functional substance includes at least one of nicotine tartaric acid salt, nicotine benzoate salt, nicotine lactate salt, nicotine citrate salt, nicotine oxalate salt and nicotine malonate salt; and / or, the binder includes at least one of carboxymethyl cellulose, povidone K30, sodium alginate and hydroxypropyl methylcellulose; and / or, the surface lubricant includes at least one of sodium stearate fumarate, magnesium stearate, stearic acid, talc and sodium lauryl sulfate; and / or, the sweetener includes xylitol, sorbitol, mannitol, iglesia, lactitol, maltitol, isomalt, hydrogenated starch hydrolysate, erythritol, maltotriitol, aspartame, acesulfame potassium, saccharin sodium, sucralose, neotame, cyclamate, alitame, steviol glycosides, At least one of arabitol and monk fruit sweetener; and / or, the fragrance includes at least one of bergamot flavor, eucalyptus flavor, citrus flavor, lemon flavor, peppermint flavor, mint flavor, menthol, licorice flavor, wintergreen flavor, tobacco flavor, coffee flavor, vanilla flavor, lime flavor, apple flavor, peach flavor, mango flavor, cherry flavor, blueberry flavor, strawberry flavor, cola flavor, cinnamon flavor, vanilla flavor and watermelon flavor; and / or, the cooling agent includes at least one of menthol, menthol derivatives, WS-3 and WS-23; and / or, the pH adjuster includes at least one of citric acid, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate and magnesium carbonate; and / or, the preservative includes at least one of ethylparaben, benzoic acid, sodium benzoate, potassium sorbate and benzalkonium chloride.

[0012] The present application also discloses a method for preparing an oral product, comprising: obtaining an adsorbent, comprising: obtaining a first adsorbent, wherein the first adsorbent comprises a first carrier and a cationic agent, and the first adsorbent is positively charged as a whole; obtaining a mixed material, comprising: mixing the first adsorbent with a functional substance to obtain a mixed material; granulation, comprising: granulating the mixed material to obtain a composition, and then obtaining the oral product from the composition.

[0013] In one implementation of the present application, the obtaining of the adsorbent further includes: obtaining a second adsorbent; wherein the second adsorbent includes a second carrier and a charge synergist, and the charge synergist is used to make the second adsorbent as a whole negatively charged; the obtaining of the mixed material includes: mixing the first adsorbent, the second adsorbent and the functional substance to obtain the mixed material; and / or, the granulation includes: spraying an adhesive solution into the mixed material for granulation to obtain a composition, covering the surface of the composition with a lubricating layer, the lubricating layer including a surface lubricant; and obtaining the oral product.

[0014] The beneficial effects of this application are:

[0015] In the oral product of the present application, the first adsorbent and the functional substance have different electrical properties, which can enhance the adsorption force of the internal substances of the oral product through electrostatic adsorption and reduce powder leakage. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 An electron micrograph of a porous sugar alcohol is shown.

[0017] Figure 2 The nicotine release profile of the buccal product is shown. DETAILED DESCRIPTION

[0018] The present invention is further described in detail below by specific embodiments in conjunction with the accompanying drawings. In the following embodiments, many detailed descriptions are intended to enable the present application to be better understood. However, those skilled in the art can readily appreciate that some of the features may be omitted in different circumstances, or may be replaced by other materials or methods. In some cases, some operations related to the present application are not shown or described in the specification. This is to avoid the core of the present application being overwhelmed by excessive descriptions, and for those skilled in the art, it is not necessary to describe these related operations in detail. They can fully understand the related operations based on the description in the specification and the general technical knowledge in the art.

[0019] In addition, the features, operations, or characteristics described in the specification may be combined in any appropriate manner to form various embodiments. Furthermore, the steps or actions in the method description may be reordered or adjusted in a manner readily apparent to those skilled in the art. Therefore, the various sequences in the specification and drawings are provided solely for the purpose of clearly describing a particular embodiment and are not intended to be mandatory, unless otherwise specified.

[0020] The serial numbers assigned to the components in this document, such as "first", "second", etc., are only used to distinguish the objects described and do not have any order or technical meaning.

[0021] In the production process of oral nicotine bags, traditional dry fluidized granulation technology has at least one of the following problems: insufficient adsorption force, mainly due to the uneven surface charge distribution of microcrystalline cellulose and sugar alcohol particles, resulting in low mutual adsorption efficiency between active ingredients (such as nicotine salt) and microcrystalline cellulose and sugar alcohol themselves. Granulation is only based on water to establish crystal bridges. After the water is dried and fluidized, powder leakage in the mouth during use is likely to occur; uncontrollable release rate: the dense structure of sugar alcohol particles limits the specific surface area, affecting the balance between rapid and sustained release of active ingredients; taste defects: traditional adhesives have strong adhesion to the surface of the particles, the products stick to each other, and are prone to adhere to the oral mucosa, causing discomfort to users.

[0022] Commonly used technical means to address the above technical problems and their drawbacks or shortcomings: 1) Adhesive adhesion technology: In the granulation process of oral products, adhesive adhesion technology uses physical mixing to allow the adhesive to work. However, this technology has obvious dosage problems (the dosage is difficult to control). When the adhesive addition level is at a high level, the product will clump due to excessive stickiness, causing the active ingredients to be encapsulated in the clumps, making it difficult to release evenly, and the adsorption stability is greatly reduced. At the same time, the problem of sticking to the mouth will occur during use, affecting the user experience. Conversely, if the adhesive addition level is low, sufficient adhesion cannot be formed between the particles, resulting in significant powder leakage, which not only causes product waste but may also affect product quality and safety. 2) Mechanical pressure molecular force technology: Mechanical pressure molecular force technology mainly uses high pressure applied by a pressure roller to compress powdered materials into granules. The principle is that high pressure shortens the distance between molecules, allowing van der Waals forces to take effect and promote particle agglomeration. However, this agglomeration state is not very stable. During transportation, vibrations and changes in high and low temperatures are inevitable. These external factors will destroy the balance of forces between molecules, causing the originally agglomerated particles to disperse again, affecting the structure and performance of the product. 3) Crystal bridge and surface cohesion technology: Crystal bridge and surface cohesion technology utilizes the characteristics of crystal water in the material. During the granulation process, crystal water can form crystal bridges between particles, connecting molecules together like a bridge, and enhancing the intermolecular binding force. However, this binding force depends on the presence of water. During the dry drying process, the water gradually evaporates, the crystal bridges break, and the intermolecular binding force disappears accordingly, which reduces the stability of the particles and may cause problems such as looseness and breakage, affecting the final quality of the product.

[0023] In view of this, the present application provides an oral product and a preparation method thereof. The advantages of the present application include at least one of the following: (1) The positive charge density of the surface of microcrystalline cellulose is increased by cationic modification, thereby enhancing its electrostatic adsorption ability with negatively charged functional substances and reducing powder leakage. The surface of the sugar alcohol particles is coated with sodium carboxymethyl cellulose (CMC-Na) to form a negative charge layer, which enhances the synergistic adsorption with the cationic modified MCC. The adsorption efficiency is increased by 40%-50%, and the powder leakage rate is reduced to ≤3%. (2) A porous sugar alcohol structure is constructed, the specific surface area of ​​the sugar alcohol is increased by 3-5 times, the functional substance loading is increased by 30%, and the release rate in the rapid release stage (0-2 minutes) is increased to 50%-55%. (3) The mouthfeel is improved. In the later stage of fluidized bed granulation, the lubricant is evenly covered on the surface of the particles by fluidized spraying to form a hydrophobic lubricating layer with a thickness of 10 to 20 μm; an adhesive is used inside and a lubricant is sprayed on the outside to achieve a "sticky inside and slippery outside" gradient structure, reducing oral adhesion and improving the smooth feeling of entry.

[0024] The present application relates to an oral product.

[0025] In one embodiment, the oral product comprises a composition comprising a first adsorbent and a functional substance.

[0026] In one embodiment, the first adsorbent and the functional substance have different electrical properties. For example, the first adsorbent is generally positively charged, and the functional substance is generally negatively charged.

[0027] In one embodiment, the functional substance is at least partially adsorbed on the first adsorbent.

[0028] In one embodiment, the composition further comprises a second adsorbent, and the functional substance is at least partially adsorbed on the second adsorbent.

[0029] In one embodiment, the functional substance includes nicotine and / or nicotine derivatives.

[0030] In a specific embodiment, nicotine includes natural nicotine and synthetic nicotine. Nicotine derivatives may include one or more of nicotine salts, nicotine in a matrix such as a sugar matrix or an organometallic complex, a nicotine-resin combination, a nicotine inclusion complex, and non-covalently bound nicotine. Non-covalently bound nicotine includes nicotine lactate, nicotine malate, nicotine salicylate, nicotine cyclodextrin inclusion complex, nicotine hydrochloride, nicotine dihydrochloride, nicotine tartrate, nicotine tartrate dihydrate, nicotine sulfate, nicotine zinc chloride, nicotine benzoate, and the like. Nicotine derivatives also include nicotine containing substituents, such as hexamethyl nicotine, hexamethyl nicotine lactate, hexamethyl nicotine malate, hexamethyl nicotine salicylate, hexamethyl nicotine cyclodextrin embedded complex, hexamethyl nicotine hydrochloride, hexamethyl nicotine dihydrochloride, hexamethyl nicotine tartrate, hexamethyl nicotine tartrate dihydrate, hexamethyl nicotine sulfate, hexamethyl nicotine zinc chloride, and hexamethyl nicotine benzoate. One or more mixtures thereof.

[0031] In one embodiment, the functional substance is nicotine salt. It should be noted that nicotine salt is negatively charged, and during the preparation process, the acid radical ions carry a negative charge, which can attract the positively charged first adsorbent.

[0032] In one embodiment, the nicotine salt includes at least one of the following: nicotine tartrate, nicotine benzoate, nicotine lactate, nicotine citrate, nicotine oxalate, and nicotine malonate. These nicotine salts are negatively charged and generally have higher bioavailability and a better taste than nicotine.

[0033] In a specific embodiment, the functional substance may also be selected from other substances with medical or other specific uses, such as vitamins, capsaicin, caffeine, etc., to meet the needs of different users.

[0034] In a specific embodiment, the functional substance can also be selected from other alkaloids or amino acids, for example, alkaloids such as tobacco, coffee, and tea.

[0035] In one embodiment, the first adsorbent and the second adsorbent each have different charges. For example, the first adsorbent has a positive charge and the second adsorbent has a negative charge; or the first adsorbent has a negative charge and the second adsorbent has a positive charge. This allows the first adsorbent and the second adsorbent to attract each other through electrostatic interaction, thereby enhancing the binding force within the oral product and reducing powder leakage.

[0036] In a specific embodiment, the first adsorbent may be positively charged, thereby enhancing the adsorption effect between the first adsorbent and the negatively charged functional substance (eg, nicotine salt).

[0037] In a specific embodiment, the oral product may include 35 to 50 parts by weight of the first adsorbent. For example, the oral product may include 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 parts by weight of the first adsorbent.

[0038] In a specific embodiment, the oral preparation may include 35 to 45 parts by weight of the second adsorbent. For example, the oral preparation may include 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, or 45 parts by weight of the second adsorbent.

[0039] In a specific embodiment, the oral preparation may include 10 to 15 parts of the functional substance by weight. For example, the oral preparation may include 10, 11, 12, 13, 14, or 15 parts of the functional substance by weight.

[0040] In a specific embodiment, the first adsorbent may include a first support and a cationic agent.

[0041] In a specific embodiment, the first carrier includes at least one of microcrystalline cellulose (MCC) and silicified microcrystalline cellulose (SMCC). It should be noted that microcrystalline cellulose can absorb functional substances through its pore structure, large specific surface area, hydrogen bonding, etc., and can continuously release functional substances when used in oral products, providing users with continuous satisfaction. Silicified microcrystalline cellulose is a specially treated microcrystalline cellulose that enhances its performance by introducing silicon dioxide (SiO2) particles on its surface. This material combines the advantages of microcrystalline cellulose (MCC) and silicon dioxide. Silicon dioxide has excellent fluidity and adsorption capacity, and silicified microcrystalline cellulose has good fluidity, adsorption capacity, disintegration and stability, and also has low hygroscopicity.

[0042] In a specific embodiment, the first carrier may include various types of microcrystalline cellulose, for example, microcrystalline cellulose 101 , microcrystalline cellulose 102 , and microcrystalline cellulose 200 .

[0043] In a specific embodiment, the particle size of the first carrier satisfies: D90≤50 μm.

[0044] In a specific embodiment, the cationic agent includes at least one of chitosan hydrochloride ε-polylysine hydrochloride, chitosan oligosaccharide hydrochloride and amino starch. It should be noted that the amino group (-NH3 +) can be adsorbed onto the surface of microcrystalline cellulose through ion exchange, forming a stable positively charged layer. This, in turn, enhances the first adsorbent's adsorption of the negatively charged functional substance and synergizes with the negatively charged second adsorbent to reduce powder leakage.

[0045] In one specific embodiment, the first adsorbent includes microcrystalline cellulose modified with chitosan hydrochloride. It should be noted that while microcrystalline cellulose typically has a negative zeta potential, modification with chitosan hydrochloride results in a first adsorbent with a positive zeta potential, which enhances adsorption of functional substances and enables synergistic adsorption with the negatively charged second adsorbent, reducing powder leakage.

[0046] In a specific embodiment, the oral preparation may include 40 to 45 parts by weight of the first carrier. For example, the oral preparation may include 40, 41, 42, 43, 44, or 45 parts by weight of the first carrier.

[0047] In a specific embodiment, the oral preparation may include 0.5 to 1 part by weight of the cationic agent. For example, the oral preparation may include 0.5, 0.6, 0.7, 0.8, 0.9, or 1 part by weight of the cationic agent.

[0048] In one embodiment, the second adsorbent may include a second support and a charge synergist.

[0049] In one embodiment, a charge synergist is used to make the second adsorbent overall negatively charged.

[0050] In one embodiment, the second carrier includes a sugar alcohol. Thus, the sugar alcohol can carry the functional substance (e.g., nicotine) through its weak adsorption effect, allowing the functional substance to be quickly released when the oral product is used, providing the user with instant gratification.

[0051] In a specific embodiment, the sugar alcohol includes at least one of lactitol, erythritol, xylitol, isomalt, mannitol, sorbitol and maltitol.

[0052] In one embodiment, the charge synergist can be an anionic modifier.

[0053] In a specific embodiment, the charge synergist may include at least one of sodium carboxymethylcellulose, citrate, malate, and tartrate.

[0054] In one embodiment, the second adsorbent is a sugar alcohol coated with sodium carboxymethyl cellulose.

[0055] In a specific embodiment, the oral preparation may include 38 to 43 parts by weight of the second carrier. For example, the oral preparation may include 38, 39, 40, 41, 42, or 43 parts by weight of the second carrier.

[0056] In a specific embodiment, the oral preparation may include 0.3 to 0.5 parts by weight of anionic agent. For example, the oral preparation may include 0.3, 0.35, 0.4, 0.45, or 0.5 parts by weight of anionic agent.

[0057] In one embodiment, the second carrier is a porous material.

[0058] In one specific embodiment, the second carrier is a porous sugar alcohol, i.e., the surface of the sugar alcohol has a plurality of pit structures. For example, the sugar alcohol can be a sphere with honeycomb-shaped blind holes on its surface. It should be noted that the dense structure of conventional sugar alcohol particles limits the specific surface area, affecting the balance between rapid and sustained release of the active ingredient. By constructing a porous sugar alcohol structure, the specific surface area can be increased, the loading capacity of the functional substance can be increased, and the release rate in the rapid release phase can be improved, thereby reducing the impact of the enhanced adsorption of the functional substance by the first adsorbent / second adsorbent on the release of the functional substance.

[0059] In one embodiment, the specific surface area of ​​the second carrier is ≥15m 2 For example, the second carrier is a porous sugar alcohol, and its specific surface area can be 15m 2 / g, 25m 2 / g、30m 2 / g、35m 2 / g, 40m 2 / g、45m 2 / g, 50m 2 / g、55m 2 / g, 60m 2 / g、65m 2 / g or 70m 2 / g.

[0060] In one embodiment, the porous sugar alcohol includes porous lactitol and porous mannitol. Porous lactitol has a relatively fast dissolution rate and can be used as a front-release carrier, while porous mannitol can be used as a rear-release carrier, providing a good rapid release effect for the functional substance in the oral product, regulating the rapid release phase (porous lactitol as a carrier, the release rate of the functional substance within 0-2 minutes reaches 50%-55%) and (porous mannitol as a carrier, the release rate of the functional substance within 3-6 minutes reaches 50%-55%).

[0061] In a specific embodiment, the size of the pits on the surface of the porous lactitol is 100 nm to 300 nm. For example, the size of the pits on the surface of the porous lactitol is 100 nm, 150 nm, 200 nm, 250 nm or 300 nm.

[0062] In one embodiment, the bulk density of the porous lactitol is 0.3 g / cm 3 ~0.5g / cm 3 For example, the bulk density of porous lactitol is 0.3 g / cm 3 , 0.4g / cm 3 or 0.5g / cm 3 .

[0063] In a specific embodiment, the oral preparation may include 22 to 25 parts by weight of porous lactitol. For example, the oral preparation may include 22, 23, 24, or 25 parts by weight of porous lactitol.

[0064] In a specific embodiment, the size of the pits on the porous mannitol surface is 50 nm to 100 nm. For example, the size of the pits on the porous mannitol surface is 50 nm, 60 nm, 70 nm, 80 nm, 90 nm or 100 nm.

[0065] In one embodiment, the specific surface area of ​​the porous mannitol is ≥50 m 2 / g.

[0066] In a specific embodiment, the buccal preparation may include 15 to 18 parts of porous mannitol by weight. For example, the buccal preparation may include 15, 16, 17, or 18 parts of porous mannitol by weight.

[0067] In a specific embodiment, the oral product further includes an adhesive, thereby further improving the binding force of the substances in the oral product and reducing powder leakage.

[0068] In a specific embodiment, the binder includes at least one of hypromellose, carboxymethyl cellulose, povidone K30 and sodium alginate.

[0069] In a specific embodiment, the oral preparation may include 3 to 5 parts of adhesive by weight. For example, the oral preparation may include 3 parts, 3.5 parts, 4 parts, 4.5 parts, or 5 parts of adhesive by weight.

[0070] In one embodiment, the surface of the oral product has a lubricating layer, which includes a lubricant.

[0071] In a specific embodiment, the lubricant includes at least one of the following: sodium stearyl fumarate, magnesium stearate, stearic acid, talc, and sodium lauryl sulfate.

[0072] In a specific embodiment, the thickness of the lubricating layer may be 10 μm to 20 μm.

[0073] In one embodiment, the average particle size of the oral preparation is 50 μm to 140 μm.

[0074] In one embodiment, the particle size D90 of the oral preparation is ≤ 150 μm.

[0075] In a specific embodiment, the oral preparation may include 0.2 to 1 part by weight of a lubricant. For example, the oral preparation may include 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or 1 part by weight of a lubricant.

[0076] In a specific embodiment, the oral preparation may further include a sweetener.

[0077] In a specific embodiment, the sweetener may include at least one of xylitol, sorbitol, mannitol, iglesia, lactitol, maltitol, isomalt, hydrogenated starch hydrolysate, erythritol, maltotriitol, aspartame, acesulfame potassium, saccharin sodium, sucralose, neotame, cyclamate, alitame, steviol glycosides, arabitol, and monk fruit sweetener. The sweetener may also be selected from other edible-grade substances, which will not be detailed here.

[0078] In a specific embodiment, the buccal preparation may include 0.1 to 0.3 parts of sweetener by weight. For example, the buccal preparation may include 0.1, 0.2, or 0.3 parts of sweetener by weight.

[0079] In one embodiment, the oral preparation may further include a fragrance.

[0080] In a specific embodiment, the fragrance can include at least one of bergamot essence, eucalyptus essence, citrus essence, lemon essence, peppermint essence, mint essence, menthol, licorice essence, wintergreen essence, tobacco essence, coffee essence, vanilla essence, lime essence, apple essence, peach essence, mango essence, cherry essence, blueberry essence, strawberry essence, cola essence, cinnamon essence, pandan essence, and watermelon essence. The fragrance can also be other types of edible flavors, which will not be detailed here.

[0081] In a specific embodiment, the oral preparation may include 0.8 to 1.5 parts of fragrance by weight. For example, the oral preparation may include 0.8, 1, 1.2, or 1.5 parts of fragrance by weight.

[0082] In a specific embodiment, the oral preparation may further include a cooling agent.

[0083] In a specific embodiment, the cooling agent may include at least one of menthol, a menthol derivative, WS-3, and WS-23.

[0084] In one embodiment, the oral preparation may further include a preservative.

[0085] In a specific embodiment, the preservative (or antibacterial agent) can be selected from at least one of the following substances: ethylparaben, benzoic acid, sodium benzoate, potassium sorbate, and benzalkonium chloride. The antibacterial agent can also be selected from other edible-grade antibacterial substances, which are not described in detail herein.

[0086] In a specific embodiment, the oral preparation may include 0.05 to 0.1 parts by weight of a preservative. For example, the oral preparation may include 0.05, 0.06, 0.07, 0.08, 0.09, or 0.1 parts by weight of a preservative.

[0087] In one embodiment, the oral preparation may further include a pH adjuster.

[0088] In a specific embodiment, the pH adjuster may include citric acid, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, magnesium carbonate, and the like.

[0089] In a specific embodiment, the oral preparation may include 0.8 to 3 parts by weight of a preservative. For example, the oral preparation may include 0.8, 1, 1.5 / 2, 2.5, or 3 parts by weight of a pH adjuster.

[0090] In one embodiment, the pH of the oral preparation is 6.5-7.2.

[0091] The present application also relates to a method for preparing an oral product, which may include: obtaining an adsorbent, including: obtaining a first adsorbent, wherein the first adsorbent includes a first carrier and a cationic agent, and the first adsorbent is positively charged as a whole; obtaining a mixed material, including: mixing the first adsorbent with a functional substance to obtain a mixed material; granulation, including: granulating the mixed material to obtain a composition, and then obtaining the oral product from the composition.

[0092] In a specific embodiment, the preparation method may include the following steps: preparing a first adsorbent: mixing a first carrier and a cationic agent with a first solvent, and drying to obtain the first adsorbent; preparing a second adsorbent: mixing a second carrier and an anionic agent with a second solvent, and drying to obtain the second adsorbent; granulating: mixing the first adsorbent, the second adsorbent and a functional substance to prepare the oral product.

[0093] In a specific embodiment, the preparation method of the second carrier includes: heating the sugar alcohol and nano-calcium carbonate to a molten state, then cooling and solidifying, adding an acidic reagent, and obtaining a sugar alcohol with a plurality of pit structures on the surface (porous sugar alcohol), which is also the second carrier. It should be noted that the nano-calcium carbonate is evenly dispersed in the sugar alcohol when melted, and a composite structure is formed after rapid cooling; after the nano-calcium carbonate is dissolved by acid washing, the remaining honeycomb pores can significantly increase the specific surface area. The porous structure can load more functional substances and regulate the release rate in the immediate release stage.

[0094] In a specific embodiment, the acidic reagent may be 5% by mass dilute hydrochloric acid.

[0095] In a specific embodiment, the granulation comprises: adding a mixture of the first adsorbent, the second adsorbent and the functional substance into a fluidized device, and spraying a binder solution into the fluidized device to perform granulation.

[0096] In a specific embodiment, the method for preparing the oral product further comprises: covering the surface of the oral product with a lubricating layer, wherein the lubricating layer comprises a lubricant.

[0097] In a specific embodiment, the oral product is prepared by the above preparation method.

[0098] This application relates to an oral product. The oral product comprises an osmotic bag and an oral product encapsulated within the osmotic bag. During use, the osmotic bag allows saliva to pass through, allowing the functional substance to dissolve in the saliva and then pass through the bag into the oral cavity for consumption.

[0099] In a specific embodiment, the material of the permeable bag can be natural fiber, synthetic fiber or a mixture thereof.

[0100] In one embodiment, the permeable bag is a non-woven fabric.

[0101] In one embodiment, the permeable bag has pores with a pore size of less than 10 μm.

[0102] In a specific embodiment, the oral product of the present application has a powder leakage rate of ≤1.5%.

[0103] In a specific embodiment, the oral preparation product of the present application has a rapid release phase: ≥50% of the functional substance is released within 0-5 minutes; and a sustained release phase: ≥80% of the functional substance is cumulatively released within 30 minutes.

[0104] In a specific embodiment, the oral product of the present application has an adhesion force of less than 0.2 N, a good mouthfeel and a smoothness, and an oral adhesion rate of ≤8%.

[0105] The present invention is further described in detail below by specific experimental process and experimental data examples. The following examples are only used to further illustrate the present invention and should not be construed as limiting the present invention. In the present embodiment, unless otherwise specified, the reagents and instruments used are all commercially available, and the experimental operations are all carried out in accordance with the product specifications and conventional experimental specifications.

[0106] Example

[0107] (1) Formulation:

[0108]

[0109] (2) Process steps:

[0110] Raw material pretreatment: Microcrystalline cellulose (MCC) is passed through a 60-mesh sieve to remove lumps and then through a 120-mesh sieve to remove fines. The resulting microcrystalline cellulose has a particle size of 100 μm ≤ D90 ≤ 250 μm. Sugar alcohols (lactitol and mannitol) are mixed with nano-calcium carbonate; the mass ratio of sugar alcohol to nano-calcium carbonate is 98:2, and the mass ratio of lactitol to mannitol is 5:3.

[0111] Preparation of modified microcrystalline cellulose charge: Pretreated microcrystalline cellulose and chitosan hydrochloride aqueous solution (mass fraction 0.5%) are mixed, the solid content of the mixed solution is controlled at 10% to 15%, the stirring speed is 500 rpm, the mixing time is 30 minutes, and the suspension after mixing must be free of particle agglomeration. It is then spray-dried (drying temperature: inlet air 60°C, outlet air 40°C, atomization pressure 0.2MP) and crushed to D90 ≤ 50μm. Moisture detection and Zeta potential detection are carried out, and the final moisture content is ≤ 3%, and the Zeta potential is +20 to +30mV. The Zeta potential of the modified microcrystalline cellulose is increased from the traditional -10mV to about +25mV, significantly enhancing the electrostatic adsorption effect with nicotine salt (negatively charged).

[0112] Preparation of porous sugar alcohol: Heat the pretreated mixture of sugar alcohol and nano-calcium carbonate to 160°C and melt and stir for 10 minutes until it is completely transparent. Quickly transfer the molten liquid to a -20°C cold trap for rapid cooling and solidification, with a cooling time of 30 minutes. Crush the solidified block, pass it through a 100-mesh sieve, soak it in a 5% dilute hydrochloric acid solution, and stir it at 200rpm for 2 hours to dissolve the nano-calcium carbonate template. After acid washing, the pH of the filtrate must be ≥6 (pH test paper test) to ensure that the template is completely removed. Wash the sugar alcohol repeatedly with purified water to neutrality (conductivity ≤10μS / cm), and then dry it in a vacuum drying oven at 40°C±2°C to a moisture content of ≤2% to obtain a porous sugar alcohol. The specific surface area of ​​the obtained porous sugar alcohol is ≥15m 2 / g (BET method detection), conductivity ≤10μS / cm (washing end point), wherein the pore size of the porous lactitol is 100nm~300nm, and the pore size of the porous mannitol is 50nm~100nm. Figure 1 An electron micrograph of a porous sugar alcohol is shown.

[0113] Then, the porous sugar alcohol was mixed with a 0.2% by mass sodium carboxymethyl cellulose (CMC-Na) solution and spray-dried (drying temperature: inlet air 60° C., outlet air 40° C.).

[0114] Active ingredient mixing: Premix modified microcrystalline cellulose, porous sugar alcohol, nicotine, flavoring, sweetener, and lubricant according to the formula ratio. Mix in a V-type mixer for 20 minutes at an ambient humidity of ≤30%. Test the mixture for uniformity (nicotine content deviation ≤±2% by HPLC random inspection).

[0115] Fluidized bed granulation: In a fluidized bed, a 3% ethanol solution of HPMC E5 was sprayed into the active ingredient mixture for dry granulation. The inlet air temperature was 50°C, the atomization pressure was 0.3 MPa, and the particle size was 20-40 mesh. Moisture and bulk density tests were performed, and the final moisture content was ≤3% and the bulk density was 0.4-0.6 g / cm. 3 .

[0116] Surface Lubrication Treatment: Using a fluidized spray process, a sodium stearate fumarate ethanol solution was evenly applied to the particle surface, forming a 10-20 μm thick hydrophobic layer. Spray rate: 10 mL / min, bed temperature: 40°C, lubricant coverage: ≥95%. The particle friction coefficient, measured using a friction coefficient meter, was ≤0.2.

[0117] Drying and Sieving: Drying was performed in stages (main drying at 55°C for 60 minutes, followed by equilibration at 25°C for 12 hours). The product was sieved through a 20-40 mesh screen to remove fine powder and lumps, yielding the oral preparation of this embodiment. The final moisture content was ≤3%, the sieving efficiency was ≥98%, the particle yield was ≥90%, and the particle size distribution (D90) was ≤150 μm.

[0118] Packaging and Quality Inspection: The finished product is packaged according to specifications and fully tested for leakage rate, taste, and release rate. Package dimensions: 15 x 30 mm, non-woven fabric pore size: less than 10 μm, non-woven fabric thickness: 0.18-0.2 mm. After packaging, the oral product of this embodiment is obtained. Quality inspection standards: leakage rate ≤ 3%, nicotine release compliance rate ≥ 95%, and SEM electron microscopy testing of non-woven fabric porosity.

[0119] (3) Performance testing

[0120] 3-1) Powder leakage rate test:

[0121] Objective: To verify whether the powder leakage rate and nicotine adhesion performance of the oral product of this embodiment are better than those of ordinary oral products after using a non-woven screen.

[0122] Test subjects: The oral product prepared in this example was packaged using a 37g non-woven mesh (pore size <10μm, thickness 0.18-0.2mm). Ordinary oral products (no microcrystalline cellulose modification, non-porous sugar alcohol and sugar alcohol not treated with sodium carboxymethyl cellulose, no added lubricant and lubricating layer, otherwise the same as in Example 1) were packaged using a 37g non-woven mesh (pore size <10μm, thickness 0.18-0.2mm).

[0123] Equipment: vibration screening device (amplitude 2 mm, frequency 50 Hz), laser particle size analyzer, electronic balance.

[0124] Method: Laser particle size analyzer detection; Powder leakage rate test: The oral preparation of this embodiment and a conventional oral preparation placed in a non-woven fabric were vibrated and sieved (10 minutes), and the powder under the sieve was collected and weighed. The powder leakage rate was calculated as follows: Powder leakage rate (%) = [mass of powder under the sieve (g) / initial mass (g)] × 100%.

[0125] Test results:

[0126] Particle size distribution results:

[0127]

[0128] Powder leakage rate:

[0129]

[0130] As can be seen from the above, the oral product of this embodiment has a powder leakage rate of only 1.36%, an 84% reduction compared to conventional products, verifying the enhanced adsorption capacity of fine powders due to charge modification and a porous structure. The particle size distribution after granulation in this embodiment shows that the fine powder particle size (D10) is increased compared to conventional products while maintaining minimal variation in the large particle size (D90), resulting in a reduced particle size span, demonstrating the invention's unique adsorption capacity enhancement effect on fine powders.

[0131] 3-2) Nicotine release model test

[0132] Purpose: To verify the nicotine release characteristics of the oral product smoke of this example in a simulated oral environment (pH 6.8) to ensure that its adsorption to fine powder does not affect nicotine release: rapid release phase: ≥50% nicotine release within 0-5 minutes; sustained release phase: cumulative release of ≥80% within 30 minutes.

[0133] Sample: The oral product prepared in this example was packaged using a 37g non-woven mesh (pore size <10µm, thickness 0.18-0.2mm). A conventional oral product (no microcrystalline cellulose modification, non-porous sugar alcohol and sugar alcohol not treated with sodium carboxymethyl cellulose, no lubricant or lubricating layer added, otherwise the same as in Example 1) was packaged using a 37g non-woven mesh (pore size <10µm, thickness 0.18-0.2mm).

[0134] Reagents and equipment: simulated saliva (pH 6.8, containing 0.5% SDS), dissolution apparatus (USPII paddle method, 37±0.5°C, rotation speed 50 rpm), HPLC system (C18 column, mobile phase: acetonitrile-phosphate buffer (pH 3.0, volume ratio 70:30), detection wavelength 260 nm).

[0135] Methods: 500 mL of simulated saliva was preheated to 37°C and added to the dissolution cup. A non-woven bag containing snus particles was fixed to the bottom of the dissolution apparatus paddle. 5 mL samples were collected at the following time points (with simultaneous rehydration): 1, 3, 5, 10, 20, 30, 45, and 60 minutes. Samples were filtered through a 0.22 μm filter membrane, and nicotine concentration was determined by HPLC. Cumulative release was calculated as follows: Cumulative release rate (%) = [(total nicotine content, test concentration × dissolution medium volume) ÷ total nicotine content] × 100. Release curve fitting: A first-order kinetic model (Weibull equation) was used.

[0136] Test results:

[0137] Nicotine release curve Figure 2 , Figure 2 The nicotine release curves of oral products are shown, where KHZY000131 is the oral product of the embodiment of the present application, and KHZY000131 is a common oral product. The nicotine release results are shown in the table below:

[0138] Time (min) Oral product of this embodiment (mg / g) Ordinary oral products (mg / g) 1 5.53 5.36 3 8.22 8.12 5 9.97 10.12 10 12.32 12.55 20 13.93 14.13 30 14.49 14.81 45 15.09 15.46 60 15.33 15.91

[0139] From the above, it can be seen that in the rapid release stage (0-5 minutes): the nicotine release rate of the oral preparation of this embodiment within 5 minutes is 58.6%, which is slightly higher than the 56.2% of ordinary oral preparations, and both meet the rapid release target (≥50%). In the sustained release stage (30 minutes and above): the cumulative release rate of the oral preparation of this embodiment within 30 minutes is 85.2%, and that of ordinary oral preparations is 82.3%, both of which exceed the target value (≥80%). In long-term release, the release rate of the oral preparation of this embodiment reaches 90.1% in 60 minutes, and that of ordinary oral preparations is 88.4%, and the difference is further narrowed to 1.7%. Performance balance analysis: This embodiment achieves a balance between adsorption force and release rate through charge-modified MCC and porous sugar alcohol structure, and does not significantly inhibit release due to enhanced adsorption.

[0140] 3-3) Adhesion Test: The oral product of this example had an initial smoothness score of ≥ 4.5 (out of 5); an oral adhesion rate of ≤ 8%. According to GB / T 2794-2022 "Determination of Viscosity of Adhesives," the adhesion of the oral product to the steel plate decreased by 80% to 90% after 7 days of storage, and the adhesion force was less than 0.2 N.

[0141] In summary, the anti-powder leakage oral product and its preparation method involved in this application can solve the problems of high powder leakage rate, poor stability and sticky taste of traditional oral products during transportation and use through charge modification, porous structure optimization and gradient lubrication technology. Specifically, the synergistic effect of cationic microcrystalline cellulose (MCC) and sodium carboxymethyl cellulose (CMC-Na) is adopted to enhance the binding force of particles through electrostatic adsorption, reduce the powder leakage rate to ≤1.5%, and significantly improve the stability of the particle structure under transportation vibration and temperature change environment; based on the nano-calcium carbonate template method, porous sugar alcohol (pore size 100-300nm) is prepared, the specific surface area is increased by 3-5 times, and combined with a gradient hydrophobic lubricating layer (sodium stearate fumarate spraying, thickness 10-20μm), a "sticky inside and slippery outside" structure is achieved, which reduces oral mucosal adhesion (adhesion rate ≤8%) and a smoothness score ≥4.5; experiments show that the powder leakage rate of this application is reduced by 84% compared with the traditional process, the nicotine adsorption efficiency is increased by 40%-50%, the cumulative release rate within 30 minutes reaches 89.1%, and the particle integrity and release stability are better after long-term storage, which is suitable for large-scale production of dry oral products.

[0142] The above content is a further detailed description of the present application in conjunction with specific implementation methods, and the specific implementation of the present application cannot be considered to be limited to these descriptions. For ordinary technicians in the technical field to which the present application belongs, several simple deductions or substitutions can be made without departing from the concept of the present application.

Claims

1. An oral product, characterized in that: The invention comprises a composition, wherein the composition comprises a first adsorbent and a functional substance, wherein the first adsorbent is positively charged as a whole, the functional substance is negatively charged as a whole, and the functional substance is at least partially adsorbed on the first adsorbent.

2. The oral product according to claim 1, wherein The first adsorbent includes a first support and a cationic agent.

3. The oral product according to claim 2, characterized in that The first carrier comprises at least one of microcrystalline cellulose and silicified microcrystalline cellulose; and / or, the cationic agent comprises at least one of chitosan hydrochloride, ε-polylysine hydrochloride, chitosan oligosaccharide hydrochloride and amino starch; And / or, the first adsorbent includes microcrystalline cellulose modified with chitosan hydrochloride.

4. The oral product according to claim 1, wherein The composition further includes a second adsorbent, which is used to adsorb at least a portion of the functional substance.

5. The oral product according to claim 4, characterized in that The second adsorbent includes a second carrier and a charge synergist, and the charge synergist is used to make the second adsorbent negatively charged as a whole.

6. The oral product according to claim 5, characterized in that The second carrier comprises a sugar alcohol; and / or, the second carrier comprises at least one of lactitol, erythritol, xylitol, isomalt, mannitol, sorbitol and maltitol; and / or, the second carrier is a porous material; And / or, the specific surface area of ​​the second carrier is ≥15m 2 / g; And / or, the charge synergist includes at least one of sodium carboxymethylcellulose, citrate, malate and tartrate.

7. The oral product according to any one of claims 1 to 6, characterized in that The composition further comprises at least one of a binder, a sweetener, a flavoring agent, a cooling agent, a pH adjuster, a preservative, and a surface lubricant.

8. The oral product according to claim 7, characterized in that The functional substance includes nicotine salt; and / or, the functional substance comprises at least one of nicotine tartrate, nicotine benzoate, nicotine lactate, nicotine citrate, nicotine oxalate, and nicotine malonate; and / or, the binder comprises at least one of carboxymethyl cellulose, povidone K30, sodium alginate and hydroxypropyl methyl cellulose; and / or, the surface lubricant comprises at least one of sodium stearate fumarate, magnesium stearate, stearic acid, talc and sodium lauryl sulfate; And / or, the sweetener comprises at least one of xylitol, sorbitol, mannitol, iglesia, lactitol, maltitol, isomalt, hydrogenated starch hydrolysate, erythritol, maltotriitol, aspartame, acesulfame potassium, saccharin sodium, sucralose, neotame, cyclamate, alitame, steviol glycosides, arabitol and monk fruit sweetener; and / or, the fragrance comprises at least one of bergamot essence, eucalyptus essence, citrus essence, lemon essence, peppermint essence, mint essence, menthol, licorice essence, wintergreen essence, tobacco essence, coffee essence, vanilla essence, lime essence, apple essence, peach essence, mango essence, cherry essence, blueberry essence, strawberry essence, cola flavor, cinnamon essence, pandan essence, and watermelon flavor; and / or, the cooling agent comprises at least one of menthol, a menthol derivative, WS-3, and WS-23; and / or, the pH adjuster comprises at least one of citric acid, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate and magnesium carbonate; And / or, the preservative includes at least one of ethylparaben, benzoic acid, sodium benzoate, potassium sorbate and benzalkonium chloride.

9. A method for preparing an oral product, characterized in that: include: Obtaining an adsorbent includes: obtaining a first adsorbent, wherein the first adsorbent includes a first carrier and a cationic agent, and the first adsorbent is positively charged as a whole; Obtaining a mixed material, comprising: mixing a first adsorbent and a functional substance to obtain a mixed material; Granulation includes: granulating the mixed material to obtain a composition, and then obtaining the oral product from the composition.

10. The preparation method according to claim 9, characterized in that The obtaining of the adsorbent further comprises: obtaining a second adsorbent; wherein the second adsorbent comprises a second carrier and a charge synergist, and the charge synergist is used to make the second adsorbent as a whole negatively charged; The obtaining of the mixed material comprises: mixing the first adsorbent, the second adsorbent and the functional substance to obtain the mixed material; And / or, the granulation comprises: spraying a binder solution into the mixed material to granulate to obtain a composition, covering a lubricating layer on the surface of the composition, wherein the lubricating layer comprises a surface lubricant; and obtaining the oral product.

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