Buccal product

Abstract

The embodiment of the invention provides a buccal product, the buccal product provided by the embodiment of the invention comprises an active substance, a TRPM5 channel blocker, a first bitterness inhibitor and a second bitterness inhibitor, the first bitterness inhibitor is used for embedding the active substance, and the second bitterness inhibitor is used for enhancing sweetness and / or covering bitterness. The active substance is embedded in the first bitter inhibitor, so that the release rate of the active substance can be controlled through the first bitter inhibitor; the TRPM5 channel blocking agent can block a bitter receptor TRPM5 channel and weaken the bitter perception capability, and then the second bitter inhibitor is combined to enhance the sweet taste and / or cover the bitter taste, so that a triple bitter inhibition mechanism is realized, a bitter perception path is blocked, and the use comfort and market acceptance of the buccal product are improved; therefore, the buccal product provided by the embodiment of the invention can effectively improve the problem of poor user experience caused by too strong natural bitter taste of the existing buccal product.

Description

Technical Field

[0001] This application belongs to the technical field of food or medicine, and particularly relates to an orally held product. Background Art

[0002] Currently, oral nicotine products or other products with active substances that relieve nicotine addiction are generally used for smoking cessation. Among these orally held products, nicotine and other active substances such as caffeine usually have a bitter taste, making it easy to cause discomfort when the active substances in the existing orally held products are released into the mouth.

[0003] Existing orally held products such as nicotine pouches have certain limitations in improving the bitter taste of nicotine. Their natural bitter taste is too strong, resulting in a poor user experience. Summary of the Invention

[0004] The technical problem to be solved by this application is to provide an orally held product and its preparation method to improve the problem that the natural bitter taste of the existing orally held products is too strong, resulting in a poor user experience.

[0005] To improve the above problems, this application is implemented through the following technical solutions:

[0006] This application provides an orally held product, which includes an active substance, a TRPM5 channel blocker, a first bitter taste inhibitor, and a second bitter taste inhibitor. Among them, the first bitter taste inhibitor is used to encapsulate the active substance, and the second bitter taste inhibitor is used to enhance sweetness and / or mask bitterness.

[0007] Further, the active substance includes at least one of nicotine or nicotine derivatives.

[0008] Further, in the orally held product, the first bitter taste inhibitor includes at least one of cyclodextrin substances, poly(lactic-co-glycolic acid), and chitosan.

[0009] Further, in the orally held product, the cyclodextrin substances include at least one of hydroxypropyl-β-cyclodextrin, sulfobutyl ether-β-cyclodextrin, and methylated cyclodextrin.

[0010] Further, in the orally held product, the TRPM5 channel blocker includes at least one of phospholipid-menthol complex, Zn 2+ food additive, La 3+ food additive.

[0011] Further, in the orally held product, the second bitter taste inhibitor includes at least one of phloridzin derivatives, naringin derivatives, glycyrrhizic acid derivatives, and quercetin.

[0012] Further, by mass parts, the amount of the first bitter inhibitor in the buccal product is 3 to 5 parts, the amount of the TRPM5 channel blocker is 1 to 2 parts, and the amount of the second bitter inhibitor is 0.3 to 0.8 parts.

[0013] Further, the buccal product further includes at least one of a filler, a flavor, a binder, a lubricant, a sweetener, an antibacterial agent, a solvent, a pH regulator, and an antioxidant.

[0014] Further, the buccal product satisfies at least one of the following conditions (I) to (VI):

[0015] (I) The binder includes at least one of sodium alginate, hypromellose, povidone, and sodium alginate;

[0016] (II) The lubricant includes at least one of talc, colloidal silica, and magnesium stearate;

[0017] (III) The sweetener includes at least one of xylitol, sorbitol, mannitol, erythritol, lactitol, maltitol, isomaltitol, hydrogenated starch hydrolysate, erythritol, maltotriitol, aspartame, acesulfame potassium, sodium saccharin, sucralose, neotame, sodium cyclamate, alitame, stevioside, arabitol, and mogroside;

[0018] (IV) The antibacterial agent includes at least one of ethylparaben, benzoic acid, and sodium benzoate;

[0019] (V) The pH regulator includes at least one of citric acid, sodium bicarbonate, and sodium carbonate;

[0020] (VI) The filler includes at least one of microcrystalline cellulose, natural cellulose, porous hydroxymethylcellulose, porous starch, gum arabic, maltodextrin, and sugar alcohols.

[0021] Further, the form of the buccal product is a buccal pouch, an orally dissolving film, or a tablet.

[0022] Compared with the prior art, the embodiments of the present application have the following advantages:

[0023] In the embodiments of the present application, the provided oral products include an active substance, a TRPM5 channel blocker, a first bitter inhibitor, and a second bitter inhibitor. Among them, the first bitter inhibitor is used to encapsulate the active substance, and the second bitter inhibitor is used to enhance sweetness and / or mask bitterness. Since the active substance is encapsulated in the first bitter inhibitor, the release rate of the active substance can be controlled by the first bitter inhibitor; while the TRPM5 channel blocker can block the bitter receptor TRPM5 channel and weaken the bitter perception ability. Combined with the second bitter inhibitor to enhance sweetness and / or mask bitterness, a triple bitter suppression mechanism is achieved, blocking the bitter perception path, and improving the use comfort and market acceptance of the oral product; therefore, the oral product provided by the embodiments of the present application can effectively improve the problem that the natural bitterness of the existing oral product is too strong, resulting in a poor user experience.

[0024] It should be understood that the above general description and the following detailed description are only exemplary and explanatory, and cannot limit the present application. Detailed implementation manners

[0025] To make the above objects, features, and advantages of the present application more obvious and understandable, the present application will be further described in detail below in conjunction with the specific implementation manners.

[0026] The terms "first" and "second" in the description and claims of the present application may explicitly or implicitly include one or more of such features. In the description of the present application, unless otherwise specified, the meaning of "a plurality" is two or more. In addition, "and / or" in the description and claims means at least one of the connected objects. The character " / " generally indicates that the associated objects before and after are in an "or" relationship.

[0027] The inventors found that although oral products such as nicotine pouches provide a convenient way of use, due to the special chemical structure of nicotine, when nicotine is released into the mouth, it often causes an uncomfortable feeling.

[0028] Regarding the natural bitterness of nicotine, the prior art generally alleviates it by means of sustained release technology, compounding of sweeteners and fragrances, adjusting nicotine concentration, adding fragrances and flavoring agents, adding pH additives, etc. Among them, the method of compounding sweeteners and fragrances fails to solve the root cause of bitterness, and the residue of sweeteners affects the taste; while adjusting the nicotine concentration easily reduces the product efficacy; the existing sustained release technology has a complex production process, which easily leads to uneven release or delayed effects; adding fragrances and flavoring agents has the problems of masking the nicotine taste or causing allergies, and the aroma is easily volatile; while pH adjustment easily causes oral irritation or unstable adjustment.

[0029] Therefore, the prior art has certain limitations in improving the bitterness of nicotine and other active substances such as caffeine, and cannot effectively reduce or inhibit the natural bitterness in oral products.

[0030] In view of the above problems, embodiments of the present application provide an oral product including an active substance, a TRPM5 channel blocker, a first bitterness inhibitor, and a second bitterness inhibitor. Among them, the first bitterness inhibitor is used to encapsulate the active substance, and the second bitterness inhibitor is used to enhance sweetness and / or mask bitterness.

[0031] In some embodiments, the active substance includes an active agent with medical properties, such as CBD; in some embodiments, the active substance includes other active agents with specific properties, such as caffeine, tea polyphenols, capsaicin, etc.

[0032] In some embodiments, the active substance is at least one of nicotine or a nicotine derivative, which can be released in the oral cavity and bring a pleasant feeling to the user, thereby helping smokers relieve withdrawal symptoms.

[0033] In some embodiments of the present application, nicotine includes natural nicotine and / or synthetic nicotine, and nicotine derivatives include nicotine salts, nicotine in a matrix such as a sugar matrix or an organometallic complex, a nicotine-resin combination, a nicotine inclusion complex, and one or several of non-covalently bound nicotine. Among them, 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, etc. Nicotine derivatives also include nicotine with substituents, such as hexamethyl nicotine, hexamethyl nicotine lactate, hexamethyl nicotine malate, hexamethyl nicotine salicylate, hexamethyl nicotine cyclodextrin inclusion complex, hexamethyl nicotine hydrochloride, hexamethyl nicotine dihydrochloride, hexamethyl nicotine tartrate, hexamethyl nicotine tartrate dihydrate, hexamethyl nicotine sulfate, hexamethyl nicotine zinc chloride, hexamethyl nicotine benzoate, and one or more mixtures thereof.

[0034] The above-mentioned active substances can not only dissolve rapidly in the oral cavity, release the active substances, and help smokers relieve withdrawal symptoms, but also achieve a long-lasting and continuous stimulating effect.

[0035] In some embodiments, the form of the oral product can be an oral pouch, an orally dissolving film, a tablet, etc.

[0036] Among them, TRPM5 (Transient Receptor Potential Cation Channel Subfamily M Member 5) is a calcium-activated non-selective cation channel that plays a key role in taste signal transduction, especially in the perception of sweet, bitter, and umami tastes. TRPM5 channel blockers can interfere with taste signal transmission through the TRPM5 channel by inhibiting the activity of this channel. For example, they can bind to the pore region or regulatory domain of the channel to block ion permeability, thereby achieving the inhibition of bitterness; or they can indirectly close TRPM5 by inhibiting the activation of upstream calcium signals (such as IP3 receptors), thereby achieving the inhibition of bitterness; and by changing the channel conformation and reducing its sensitivity to calcium ions, thereby achieving the inhibition of bitterness.

[0037] Among them, the first bitter inhibitor is the main bitter inhibitor, which can encapsulate the active substance through host-guest interaction, thereby achieving the control of the release rate of the active substance.

[0038] Among them, the second bitter inhibitor is the auxiliary bitter inhibitor, which acts on the taste system and reduces the bitter taste perception ability to relieve the bitter taste by masking the bitterness or enhancing the sweetness.

[0039] In the embodiments of the present application, since the active substance is encapsulated in the first bitter inhibitor, the release rate of the active substance can be controlled by the first bitter inhibitor; the TRPM5 channel blocker can block the TRPM5 channel of the bitter receptor and weaken the bitter taste perception ability; while the second bitter inhibitor can enhance the perception ability of the sweet taste signal, thereby forming a triple bitter inhibition mechanism of "physical encapsulation + receptor blocking + signal regulation", blocking the bitter taste and enhancing the sweet taste perception, and improving the use comfort and market acceptance of the buccal products; therefore, the buccal products provided by the embodiments of the present application can effectively improve the problem that the natural bitterness of the active substance in the existing buccal products is too strong, resulting in poor user experience.

[0040] In some embodiments, the first bitter inhibitor includes at least one of polycyclodextrin substances, lactic acid-glycolic acid copolymer, and chitosan.

[0041] Among them, cyclodextrins (CDs) are a class of cyclic oligosaccharide molecules generated by enzymatic hydrolysis of starch, with unique hydrophobic cavities and hydrophilic outer surfaces, and can encapsulate active substances through host-guest interaction, thereby achieving the control of the release rate of active substances.

[0042] In some embodiments, the poly(lactic-co-glycolic acid) can be used to prepare nicotine-loaded nanoparticles by emulsion or solvent diffusion methods, enabling sustained release over several hours. In some embodiments, chitosan can achieve nicotine sustained release by relying on polymer degradation or swelling. Chitosan has mucoadhesive properties, which can prolong the local action time.

[0043] In some embodiments, the cyclodextrin substances include at least one of hydroxypropyl-β-cyclodextrin, sulfobutyl ether-β-cyclodextrin, and methylated cyclodextrin.

[0044] In this embodiment, considering the poor solubility, stability, and inclusion ability of existing natural cyclodextrins, chemical modification of cyclodextrin substances can improve the solubility, stability, and inclusion ability of natural cyclodextrins.

[0045] Among them, hydroxypropyl-β-cyclodextrin (HP-β-CD) has good water solubility and can reduce renal toxicity; the sulfobutyl ether modification in sulfobutyl ether-β-cyclodextrin (SBE-β-CD) significantly improves the water solubility of β-cyclodextrin, can improve the dispersion of active substances by inclusion, reduce their free concentration in the oral cavity, reduce taste irritation, and the formed inclusion complex gradually releases the active substance during digestion, avoiding the strong bitter taste caused by instant high concentration; while methylated cyclodextrin (such as RM-β-CD) has a stronger inclusion ability for active substances.

[0046] In one embodiment, the TRPM5 channel blockers include at least one of phospholipid-menthol complexes, Zn 2+ food additives, La 3+ food additives.

[0047] Among them, Zn 2+ in the Zn 2+ food additive can change the enzyme activity (such as alkaline phosphatase and lipase), conformation or function of TRPM5 through coordination with proteins, thereby achieving the blocking effect on TRPM5.

[0048] Among them, La 3+ in the La 3+ food additive has stronger charge attraction and can occupy the Ca 2+ binding site of TRPM5 to block channel activation, thereby achieving the blocking effect on TRPM5.

[0049] Among them, phospholipids can fuse with cell membranes and change their physical properties, such as fluidity and permeability, thereby affecting the activity of TRPM5; while menthol can act on TRP channels (such as TRPM8) and can regulate the TRPM5 channel in a competitive or non-competitive manner to reduce its response to bitter substances.

[0050] In some embodiments, the phospholipid-menthol complex is a thin film or liposome, which is more soluble and acts on the TRPM5 channel. Among them, phospholipids and menthol are dissolved in an organic solvent (such as ethanol, acetone), and then the solvent is removed by rotary evaporation to form a phospholipid-menthol thin film; while phospholipids and menthol are hydrated with water or buffer, and then nanoparticles are formed by stirring or sonication to form liposomes.

[0051] In some embodiments, the second bitter taste inhibitor described above includes at least one of phloridzin derivatives, naringin derivatives, glycyrrhizic acid derivatives, and quercetin.

[0052] Among them, phloridzin derivatives, naringin derivatives, glycyrrhizic acid derivatives, and quercetin help to enhance the perception ability of sweetness.

[0053] In this embodiment, since the active substance is embedded in the first bitter taste inhibitor, the active substance can be embedded through host-guest interaction, and the release rate of the active substance can be controlled by the first bitter taste inhibitor; the TRPM5 channel blocker can block the bitter taste receptor TRPM5 channel and weaken the bitter taste perception ability; while phloridzin derivatives, naringin derivatives, glycyrrhizic acid derivatives, quercetin, etc. help to enhance the perception ability of sweetness, thus forming a triple bitter taste inhibition mechanism of "physical embedding + receptor blocking + signal regulation", blocking bitter taste and enhancing sweet taste perception, and improving the use comfort and market acceptance of the buccal products; therefore, the buccal products provided by the embodiments of the present application can effectively improve the problem that the natural bitter taste of the existing buccal products is too strong, resulting in poor user experience.

[0054] In some embodiments, by mass fraction, the amount of the first bitter taste inhibitor in the buccal product is 3 to 5 parts, the amount of the TRPM5 channel blocker is 1 to 2 parts, and the amount of the second bitter taste inhibitor is 0.3 to 0.8 parts, which can effectively balance the bitter taste inhibition effect and the long-lasting and continuous stimulation effect produced by the active substance.

[0055] Exemplarily, by mass fraction, the amount of the first bitter taste inhibitor in the buccal product can be one of 3 parts, 4 parts, 5 parts or any range value between any two of them, the amount of the TRPM5 channel blocker can be one of 1 part, 1.5 parts, 3 parts or any range value between any two of them, and the amount of the second bitter taste inhibitor can be one of 0.3 parts, 0.5 parts, 0.8 parts or any range value between any two of them.

[0056] In some embodiments, the buccal product further includes at least one of a filler, a fragrance, a binder, a lubricant, a sweetener, an antibacterial agent, a solvent, a pH regulator, and an antioxidant.

[0057] Among them, the filler can ensure the stable product form of the buccal product by increasing the solid content, that is, maintaining the volume and shape of the buccal product, such as in the form of small bags or loose forms. The filler can be at least one of microcrystalline cellulose (MCC), natural cellulose, porous hydroxymethyl cellulose, porous starch, gum arabic, maltodextrin, sugar alcohols, etc.

[0058] Among them, microcrystalline cellulose can not only absorb water during the wet granulation process to form a viscous network to help the particles form, but also regulate the distribution of moisture and humectants (such as glycerol) in the buccal tobacco, prevent caking or excessive moisture, and the delicate powder texture of microcrystalline cellulose can reduce the graininess and improve the user's comfort.

[0059] Among them, the sugar alcohol filler can effectively fill the surface of the active substance and flavor, and extend their action time. The sugar alcohol filler can include substances such as xylitol, mannitol, lactitol, erythritol, isomaltulose, sorbitol, etc.

[0060] Among them, the flavor can improve the taste and flavor, cover the odor of active substances such as nicotine agents, and enhance the use experience; at the same time, flavors such as mint and spicy spices can stimulate the oral mucosa, promote saliva secretion, help the active substances to be released faster and absorbed through the oral cavity, and enhance the effect; in addition, the diverse fragrance types of flavors (such as coffee, chocolate, cinnamon, etc.) can meet the preferences of different consumers and increase the product attractiveness.

[0061] Among them, the binder can not only bond powders or particles such as active substances and flavors into a uniform solid (such as small bags or tablets), prevent loosening or fragmentation, so as to maintain the product form and structure, but also slow down the release of active substances and flavor substances such as flavors by adjusting the dissolution rate, avoiding a large amount of release at one time, which may cause oral irritation or overbearing taste. And by controlling the type and proportion of the binder, the buccal product can be maintained in the oral cavity for a longer time, improving the user experience; in addition, the binder bonds the fine particles into a smooth texture, avoiding a gritty feeling or discomfort during use, and can also help the components such as active substances, flavors, and pH regulators to be evenly distributed in the product, ensuring the consistency of each dose.

[0062] Among them, the lubricant can not only maintain the humidity, give the product a soft and smooth touch, reduce the graininess, but also affect the dissolution rate of the active substance by adjusting the water activity to achieve a sustained release effect, avoiding discomfort caused by a sudden increase in concentration; in addition, the lubricant can maintain the uniformity of the mixture, avoiding uneven dryness and wetness or component separation during storage.

[0063] Among them, the above-mentioned sweeteners can mask the bitter or pungent taste of the active substance, enhance the palatability of the product; at the same time, the sweeteners can also enhance the sense of pleasure, make the product closer to the experience of snacks or candies, and reduce the resistance to use; in addition, the sweeteners act synergistically with the flavoring agents to strengthen the flavor expressions such as fruit flavor and mint flavor.

[0064] Among them, bacteriostatic agents and the like can inhibit the oxidation reaction of the active substance, flavoring agents, etc., avoid rancidity, discoloration or invalidation, slow down the degradation of components, and maintain the stability and flavor consistency of the buccal product.

[0065] In some embodiments, the buccal product further includes a solvent, and the above-mentioned solvent is used to enhance the uniform dispersion of fat-soluble or water-soluble components such as the active substance and the flavoring agent in the matrix, and can also enhance the permeability of nicotine through the oral mucosa.

[0066] Among them, the pH regulator can neutralize the irritation of acidic components, reduce the burning sensation in the mouth, and maintain a weak alkaline environment. In some embodiments, the active substance includes nicotine or nicotine derivatives, which are in a non-ionic state in an alkaline environment (pH 8-9), not only are not easily degraded, but are also more easily absorbed through the oral mucosa, enhancing bioavailability, extending the shelf life, and adding a pH regulator also helps to control the release rate of nicotine.

[0067] In some embodiments, the binder may include at least one of sodium alginate, hypromellose, povidone, and sodium alginate. In some embodiments, the lubricant includes at least one of talc, colloidal silica, and magnesium stearate. In some embodiments, the sweetener includes at least one of xylitol, sorbitol, mannitol, erythritol, lactitol, maltitol, isomaltulose, hydrogenated starch hydrolysate, erythritol, maltotriitol, aspartame, acesulfame potassium, sodium saccharin, sucralose, neotame, sodium cyclamate, alitame, stevioside, arabitol, and mogroside. In some embodiments, the bacteriostatic agent includes at least one of ethyl paraben, benzoic acid, and sodium benzoate. In some embodiments, the pH regulator includes at least one of citric acid, sodium bicarbonate, and sodium carbonate.

[0068] In some embodiments, the water content of the buccal product does not exceed 35%. Exemplarily, the water content of the buccal product can be one of 5%, 6%, 10%, 15%, 20%, 30%, 35% or any range value between any two of them.

[0069] In some embodiments, by mass fraction, the buccal product includes the following substances:

[0070] 1 - 20 parts of nicotine agent, 30 - 81 parts of filler, 0 - 10 parts of binder, 0 - 5 parts of lubricant, 0.1 - 1 part of sweetener, 1 - 15 parts of essence, 0.1 - 5 parts of bacteriostatic agent, 0 - 1 part of pH regulator, 3 - 5 parts of first bitter inhibitor, 1 - 2 parts of TRPM5 channel blocker, and the amount of the second bitter inhibitor is 0.3 - 0.8 parts.

[0071] In some embodiments, the shape of the above-mentioned buccal product can be cylindrical, granular, strip-shaped, sheet-shaped, filamentous, spherical, film-shaped or other irregular shapes, which can be specifically adjusted according to different design requirements.

[0072] In some embodiments, the buccal product provided by the embodiments of the present application is a buccal pouch, including a pouch body permeable to saliva, and the pouch body is used to fill substances such as active substances, TRPM5 channel blockers, first bitter inhibitors and second bitter inhibitors.

[0073] Among them, the pouch body can be a fiber bag, and is treated with surface pure water, sodium alginate solution, sodium hyaluronate solution, hydroxypropyl methylcellulose solution, etc. to maintain the humidity of the buccal product.

[0074] In some embodiments, the buccal product in the embodiments of the present application can be prepared according to the following steps based on the formula in Table 1:

[0075] (1) Weigh nicotine, edible essence, bacteriostatic agent, sweetener, TRPM5 channel blocker, first bitter inhibitor, second bitter inhibitor, and pH regulator according to the formula ratio, add an appropriate amount of water to dissolve, and stir with a blender until clarified to obtain a butyl salt solution.

[0076] (2) Weigh the filler and binder according to the formula ratio, add them to a wet granulation pot, and mix at a rotation speed of 100 rpm - 200 rpm for 1 min - 10 min to obtain a homogeneous slurry.

[0077] (3) Under the condition that the cutter speed is 500 rpm - 2000 rpm, carry out wet granulation on the above-mentioned homogeneous slurry, and control the water content to be 10% - 20% to obtain active granules.

[0078] (4) Weigh the lubricant according to the formula ratio, add it to the active granules for total mixing to obtain a finished powder, and control the mixing time to be 1 min - 5 min, the stirring speed to be 100 rpm - 200 rpm, and the cutter speed to be 500 rpm - 2000 rpm.

[0079] (5) Fill the finished powder into a fiber bag for encapsulation according to a filling amount of 600 mg. Among them, control the longitudinal sealing temperature to be 200 ± 10 °C, the front sealing temperature to be 150 ± 10 °C, and the rear sealing temperature to be 130 ± 10 °C.

[0080] (6) Spray purified water, 0.1% sodium alginate aqueous solution, 0.1% sodium hyaluronate aqueous solution, 0.5% hydroxypropyl methylcellulose aqueous solution, etc. onto the surface of the fiber bag to obtain the finished oral product.

[0081] Table 1

[0082] Ingredient Use Parts by mass / part Active substance Active ingredient 1～20 Filler Fill and adsorb 30～81 Binder Binder 0～10 Lubricant Anti-adhesive 0～5 Sweetener Provide sweetness 0.1～1 First bitter taste inhibitor Inhibit bitter taste 3～5 TRPM5 channel blocker Inhibit bitter taste 1～2 Second bitter taste inhibitor Inhibit bitter taste 0.3～0.8 Food flavor Provide taste 1～15 Bacteriostat Bacteriostat 0.1～5 Moisture Promote release 5～30 pH regulator pH adjustment 0～1

[0083] The oral product provided by the embodiment of the present application can effectively improve the key problems of traditional oral tobacco in terms of taste, nicotine release, stability, flavor retention, hygroscopicity, etc., and can significantly improve the quality of the product and the user experience.

[0084] In order to make the invention purpose, technical solution and beneficial effects of the present application clearer, the present application will be further described below in conjunction with embodiments. It should be understood that these embodiments are only used to illustrate the present application and not to limit the scope of the present application.

[0085] The present application will be described in detail below through embodiments.

[0086] Test method

[0087] (1) Nicotine dissolution ratio test:

[0088] Put 500 mg of the sample into a dissolution apparatus (paddle method, USP II), then add it to 900 mL of simulated saliva (pH 6.8, containing 0.5% SDS), control the temperature at 37°C ± 0.5°C and the rotation speed at 50 rpm, and then take samples at 1, 3, 5, 10, 20, 30, 45, and 60 minutes respectively, filter the sample solution through a 0.22 μm filter membrane, and then send the filtrate to HPLC (C18 column, detection wavelength 260 nm) to detect the nicotine concentration.

[0089] (2) Product taste evaluation:

[0090] Sweetness (1 - 5 points): The higher the score, the more pleasant, natural and harmonious the sweet feeling is;

[0091] Bitterness (1 - 5 points): The lower the score, the lighter the bitterness and the better the taste;

[0092] Fragrance (1 - 5 points): The higher the score, the stronger, more stable and higher acceptance of the aroma.

[0093] Prepare oral products respectively according to the following preparation process based on the formulas shown in Table 2:

[0094] (1) Weigh nicotine, edible essence, bacteriostatic agent, sweetener, the first bitterness inhibitor, the first bitterness inhibitor, the second bitterness inhibitor, and pH regulator according to the formula ratio, dissolve them in an appropriate amount of water, and stir with a stirrer until clear to obtain a butyl salt solution.

[0095] (2) Weigh the filler and binder according to the formulation ratio, add them to the wet granulation pot, and mix for 10 min at a rotation speed of 200 rpm to obtain a homogeneous slurry.

[0096] (3) Under the condition that the cutter speed is 1500 rpm, perform wet granulation on the above homogeneous slurry, and control the water content to be 10 - 20%, to obtain active granules.

[0097] (4) Weigh the lubricant according to the formulation ratio, add it to the active granules for overall mixing to obtain the finished powder, and control the mixing time to be 5 min, the stirring speed to be 200 rpm, and the cutter speed to be 1500 rpm.

[0098] (5) Load the finished powder into the fiber bag according to a filling amount of 600 mg, and control the longitudinal sealing temperature to be 200 ± 10 °C, the front sealing temperature to be 150 ± 10 °C, and the rear sealing temperature to be 130 ± 10 °C.

[0099] (6) Spray the surface treatment agent onto the surface of the nicotine bag to obtain the finished oral product.

[0100] Table 2

[0101]

[0102] The nicotine dissolution ratio tests were carried out on the oral products prepared in each example and comparative example, and the results are shown in Table 3 respectively.

[0103] Table 3

[0104]

[0105] Judging from the nicotine dissolution curve, since the first bitter taste inhibitor effectively entraps the active substance nicotine, it can effectively control the release rate of nicotine, make the release of nicotine more uniform, maintain the stability of nicotine, not only improve the user experience, but also reduce the waste of nicotine, and provide a more comfortable taste.

[0106] Product taste evaluations were carried out on the products prepared in each example and comparative example, and the results are shown in Table 4 respectively.

[0107] Table 4

[0108]

[0109] As can be seen from Table 2, after adding the bitter taste inhibitor in Example 1 and Example 2, the sweetness and fragrance scores are significantly better than those of the comparative example;

[0110] The bitter taste inhibition effect of Example 2 is the strongest (average 1.625 points), but the sweetness is slightly higher and on the sweeter side, which is suitable for those with a mild taste;

[0111] The comparative example had the highest bitterness score (the strongest bitterness), and both the fragrance and sweetness were relatively low;

[0112] The comprehensive score recommended Example 1, which achieved a good balance in controlling sweetness, fragrance, and bitterness, and was suitable for popularization and application.

[0113] In summary, in the buccal products provided by the embodiments of the present application, the active substance is embedded in the first bitterness inhibitor, which can control the release rate of the active substance through the first bitterness inhibitor, while the TRPM5 channel blocker can block the TRPM5 channel of the bitter receptor and weaken the bitter taste perception ability. Combined with the second bitterness inhibitor to enhance sweetness and / or mask bitterness, a triple bitter taste inhibition mechanism is achieved to block the bitter taste perception path and improve the use comfort and market acceptance of the buccal products; therefore, the buccal products provided by the embodiments of the present application can effectively improve the problem that the existing buccal products have too strong natural bitterness, resulting in poor user experience.

[0114] Although the preferred embodiments of the embodiments of the present application have been described, those skilled in the art can make additional changes and modifications to these embodiments once they know the basic creative concept. Therefore, the claims are intended to be interpreted to include the preferred embodiments as well as all changes and modifications falling within the scope of the embodiments of the present application.

[0115] The above has introduced in detail a buccal product provided by the present application. Specific examples are used in this article to elaborate on the principle and implementation manner of the present application. The description of the above embodiments is only used to help understand the method and its core idea of the present application; at the same time, for those of ordinary skill in the art, according to the idea of the present application, there will be changes in the specific implementation manner and application scope. In summary, the content of this specification should not be construed as a limitation to the present application.

Claims

1. An oral product, characterized in that, It includes an active substance, a TRPM5 channel blocker, a first bitterness inhibitor, and a second bitterness inhibitor. Among them, the first bitterness inhibitor is used to encapsulate the active substance, and the second bitterness inhibitor is used to enhance sweetness and / or mask bitterness.

2. The oral product according to claim 1, wherein The active substance includes at least one of nicotine or a nicotine derivative.

3. The oral product according to claim 1, characterized in that, The second bitterness inhibitor includes at least one of phloridzin derivatives, naringin derivatives, glycyrrhizic acid derivatives, and quercetin.

4. The oral product according to claim 1, characterized in that, The first bitterness inhibitor includes at least one of cyclodextrin substances, poly(lactic-co-glycolic acid), and chitosan.

5. The oral product according to claim 4, wherein The cyclodextrin substances include at least one of hydroxypropyl-β-cyclodextrin, sulfobutyl ether-β-cyclodextrin, and methylated cyclodextrin.

6. The oral product according to claim 1, characterized in that, The TRPM5 channel blockers include at least one of phospholipid-menthol complexes, Zn2+-containing food additives, and La 3 +-containing food additives.

7. The oral product according to claim 1, characterized in that, By mass fraction, the amount of the first bitterness inhibitor in the buccal product is 3 to 5 parts, the amount of the TRPM5 channel blocker is 1 to 2 parts, and the amount of the second bitterness inhibitor is 0.3 to 0.8 parts.

8. The oral product according to claim 1, wherein The buccal product further includes at least one of a filler, a flavor, a binder, a lubricant, a sweetener, an antibacterial agent, and a pH regulator.

9. The oral product according to claim 8, wherein The buccal product satisfies at least one of the following conditions (I) to (VI): (I) The binder includes at least one of sodium alginate, hypromellose, polyvinylpyrrolidone, and sodium alginate; (II) The lubricant includes at least one of talc, colloidal silica, and magnesium stearate; (III) The sweetener includes at least one of xylitol, sorbitol, mannitol, erythritol, lactitol, maltitol, isomaltulose, hydrogenated starch hydrolysate, erythritol, maltotriitol, aspartame, acesulfame potassium, sodium saccharin, sucralose, neotame, sodium cyclamate, alitame, stevioside, arabitol, and mogroside; (IV) The antibacterial agent includes at least one of ethylparaben, benzoic acid, and sodium benzoate; (V) The pH regulator includes at least one of citric acid, sodium bicarbonate, and sodium carbonate; (VI) The filler includes at least one of microcrystalline cellulose, natural cellulose, porous hydroxymethylcellulose, porous starch, gum arabic, maltodextrin, and sugar alcohols.

10. The oral product according to any one of claims 1 to 9, characterized in that, The form of the buccal product is a buccal pouch, an orally dissolving film, or a tablet.

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