A system and method for detecting nicotine dissolution in nicotine pouches

Abstract

This invention discloses a nicotine pouch nicotine dissolution detection system and method. The detection system includes: a constant temperature water bath; a detection container disposed inside the constant temperature water bath; a release unit disposed within the detection container for containing the nicotine pouch; an artificial saliva supply unit for supplying artificial saliva to the release unit; a detection unit for detecting the nicotine absorbance of the artificial saliva in the detection container; and a simulated oral mucosa layer disposed between the release unit and the detection container to simulate the human oral mucosal barrier. The release unit and the detection container are connected by a simulated oral mucosa layer, allowing the artificial saliva dissolved from the nicotine pouch to permeate through the simulated oral mucosa layer into the detection container. This invention also provides a detection method based on this system. By introducing a simulated oral mucosa layer and dynamic artificial saliva circulation, this invention realistically simulates the nicotine release and mucosal permeation process of the nicotine pouch in the oral environment.

Description

Technical Field

[0001] This application relates to the field of testing new tobacco products, specifically to a nicotine pouch nicotine dissolution testing system and method. Background Technology

[0002] As a new type of smokeless tobacco product, nicotine-containing products have experienced rapid growth in the international market in recent years, particularly in North America and Northern Europe. Among them, nicotine pouches are the most representative type of modern nicotine-containing products. Nicotine pouches are typically composed of plant fibers, fillers, pH adjusters, sweeteners, flavorings, and nicotine salts, packaged in small sachets similar to tea bags. When used, they are placed between the gums and lips in the mouth. The nicotine salts are converted into free nicotine under the influence of saliva and the pH environment of the mouth, and are absorbed into the bloodstream through the oral mucosa, thus producing a physiological sense of satisfaction. Because nicotine pouches do not contain tobacco leaves or shredded tobacco, do not produce smoke, and do not involve combustion, they are considered by consumers to be a relatively low-harm method of nicotine intake. Statistics show that in 2023, global nicotine pouch sales reached 15.51 billion pouches, a year-on-year increase of 43.5%, with sales revenue reaching US$7.86 billion. The US market accounted for more than 75% of this, demonstrating strong market growth potential.

[0003] In the classification of oral nicotine products, nicotine pouches differ significantly from traditional oral cigarettes. Traditional oral cigarettes primarily consist of processed tobacco leaves or shredded tobacco, containing harmful components such as nitrosamines unique to tobacco. Furthermore, they often require the user to exhale the tobacco, resulting in a rather rudimentary experience. Nicotine pouches, on the other hand, contain no tobacco leaves whatsoever. Their core components are synthetic nicotine salts or purified nicotine extracted from tobacco, combined with food-grade fillers and flavorings, resulting in a cleaner product, better taste, and lower levels of harmful substances. Moreover, the nicotine release from traditional oral cigarettes is typically slow and prolonged, while nicotine pouches, due to their flexible formulation design, allow for precise control of the nicotine release rate and duration by adjusting pH levels, filler types, and nicotine salt forms. Therefore, nicotine pouches place higher demands on testing technologies for product quality evaluation and release kinetic studies.

[0004] Currently, the industry primarily relies on sensory evaluation methods for quality assessment of nicotine pouches. Sensory evaluation typically involves trained evaluators subjectively scoring indicators such as onset speed, intensity of satisfaction, duration of satisfaction, and mouthfeel comfort according to established scoring criteria. However, sensory evaluation has significant limitations: First, different evaluators exhibit significant differences in nicotine tolerance, metabolic rate, and oral physiological environment, leading to individualized evaluation results and poor repeatability; second, sensory evaluation cannot provide quantitative, continuous nicotine release data, making it difficult to reveal the real-time release kinetics of the product in the oral environment; third, sensory evaluation is time-consuming and labor-intensive, and difficult to apply on a large scale to multi-formulation screening and quality control during product development.

[0005] To address the aforementioned issues, some in vitro dissolution testing methods have been attempted in the existing technology. For example, using a conventional dissolution meter, the oral nicotine product is placed in artificial saliva, and the amount of nicotine released is determined by periodic sampling and high-performance liquid chromatography analysis. However, such methods typically involve immersing the entire product in a large amount of artificial saliva, ignoring the real conditions of continuous flow of artificial saliva in the oral cavity and local contact between the product and the mucous membrane, and the sampling and testing methods cannot achieve true real-time monitoring.

[0006] Therefore, there is an urgent need to develop a detection system and method that can realistically simulate the human oral consumption environment, achieve real-time detection of nicotine dissolution, and be applicable to nicotine pouches. Summary of the Invention

[0007] In a first aspect, this application provides a nicotine pouch nicotine dissolution detection system, comprising: Constant temperature water bath; The testing container is placed inside a constant temperature water bath. A release unit, located inside the detection container, is used to hold the nicotine bag; An artificial saliva supply unit is used to supply artificial saliva into the release unit; The detection unit is used to detect the nicotine absorbance of artificial saliva in the detection container; A simulated oral mucosa layer is placed between the release unit and the detection container to simulate the human oral mucosal barrier; The release unit and the detection container are connected by a simulated oral mucosal layer liquid, allowing the artificial saliva dissolved from the nicotine bag to pass through the simulated oral mucosal layer and enter the detection container.

[0008] Furthermore, the detection unit includes a fiber optic probe and an ultraviolet detector. One end of the fiber optic probe extends into the detection container, and the other end is connected to the ultraviolet detector. The fiber optic probe and the ultraviolet detector are used in combination to monitor the nicotine absorbance of the artificial saliva in the detection container in real time.

[0009] Furthermore, the artificial saliva supply unit includes a reservoir, a flow controller, and a dropper; the reservoir is used to store artificial saliva; the inlet of the dropper is connected to the reservoir, and the outlet of the dropper is aligned with the nicotine bag within the release unit; the flow controller is used to regulate the flow rate of the artificial saliva.

[0010] Furthermore, the nicotine bag nicotine dissolution detection system also includes a stirring unit; the stirring unit includes a stirring component, a rotating shaft, and a stirring controller. The stirring component is located inside the detection container, and the stirring controller drives the stirring component through the rotating shaft.

[0011] Furthermore, the release unit is connected to the rotating shaft via a clamp-type connector.

[0012] Furthermore, the simulated oral mucosa layer is a biological tissue mucosa layer or a biomimetic oral mucosa layer; for example, the simulated oral mucosa layer is the porcine oral mucosa.

[0013] In a second aspect, this application provides a detection method for the nicotine dissolution detection system of the first aspect, comprising the following steps: Step S1: Place the nicotine pouch into the release unit; Step S2: Start the constant temperature water bath to keep the ambient temperature constant to the simulated oral cavity temperature, and at the same time start the stirring unit to make the liquid in the test container uniform. Step S3: Inject artificial saliva into the release unit at a set flow rate through the artificial saliva supply unit, allowing the artificial saliva to flow through the nicotine bag; Step S4: The artificial saliva dissolved in the nicotine bag passes through the simulated oral mucosa layer and enters the test container; Step S5: The absorbance signal of the liquid in the detection container is collected in real time by an optical fiber probe and transmitted to an ultraviolet detector. The release curve of nicotine dissolution over time is obtained after data processing.

[0014] Furthermore, the simulated oral temperature was between 36.3°C and 37.2°C.

[0015] Furthermore, the flow rate of artificial saliva is set at 2.0-2.5 mL / min.

[0016] Furthermore, the testing method also includes step S6: comparing and verifying the obtained nicotine dissolution release curve data with the physiological satisfaction, intoxication, and duration data obtained from human sensory evaluation, in order to evaluate the quality of the nicotine pouch.

[0017] This application has the following beneficial effects: By setting up a simulated oral mucosa layer and combining it with dynamic artificial saliva dripping, the process of saliva flow, local contact and mucosal absorption of nicotine bags in the oral cavity is realistically simulated, overcoming the defect of the product being completely immersed in artificial saliva in traditional dissolution meters.

[0018] By using a combination of fiber optic probe and ultraviolet detector, the fiber optic probe is directly inserted into the detection container to collect nicotine absorbance signals in real time and convert them into nicotine concentration data instantly. This enables online and continuous monitoring of nicotine dissolution, avoiding the time lag and data discontinuity caused by manual sampling and intermittent testing.

[0019] By separating the release unit and the detection container through a simulated oral mucosa layer and using a stirring component, the process of nicotine being released from the nicotine pouch, passing through the mucosa layer, and entering the detection container does not interfere with the detection process, thus avoiding the impact of a high-concentration release environment on detection sensitivity and accuracy. Attached Figure Description

[0020] To more clearly illustrate the technical solution of this application, the drawings used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of this patent and should not be regarded as a limitation of the scope. For those skilled in the art, other related drawings can be obtained from these drawings without creative effort.

[0021] Figure 1 This is a schematic diagram of a nicotine dissolution detection system according to one embodiment of the present invention.

[0022] Figure 2 The results of detecting the nicotine dissolution curve of ZYN brand nicotine pouches using the system of the present invention. Detailed Implementation

[0023] The detailed features and advantages of this application are described below in the specific embodiments. The content of this description is sufficient to enable any person skilled in the art to understand the technical content of this application and implement it accordingly. Based on the specification, claims and drawings disclosed in this specification, a person skilled in the art can easily understand the related objectives and advantages of this application.

[0024] In this specification and claims, several terms will be used, and unless otherwise indicated, these terms will be defined to have the following meanings: All figures used to represent component amounts, properties (e.g., weight-average molecular weight), reaction conditions, etc., should be considered in all cases modified by the terms "within the unavoidable margin of error" or "about". Therefore, the numerical values ​​set forth herein are approximate and may vary depending on the desired properties sought to be obtained by the present invention. The principle of equivalents, which is applied to a minimum and not intended to limit the scope of the claims, should be applied, for example, each value should be interpreted at least according to the reported significant digits and by applying conventional rounding techniques.

[0025] All other terms used herein for special definition are intended to have the general meaning understood by one of ordinary skill in the art, in particular meaning that one of ordinary skill in the art can directly and without doubt determine how the technical solutions of the invention can be implemented after reading the claims, specification and drawings.

[0026] Even if there are incomplete descriptions, omissions, or ambiguities in the grammar, words, punctuation, graphics, symbols, etc. of the claims, specification, and drawings of this invention, those skilled in the art can still arrive at the only correct understanding by reading the claims, specification, and drawings as a whole without extensive reasoning or experimentation, and effectively exclude various incorrect interpretations that are not aimed at achieving the purpose of this invention.

[0027] The "range" disclosed herein is defined by a lower limit and an upper limit. A given range is defined by selecting a lower limit and an upper limit, which define the boundaries of a particular range. Ranges defined in this way can include or exclude endpoints and can be arbitrarily combined; that is, any lower limit can be combined with any upper limit to form a range. For example, if ranges of 60-120 and 80-110 are listed for a specific parameter, it is expected that ranges of 60-110 and 80-120 are also expected. Furthermore, if minimum range values ​​of 1 and 2 are listed, and if maximum range values ​​of 3, 4, and 5 are listed, then the following ranges are all expected: 1-3, 1-4, 1-5, 2-3, 2-4, and 2-5. In this application, unless otherwise stated, the numerical range "ab" represents a shortened representation of any combination of real numbers between a and b, where a and b are real numbers. For example, the numerical range "0-5" indicates that all real numbers between "0-5" have been listed in this article; "0-5" is simply a shortened representation of these numerical combinations. Furthermore, when a parameter is stated as an integer ≥2, it is equivalent to disclosing that the parameter is, for example, an integer such as 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, etc.

[0028] Unless otherwise specified, all embodiments and preferred embodiments mentioned herein can be combined to form new technical solutions.

[0029] Unless otherwise specified, all the technical features and preferred features mentioned herein can be combined to form new technical solutions.

[0030] Unless otherwise specified, all steps mentioned herein may be performed sequentially or randomly, but are preferably performed sequentially. For example, the method includes steps (a) and (b), indicating that the method may include steps (a) and (b) performed sequentially, or it may include steps (b) and (a) performed sequentially. For example, the mention that the method may also include step (c) indicates that step (c) may be added to the method in any order; for example, the method may include steps (a), (b), and (c), or it may include steps (a), (c), and (b), or it may include steps (c), (a), and (b), etc.

[0031] Unless otherwise specified, the terms "comprising" and "including" as used herein can be open-ended or closed-ended. For example, "comprising" and "including" may mean that other components not listed may also be included, or that only the listed components may be included.

[0032] In the description of this article, it should be noted that, unless otherwise stated, "above" and "below" include the number itself, and "several" in "one or more" means two or more.

[0033] In this description, unless otherwise stated, the term "or" is inclusive. For example, the phrase "A or B" means "A, B, or both A and B". More specifically, the condition "A or B" is satisfied by any of the following conditions: A is true (or exists) and B is false (or does not exist); A is false (or does not exist) and B is true (or exists); or both A and B are true (or exist).

[0034] Unless otherwise specified, percentages (%) in this document refer to percentages by mass relative to the composition.

[0035] Unless otherwise stated herein, the sum of the contents of the components in the composition is 100%.

[0036] In this document, unless otherwise stated, “combination of” means a multi-component mixture of the elements, such as two, three, four, and up to the maximum possible multi-component mixture.

[0037] Unless otherwise specified, the term "a" as used in this specification means "at least one".

[0038] The terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one of that feature. In the description of this invention, "a plurality of" means at least two, such as two, three, etc., unless otherwise explicitly specified.

[0039] 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 invention pertains. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.

[0040] To make the objectives, technical solutions, and advantages of the present invention clearer, the embodiments of the present invention will be further described in detail below with reference to the accompanying drawings. Unless otherwise specified, the experimental methods described in the embodiments of the present invention are conventional methods, and the materials and reagents used in the following embodiments are commercially available unless otherwise specified.

[0041] One object of the present invention is to provide a nicotine leaching detection system, comprising: Constant temperature water bath; The testing container is placed inside a constant temperature water bath. A release unit, located inside the detection container, is used to hold the nicotine bag; An artificial saliva supply unit is used to supply artificial saliva into the release unit; The detection unit is used to detect the nicotine absorbance of artificial saliva in the detection container; A simulated oral mucosa layer is placed between the release unit and the detection container to simulate the human oral mucosal barrier; The release unit and the detection container are connected by a simulated oral mucosal layer liquid, allowing the artificial saliva dissolved from the nicotine bag to pass through the simulated oral mucosal layer and enter the detection container.

[0042] As used herein, a “nicotine pouch” refers to a product in the form of a mixture of one or more components contained in a liquid-permeable container (e.g., a liquid-permeable pouch). Such mixtures in the form of liquid-permeable delivery pouches are typically used by placing a delivery pouch containing the mixture in the mouth of a human subject / user. Typically, the delivery pouch is placed somewhere in the user’s mouth, such as below the lips, in the same manner as commonly used oral tobacco products. The pouch is preferably not chewed or swallowed. Exposure to saliva then allows some components of the mixture (e.g., flavorings and / or nicotine) to pass through the, for example, water-permeable pouch, providing the user with flavor and satisfaction, and the user does not need to spit out any part of the mixture. After approximately 10 to 60 minutes of use / enjoyment, typically approximately 15 to 45 minutes, a significant portion of the mixture has been ingested by the human subject, and the delivery pouch can be removed from the consumer’s mouth for disposal. Nicotine pouches typically do not contain tobacco but contain nicotine directly.

[0043] As used in this article, "nicotine," also known as nicotine, is an organic compound with the chemical formula C. 10 H 14 N2, with the structural formula shown in Formula I. Nicotine belongs to the alkaloid class of compounds. Alkaloids are a class of nitrogen-containing basic organic molecules that exhibit base-like chemical properties, forming salt solutes in water or reacting with acids. The nicotine structure contains a pyridine ring and a pyrrolidine ring, and its nitrogen atom readily accepts protons (H). + Nicotine is alkaline and can neutralize acids to form salt compounds. Free nicotine has a high pH (approximately 8.0-10.0) and causes strong irritation to the mucous membranes of the mouth and throat. Nicotine salts significantly reduce irritation and provide a gentler user experience by lowering the pH (approximately 5.0-7.0).

[0044] (I)

[0045] As used herein, artificial saliva refers to a liquid medium used to simulate the composition and properties of human oral saliva. In some embodiments, artificial saliva may contain water and one or more of the following components: sodium carboxymethyl cellulose, sorbitol, potassium chloride, sodium chloride, magnesium chloride, calcium phosphate, sodium phosphate, parabens, distilled water, pH adjuster, α-amylase, lysozyme, lipase, and peroxidase. Artificial saliva is prepared as follows: Sodium carboxymethyl cellulose is added to 700 ml of distilled water and soaked overnight until it swells. Then, sorbitol, sodium chloride, magnesium chloride, potassium chloride, and parabens are added and stirred until dissolved. Calcium phosphate and sodium phosphate solutions are added, and distilled water is added to the required volume. After stirring well, the pH is adjusted to 7 with 0.01% hydrochloric acid or 0.05% sodium hydroxide. The solution is then bottled and sterilized with flowing steam at 100 degrees Celsius for 30 minutes.

[0046] As used herein, a test container refers to a container used to collect artificial saliva that has passed through a simulated oral mucosa layer for measurement by a test unit. In some embodiments, the test container is a test cup with an open top, the upper edge of which extends beyond the liquid level in a constant-temperature water bath.

[0047] In some embodiments, the detection unit includes a fiber optic probe and an ultraviolet detector. One end of the fiber optic probe extends into the detection container, and the other end is connected to the ultraviolet detector. The fiber optic probe and the ultraviolet detector are used in combination to monitor the nicotine absorbance of the artificial saliva in the detection container in real time.

[0048] In some embodiments, the artificial saliva supply unit includes a reservoir, a flow controller, and a dropper; the reservoir is used to store artificial saliva; the inlet of the dropper is connected to the reservoir, and the outlet of the dropper is aligned with the nicotine bag within the release unit; the flow controller is used to regulate the flow rate of the artificial saliva.

[0049] In some embodiments, the nicotine leaching detection system further includes a stirring unit; the stirring unit includes a stirring component, a rotating shaft, and a stirring controller. The stirring component is disposed within the detection container, and the stirring controller drives the stirring component via the rotating shaft. In some embodiments, the stirring component is a stirring rotor. In some embodiments, the release unit is connected to the rotating shaft via a clamp-type connector.

[0050] In some embodiments, the simulated oral mucosa layer is a biological tissue mucosa layer or a biomimetic oral mucosa layer. A biological tissue mucosa layer refers to a material layer derived from natural oral mucosa tissue of an organism (such as an animal) and used to simulate the oral mucosa. A biomimetic oral mucosa layer refers to a substitute layer that simulates the structure and function of the natural oral mucosa, prepared using artificial materials or tissue engineering methods (e.g., in vitro oral mucosa culture systems or 3D oral mucosa organoids). For example, a simulated oral mucosa layer is a porcine oral mucosa. Besides porcine oral mucosa, animal mucosa can also be canine, bovine, or rabbit oral mucosa, etc.

[0051] One object of the present invention is to provide a detection method based on the nicotine dissolution detection system of the present invention, comprising the following steps: Step S1: Place the nicotine pouch into the release unit; Step S2: Start the constant temperature water bath to keep the ambient temperature constant to the simulated oral cavity temperature, and at the same time start the stirring unit to make the liquid in the test container uniform. Step S3: Inject artificial saliva into the release unit at a set flow rate through the artificial saliva supply unit, allowing the artificial saliva to flow through the nicotine bag; Step S4: The artificial saliva dissolved in the nicotine bag passes through the simulated oral mucosa layer and enters the test container; Step S5: The absorbance signal of the liquid in the detection container is collected in real time by an optical fiber probe and transmitted to an ultraviolet detector. The release curve of nicotine dissolution over time is obtained after data processing.

[0052] In some implementations, the simulated oral temperature is between 36.3°C and 37.2°C.

[0053] In some implementations, the set flow rate of artificial saliva is 2.0-2.5 mL / min.

[0054] In some embodiments, the detection method further includes step S6: comparing and verifying the obtained nicotine dissolution release curve data with the physiological satisfaction, intoxication, and duration data obtained from human sensory evaluation, in order to evaluate the quality of the nicotine pouch.

[0055] refer to Figure 1A nicotine pouch nicotine dissolution detection system (100) according to an embodiment of the present invention is shown, comprising: a constant temperature water bath (110); a detection container (120) disposed inside the constant temperature water bath (110); a release unit (130) disposed inside the detection container (120) for containing the nicotine pouch (200); an artificial saliva supply unit (140) for supplying artificial saliva into the release unit (130); a detection unit (150) for detecting the nicotine absorbance of the artificial saliva in the detection container; a simulated oral mucosa layer (160) disposed between the release unit (130) and the detection container (120) for simulating the human oral mucosa barrier; the release unit (130) and the detection container (120) are in liquid communication through the simulated oral mucosa layer (160), so that the artificial saliva dissolved from the nicotine pouch (200) passes through the simulated oral mucosa layer (160) and enters the detection container (120).

[0056] The detection unit (150) includes a fiber optic probe (151) and an ultraviolet detector (152). One end of the fiber optic probe (151) extends into the detection container (120), and the other end is connected to the ultraviolet detector (152). The fiber optic probe (151) and the ultraviolet detector (152) are used in conjunction to monitor the nicotine absorbance of the artificial saliva in the detection container (120) in real time. The artificial saliva supply unit (140) includes a reservoir (141), a flow controller (142), and a dropper (143). The reservoir (141) is used to store artificial saliva. The inlet of the dropper (143) is connected to the reservoir (141), and the outlet of the dropper (143) is aligned with the nicotine bag (200) in the release unit (130). The flow controller (142) is used to adjust the flow rate of the artificial saliva. The nicotine leaching detection system (100) also includes a stirring unit (170); the stirring unit (170) includes a stirring component (171), a rotating shaft (172), and a stirring controller (173). The stirring component (171) is disposed inside the detection container (120), and the stirring controller (173) drives the stirring component (171) through the rotating shaft (172). The release unit (130) is connected to the rotating shaft (172) through a clamp-type connector (180).

[0057] Example

[0058] System detection of nicotine dissolution

[0059] Detection system preparation

[0060] according to Figure 1 The diagram shows the setup for a nicotine leaching detection system for nicotine pouches. The main components and parameter settings are as follows: Thermostatic water bath: The temperature is set at 37.0℃ to simulate oral temperature.

[0061] Test container: Placed in a constant temperature water bath, it is a glass container that is closed at the bottom and open at the top, with its upper edge above the water bath liquid level to prevent external water from entering.

[0062] Release Unit: A cylindrical container made of glass or stainless steel with an inner diameter of 12 mm and a length of 30 mm, with a bottom opening covering a simulated oral mucosa layer. In this embodiment, the simulated oral mucosa layer is made of fresh porcine oral mucosa (taken from commercially available slaughtered pigs, with the submucosal fat removed, approximately 0.5 mm thick, rinsed with physiological saline and soaked in artificial saliva for 30 minutes before use). The mucosa layer is sealed and fixed to the bottom of the release unit using silicone gaskets and clamp-type connectors.

[0063] Artificial saliva supply unit: The reservoir contains pre-prepared artificial saliva (formula: 10g sodium carboxymethyl cellulose, 20g sorbitol, 5g sodium chloride, 0.5g potassium chloride, 0.5g magnesium chloride, 0.2g calcium phosphate, 0.1g sodium phosphate, 1g ethylparaben, diluted with distilled water to 1000mL, and adjusted to pH 7.0±0.1). The flow controller adjusts the drip rate to 2.2 mL / min, and the artificial saliva is continuously dripped onto the surface of the nicotine pouch in the release unit through the drip tube.

[0064] Stirring unit: The stirring component is a polytetrafluoroethylene stirring rotor, which is placed at the bottom of the test container. It rotates at a constant speed of 200 rpm through the rotating shaft and stirring controller, so that the artificial saliva that has passed through the mucous membrane layer into the test container is quickly and evenly mixed, which is convenient for testing.

[0065] Detection Unit: An optical fiber probe extends approximately 1 cm below the liquid surface in the detection container, with the other end connected to a UV detector. Continuous spectroscopy (200–400 nm) is used, with absorbance signals acquired in real-time at a wavelength of 259 nm, at a sampling frequency of 1 time / second. The data is converted from a pre-calibrated standard curve to nicotine concentration (mg / L), and a dissolution-time curve is dynamically plotted.

[0066] Testing process

[0067] Sample placement: Take one ZYN brand mint-flavored nicotine pouch (with nominal nicotine content of 1 mg, 3 mg, and 6 mg respectively) and place them in the release unit of the three parallel detection systems, ensuring that the pouch is laid flat on the simulated oral mucosa layer.

[0068] Start the system: Start the constant temperature water bath and wait for the temperature to stabilize at 37.0℃±0.2℃; start the stirring unit and adjust the rotor speed to 200 rpm; turn on the ultraviolet detector and fiber optic probe and collect baseline (detect the absorbance in the container without artificial saliva) for 3 minutes.

[0069] Artificial saliva instillation: The artificial saliva supply unit is activated, and artificial saliva is continuously instilled into the release unit at a flow rate of 2.2 mL / min. The artificial saliva first wets the nicotine bag, and the nicotine salts inside the bag are converted into free nicotine under the action of an alkaline pH adjuster, which then dissolves through the pores of the bag along with the saliva. The dissolved artificial saliva then passes through the simulated oral mucosa layer (pig oral mucosa) at the bottom into the detection container.

[0070] Real-time detection: Artificial saliva is uniformly mixed in the detection container with stirring, and the absorbance of the solution at 259 nm is continuously collected by a fiber optic probe. Detection continues for 60 minutes, or until the absorbance tends to stabilize (change <0.5% over 5 consecutive minutes).

[0071] Data processing: Substitute the real-time absorbance into the pre-prepared nicotine standard curve (concentration range 0.5–50 mg / L, R² = 0.9998) to calculate the nicotine concentration at each time point. Plot the nicotine dissolution release curve with time on the x-axis and cumulative nicotine release (mg) on ​​the y-axis. Release curves for the three sample specifications are shown below. Figure 2 .

[0072] Sensory evaluation process and results

[0073] The evaluation was conducted by 10 professional evaluators. Samples (ZYN brand mint-flavored nicotine pouches, with labeled nicotine contents of 1 mg, 3 mg, and 6 mg respectively) were placed between the upper lip and gums and taken orally. The evaluators evaluated each sample according to the following evaluation index system, and the evaluation results are expressed using descriptive terms and evaluation scales.

[0074] Table 3. Evaluation Index System

[0075] The main evaluation results are as follows: Release rate: The 1 mg sample has a slow release rate and a mild sense of satisfaction; the 3 mg sample has a moderate release rate and a mild sense of intoxication; the 6 mg sample has a fast release rate and a noticeable sense of intoxication.

[0076] Duration of satisfaction: The duration of satisfaction for all three doses was between 25 and 35 minutes, consistent with the nicotine dissolution test curve ( Figure 2 The duration of nicotine release is consistent with that of other substances.

[0077] Flavor intensity and irritation: The flavor intensity of mint slightly increased with increasing nicotine dosage, while the irritation was within an acceptable range, consistent with the dose dependence of cumulative nicotine release in the dissolution curve.

[0078] Consistency comparison

[0079] Sensory evaluation results and Figure 2The nicotine dissolution and release curves shown were compared: the nicotine dissolution curves of the three dose samples all showed a trend of rapid initial increase (0–5 min), followed by stable release (5–25 min), and then gradual decrease (after 25 min), which is highly consistent with the subjective feelings of the evaluators regarding "speed of onset, peak time of satisfaction, and duration of effective effect." These results indicate that the detection system constructed in this invention can accurately reflect the nicotine release behavior of nicotine pouches in the oral environment, and the detection data has a good correlation with human sensory experience, verifying the reliability of this detection system and method.

[0080] 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 patent belongs. The terminology used herein in the specification of this patent is for the purpose of describing particular embodiments only and is not intended to be limiting of this patent. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0081] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable way without contradiction. In order to avoid unnecessary repetition, this patent will not describe the various possible combinations separately.

[0082] Furthermore, various implementations of this patent can be combined in any way, and as long as they do not violate the spirit of this patent, they should also be regarded as the content disclosed in this patent.

[0083] In the foregoing description of exemplary embodiments / specific implementations of the present invention, various features of the invention are sometimes combined in a single embodiment / specific implementation or its figures and description, with the aim of simplifying the disclosure and aiding in the understanding of one or more of the various aspects of the invention. However, the method of description of the invention should not be construed as reflecting an intention that the claimed features are more than expressly stated in each claim, except where explicitly stated otherwise or in obvious technical contradiction or exclusion. Rather, the inventive aspect reflected in the claims lies in not all the features of a single foregoing disclosed embodiment / specific implementation. Therefore, the claims following the detailed description are expressly incorporated herein by reference, each claim existing independently as a separate embodiment / specific implementation of the invention.

[0084] The terminology and expressions used in this specification are for illustrative purposes and not for limitation. Their use is not intended to exclude any equivalents of the shown and described features or portions thereof, but rather to facilitate the understanding that various modifications may be possible within the scope of the invention. Therefore, it should be understood that while the invention has been specifically disclosed through preferred embodiments, exemplary embodiments, and optional features, variations or modifications of the concepts disclosed herein may be adopted by those skilled in the art, and such variations and modifications are therefore considered to be within the scope of the invention as defined by the appended claims. The specific embodiments given in this specification are examples of useful embodiments of the invention, and it will be apparent to those skilled in the art that the invention can be practiced using many variations of the devices, device components, and method steps disclosed herein.

[0085] The foregoing description of specific embodiments has fully disclosed the general features of the invention, enabling others to easily modify and / or adapt such embodiments for various applications by applying knowledge within the scope of the art, without excessive experimentation and without departing from the general conception of the invention. Therefore, based on the teachings and guidance provided herein, it is intended that such modifications and alterations be included within the meaning and scope of equivalents of the disclosed embodiments. It should be understood that the wording or terminology used herein is for descriptive purposes and is not intended to be limiting; thus, the wording or terminology in this specification will be interpreted by those skilled in the art based on the foregoing teachings and guidance.

[0086] Furthermore, the scope of the invention should not be limited to any of the exemplary embodiments described above, but only to the appended claims and their equivalents.

Claims

1. A nicotine leaching detection system for nicotine pouches, characterized in that, include: Constant temperature water bath; The testing container is placed inside the constant temperature water bath; A release unit is disposed within the detection container to accommodate the nicotine bag; An artificial saliva supply unit is used to supply artificial saliva into the release unit; The detection unit is used to detect the nicotine absorbance of the artificial saliva in the detection container; A simulated oral mucosa layer is disposed between the release unit and the detection container to simulate the human oral mucosal barrier; The release unit and the detection container are connected by the simulated oral mucosa liquid, so that the artificial saliva dissolved from the nicotine bag can pass through the simulated oral mucosa and enter the detection container.

2. The nicotine dissolution detection system for nicotine pouches according to claim 1, characterized in that, The detection unit includes an optical fiber probe and an ultraviolet detector. One end of the optical fiber probe extends into the detection container, and the other end is connected to the ultraviolet detector. The optical fiber probe and the ultraviolet detector are used in conjunction to monitor the nicotine absorbance of the artificial saliva in the detection container in real time.

3. The nicotine dissolution detection system for nicotine pouches according to claim 2, characterized in that, The artificial saliva supply unit includes a reservoir, a flow controller, and a dropper; the reservoir is used to store artificial saliva; the inlet of the dropper is connected to the reservoir, and the outlet of the dropper is aligned with the nicotine bag within the release unit; the flow controller is used to regulate the flow rate of the artificial saliva.

4. The nicotine dissolution detection system for nicotine pouches according to claim 3, characterized in that, The nicotine leaching detection system also includes a stirring unit; the stirring unit includes a stirring component, a rotating shaft, and a stirring controller. The stirring component is disposed inside the detection container, and the stirring controller drives the stirring component through the rotating shaft.

5. The nicotine dissolution detection system for nicotine pouches according to claim 4, characterized in that, The release unit is connected to the rotating shaft via a clamp-type connector.

6. The nicotine dissolution detection system for nicotine pouches according to claim 4, characterized in that, The simulated oral mucosa layer is a biological tissue mucosa layer or a biomimetic oral mucosa layer; for example, the simulated oral mucosa layer is the porcine oral mucosa.

7. A detection method based on the nicotine dissolution detection system according to any one of claims 1 to 6, characterized in that, Includes the following steps: Step S1: Place the nicotine bag into the release unit; Step S2: Start the constant temperature water bath to keep the ambient temperature constant to the simulated oral cavity temperature, and at the same time start the stirring unit to make the liquid in the test container uniform. Step S3: Artificial saliva is dripped into the release unit at a set flow rate through the artificial saliva supply unit, so that the artificial saliva flows through the nicotine bag; Step S4: The artificial saliva dissolved in the nicotine bag passes through the simulated oral mucosa layer and enters the detection container; Step S5: The absorbance signal of the liquid in the detection container is collected in real time by the fiber optic probe and transmitted to the ultraviolet detector. The release curve of nicotine dissolution over time is obtained after data processing.

8. The detection method according to claim 7, characterized in that, The simulated oral temperature is between 36.3°C and 37.2°C.

9. The detection method according to claim 7, characterized in that, The set flow rate of the artificial saliva is 2.0-2.5 ml / min.

10. The detection method according to claim 7, characterized in that, It also includes step S6: comparing and verifying the obtained nicotine dissolution release curve data with the physiological satisfaction, intoxication, and duration data obtained from human sensory evaluation, in order to evaluate the quality of the nicotine pouch.

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