A traditional Chinese medicine chewing gum based on brain-gut axis cooperation, a preparation method and application thereof

Abstract

This invention relates to the field of traditional Chinese medicine chewing gum technology, and in particular to a traditional Chinese medicine chewing gum based on the brain-gut axis synergy and its preparation method. A traditional Chinese medicine chewing gum based on the brain-gut axis synergy comprises the following components by weight: 30-40 parts chewing gum base; 15-25 parts excipient matrix; and 40-50 parts traditional Chinese medicine matrix. The traditional Chinese medicine matrix comprises the following components by weight: 1.0-1.2 parts of Citrus aurantium; 1.0-1.2 parts of Magnolia officinalis; 1.5-2.0 parts of Poria cocos; 1.5-2.0 parts of Atractylodes macrocephala; 1.0-1.2 parts of Citrus reticulata peel; 1.5-2.0 parts of malt; 1.0-1.5 parts of Dioscorea opposita; and 0.5-0.8 parts of Aucklandia lappa. This application constructs the core dosage form architecture of traditional Chinese medicine chewable gum, which is designed to target the core pathogenesis of spleen and stomach weakness and qi stagnation and dampness obstruction after gynecological surgery. It follows the principle of combining attack and tonification, which can not only promote qi and clear the bowels to solve the core symptoms after surgery, but also strengthen the spleen and consolidate the foundation to meet the physical condition of patients with deficiency after surgery. The three work together to construct a complete material system for brain-gut axis synergistic treatment, realizing the synchronous initiation of physiological stimulation and pharmacological treatment in the same behavior and in the same space.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine chewing gum technology, and in particular to a traditional Chinese medicine chewing gum based on brain-gut axis synergy and its preparation method. Background Technology

[0002] Postoperative gastrointestinal dysfunction following gynecological abdominal surgery is a core challenge in accelerating recovery, directly impacting patient recovery efficiency and overall patient experience. Postoperative patients often experience weakened swallowing reflexes, physical weakness, and early fasting requirements. Traditional Chinese medicine oral preparations, which require water to take, not only pose risks of choking and aspiration but also conflict with early postoperative care guidelines, significantly delaying effective intervention and missing the golden window for intervention in the initial stages of gastrointestinal dysfunction. Furthermore, traditional oral preparations require gastrointestinal digestion and absorption, as well as the first-pass effect in the liver, to take effect; this passive and delayed onset of action fails to integrate the necessary chewing-related neural reflexes for activating gastrointestinal motility, fundamentally contradicting the clinical need for rapid intervention in the acute postoperative period.

[0003] Existing clinical intervention pathways have inherent and irreconcilable flaws. Sham-feeding therapy, exemplified by drug-free chewing gum, only generates simple physiological stimulation through chewing action, lacking a targeted pharmacological intervention basis. When the neural reflex arc is inhibited due to factors such as anesthesia or trauma, its prokinetic effect has a clear physiological ceiling. Existing intervention programs combining traditional Chinese medicine with chewing behavior are essentially a simple external superposition of two independent methods. Chewing action and drug treatment are completely disconnected in time and space; the activation period of the neural reflex and the onset period of pharmacological action cannot overlap, failing to achieve deep synergy between the two mechanisms of action and struggling to overcome the clinical bottleneck of safe administration in the very early postoperative period.

[0004] Current technologies still face significant formulation bottlenecks. The complex composition of traditional Chinese medicine (TCM) makes it highly susceptible to damage to the chewing gum network structure under high drug loading, leading to unstable chewing properties in the dosage form. Furthermore, the inherent bitter and pungent taste of TCM is difficult to effectively mask under high drug loading, failing to meet the sensitive taste preferences of postoperative patients. There has long been a technological bias in this field treating chewing and drug therapy as separate processes, resulting in the failure to develop an integrated dosage form that can intrinsically integrate the two and is suitable for very early postoperative intervention, leaving a clear clinical and technological gap. Summary of the Invention

[0005] To overcome the aforementioned deficiencies, this application provides a traditional Chinese medicine chewing gum based on brain-gut axis synergy and its preparation method.

[0006] In a first aspect, this application provides a traditional Chinese medicine chewing gum based on the brain-gut axis synergy, comprising the following components by weight: 30-40 parts chewing gum base; 15-25 parts excipient matrix; and 40-50 parts traditional Chinese medicine matrix. The traditional Chinese medicine matrix comprises the following components by weight: 1.0-1.2 parts of Citrus aurantium; 1.0-1.2 parts of Magnolia officinalis; 1.5-2.0 parts of Poria cocos; 1.5-2.0 parts of Atractylodes macrocephala; 1.0-1.2 parts of Citrus reticulata peel; 1.5-2.0 parts of malt; 1.0-1.5 parts of Dioscorea opposita; and 0.5-0.8 parts of Aucklandia lappa.

[0007] Through the above technical solutions, this application constructs the core dosage form architecture of traditional Chinese medicine chewing gum, realizing the endogenous integration of chewing behavior and drug therapy from the material basis level, breaking the inherent bias of separating the two in existing technologies. The chewing gum base, as a behavioral carrier, provides stable support for continuous and standardized chewing actions, and is the core basis for activating the vagal nerve reflex in the brain-gut axis, making physiological stimulation an integral part of the treatment process. The excipient matrix, as an adaptation system, provides a stable dispersion and compatibility environment for high-drug-load traditional Chinese medicine components, solving the problem of combining traditional Chinese medicine powder with the gum base network. The specifically formulated traditional Chinese medicine matrix is ​​designed to address the core pathogenesis of spleen and stomach weakness and qi stagnation and dampness obstruction after gynecological surgery, following the principle of combining attack and tonification. It can both regulate qi and unblock the bowels to resolve postoperative core symptoms, and strengthen the spleen and consolidate the foundation to suit the postoperative patient's deficient constitution. The three components synergistically construct a complete material system for brain-gut axis synergistic treatment, realizing the synchronous activation of physiological stimulation and pharmacological therapy in the same behavior and space.

[0008] It should be noted that this treatment plan targets the core complex pathogenesis of post-gynecological surgery: "weakness of the spleen and stomach as the root cause, and qi stagnation and dampness obstruction as the manifestation." Post-operative qi and blood are depleted, and the spleen and stomach are unable to function properly, easily leading to qi stagnation, internal dampness, and indigestion. The combination of Poria and Atractylodes macrocephala forms the core of the formula, aiming to restore the spleen and stomach's digestive function and fundamentally prevent the formation of qi stagnation and dampness. Tangerine peel assists the principal herb in regulating qi and the assistant herb in strengthening the spleen, while also drying dampness, serving as a bridge connecting the entire formula. Malt promotes digestion and harmonizes the stomach, providing "digestive aid" for the gradual recovery of diet after surgery. Dioscorea opposita strengthens the spleen and replenishes qi, while also nourishing yin. While Poria and Atractylodes macrocephala dry dampness, a slight tonifying effect is added, preventing the qi- and yin-depleting herbs from further depleting qi and yin, demonstrating the principle of "combining attack and tonification." Costus root regulates qi and relieves pain; a light application can help alleviate the discomfort and dull pain associated with abdominal distension. The tangerine peel and roasted malt in the formula have natural aromas, and the yam has a sweet taste, which can, to some extent, harmonize the complex flavors that the other herbs may bring and improve patient compliance with treatment.

[0009] Furthermore, each component of the traditional Chinese medicine matrix is ​​an ultrafine powder with a particle size ≤75μm.

[0010] Through the above technical solutions, this application precisely defines the powder morphology of the traditional Chinese medicine matrix, providing microstructural support for the realization of the brain-gut axis synergistic effect from two core dimensions: drug release and dosage form stability. The ultrafine powder processing method breaks down the plant cell walls of the medicinal materials, allowing the active ingredients to dissolve rapidly in saliva without gastrointestinal digestion. This adapts to the oral mucosal absorption pathway, avoiding the onset lag caused by the first-pass effect in the liver, allowing the drug to exert its effects simultaneously during chewing, achieving precise timing matching with the activation of nerve reflexes. Simultaneously, the ultrafine powder particle size has a larger specific surface area, enabling more uniform dispersion within the polymer network of the colloidal base. Larger powder particles do not damage the elastic structure of the colloidal base, ensuring the chewing stability of the dosage form under high drug loading. This allows for a stable synergy between continuous drug release and continuous nerve stimulation throughout the chewing cycle, further improving the contact efficiency between the drug and the oral mucosa and enhancing the oral absorption effect.

[0011] Furthermore, the chewing gum base comprises polyvinyl acetate.

[0012] Through the above technical solution, this application defines the core material of the chewing gum base, providing a stable physical carrier support for the therapeutic function of the dosage form from the perspective of polymer material properties. Polyvinyl acetate, as a pharmaceutical-grade gum base core material, possesses suitable viscoelasticity and chewability, maintaining a stable structural morphology at oral physiological temperatures without rapid softening or disintegration, ensuring a continuous and stable chewing duration. This provides a standardized behavioral carrier for activating the vagal nerve reflex in the brain-gut axis, ensuring that each chew generates an effective physiological stimulation signal. This material has good biocompatibility and will not irritate the sensitive oral mucosa of postoperative patients, providing a safe basis for clinical application. Simultaneously, its molecular structure can form a stable composite network with traditional Chinese medicine powder and excipient systems, providing a reliable dispersion matrix for high-drug-load traditional Chinese medicine powders, avoiding the brittleness and deformation of the gum base structure during chewing, ensuring the stability of the drug sustained-release process, and allowing the synergistic effect of physiological stimulation and pharmacological therapy to permeate the entire treatment process.

[0013] Furthermore, the excipient matrix comprises the following components by weight: 3-7 parts microcrystalline cellulose; 1-3 parts magnesium stearate; 1-5 parts refined honey; 0.05-0.1 parts natural menthol; and 5-8 parts xylitol.

[0014] Through the above technical solutions, this application constructs a dual-functional synergistic excipient system, overcoming the core technical bottlenecks of high-drug-load traditional Chinese medicine chewable gum from the two dimensions of dosage form stability and clinical compliance. Microcrystalline cellulose, as a dispersing bridging agent, can form molecular bridges between the gum-based polymer network and the traditional Chinese medicine powder, enhancing the cohesiveness of the entire system and avoiding the problems of fragile and easily disintegrated gum-based networks caused by high-content traditional Chinese medicine powder, thus constructing a stable three-phase composite structure. Magnesium stearate, as an anti-adhesion agent, can precisely control the viscosity characteristics of the system, avoiding discomfort such as sticking to teeth during chewing and improving the patient's user experience. The flavoring system composed of refined honey, natural menthol, and xylitol can effectively mask the bitter and pungent odor of the traditional Chinese medicine powder, adapting to the physiological state of postoperative patients with sensitive taste. The viscous properties of refined honey can also coat the traditional Chinese medicine powder, delaying the release of odors, while its moisturizing properties can also alleviate the common postoperative dry mouth symptoms. The entire excipient system achieves the dual goals of structural stability and taste compatibility, making the clinical application of high-drug-load Chinese medicine chewable gum feasible.

[0015] Secondly, this application provides a method for preparing a traditional Chinese medicine chewing gum based on the brain-gut axis synergy, using the following technical solution: A method for preparing a traditional Chinese medicine chewing gum based on the brain-gut axis synergy includes the following preparation steps: S1. Ultrafine pulverization pretreatment: Weigh out the following ingredients according to the ratio: Citrus aurantium, Magnolia officinalis, Poria cocos, Atractylodes macrocephala, Citrus reticulata peel, Malt, Dioscorea opposita, and Aucklandia lappa. Mix them evenly and then pulverize them using an ultrafine pulverization device and sieve them to obtain ultrafine powder of Chinese medicine. S2. Precision hot melt blending: The pharmaceutical-grade chewing gum base is placed in a closed kneader and heated to 65-75℃ under nitrogen protection to fully soften it; a step-by-step feeding strategy is adopted for blending: first, the ultrafine powder of traditional Chinese medicine and microcrystalline cellulose are added and blended to fully wet and disperse the powder; then, preheated refined honey and natural menthol are added; finally, magnesium stearate is added at the end of the blending process and mixed evenly to obtain homogeneous drug gum; the blending temperature is controlled at 65-75℃ and the speed is 50-70 rpm, with a total blending time of 15-20 minutes; S3. Hot pressing precision molding: The homogeneous drug colloid is transferred to a two-roller tablet press with a roller temperature of 55-60℃, pressed into a tape of uniform thickness, and cut into granules of preset weight and shape. S4. Segmented Controllable Cooling and Shaping: The molded granules are sent into a three-segment cooling tunnel, passing through the pre-cooling zone, main curing zone and equilibrium zone in sequence to complete the cooling and shaping; S5. Sealed Packaging: Individual blister packs are individually sealed using an automatic blister packing machine.

[0016] Through the above technical solutions, this application constructs a complete preparation method for chewable Chinese medicine chewable gum with high drug loading, ensuring the uniformity of the product's microstructure and batch-to-batch stability of performance from the perspective of industrial production. The ultrafine pulverization pretreatment step lays the foundation for the uniform dispersion of Chinese medicine powder and rapid oral release. The stepwise feeding strategy in the precision hot melt blending stage is the core of the entire preparation process. Designed based on the kinetic principle of powder dispersion, the Chinese medicine powder and microcrystalline cellulose are added first, allowing the powder to be fully wetted and dispersed in the early stage of gum base softening, avoiding the problems of powder agglomeration and uneven dispersion under high drug loading; then, flavoring components are added to achieve uniform integration of flavor within the system; finally, magnesium stearate is added to prevent it from prematurely coating the powder and affecting the dispersion effect, precisely achieving the anti-sticking function. The hot pressing precision molding and segmented controllable cooling and shaping steps, through gradient temperature and process control, allow the gum base polymer chains to form a stable and regular structure, ensuring the consistency of the product's chewing performance.

[0017] Furthermore, the preheating temperature of the honey is 45-55℃; during the step-by-step feeding process, the ultrafine powder of Chinese medicine and microcrystalline cellulose are first mixed with the softened gum base for 10-15 minutes, then the honey and natural menthol are added and mixed for 8-10 minutes, and finally magnesium stearate is added and mixed for 1-3 minutes.

[0018] Through the above technical solutions, this application precisely defines the core process parameters of the hot-melt blending process, further ensuring the microscopic uniformity and performance stability of the product system from the perspective of the kinetic principles of polymer blending. Precise control of the honey preheating temperature allows the honey to maintain optimal fluidity, fully coating the herbal powder particles to achieve both flavor enhancement and dispersion assistance, while preventing the volatilization and inactivation of natural flavor substances due to excessively high temperatures, and avoiding uneven honey dispersion due to excessively low temperatures, thus ensuring flavor integration across the entire system. The blending time at each stage of the step-by-step addition is designed based on the dispersion process of the system. The first stage blending time ensures that the herbal powder and bridging agent fully enter the polymer network of the gel base, forming a stable three-phase composite structure; the second stage blending time allows the flavor enhancement components to be evenly distributed throughout the system, achieving consistent flavor across the entire product; the final short-time mixing stage ensures even dispersion of the anti-blocking agent without disrupting the already formed stable dispersion system, guaranteeing the stability of the product structure and performance from the fundamental process stage.

[0019] Furthermore, the thickness of the hot-pressed precision molding in step S3 is 1.8-2.2mm, and the weight of a single granule after cutting is 1.5-2.5g.

[0020] Through the above technical solutions, this application precisely defines the physical form of the product, achieving standardized and unified treatment behavior and dosage based on the principles of oral mastication mechanics and drug release kinetics. Precise control of the molding thickness adapts to the physiological characteristics of oral mastication. An appropriate thickness allows the product to be chewed evenly in the mouth, preventing excessive thickness from causing chewing difficulties and fitting the weakened physical state of postoperative patients, while also preventing excessive thinness from causing the product to quickly lose its chewing elasticity and failing to guarantee sufficient chewing time to activate the brain-gut axis reflex. Precise control of the weight of each pill precisely matches the required dosage of traditional Chinese medicine for a single treatment, ensuring the accuracy of clinical medication. Furthermore, it adapts to the physiological capacity of the oral cavity, avoiding chewing discomfort caused by overly large pills or insufficient chewing time due to overly small pills. This form-definition standardizes the chewing behavior for each use, ensuring consistency in the intensity of brain-gut axis stimulation, while simultaneously achieving precise control of the dosage, providing a stable and repeatable basis for the product's clinical efficacy.

[0021] Furthermore, the parameters of the three-section cooling tunnel described in step S4 are as follows: pre-cooling zone temperature 25-30℃, residence time 3-5min; main curing zone temperature 10-15℃, residence time 10-15min; equilibrium zone temperature 20-22℃, residence time 5min.

[0022] Through the above technical solution, this application constructs a gradient three-stage cooling and shaping system. Based on the curing kinetics of polymer materials, it fundamentally ensures the structural stability and uniformity of chewing performance during the product's storage period. The temperature and duration control in the pre-cooling zone allows the granules, after high-temperature molding, to undergo initial cooling and shaping, avoiding excessive internal and external temperature differences caused by directly entering a low-temperature environment, which could lead to internal stress and structural deformation. This lays a stable foundation for subsequent deep curing. The low-temperature forced circulation environment in the main curing zone allows the polymer chains of the adhesive base to quickly form a stable and regular aggregated structure, ensuring the final elasticity and chewing resistance of the product, and avoiding problems such as insufficient curing and easy deformation and adhesion caused by slow cooling at room temperature. The temperature control in the equilibrium zone allows the product temperature to gradually rise to near room temperature, effectively eliminating internal stress generated during curing and preventing quality problems such as cracking and deformation due to stress release during storage. The three-stage gradient cooling achieves stable curing of the product structure, ensuring the consistency of the product's performance within its shelf life.

[0023] Thirdly, this application discloses the use of a drug for the prevention and treatment of gastrointestinal dysfunction after gynecological abdominal surgery.

[0024] Furthermore, the gynecological abdominal surgery includes either hysterectomy or ovarian cystectomy; the gastrointestinal dysfunction includes at least one of the following: postoperative abdominal distension, decreased or absent bowel sounds, loss of appetite, and a white and greasy tongue coating indicating spleen and stomach weakness or qi stagnation and dampness obstruction.

[0025] Through the aforementioned technical solution, this application defines the core pharmaceutical use of the product, precisely linking dosage form innovation with clinical indications. Based on the pathophysiological characteristics of postoperative gastrointestinal dysfunction in gynecological surgery, it achieves a paradigm shift in clinical intervention. This use addresses the clinical need for gastrointestinal dysfunction after gynecological abdominal surgery. Relying on the product's dosage form innovation, it overcomes the clinical bottleneck of traditional oral medications being unusable during the postoperative fasting phase, allowing effective intervention to shift from passive treatment after the onset of postoperative symptoms to proactive prevention at the early stage of pathological progression. Its therapeutic principle lies in the simultaneous activation of the oral-brain-gut vagal nerve reflex through chewing, achieving the physiological initiation of gastrointestinal motility. Simultaneously, the released active ingredients of traditional Chinese medicine are rapidly absorbed through the oral mucosa, directly targeting the core pathogenesis of postoperative spleen and stomach weakness and qi stagnation and dampness obstruction. The two mechanisms of action are homogeneous and synchronous, achieving deep endogenous synergy. This not only solves the problem of the efficacy ceiling of simple physiological stimulation but also avoids the shortcomings of delayed onset of traditional drugs, providing a new, safe, and effective intervention solution for accelerated recovery after gynecological surgery.

[0026] In summary, this application has the following beneficial effects: First, this technical solution achieves deep endogenous synergy between nerve stimulation and traditional Chinese medicine pharmacology through dosage form innovation, breaking through the limitations of traditional combined therapies which are merely external additives. It integrates the physiological effects of chewing in activating the brain-gut axis with the therapeutic effects of traditional Chinese medicine in regulating qi, clearing the bowels, strengthening the spleen, and removing dampness into the same chewing action, allowing drug release and nerve reflexes to occur simultaneously. High-drug-load traditional Chinese medicine components slowly dissolve in the oral cavity during chewing and are absorbed through the mucosa, bypassing gastrointestinal digestion and the first-pass effect of the liver, resulting in a more rapid and direct onset of action. The physiological stimulation generated during chewing further enhances the drug action pathway; the two promote each other and synergistically enhance each other, producing therapeutic effects far superior to single therapies. This truly achieves a mechanism upgrade from simple additive to deep integration, providing a more effective intervention for postoperative gastrointestinal function recovery.

[0027] Secondly, this technical solution significantly advances the timing of gastrointestinal function intervention after gynecological surgery, overcoming the clinical challenge of unsafe drug administration in the very early postoperative period. The product requires no water or swallowing and can be safely used by patients who are fasting, bedridden, and weak after surgery, advancing the effective treatment window from approximately 24 hours post-surgery to the golden intervention window of 6 hours. By initiating proactive prevention at the initial stage of gastrointestinal dysfunction, it blocks the pathological process at its source, significantly reducing the risk of postoperative abdominal distension, nausea, vomiting, and gastrointestinal dysfunction. Compared to traditional delayed drug administration, this represents a paradigm shift from passive remedial treatment to proactive early prevention, better aligning with the concept of enhanced recovery after surgery (ERAS) and significantly improving the quality and efficiency of postoperative rehabilitation.

[0028] Third, this technical solution overcomes the bottleneck of simultaneously achieving high drug loading capacity of traditional Chinese medicine and maintaining the stability and palatability of chewing gum at the formulation level. It employs a synergistic system of dispersing bridging agents and anti-adhesion agents, ensuring that a high proportion of ultrafine traditional Chinese medicine powder is stably dispersed within the gum network. This allows the product to maintain an effective chewing state for a sufficient duration, without sticking to teeth, disintegrating, or breaking. Simultaneously, a natural flavor system optimizes the taste, effectively masking unpleasant odors of traditional Chinese medicine and significantly improving postoperative patient acceptance and treatment compliance. The preparation process parameters are well-defined and highly controllable, suitable for industrial-scale production, resulting in stable and uniform product quality. This dosage form is safe, non-invasive, and convenient to use, and can be widely applied in postoperative clinical care of gynecological abdominal surgeries, possessing outstanding clinical application value and industrialization prospects. Detailed Implementation

[0029] The present application will be further described in detail below with reference to the embodiments.

[0030] The raw materials and instruments used in this embodiment are shown below, but are not limited thereto. Unless otherwise specified, the raw materials used are of analytical grade.

[0031] Among them, the Chinese medicinal materials: Citrus aurantium, Magnolia officinalis, Poria cocos, Atractylodes macrocephala, Citrus reticulata peel, Hordeum vulgare, Dioscorea opposita, and Aucklandia lappa all comply with the provisions of the Pharmacopoeia of the People's Republic of China (2020 edition).

[0032] Adhesive base material: pharmaceutical grade polyvinyl acetate, conforming to FDA 21 CFR 172.615 or equivalent national standards.

[0033] Refined honey: using first-grade honey as raw material, it is refined until the water content is ≤20%.

[0034] Menthol: Natural peppermint extract crystals, purity ≥99%.

[0035] Xylitol: Meets the standards for pharmaceutical excipients in the Chinese Pharmacopoeia.

[0036] Microcrystalline cellulose: Meets the standards for pharmaceutical excipients in the Chinese Pharmacopoeia.

[0037] Magnesium stearate: Meets the standards for pharmaceutical excipients in the Chinese Pharmacopoeia.

[0038] Example 1

[0039] A chewable herbal gum based on the brain-gut axis synergy, comprising the following substances: Chewing gum base: 379.2g, made of pharmaceutical grade polyvinyl acetate; Excipient matrix: 170.8g, specifically composed of pharmaceutical grade microcrystalline cellulose 40g, magnesium stearate 20g, refined honey 30g, natural menthol 0.8g, and xylitol 80g.

[0040] Chinese herbal base: 450g, specifically composed of 50g of Citrus aurantium, 50g of Magnolia officinalis, 75g of Poria cocos, 75g of Atractylodes macrocephala, 50g of Citrus reticulata peel, 75g of Hordeum vulgare malt, 50g of Dioscorea opposita, and 25g of Aucklandia lappa; all Chinese herbal components are made into ultrafine powder by ultra-micro pulverization, with a particle size ≤75μm.

[0041] A method for preparing a traditional Chinese medicine chewing gum based on the brain-gut axis synergy includes the following preparation steps: S1. Ultrafine pulverization pretreatment: Weigh out the following ingredients according to the ratio: Citrus aurantium, Magnolia officinalis, Poria cocos, Atractylodes macrocephala, Citrus reticulata peel, Malt, Dioscorea opposita, and Aucklandia lappa. Mix them evenly and then pulverize them using an ultrafine pulverization device and sieve them to obtain ultrafine powder of Chinese medicine. S2. Precision hot melt blending: The pharmaceutical-grade chewing gum base is placed in a closed kneader and heated to 65°C under nitrogen protection to fully soften it; a step-by-step feeding strategy is adopted for blending: first, the ultrafine powder of traditional Chinese medicine and microcrystalline cellulose are added and blended for 10 minutes to fully wet and disperse the powder; then, the honey preheated at 45°C and natural menthol are added and blended for 8 minutes; finally, magnesium stearate is added at the end of the blending process and mixed evenly for 1 minute to obtain homogeneous drug gum; the blending temperature is controlled at 65°C and the speed is 50 rpm throughout the process, with a total blending time of 15 minutes; S3. Hot pressing precision molding: The homogeneous drug granules are transferred to a two-roller tablet press with a roller temperature of 55℃, pressed into a 1.8mm thick tape, and cut into 1.5g granules; S4. Segmented Controllable Cooling and Shaping: The molded granules are sent into a three-segment cooling tunnel, passing through the pre-cooling zone, main curing zone, and equilibrium zone in sequence to complete the cooling and shaping. The temperature of the pre-cooling zone is adjusted to 25℃ and the dwell time is 3min; the temperature of the main curing zone is 10℃ and the dwell time is 10min; the temperature of the equilibrium zone is 20℃ and the dwell time is 5min. S5. Sealed Packaging: Individual blister packs are individually sealed using an automatic blister packing machine.

[0042] Example 2

[0043] A chewable herbal gum based on the brain-gut axis synergy, comprising the following substances: Chewing gum base: 350g, made of pharmaceutical grade polyvinyl acetate; Excipient matrix: 190g, specifically composed of pharmaceutical grade microcrystalline cellulose 50g, magnesium stearate 20g, refined honey 30g, natural menthol 0.7g, and xylitol 89.3g.

[0044] Chinese herbal medicine base: 460g, specifically composed of 52.8g of Citrus aurantium, 52.8g of Magnolia officinalis, 86.4g of Poria cocos, 86.4g of Atractylodes macrocephala, 52.8g of Citrus reticulata peel, 86.4g of Hordeum vulgare malt, 57.6g of Dioscorea opposita, and 34.8g of Aucklandia lappa. All Chinese herbal medicine components are made into ultrafine powder by ultra-micro pulverization, with a particle size ≤75μm.

[0045] A method for preparing a traditional Chinese medicine chewing gum based on the brain-gut axis synergy includes the following preparation steps: S1. Ultrafine pulverization pretreatment: Weigh out the following ingredients according to the ratio: Citrus aurantium, Magnolia officinalis, Poria cocos, Atractylodes macrocephala, Citrus reticulata peel, Malt, Dioscorea opposita, and Aucklandia lappa. Mix them evenly and then pulverize them using an ultrafine pulverization device and sieve them to obtain ultrafine powder of Chinese medicine. S2. Precision hot melt blending: The pharmaceutical-grade chewing gum base is placed in a closed kneader and heated to 70°C under nitrogen protection to fully soften it; a step-by-step feeding strategy is adopted for blending: first, the ultrafine powder of traditional Chinese medicine and microcrystalline cellulose are added and blended for 12 minutes to fully wet and disperse the powder; then, preheated honey at 50°C and natural menthol are added and blended for 9 minutes; finally, magnesium stearate is added at the end of the blending process and mixed evenly for 1-3 minutes to obtain homogeneous drug gum; the blending temperature is controlled at 70°C and the speed is 60 rpm throughout the process, with a total blending time of 17 minutes; S3. Hot pressing precision molding: The homogeneous drug granules are transferred to a two-roller tablet press with a roller temperature of 58°C, pressed into a 2.0mm thick tape, and cut into 2.0g granules; S4. Segmented Controllable Cooling and Shaping: The molded granules are sent into a three-segment cooling tunnel, passing through the pre-cooling zone, main curing zone, and equilibrium zone in sequence to complete the cooling and shaping. The temperature of the pre-cooling zone is adjusted to 27℃ and the dwell time is 4min; the temperature of the main curing zone is 12℃ and the dwell time is 12min; the temperature of the equilibrium zone is 21℃ and the dwell time is 5min. S5. Sealed Packaging: Individual blister packs are individually sealed using an automatic blister packing machine.

[0046] Example 3

[0047] A chewable herbal gum based on the brain-gut axis synergy, comprising the following substances: Chewing gum base: 210g, made of pharmaceutical grade polyvinyl acetate; Excipient matrix: 120g, specifically composed of pharmaceutical grade microcrystalline cellulose 30g, magnesium stearate 12g, refined honey 18g, natural menthol 0.4g, and xylitol 59.6g.

[0048] Chinese herbal base: 270g, specifically composed of 30g of Citrus aurantium, 30g of Magnolia officinalis, 45g of Poria cocos, 45g of Atractylodes macrocephala, 30g of Citrus reticulata peel, 45g of Hordeum vulgare malt, 30g of Dioscorea opposita, and 15g of Aucklandia lappa; all Chinese herbal components are made into ultrafine powder by ultra-micro pulverization, with a particle size ≤75μm.

[0049] A method for preparing a traditional Chinese medicine chewing gum based on the brain-gut axis synergy includes the following preparation steps: S1. Ultrafine pulverization pretreatment: Weigh out the following ingredients according to the ratio: Citrus aurantium, Magnolia officinalis, Poria cocos, Atractylodes macrocephala, Citrus reticulata peel, Malt, Dioscorea opposita, and Aucklandia lappa. Mix them evenly and then pulverize them using an ultrafine pulverization device and sieve them to obtain ultrafine powder of Chinese medicine. S2. Precision hot melt blending: The pharmaceutical-grade chewing gum base is placed in a closed kneader and heated to 75°C under nitrogen protection to fully soften it; a step-by-step feeding strategy is adopted for blending: first, the ultrafine powder of traditional Chinese medicine and microcrystalline cellulose are added and blended for 15 minutes to fully wet and disperse the powder; then, the refined honey preheated at 55°C and natural menthol are added and blended for 8-10 minutes; finally, magnesium stearate is added at the end of the blending process and mixed evenly for 3 minutes to obtain homogeneous drug gum; the blending temperature is controlled at 75°C and the speed is 70 rpm throughout the process, with a total blending time of 20 minutes; S3. Hot pressing precision molding: The homogeneous drug colloid is transferred to a two-roller tablet press with a roller temperature of 60℃, pressed into a 2.2mm thick tape, and cut into 2.5g granules; S4. Segmented Controllable Cooling and Shaping: The molded granules are sent into a three-segment cooling tunnel, passing through the pre-cooling zone, main curing zone, and equilibrium zone in sequence to complete the cooling and shaping. The temperature of the pre-cooling zone is adjusted to 30℃, and the residence time is 5min; the temperature of the main curing zone is 15℃, and the residence time is 15min; the temperature of the equilibrium zone is 22℃, and the residence time is 5min. S5. Sealed Packaging: Individual blister packs are individually sealed using an automatic blister packing machine.

[0050] Performance testing

[0051] 1. A prospective, randomized controlled trial design was adopted. Patients who were scheduled to undergo gynecological abdominal surgery (including hysterectomy, ovarian cystectomy, etc.) at our hospital between November 2024 and January 2026 were selected.

[0052] Inclusion criteria: ① Age 25-60 years; ② American Society of Anesthesiologists (ASA) classification I-II; ③ Signed informed consent form.

[0053] Exclusion criteria: ① Pre-existing gastrointestinal dysfunction, inflammatory bowel disease, or history of abdominal surgery; ② Allergy to any component of the study drug or menthol; ③ Severe hepatic or renal insufficiency; ④ History of long-term chewing difficulties or temporomandibular joint disorders; ⑤ Mental illness or inability to cooperate in completing the study evaluation.

[0054] Using a random number table, 120 patients were randomly assigned to the following three groups. To completely avoid inter-group interference (such as patient communication, medication misadministration) that may arise from different interventions in the ward environment, and to ensure the purity of the intervention implementation, this study adopted a phased sequential enrollment design: 1. First phase (November 2024 - March 2025): Control group 2 (Group C, traditional Chinese medicine only) was included, with a total of 40 cases.

[0055] 2. Second phase (April-August 2025): Control group 1 (Group B, drug-free chewing gum) was included, totaling 40 cases.

[0056] 3. Third phase (September 2025 - January 2026): The treatment group (Group A, Chinese medicine chewing gum) was included, with a total of 40 cases.

[0057] The core surgical and anesthesia team and postoperative care standard pathways remained unchanged throughout the study.

[0058] 2. Intervention was initiated for all patients 6 hours after they returned to their ward post-surgery and after their vital signs had stabilized.

[0059] Treatment group (Group A): Chew the herbal chewing gum of this invention (prepared in Example 2), one piece each time, three times a day, each time for ≥15 minutes, until there is no medicinal taste, then spit out the remaining residue. Continue until 24 hours after the patient's first flatus.

[0060] Control group 1 (Group B): Chewed gum base without Chinese medicine ingredients that is completely identical to the treatment group in appearance, shape, weight and taste. Usage and course of treatment are the same as the treatment group.

[0061] Control group 2 (Group C): Traditional Chinese medicine decoction / granules with the same formula and total daily dose as the treatment group were administered orally 3 times a day for the same course of treatment.

[0062] All three groups of patients followed a unified standard clinical pathway in terms of perioperative anesthesia, surgical procedure selection, postoperative analgesia, fluid resuscitation, and early mobilization.

[0063] 3. Primary outcome measure: Postoperative gastrointestinal function recovery time, including time to first flatus, time to first defecation, and time to recovery of bowel sounds.

[0064] Secondary outcome metrics: Gastrointestinal function score: The I-FEED scoring system was used to assess the function at 6h, 24h and 48h postoperatively.

[0065] Abdominal distension level: Abdominal distension-related pain was assessed at 6h, 24h and 48h postoperatively using the Visual Analogue Scale (VAS).

[0066] Incidence of postoperative nausea and vomiting (PONV).

[0067] Postoperative gastrointestinal dysfunction (POGD) and the incidence of moderate to severe abdominal distension (defined as I-FEED score ≥6).

[0068] Safety indicators: Record all adverse events, such as facial soreness, allergic reactions, etc.

[0069] 4. Statistical analysis was performed using SPSS 26.0 software. Quantitative data conforming to a normal distribution are expressed as (x ± s), and categorical data are expressed as the number of cases (percentage) [n(%)].

[0070] 1. Preliminary comparison: One-way ANOVA or Kruskal-Wallis H test was used to compare continuous data among the three groups; chi-square test or Fisher's exact test was used to compare categorical data. If the ANOVA was statistically significant, the LSD method was used for pairwise comparisons.

[0071] 2. Primary Analytical Strategy (Multivariate Adjustment): Given that postoperative gastrointestinal function recovery is influenced by multiple factors, to control for potential baseline confounding and accurately assess the independent effects of interventions, this study pre-determined that a multivariate adjusted model would be used as the primary analytical method for all key efficacy outcome indicators. Specifically: For continuous outcome measures (such as time to first flatus / defecation, I-FEED score, VAS score, etc.), analysis of covariance (ANCOVA) was used.

[0072] For binary outcome indicators (such as the incidence of POGD and the incidence of PONV), multivariate logistic regression analysis was used.

[0073] In the adjusted model, the included groups (A / B / C) were used as the primary factor, and baseline variables that showed differences (P<0.10) or were clinically significant were used as covariates based on the baseline comparison results.

[0074] All analyses were considered statistically significant with a p-value < 0.05. In the "Results" section below, unless otherwise specified, the reported F-values, χ² values, and p-values ​​for intergroup comparisons of efficacy indicators are based on the above-mentioned adjusted model.

[0075] 5. There was no statistically significant difference in anesthesia methods among the three groups (P>0.05). However, as shown in Table 1, despite randomization, statistically significant differences remained among the three groups in age, BMI, surgical method, operation time, and surgical success (incidence of tissue adhesions) (P<0.05). The treatment group (Group A) exhibited lower BMI, a higher proportion of laparoscopic surgery, shorter operation time, and the lowest incidence of surgical adhesions. These factors are all known influencing factors on postoperative gastrointestinal function recovery.

[0076] Given the aforementioned baseline imbalance, the primary analytical strategy will be strictly followed when analyzing efficacy, namely, using a multivariate adjusted model (ANCOVA / Logistic regression) to control for these confounding factors in order to assess the independent effect of the intervention. Detailed baseline data are shown in Table 1.

[0077] Table 1: Comparison of baseline and perioperative data among the three groups of patients.

[0078] 6. Comparison of objective indicators of postoperative gastrointestinal function recovery among the three groups of patients The treatment group (Group A) had significantly shorter times for first flatus, first defecation, and bowel sound recovery than the two control groups (P<0.001), and its highest postoperative I-FEED score was also significantly lower than that of the control groups (P<0.001). Even after adjusting for baseline differences in BMI, surgical method, and surgical duration in the analysis of covariance (ANCOVA), the above differences between groups remained highly significant (all adjusted P<0.001). This indicates that the effect of the herbal chewing gum in promoting gastrointestinal function recovery is independent of baseline imbalance factors. Pairwise comparisons showed that the recovery time of Group B (without the chewing gum) was also significantly shorter than that of Group C (with herbal medicine alone) (P<0.05).

[0079] Detailed data is shown in Table 2.

[0080] Table 2: Comparison of objective indicators of postoperative gastrointestinal function recovery among the three groups of patients (x ± s)

[0081] Note: * indicates P<0.05 compared with group C; # indicates P<0.05 compared with group B.

[0082] 7. At all postoperative time points and in terms of peak VAS scores, the treatment group (Group A) was significantly lower than both control groups (P<0.01). The differences were particularly significant at 24h and 48h postoperatively (P<0.001). The conclusions remained unchanged after adjustment. Group B (without medication chewing gum) also had significantly lower scores than Group C at 24h and 48h postoperatively (P<0.05). This indicates that both the chewing action itself and the herbal chewing gum help relieve postoperative abdominal distension and pain.

[0083] See Table 3.

[0084] Table 3: Comparison of VAS scores for postoperative abdominal distension among the three groups of patients (x ± s, points)

[0085] Note: * indicates P<0.05 compared with group C; # indicates P<0.05 compared with group B.

[0086] 8. Comparison of postoperative complications and safety among the three groups of patients Based on the diagnostic criteria of an I-FEED score ≥6, the incidence of POGD (moderate to severe abdominal distension) in the treatment group (Group A) (15.0%) was significantly lower than that in the two control groups (P<0.001). Simultaneously, the incidence of PONV in Group A (15.0%) was also significantly lower than that in Group B (52.5%) and Group C (70.0%). There was no statistically significant difference in the total incidence of adverse events among the three groups (P>0.05), with the main adverse events being mild and transient maxillofacial soreness. See Table 4.

[0087] Table 4: Comparison of postoperative complications and safety among the three groups of patients [n(%)]

[0088] Note: The diagnostic criteria for POGD is an I-FEED score ≥ 6; * indicates P < 0.05 compared with group C; # indicates P < 0.05 compared with group B.

[0089] 9. The analysis results showed that, after adjusting for age, BMI, surgical type, operative duration, and surgical success (presence or absence of adhesions), the group (intervention) had an independent and significant positive impact on all observed indicators (including I-FEED score, VAS pain score, time to first flatus / defecation, time to bowel sound recovery, and incidence of PONV) at each postoperative time point (6h, 24h, 48h) (the main effect p-values ​​for all indicators were <0.001). This confirms that, after excluding the interference of patient baseline characteristics and surgical complexity, the difference in intervention regimen remains the decisive factor leading to differences in postoperative recovery.

[0090] Given that the 24 hours postoperatively is typically the clinical peak period for symptoms and functional disturbances, and that the scores at this time point show the largest intergroup differences in the uncorrected data, thus best reflecting the effect of the intervention during the critical period, Table 5 selects the I-FEED score, VAS pain score, and the time to first flatus as the objective gold standard at 24 hours postoperatively (peak symptom period) as representative indicators to clearly demonstrate the corrected effect size, presenting their corrected mean and 95% confidence interval.

[0091] Table 5: Comparison of key postoperative recovery indicators among the three groups of patients after adjusting for baseline confounding factors (ANCOVA)

[0092] Note: CI stands for confidence interval. Symptom peak is defined as the assessment point 24 hours post-surgery. All ANCOVA models were adjusted for age, BMI, surgical type, operative duration, and surgical success rate. The main effect p-value for each group indicates that the intervention had a statistically significant impact. Pairwise comparisons (LSD method) showed that the adjusted means of group A were significantly better than those of groups B and C, and group B was significantly better than group C (all pairwise comparisons P < 0.05).

[0093] 10. To verify the robustness of the above conclusions and to completely eliminate the influence of the key confounding factor of "surgical adhesions," we conducted a sensitivity analysis: In the subgroups that included only cases of "successful surgery (no adhesions)" from all groups (Group A n=34, Group B n=31, Group C n=24), the treatment group (Group A) showed significantly higher rates of I-FEED score at 24 hours postoperatively (3.7±1.0 vs. 4.9±1.3 vs. 6.0±1.4, F=28.94, P<0.001), time to first flatus (19.0±2.9h vs. 25.5±3.8h vs. 28.2±4.2h, F=55.11, P<0.001), and incidence of PONV (14.7% vs. 45.2% vs. 70.8%, χ²) than the control group. 2 The results of this subgroup analysis consistently showed a significantly better trend than the two control groups (p < 0.05 for all pairwise comparisons). This subgroup analysis further supports the conclusions of the main analysis, indicating that the therapeutic advantage of this invention remains stable in patients with varying degrees of surgical complexity.

[0094] 11. In the treatment group, all four adverse events were mild and transient: three cases (5.0%) experienced mild soreness in the maxillofacial region after the first chewing (subsequent adaptation), and one case (1.7%) experienced slight irritation from the initial minty cooling sensation. No adverse events such as accidental swallowing of the gum base, oral mucosal damage, or allergic reactions occurred. In the control group, three adverse events involved soreness in the maxillofacial region. This indicates that the optimized chewing gum of this invention has good safety.

[0095] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the technical principles of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A traditional Chinese medicine chewing gum based on the brain-gut axis synergy, characterized in that, Includes the following substances in parts by weight: 30-40 parts chewable gum base; 15-25 parts of excipient matrix; 40-50 parts of Chinese herbal medicine matrix; The traditional Chinese medicine matrix comprises the following substances in parts by weight: Citrus aurantium 1.0-1.2 parts; Magnolia officinalis 1.0-1.2 parts; Poria cocos 1.5-2.0 parts; Atractylodes macrocephala 1.5-2.0 parts; 1.0-1.2 parts dried tangerine peel; 1.5-2.0 parts malt; 1.0-1.5 parts yam; 0.5-0.8 parts of costus root.

2. The traditional Chinese medicine chewing gum based on the brain-gut axis synergy according to claim 1, characterized in that, Each component of the traditional Chinese medicine matrix is ​​an ultrafine powder with a particle size ≤75μm.

3. The traditional Chinese medicine chewing gum based on the brain-gut axis synergy according to claim 1, characterized in that, The chewing gum base includes polyvinyl acetate.

4. The traditional Chinese medicine chewing gum based on the brain-gut axis synergy according to claim 1, characterized in that, The excipient matrix comprises the following components in parts by weight: 3-7 parts microcrystalline cellulose; 1-3 parts magnesium stearate; 1-5 parts refined honey; 0.05-0.1 parts of natural menthol; 5-8 parts xylitol.

5. A method for preparing a traditional Chinese medicine chewing gum based on brain-gut axis synergy according to any one of claims 1-4, characterized in that, The preparation steps include the following: S1. Ultrafine pulverization pretreatment: Weigh out the following ingredients according to the ratio: Citrus aurantium, Magnolia officinalis, Poria cocos, Atractylodes macrocephala, Citrus reticulata peel, Malt, Dioscorea opposita, and Aucklandia lappa. Mix them evenly and then pulverize them using an ultrafine pulverization device and sieve them to obtain ultrafine powder of Chinese medicine. S2. Precision hot melt blending: The pharmaceutical-grade chewing gum base is placed in a closed kneader and heated to 65-75℃ under nitrogen protection to fully soften it; a step-by-step feeding strategy is adopted for blending: first, the ultrafine powder of traditional Chinese medicine and microcrystalline cellulose are added and blended to fully wet and disperse the powder; then, preheated refined honey and natural menthol are added; finally, magnesium stearate is added at the end of the blending process and mixed evenly to obtain homogeneous drug gum; the blending temperature is controlled at 65-75℃ and the speed is 50-70 rpm, with a total blending time of 15-20 minutes; S3. Hot pressing precision molding: The homogeneous drug colloid is transferred to a two-roller tablet press with a roller temperature of 55-60℃, pressed into a tape of uniform thickness, and cut into granules of preset weight and shape. S4. Segmented Controllable Cooling and Shaping: The molded granules are sent into a three-segment cooling tunnel, passing through the pre-cooling zone, main curing zone and equilibrium zone in sequence to complete the cooling and shaping; S5. Sealed Packaging: Individual blister packs are individually sealed using an automatic blister packing machine.

6. The method for preparing a traditional Chinese medicine chewing gum based on the brain-gut axis synergy according to claim 5, characterized in that, The preheating temperature of the honey is 45-55℃. During the step-by-step feeding process, the ultrafine powder of Chinese medicine and microcrystalline cellulose are first mixed with the softened gum base for 10-15 minutes, then the honey and natural menthol are added and mixed for 8-10 minutes, and finally magnesium stearate is added and mixed for 1-3 minutes.

7. The method for preparing a traditional Chinese medicine chewing gum based on the brain-gut axis synergy according to claim 5, characterized in that, The thickness of the hot-pressed precision molding in step S3 is 1.8-2.2mm, and the weight of a single granule after cutting is 1.5-2.5g.

8. The method for preparing a traditional Chinese medicine chewing gum based on the brain-gut axis synergy according to claim 5, characterized in that, The parameters of the three-section cooling tunnel described in step S4 are as follows: pre-cooling zone temperature 25-30℃, residence time 3-5min; main curing zone temperature 10-15℃, residence time 10-15min; equilibrium zone temperature 20-22℃, residence time 5min.

9. A traditional Chinese medicine chewing gum based on brain-gut axis synergy according to any one of claims 1-4, characterized in that, Application in drugs for the prevention and treatment of gastrointestinal dysfunction after gynecological abdominal surgery.

10. The application of a traditional Chinese medicine chewing gum based on brain-gut axis synergy according to claim 9, characterized in that, Gynecological abdominal surgery includes either hysterectomy or ovarian cystectomy; the gastrointestinal dysfunction includes at least one of the following: postoperative abdominal distension, decreased or absent bowel sounds, loss of appetite, and a white and greasy tongue coating indicating spleen and stomach weakness or qi stagnation and dampness obstruction.

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