Traditional Chinese medicine composition for treating functional dyspepsia, preparation of traditional Chinese medicine composition and preparation method of preparation

Abstract

The invention relates to the technical field of medicines, in particular to a traditional Chinese medicine composition for treating functional dyspepsia, a preparation of the traditional Chinese medicine composition and a preparation method of the preparation. The traditional Chinese medicine composition comprises the following components in parts by weight: 8-12 parts of codonopsis pilosula, 8-12 parts of poria cocos, 8-12 parts of pinellia ternate, 8-12 parts of honey-fried licorice root, 8-12 parts of pericarpium citri reticulatae, 15-25 parts of raw bighead atractylodes rhizome, 3-6 parts of coptis chinensis, 25-35 parts of dandelion, 15-25 parts of eupatorium, 8-12 parts of mangnolia officinalis, 8-12 parts of immature bitter orange, 9-12 parts of elecampane, 15-25 parts of cuttlebone and 10-20 parts of fried endothelium corneum gigeriae galli. The traditional Chinese medicine composition for treating functional dyspepsia, the preparation of the traditional Chinese medicine composition and the preparation method of the preparation are suitable for spleen deficiency and qi stagnation and spleen and stomach damp-heat type functional dyspepsia and can synchronously improve pathological states such as gastrointestinal motility disorder, intestinal flora disorder, mucosal lesion and intestinal-brain interaction abnormality.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, and in particular to a traditional Chinese medicine composition for treating functional dyspepsia, its preparation, and a method for preparing the preparation. Background Technology

[0002] Functional dyspepsia (FD) is a common clinical disorder of gut-brain interaction, characterized by postprandial fullness, early satiety, epigastric fullness, and heartburn as core symptoms. Its global incidence ranges from 8% to 23%, with postprandial discomfort syndrome (PDS) being the predominant subtype, accounting for approximately 61% of all FD cases. Clinical studies have shown that FD patients often have concurrent small intestinal bacterial overgrowth (SIBO), Helicobacter pylori infection, low-grade duodenal inflammation, and mucosal barrier damage. Furthermore, most patients experience emotional problems such as anxiety and depression, creating a vicious cycle of spleen deficiency, damp-heat, qi stagnation, mucosal damage, and dysbiosis.

[0003] Currently, Western medicine treatment mainly involves a combination of proton pump inhibitors, probiotics, and acid suppressants. However, this approach has limitations in efficacy, a high relapse rate, and numerous adverse reactions. For example, long-term use of proton pump inhibitors may lead to osteoporosis, proton pump inhibitors may cause arrhythmias, and antibiotic treatment for SIBO can easily disrupt the balance of gut microbiota and lead to drug resistance. Traditional Chinese medicine classifies FD (fibrillary dysplasia) under the category of gastric fullness, with the core pathogenesis being spleen deficiency and qi stagnation, and damp-heat accumulation. Although classic formulas and proprietary Chinese medicines such as Lianpu Decoction and Zhishu Kuanzhong Capsules are used, traditional preparations have drawbacks such as low bioavailability, easy destruction of active ingredients by gastric acid, and insufficient targeting. Furthermore, a single formula cannot cover the complex and multifaceted pathogenesis of FD. Summary of the Invention

[0004] The purpose of this invention is to provide a traditional Chinese medicine composition for treating functional dyspepsia, its preparation and preparation method, which is suitable for functional dyspepsia of spleen deficiency and qi stagnation with damp-heat in the spleen and stomach, and can simultaneously improve pathological conditions such as gastrointestinal motility disorders, intestinal flora imbalance, mucosal damage and abnormal gut-brain interaction.

[0005] To achieve the above objectives, the present invention provides a traditional Chinese medicine composition for treating functional dyspepsia. The traditional Chinese medicine composition comprises, by weight, 8-12 parts of Codonopsis pilosula, 8-12 parts of Poria cocos, 8-12 parts of Pinellia ternata, 8-12 parts of prepared Glycyrrhiza uralensis, 8-12 parts of Citrus reticulata peel, 15-25 parts of raw Atractylodes macrocephala, 3-6 parts of Coptis chinensis, 25-35 parts of Taraxacum mongolicum, 15-25 parts of Eupatorium fortunei, 8-12 parts of Magnolia officinalis, 8-12 parts of Citrus aurantium, 9-12 parts of Aucklandia lappa, 15-25 parts of Cuttlebone, and 10-20 parts of stir-fried chicken gizzard lining.

[0006] The present invention also provides a traditional Chinese medicine preparation for treating functional dyspepsia, comprising a traditional Chinese medicine composition for treating functional dyspepsia as described above. The dosage form of the traditional Chinese medicine preparation is tablets, capsules or granules. The traditional Chinese medicine preparation is prepared from traditional Chinese medicine granules with a three-layer structure. The traditional Chinese medicine granules, from the inside out, are a core layer, an intermediate functional buffer layer and an outer responsive shell layer. The core layer is made from a composite extract of the above-mentioned traditional Chinese medicine composition. The intermediate functional buffer layer is a calcium alginate gel layer containing mucosal repair and barrier enhancement components and pH buffer pairs. The outer responsive shell layer is a coating layer containing pH responsive material.

[0007] Preferably, the mucosal repair and barrier enhancement component is composed of Bletilla striata polysaccharide, glutamine, and L-arginine in a mass ratio of (2.5~3.5):(1.5~2.5):(0.8~1.2).

[0008] Preferably, the pH buffer pair is sodium dihydrogen phosphate-disodium hydrogen phosphate, with a buffer capacity of 10~50 mmol / L.

[0009] Preferably, the pH-responsive material is one or more of methacrylate-ethyl acrylate copolymer and methacrylate-methyl methacrylate copolymer.

[0010] This invention also provides a method for preparing a traditional Chinese medicine preparation for treating functional dyspepsia, comprising the following steps: S1. Extraction of compound extract of traditional Chinese medicine: Codonopsis pilosula, Poria cocos, prepared licorice root, tangerine peel, Pinellia ternata, raw Atractylodes macrocephala, Magnolia officinalis, Citrus aurantium, Aucklandia lappa, cuttlebone, and stir-fried chicken gizzard lining are decocted in water to obtain an aqueous extract. Coptis chinensis, Taraxacum mongolicum, and Eupatorium fortunei are extracted by ethanol reflux to obtain an alcoholic extract. The aqueous extract and alcoholic extract are combined and spray-dried to obtain a dry powder of compound extract of traditional Chinese medicine. S2. Preparation of mucosal repair and barrier enhancement components: Mix and grind Bletilla striata polysaccharide, glutamine, and L-arginine, add dispersant, and obtain mucosal repair and barrier enhancement component powder; S3. Constructing an intermediate functional buffer layer: Prepare a sodium alginate solution containing pH buffer pairs, mix the dry powder of the traditional Chinese medicine compound extract of S1 and the powder of the mucosal repair and barrier enhancement component of S2 with the sodium alginate solution containing pH buffer pairs, and inject it into the calcium chloride solution for ionic cross-linking to form a calcium alginate gel layer. S4. Preparation of outer responsive shell: Prepare a coating solution containing pH responsive material. Using fluidized bed coating technology, spray the coating solution onto the surface of the calcium alginate gel layer in S3 to obtain traditional Chinese medicine granules. S5. Formulation: Mix Chinese herbal granules with pharmaceutical excipients and compress them into tablets, fill capsules, or granulate them to obtain granules.

[0011] Preferably, in S1, the spray drying conditions are: inlet air temperature 170~190℃, outlet air temperature 75~85℃, and feed rate 5~10mL / min.

[0012] Preferably, in S2, the dispersant includes one of polyethylene glycol 4000, polyethylene glycol 8000, or Tween 80, and the mass of the dispersant accounts for 0.5% to 12% of the mucosal repair and barrier enhancement component powder.

[0013] Preferably, in S3, the preparation of the sodium alginate solution containing a pH buffer pair is as follows: sodium alginate is mixed with a sodium dihydrogen phosphate-disodium hydrogen phosphate buffer solution with a mass fraction of 2%~8%, stirred and dissolved to obtain a sodium alginate solution containing a pH buffer pair with a mass fraction of 1.5%~3.0%; the mass-volume percentage of calcium chloride solution is 0.5~5.0%, and the ion crosslinking time is 10~60 min.

[0014] Preferably, in step S4, the coating solution containing the pH-responsive material is prepared by mixing the pH-responsive material with a mixed solution of ethanol and water, adding a plasticizer with a mass fraction of 0.5% to 2.0%, stirring to dissolve, and obtaining a coating solution with a mass fraction of 5% to 15%.

[0015] Therefore, the present invention employs the above-mentioned traditional Chinese medicine composition for treating functional dyspepsia, its preparation, and its preparation method, which has the following beneficial effects: (1) The Chinese medicine composition of the present invention strictly follows the principles of syndrome differentiation and treatment in traditional Chinese medicine. It uses Codonopsis pilosula, Atractylodes macrocephala, Poria cocos and other herbs to build the core of strengthening the spleen and replenishing qi, targeting the root cause of spleen deficiency and dysfunction. It uses Coptis chinensis, Taraxacum mongolicum and Eupatorium fortunei to clear heat and resolve dampness, directly targeting the symptoms of damp heat in the spleen and stomach. It is combined with Magnolia officinalis, Citrus aurantium and Aucklandia lappa to regulate qi and eliminate stagnation, Cuttlebone to repair the mucosa, and stir-fried chicken gizzard to promote digestion and relieve stagnation, comprehensively covering the complex pathogenesis of functional dyspepsia, which is spleen deficiency, damp heat, qi stagnation and mucosal damage.

[0016] (2) The traditional Chinese medicine composition of the present invention follows the logic of monarch, minister, assistant and guide. The monarch drug strengthens the spleen and clears dampness, the minister drug regulates qi and repairs, the assistant drug promotes digestion and harmonizes, and the guide drug guides the medicine to enhance efficacy. The cold and hot properties of the medicine are harmonized by roasted licorice. It combines tonification and purgation, promotes qi without consuming qi, and clears heat without harming the spleen, thus avoiding the limitations of single-effect prescriptions.

[0017] (3) The traditional Chinese medicine preparation of the present invention adopts a three-layer structure of core layer - intermediate functional buffer layer - outer responsive shell layer. The outer pH responsive material remains stable in gastric juice (pH 1.2), effectively protecting the traditional Chinese medicine compound extract from gastric acid damage; after entering the intestine (pH 6.8), it swells rapidly to achieve targeted delivery to the intestine. The mucosal repair and barrier enhancement components of the intermediate functional buffer layer can simultaneously upregulate the expression of tight junction protein ZO-1, enhance the intestinal mucosal barrier function, and further improve the therapeutic effect.

[0018] (4) The preparation process of the present invention adopts conventional decoction, reflux extraction, spray drying and fluidized bed coating technology. The equipment is highly versatile, does not require special high-end equipment, is easy to scale up, and has no toxic or harmful reagent residues during the production process, which is in line with the concept of green pharmaceutical manufacturing.

[0019] The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. Attached Figure Description

[0020] Figure 1 This is a schematic diagram showing the in vitro release performance test results of different traditional Chinese medicine preparations of the present invention. Detailed Implementation

[0021] The present invention will be further described below with reference to the accompanying drawings and embodiments. Unless otherwise defined, the technical or scientific terms used in this invention should be understood in their ordinary sense by those skilled in the art. The features mentioned above or in the specific examples mentioned in this invention can be combined arbitrarily, and these specific embodiments are only used to illustrate the invention and are not intended to limit the scope of the invention.

[0022] A traditional Chinese medicine composition for treating functional dyspepsia, comprising, by weight, 8-12 parts of Codonopsis pilosula, 8-12 parts of Poria cocos, 8-12 parts of Pinellia ternata, 8-12 parts of Glycyrrhiza uralensis (processed), 8-12 parts of Citrus reticulata peel, 15-25 parts of Atractylodes macrocephala (raw), 3-6 parts of Coptis chinensis, 25-35 parts of Taraxacum mongolicum, 15-25 parts of Eupatorium fortunei, 8-12 parts of Magnolia officinalis, 8-12 parts of Citrus aurantium, 9-12 parts of Aucklandia lappa, 15-25 parts of Cuttlebone, and 10-20 parts of stir-fried chicken gizzard lining.

[0023] A further preferred embodiment of the traditional Chinese medicine composition includes, by weight, 10 parts of Codonopsis pilosula, 10 parts of Poria cocos, 10 parts of Pinellia ternata, 10 parts of prepared Glycyrrhiza uralensis, 10 parts of Citrus reticulata peel, 20 parts of raw Atractylodes macrocephala, 5 parts of Coptis chinensis, 30 parts of Taraxacum mongolicum, 20 parts of Eupatorium fortunei, 10 parts of Magnolia officinalis, 10 parts of Citrus aurantium, 10 parts of Aucklandia lappa, 20 parts of Cuttlebone, and 15 parts of stir-fried chicken gizzard lining.

[0024] This invention's traditional Chinese medicine composition uses Codonopsis pilosula, Atractylodes macrocephala, Poria cocos, Coptis chinensis, and Taraxacum mongolicum as principal herbs; Magnolia officinalis, Citrus aurantium, Aucklandia lappa, Eupatorium fortunei, Citrus reticulata, Pinellia ternata, and Sepia esculenta as assistant herbs; stir-fried chicken gizzard lining and prepared licorice root as adjuvant herbs; and Aucklandia lappa, Citrus reticulata, and prepared licorice root as guiding herbs. It strictly adheres to the traditional Chinese medicine principle of prioritizing the principal herb, with assistant herbs supporting the principal herb's function, and adjuvant herbs harmonizing and guiding the medicine through the meridians. Combining the synergistic effects of the components with modern pharmacological targets, it forms a comprehensive system that addresses both the root cause and symptoms, balances cold and heat, and harmonizes Qi and blood. Specifically: The principal herb: Strengthens the spleen and clears dampness, directly targeting the core pathogenesis. It is designed to address the core pathogenesis of functional dyspepsia, which involves spleen deficiency and qi stagnation, and damp-heat accumulation. It establishes a dual-core principal herb combination that takes strengthening the spleen and replenishing qi as the fundamental principle and clearing heat and resolving dampness as the secondary principle, taking into account both the etiology and symptoms, and laying a solid foundation for treatment.

[0025] The combination of Codonopsis pilosula, Atractylodes macrocephala, and Poria cocos strengthens the spleen, replenishes qi, dries dampness, and promotes diuresis. These three ingredients form the core of the spleen-strengthening formula: Codonopsis pilosula replenishes qi, Atractylodes macrocephala strengthens the spleen and dries dampness, and Poria cocos strengthens the spleen and promotes diuresis. Together, they restore the spleen and stomach's digestive function, reducing internal dampness at its root. This addresses the root cause of spleen deficiency and dysfunction, laying the foundation for the entire formula to strengthen the spleen. The combination of Coptis chinensis and Taraxacum mongolicum clears heat, dries dampness, detoxifies, and inhibits bacteria. This addresses the symptoms of damp-heat in the spleen and stomach: Coptis chinensis effectively clears damp-heat in the middle jiao, while Taraxacum mongolicum clears heat, detoxifies, and inhibits Helicobacter pylori. Together, they clear damp-heat in the middle jiao, relieving symptoms such as burning sensation in the stomach, bitter taste, and sticky mouth. Furthermore, the bitter and cold nature of Coptis chinensis is moderated by the spleen-strengthening herbs, preventing damage to the spleen.

[0026] The assistant herbs regulate Qi and repair, strengthening the core efficacy and assisting the principal herbs in enhancing the spleen-strengthening and dampness-clearing effects. At the same time, they address secondary pathogenesis such as Qi stagnation and mucosal damage, supplementing the pathological links not covered by the principal herbs, thus forming a comprehensive and synergistic treatment system that addresses both the root cause and symptoms.

[0027] The combination of Magnolia officinalis, Citrus aurantium, and Aucklandia lappa promotes qi circulation, relieves fullness, and enhances gastrointestinal motility, assisting the principal herb in regulating the qi mechanism of the middle jiao: Magnolia officinalis relieves fullness, Citrus aurantium breaks up qi stagnation and eliminates accumulation, and Aucklandia lappa promotes qi circulation and relieves pain. The three work together to enhance gastrointestinal motility, alleviate symptoms of qi stagnation such as epigastric fullness and postprandial bloating, and resolve the disorder of qi circulation caused by spleen deficiency and qi stagnation. The combination of Eupatorium fortunei, Citrus reticulata peel, and Pinellia ternata resolves dampness, harmonizes the stomach, and relieves nausea and vomiting, assisting the principal herb in resolving dampness and harmonizing the stomach: Eupatorium fortunei aromatically resolves dampness and invigorates the spleen, Citrus reticulata peel regulates qi and dries dampness, and Pinellia ternata relieves nausea and eliminates fullness. It strengthens the dampness-resolving effect for poor appetite, nausea, and vomiting caused by damp-heat and phlegm-dampness, while harmonizing the qi mechanism of the spleen and stomach. Cuttlebone neutralizes acid, relieves pain, and repairs the mucosa, targeting mucosal damage and excessive gastric acid in FD patients: Cuttlebone neutralizes gastric acid and astringes and stops bleeding, assisting the principal herb in protecting the gastrointestinal mucosa, relieving acid reflux, heartburn, and stomach pain, and filling the gap in the principal herb's role in mucosal repair.

[0028] Adjuvant medicines: These medicines aid digestion and harmonize the body, taking into account both the medicinal properties and absorption. They are divided into two categories: adjuvant medicines and adjuvant drugs. Adjuvant medicines enhance the efficacy of the principal and assistant medicines and promote digestion and absorption. Adjuvant drugs harmonize the cold and hot properties of the medicines in the formula, preventing harsh ingredients from damaging the spleen and stomach, and improving the safety and applicability of the formula.

[0029] Fried chicken gizzard lining is an adjuvant herb that strengthens the stomach, aids digestion, and resolves food stagnation. It addresses insufficient digestive enzyme secretion and food stagnation caused by spleen deficiency. Fried chicken gizzard lining promotes digestive juice secretion, improves poor appetite and abdominal distension, and avoids the cloying and cloying nature of tonifying herbs like Codonopsis pilosula and Atractylodes macrocephala, thus enhancing the spleen and stomach's absorption efficiency of medicines and food. Prepared licorice root is another adjuvant herb that invigorates qi, strengthens the middle jiao, and harmonizes the properties of other herbs. It moderates the bitter and cold nature of Coptis chinensis and Taraxacum mongolicum, preventing damage to spleen yang; it also moderates the strong qi-regulating properties of Magnolia officinalis and Citrus aurantium, preventing depletion of vital energy. Furthermore, its qi-invigorating effect assists the principal herb in strengthening the spleen.

[0030] Guiding herbs: They guide the medicinal properties to the affected area, acting as both guiding and harmonizing herbs. They direct the medicinal properties of the entire formula to the spleen and stomach in the middle jiao (middle burner), while further harmonizing the components of the various herbs to ensure synergistic effects at each target point and enhance the overall efficacy.

[0031] The combination of costus root and dried tangerine peel promotes qi circulation, guides qi through the meridians, harmonizes the stomach, and relieves pain. Costus root, being a qi-regulating herb, effectively moves qi stagnation in the spleen and stomach, guiding the principal and assistant herbs directly to the affected area in the middle jiao, enhancing the targeted effect of qi regulation. Dried tangerine peel, working synergistically with costus root, both regulates qi and guides the herbs through the meridians, ensuring that the entire formula's efficacy is concentrated on the spleen and stomach. Prepared licorice root (also serving as an adjuvant herb) harmonizes the various herbs and guides them to their respective meridians. Prepared licorice root not only acts as an adjuvant herb but also serves as an adjuvant: its sweet and neutral nature harmonizes the properties of various components in the formula, such as those related to cold and heat, tonification and purgation, and qi circulation, allowing each component to synergistically enhance its effects without antagonism. At the same time, it guides the herbs to the spleen and stomach meridians, improving the targeted therapeutic effect.

[0032] The components of the herbal composition of this invention closely address the complex pathogenesis of functional dyspepsia due to spleen deficiency and qi stagnation combined with damp-heat in the spleen and stomach, synergistically exerting multi-target therapeutic effects. The pharmacological effects are as follows: (1) The core components of strengthening the spleen and replenishing qi lay the foundation for spleen deficiency and restore the digestive function: Codonopsis pilosula: It tonifies the middle energizer, replenishes qi, strengthens the spleen and lungs, and is a key herb for strengthening the spleen; it contains Codonopsis pilosula polysaccharides, which enhance the gastrointestinal mucosal barrier function, promote gastrointestinal motility, and improve spleen deficiency, fatigue, and poor appetite. Targeting the core pathogenesis of functional dyspepsia due to spleen deficiency and impaired digestion, it enhances the spleen and stomach's digestive capacity, reduces internal dampness, and alleviates postprandial fullness and early satiety from the root cause.

[0033] Poria cocos: It promotes diuresis and eliminates dampness, strengthens the spleen and calms the mind, and strengthens the spleen without being greasy; it contains poria cocos polysaccharides, which regulate the balance of intestinal flora, inhibit the proliferation of harmful bacteria in the intestine, and improve loose or sticky stools. It assists Codonopsis pilosula in strengthening the spleen, while eliminating dampness in the middle jiao, relieving abdominal distension, heaviness and fatigue caused by spleen deficiency and dampness.

[0034] Raw Atractylodes macrocephala: It strengthens the spleen and dries dampness, invigorates qi and promotes diuresis, and enhances the digestive function of the spleen and stomach; Atractylodes macrocephala lactone I can promote gastric emptying and small intestinal propulsion rate, regulate gastrointestinal smooth muscle contraction, reduce gastric acidity, protect gastric mucosa, strengthen the spleen-strengthening and dampness-drying effects, improve gastrointestinal motility deficiency, abnormal gastric acid secretion and mucosal damage in patients with functional dyspepsia, and relieve poor appetite and abdominal distension.

[0035] Prepared licorice root: It invigorates qi and nourishes the middle jiao, harmonizes the properties of various medicines, and moderates the cold and hot properties of medicines; it contains glycyrrhizin, which has anti-inflammatory and anti-ulcer effects, reduces inflammatory damage to the gastrointestinal mucosa, and relieves stomach pain. It can enhance the spleen-strengthening and qi-boosting effects, and also harmonize the properties of cold medicines such as Coptis chinensis and dandelion with warm medicines such as Codonopsis pilosula and Atractylodes macrocephala, thus avoiding damage to the spleen.

[0036] Dried tangerine peel: It regulates qi and strengthens the spleen, dries dampness and resolves phlegm, and promotes the flow of qi in the spleen and stomach; it contains volatile oil, which promotes the secretion of digestive juices, enhances gastrointestinal motility, and relieves symptoms of qi stagnation such as belching and nausea. It is effective for abdominal distension caused by spleen deficiency and qi stagnation, promotes the flow of qi and resolves dampness without depleting qi, and assists the spleen-strengthening components in restoring the ascending and descending of qi in the spleen and stomach.

[0037] Pinellia ternata: It dries dampness and resolves phlegm, relieves nausea and vomiting, harmonizes the stomach and eliminates bloating; it regulates the levels of gastrointestinal neurotransmitters (5-HT, dopamine), relieves nausea and vomiting, epigastric fullness and discomfort, and improves delayed gastric emptying. It is suitable for patients with functional dyspepsia who experience stomach disharmony and nausea, and relieves core symptoms such as postprandial fullness and nausea, especially those with vomiting symptoms.

[0038] (2) The heat-clearing and dampness-resolving components clear away damp-heat symptoms and inhibit bacterial infection: Coptis chinensis: Clears heat and dries dampness, drains fire and detoxifies, and is good at clearing damp-heat in the middle jiao; it contains berberine, which has a broad spectrum of antibacterial activity, inhibits the growth of Helicobacter pylori and harmful intestinal bacteria, and reduces the level of inflammatory factors (IL-18, IL-1β). It targets the core symptoms of damp-heat in the spleen and stomach, clears damp-heat in the middle jiao, relieves burning sensation in the stomach, bitter taste and sticky mouth, and inhibits SIBO and Helicobacter pylori infection.

[0039] Dandelion: Clears heat and detoxifies, reduces swelling and dissipates nodules, promotes diuresis and relieves strangury; contains taraxerol and choline, inhibits Helicobacter pylori and intestinal pathogens, protects the gastric mucosa, promotes mucosal repair, and relieves acid reflux and heartburn; works synergistically with Coptis chinensis to enhance the heat-clearing and dampness-resolving effects, while strengthening mucosal protection and improving symptoms such as short and yellow urine and sticky stools caused by damp-heat accumulation in patients with functional dyspepsia.

[0040] Peilan: Aromatic and dampness-resolving, invigorating the spleen and stomach, effectively removing dampness and turbidity in the middle jiao; stimulating gastric smooth muscle, enhancing gastrointestinal motility, improving digestive juice secretion, relieving loss of appetite, bitter taste and sticky mouth. Targeting spleen dysfunction caused by damp-heat accumulation in the middle jiao, it aromatically resolves dampness without harming yin, improving poor appetite and abdominal distension in patients with functional dyspepsia.

[0041] (3) The components that regulate qi and harmonize the stomach can unblock the qi mechanism in the middle jiao and relieve fullness, distension and pain: Magnolia officinalis: It dries dampness and eliminates phlegm, lowers qi and relieves fullness, promotes qi circulation and disperses dampness; it contains magnolol, which regulates the tension of gastrointestinal smooth muscle, promotes gastrointestinal motility, relieves gastrointestinal bloating, and inhibits excessive gastric acid secretion. It targets the core symptoms of qi stagnation in patients with functional dyspepsia, lowers gastrointestinal qi stagnation, and relieves abdominal fullness, bloating and pain, especially suitable for those with significant postprandial fullness.

[0042] Fructus Aurantii Immaturus: It breaks up qi stagnation, eliminates phlegm and dissipates lumps, and enhances the qi-regulating effect; it contains flavonoids, which stimulate gastrointestinal smooth muscle, promote small intestinal propulsion, improve gastrointestinal motility disorders, relieve food stagnation, and work synergistically with Cortex Magnoliae Officinalis to enhance the qi-regulating and lumps-dissipating effects. It is effective for stubborn abdominal distension and indigestion, and can quickly clear the obstructed qi flow in the middle jiao.

[0043] Costus root: It promotes qi circulation, relieves pain, strengthens the spleen and aids digestion, and is good at clearing qi stagnation in the spleen and stomach; it contains costus lactone, which promotes the secretion of motilin (MTL), enhances gastrointestinal motility, and relieves gastrointestinal spasmodic pain; as a qi-regulating medicine, it guides the qi-regulating components directly to the affected area, relieves qi stagnation-related symptoms such as stomach pain, belching, and abdominal distension in patients with functional dyspepsia, and enhances the targeted efficacy of qi-regulating.

[0044] (4) Mucosal repair and protection components protect the gastrointestinal mucosa and enhance barrier function: Cuttlebone: It has astringent and hemostatic properties, neutralizes acid and relieves pain, and protects the gastric mucosa; it mainly contains calcium carbonate, which neutralizes gastric acid, reduces the stimulation of gastric acid on the mucosa, promotes ulcer healing, and upregulates the expression of tight junction protein ZO-1. It is effective for patients with functional dyspepsia who have mucosal damage and excessive gastric acid secretion, relieves acid reflux, heartburn, and stomach pain, repairs the duodenal mucosal barrier, and reduces intestinal mucosal permeability.

[0045] (5) The digestive aids promote digestion and absorption, and prevent greasy foods from irritating the stomach. Stir-fried chicken gizzard: It strengthens the stomach and aids digestion, eliminates food stagnation and stagnation, and enhances digestive function; it contains pepsin, amylase and other ingredients to promote the secretion of digestive juices, improve food stagnation, relieve abdominal distension and loss of appetite, and assist in strengthening the spleen. It is designed for patients with functional dyspepsia who have insufficient digestive enzyme secretion and undigested food, promotes food digestion and absorption, and avoids the greasy and cloying effects of tonifying herbs such as Codonopsis pilosula and Atractylodes macrocephala.

[0046] A traditional Chinese medicine preparation for treating functional dyspepsia includes a traditional Chinese medicine composition for treating functional dyspepsia as described above. The dosage form of the traditional Chinese medicine preparation is tablets, capsules, or granules. The traditional Chinese medicine preparation is made from traditional Chinese medicine granules with a three-layer structure. From the inside out, the traditional Chinese medicine granules consist of an inner core layer, an intermediate functional buffer layer, and an outer responsive shell layer. The inner core layer is made from a composite extract of the above-mentioned traditional Chinese medicine composition. The intermediate functional buffer layer is a calcium alginate gel layer containing mucosal repair and barrier enhancement components and pH buffer pairs. The outer responsive shell layer is a coating layer containing pH responsive materials.

[0047] Preferably, the mucosal repair and barrier enhancement component is composed of Bletilla striata polysaccharide, glutamine, and L-arginine in a mass ratio of (2.5~3.5):(1.5~2.5):(0.8~1.2).

[0048] Preferably, the mass ratio of Bletilla striata polysaccharide, glutamine, and L-arginine is 3:2:1. In this invention, Bletilla striata polysaccharide forms a physical barrier, glutamine provides an energy substrate for intestinal epithelial cells to promote proliferation, and L-arginine regulates microcirculation and tight junctions by synthesizing NO. These three components synergistically repair the barrier at the physical, cellular, and molecular levels, respectively, constituting a complete repair system.

[0049] Preferably, the pH buffer pair is sodium dihydrogen phosphate-disodium hydrogen phosphate, with a buffer capacity of 10~50 mmol / L.

[0050] The preferred buffer capacity is 25 mmol / L.

[0051] Preferably, the pH-responsive material is one or more of methacrylate-ethyl acrylate copolymer and methacrylate-methyl methacrylate copolymer.

[0052] A further preferred pH-responsive material is a copolymer of methacrylate and ethyl acrylate (Eudragit L100-55).

[0053] A method for preparing a traditional Chinese medicine preparation for treating functional dyspepsia includes the following steps: S1. Extraction of compound extract of traditional Chinese medicine: Codonopsis pilosula, Poria cocos, prepared licorice root, tangerine peel, Pinellia ternata, raw Atractylodes macrocephala, Magnolia officinalis, Citrus aurantium, Aucklandia lappa, cuttlebone, and stir-fried chicken gizzard lining are decocted in water to obtain an aqueous extract. Coptis chinensis, Taraxacum mongolicum, and Eupatorium fortunei are extracted by ethanol reflux to obtain an alcoholic extract. The aqueous extract and alcoholic extract are combined and spray-dried to obtain a dry powder of compound extract of traditional Chinese medicine. S2. Preparation of mucosal repair and barrier enhancement components: Mix and grind Bletilla striata polysaccharide, glutamine, and L-arginine, add dispersant, and obtain mucosal repair and barrier enhancement component powder; S3. Constructing an intermediate functional buffer layer: Prepare a sodium alginate solution containing pH buffer pairs, mix the dry powder of the traditional Chinese medicine compound extract of S1 and the powder of the mucosal repair and barrier enhancement component of S2 with the sodium alginate solution containing pH buffer pairs, and inject it into the calcium chloride solution for ionic cross-linking to form a calcium alginate gel layer. S4. Preparation of outer responsive shell: Prepare a coating solution containing pH responsive material. Using fluidized bed coating technology, spray the coating solution onto the surface of the calcium alginate gel layer in S3 to obtain traditional Chinese medicine granules. S5. Formulation: Mix Chinese herbal granules with pharmaceutical excipients and compress them into tablets, fill capsules, or granulate them to obtain granules.

[0054] Preferably, in S1, the water decoction extraction is performed as follows: the water-soluble medicinal material is pulverized to a particle size of 20-40 mesh, 8-12 times the amount of purified water is added, soaked for 30 minutes, brought to a boil over high heat, and then simmered over low heat twice for 30-40 minutes each time. The decoctions obtained from the two decoctions are combined and concentrated under reduced pressure at 60-70℃ and -0.08--0.1MPa to obtain the water extract.

[0055] Preferably, in S1, the ethanol reflux extraction is performed as follows: Coptis chinensis, dandelion, and agastache rugosa are pulverized to a particle size of 20-40 mesh, and extracted twice with 70% (v / v) ethanol for 1.2-1.5 hours each time. The ethanol in the extract is recovered until there is no alcohol odor under the conditions of 50-60℃ and -0.08--0.1MPa to obtain the ethanol extract.

[0056] In this invention, based on the differences in the solubility of the effective components of medicinal materials, water-soluble medicinal materials (such as Codonopsis pilosula, Poria cocos, and Atractylodes macrocephala) are extracted by decoction, which is adapted to the dissolution patterns of water-soluble active components such as polysaccharides, saponins, and alkaloid salts; while medicinal materials containing fat-soluble and alcohol-soluble active components (such as berberine, taraxerol, and volatile oils) such as Coptis chinensis, Taraxacum mongolicum, and Eupatorium fortunei are extracted by reflux extraction with 70% ethanol, which improves the extraction rate of alcohol-soluble effective components and avoids the loss of effective components caused by a single extraction method.

[0057] Preferably, in S1, the spray drying conditions are: inlet air temperature 170~190℃, outlet air temperature 75~85℃, and feed rate 5~10mL / min.

[0058] In this invention, vacuum concentration is carried out under low temperature and negative pressure conditions to reduce the risk of thermal degradation of active ingredients; spray drying avoids the destruction of active ingredients due to prolonged high temperature through instantaneous atomization and rapid drying, while turning the extract into dry powder improves the stability of active ingredients and facilitates subsequent mixing and molding with other components.

[0059] Preferably, in S2, the dispersant includes one of polyethylene glycol 4000, polyethylene glycol 8000, or Tween 80, and the mass of the dispersant accounts for 0.5% to 12% of the mucosal repair and barrier enhancement component powder; In this invention, Bletilla striata polysaccharide, glutamine, and L-arginine are compounded in a certain proportion. Bletilla striata polysaccharide can form a gel protective film on the mucosal surface. Glutamine provides energy for intestinal mucosal epithelial cells and promotes cell proliferation. L-arginine participates in the synthesis of nitric oxide, regulates mucosal microcirculation, and enhances tight junction function. The three work synergistically to achieve a triple mucosal repair effect of physical protection, cell repair, and barrier strengthening. Dispersants such as polyethylene glycol 4000, polyethylene glycol 8000, or Tween 80 can reduce the surface tension of the component powder, improve its dispersibility and stability in sodium alginate solution, avoid agglomeration and stratification in subsequent processes, and ensure the uniformity of the components of the intermediate functional buffer layer.

[0060] Preferably, in S3, the preparation of the sodium alginate solution containing a pH buffer pair is as follows: sodium alginate is mixed with a sodium dihydrogen phosphate-disodium hydrogen phosphate buffer solution with a mass fraction of 2%~8%, stirred and dissolved to obtain a sodium alginate solution containing a pH buffer pair with a mass fraction of 1.5%~3.0%; the mass-volume percentage of calcium chloride solution is 0.5~5.0%, and the ion crosslinking time is 10~60 min.

[0061] In an even more preferred embodiment, in S3, the mass ratio of the dry powder of the traditional Chinese medicine compound extract to the powder of the mucosal repair and barrier enhancement components is (8~12):1.

[0062] In this invention, sodium alginate and calcium chloride undergo ionic cross-linking to form a three-dimensional network gel structure, which serves as an intermediate functional buffer layer encapsulating the dry powder of the traditional Chinese medicine compound extract and the mucosal repair components. This provides physical protection for the core layer and enables the slow release of the active ingredients. Simultaneously, the gel structure exhibits good biocompatibility and is non-irritating to the gastrointestinal tract. The sodium dihydrogen phosphate-disodium hydrogen phosphate buffer pair maintains a stable pH within the gel layer at 6.0-7.0, preventing pH fluctuations in the intestine after the outer coating dissolves from affecting the active ingredients. It also provides a suitable acid-base environment for the mucosal repair components, ensuring their reparative activity. By co-encapsulating the traditional Chinese medicine compound extract and the mucosal repair components in the gel layer, both are released simultaneously in the intestine. While the active ingredients of the traditional Chinese medicine exert their therapeutic effects, the mucosal repair components simultaneously repair the damaged mucosa, achieving a synergistic effect of drug efficacy and mucosal protection, thus improving overall treatment efficiency.

[0063] Preferably, in step S4, the coating solution containing the pH-responsive material is prepared by mixing the pH-responsive material with a mixed solution of ethanol and water, adding a plasticizer with a mass fraction of 0.5% to 2.0%, stirring to dissolve, and obtaining a coating solution with a mass fraction of 5% to 15%.

[0064] More preferably, the volume ratio of ethanol to water in the mixed solution is 1:1 to 3:1, and the plasticizer includes one or more of diethyl phthalate and polyethylene glycol 6000.

[0065] In this invention, the methacrylic acid-ethyl acrylate copolymer (Eudragit L100-55) and methacrylic acid-methyl methacrylate copolymer are enteric-soluble pH-responsive materials. They are insoluble in gastric juice (pH≤3.0) and can effectively encapsulate the intermediate functional buffer layer, preventing the active ingredients from being released and destroyed by gastric acid in the stomach. After entering the intestine (pH≥6.0), the material rapidly swells and dissolves, allowing the inner active ingredients to be released in a targeted manner in the intestine, improving bioavailability. Plasticizers such as diethyl phthalate and polyethylene glycol 6000 can lower the glass transition temperature of the coating material, improve the flexibility and extensibility of the coating film, prevent the coating film from cracking or falling off during storage and transportation, and ensure the integrity of the coating film during gastrointestinal motility.

[0066] In a further preferred embodiment, in S4, the fluidized bed coating temperature is 40~80℃, and the air inlet volume is 20~50m³. 3 / h, atomization pressure is 0.1~0.3MPa, and coating weight gain is controlled at 15%~40%.

[0067] Preferably, the pharmaceutical excipients in S5 include one or more of microcrystalline cellulose, sodium carboxymethyl starch, magnesium stearate, and silicon dioxide.

[0068] In a further preferred embodiment, in S5, when preparing tablets, the amount of pharmaceutical excipients is as follows: microcrystalline cellulose accounts for 30% to 50% of the total mass of the preparation, sodium carboxymethyl starch accounts for 2% to 10%, magnesium stearate accounts for 0.5% to 3%, and silicon dioxide accounts for 0.2% to 2%.

[0069] In a further preferred embodiment, in S5, when preparing capsules, the pharmaceutical excipient is magnesium stearate, and the amount used accounts for 0.5% to 2% of the total mass of the Chinese medicine granules.

[0070] In a further preferred embodiment, in S5, when preparing granules, the pharmaceutical excipients include mannitol and steviol glycosides, with mannitol accounting for 20% to 40% of the total mass of the preparation and steviol glycosides accounting for 0.1% to 0.5%.

[0071] Example 1 This invention provides a traditional Chinese medicine composition for treating functional dyspepsia, comprising, by weight: 10 parts Codonopsis pilosula, 10 parts Poria cocos, 10 parts Pinellia ternata, 10 parts prepared Glycyrrhiza uralensis, 10 parts Citrus reticulata peel, 20 parts raw Atractylodes macrocephala, 5 parts Coptis chinensis, 30 parts Taraxacum mongolicum, 20 parts Eupatorium fortunei, 10 parts Magnolia officinalis, 10 parts Citrus aurantium, 10 parts Aucklandia lappa, 20 parts Cuttlebone, and 15 parts stir-fried chicken gizzard lining.

[0072] The preparation method of the above-mentioned traditional Chinese medicine composition for treating functional dyspepsia includes the following steps: S1. Extraction of the compound extract of traditional Chinese medicine: Codonopsis pilosula, Poria cocos, prepared licorice root, tangerine peel, Pinellia ternata, raw Atractylodes macrocephala, Magnolia officinalis, Citrus aurantium, Aucklandia lappa, cuttlebone, and stir-fried chicken gizzard lining are pulverized to 30 mesh, soaked in 10 times the amount of purified water for 30 min, brought to a boil over high heat, then simmered twice over low heat (35 min each time). The decoctions are combined and concentrated under reduced pressure at 65℃ and -0.09 MPa to a relative density of 1.18 (60℃) to obtain an aqueous extract. Coptis chinensis, Taraxacum mongolicum, and Eupatorium fortunei are pulverized to 30 mesh and extracted twice by reflux with 70% (v / v) ethanol (1.3 h each time). The ethanol is recovered at 55℃ and -0.09 MPa until no alcohol odor is detected to obtain an alcoholic extract. The aqueous and alcoholic extracts are combined and dried under spray drying conditions (inlet air temperature 180℃, outlet air temperature 80℃, feed rate 8 mL / min) to obtain a dry powder of the compound extract of traditional Chinese medicine.

[0073] S2. Preparation of mucosal repair and barrier enhancement components: Weigh out Bletilla striata polysaccharide, glutamine, and L-arginine in a mass ratio of 3:2:1, mix and grind until the particle size is ≤40μm, add 5% of polyethylene glycol 6000 as a dispersant, and mix well to obtain mucosal repair and barrier enhancement component powder.

[0074] S3. Constructing an intermediate functional buffer layer: Sodium alginate was mixed with 4% sodium dihydrogen phosphate-disodium hydrogen phosphate buffer (buffer capacity 25 mmol / L) and stirred to dissolve, thus preparing a 2.0% sodium alginate solution containing a pH buffer pair. The dry powder of the traditional Chinese medicine compound extract and the powder of the mucosal repair and barrier enhancement component were mixed at a mass ratio of 10:1, and then added to the above sodium alginate solution containing a pH buffer pair. After stirring evenly, the mixture was injected into a 2.0% (w / v) calcium chloride solution and ion crosslinked at 25°C for 30 min to form a calcium alginate gel layer.

[0075] S4. Preparation of the outer responsive shell: A methacrylate-ethyl acrylate copolymer (Eudragit L100-55) was mixed with a mixed solution of ethanol and water (volume ratio 2:1). 1.0% (w / w) of polyethylene glycol 6000 was added as a plasticizer, and the mixture was stirred to dissolve, yielding a 10% (w / w) coating solution. Fluidized bed coating technology was used, with a coating temperature of 60℃ and an air inlet volume of 35m³. 3 / h, atomization pressure 0.2MPa, coating weight gain 25%, to obtain three-layer structured Chinese medicine granules.

[0076] S5. Formulation: Mix the Chinese herbal granules with pharmaceutical excipients (microcrystalline cellulose accounting for 40% of the total mass of the preparation, sodium carboxymethyl starch accounting for 5% of the total mass of the preparation, magnesium stearate accounting for 1.5% of the total mass of the preparation, and silicon dioxide accounting for 1% of the total mass of the preparation) evenly, and compress them into tablets (each tablet weighing 0.5g), with a tablet hardness of 105N and a disintegration time of 28min.

[0077] Example 2 This invention provides a traditional Chinese medicine composition for treating functional dyspepsia, comprising, by weight: 8 parts Codonopsis pilosula, 12 parts Poria cocos, 8 parts Pinellia ternata, 12 parts prepared Glycyrrhiza uralensis, 8 parts Citrus reticulata peel, 25 parts raw Atractylodes macrocephala, 3 parts Coptis chinensis, 35 parts Taraxacum mongolicum, 15 parts Eupatorium fortunei, 12 parts Magnolia officinalis, 8 parts Citrus aurantium, 12 parts Aucklandia lappa, 15 parts Cuttlebone, and 20 parts stir-fried chicken gizzard lining.

[0078] The preparation method of the above-mentioned traditional Chinese medicine composition for treating functional dyspepsia includes the following steps: S1. Extraction of compound extract from traditional Chinese medicine: Codonopsis pilosula, Poria cocos, prepared licorice root, tangerine peel, Pinellia ternata, raw Atractylodes macrocephala, Magnolia officinalis, Citrus aurantium, Aucklandia lappa, cuttlebone, and stir-fried chicken gizzard lining were pulverized to 20 mesh, 8 times the amount of purified water was added, and the mixture was soaked for 30 min. After boiling over high heat, it was simmered twice over low heat (30 min each time). The decoctions were combined and concentrated under reduced pressure at 60℃ and -0.08 MPa to a relative density of 1.18 (60℃) to obtain an aqueous extract. Coptis chinensis, Taraxacum mongolicum, and Eupatorium fortunei were pulverized to 20 mesh and extracted twice by reflux with 70% (v / v) ethanol (1.2 h each time). The ethanol was recovered at 55℃ and -0.09 MPa until no alcohol odor was found to obtain an alcoholic extract. The aqueous extract and alcoholic extract were combined and dried under spray drying conditions (inlet air temperature 170℃, outlet air temperature 75℃, feed rate 5 mL / min) to obtain a dry powder of compound extract from traditional Chinese medicine.

[0079] S2. Preparation of mucosal repair and barrier enhancement components: Weigh out Bletilla striata polysaccharide, glutamine, and L-arginine in a mass ratio of 2.5:2.5:0.8, mix and grind until the particle size is ≤50μm, add 0.5% of Tween 80 as a dispersant, and mix well to obtain the mucosal repair and barrier enhancement component powder.

[0080] S3. Constructing an intermediate functional buffer layer: Sodium alginate was mixed with 2% sodium dihydrogen phosphate-disodium hydrogen phosphate buffer (buffer capacity 25 mmol / L) and stirred to dissolve, thus preparing a 1.5% sodium alginate solution containing a pH buffer pair. The dry powder of the traditional Chinese medicine compound extract and the powder of the mucosal repair and barrier enhancement component were mixed at a mass ratio of 8:1, and then added to the above sodium alginate solution containing a pH buffer pair. After stirring evenly, the mixture was injected into a 0.5% (w / v) calcium chloride solution and ion crosslinked at 20°C for 10 min to form a calcium alginate gel layer.

[0081] S4. Preparation of the outer responsive shell: A methacrylic acid-methyl methacrylate copolymer (Eudragit S100) was mixed with a mixed solution of ethanol and water (volume ratio 1:1), and 0.5% (w / w) of diethyl phthalate was added as a plasticizer. The mixture was stirred and dissolved to obtain a 5% (w / w) coating solution. Fluidized bed coating technology was used, with the coating temperature set at 40℃ and the air inlet volume at 20m³ / h. 3 / h, atomization pressure 0.1MPa, coating weight gain 15%, to obtain three-layer structured Chinese medicine granules.

[0082] S5. Formulation: Mix the Chinese herbal medicine granules with pharmaceutical excipients (magnesium stearate accounts for 0.5% of the total mass of the formulation) evenly, fill the capsules (0.3g per capsule), and achieve a cumulative release rate of 82.3% over 60 minutes.

[0083] Example 3 This invention provides a traditional Chinese medicine composition for treating functional dyspepsia, comprising, by weight: 12 parts Codonopsis pilosula, 8 parts Poria cocos, 12 parts Pinellia ternata, 8 parts Glycyrrhiza uralensis (processed), 12 parts Citrus reticulata peel, 15 parts Atractylodes macrocephala (raw), 6 parts Coptis chinensis, 25 parts Taraxacum mongolicum, 25 parts Eupatorium fortunei, 8 parts Magnolia officinalis, 12 parts Citrus aurantium, 9 parts Aucklandia lappa, 25 parts Cuttlebone, and 10 parts stir-fried chicken gizzard lining.

[0084] The preparation method of the above-mentioned traditional Chinese medicine composition for treating functional dyspepsia includes the following steps: S1. Extraction of the compound extract of traditional Chinese medicine: Codonopsis pilosula, Poria cocos, prepared licorice root, tangerine peel, Pinellia ternata, raw Atractylodes macrocephala, Magnolia officinalis, Citrus aurantium, Aucklandia lappa, cuttlebone, and stir-fried chicken gizzard lining are pulverized to 40 mesh, soaked in 12 times the amount of purified water for 30 min, brought to a boil over high heat, then simmered twice over low heat (40 min each time). The decoctions are combined and concentrated under reduced pressure at 70℃ and -0.1 MPa to a relative density of 1.18 (60℃) to obtain an aqueous extract. Coptis chinensis, Taraxacum mongolicum, and Eupatorium fortunei are pulverized to 40 mesh and extracted twice by reflux with 70% (v / v) ethanol (1.5 h each time). The ethanol is recovered at 55℃ and -0.09 MPa until no alcohol odor is detected to obtain an alcoholic extract. The aqueous and alcoholic extracts are combined and dried under spray drying conditions (inlet air temperature 190℃, outlet air temperature 85℃, feed rate 10 mL / min) to obtain a dry powder of the compound extract of traditional Chinese medicine.

[0085] S2. Preparation of mucosal repair and barrier enhancement components: Weigh out Bletilla striata polysaccharide, glutamine, and L-arginine in a mass ratio of 3.5:1.5:1.2, grind them to a particle size ≤30μm, add polyethylene glycol 8000 at 12% of the total mass as a dispersant, and mix well to obtain the mucosal repair and barrier enhancement component powder.

[0086] S3. Constructing an intermediate functional buffer layer: Sodium alginate was mixed with 8% sodium dihydrogen phosphate-disodium hydrogen phosphate buffer (buffer capacity 25 mmol / L) and stirred to dissolve, thus preparing a 3.0% sodium alginate solution containing a pH buffer pair. The dry powder of the traditional Chinese medicine compound extract and the powder of the mucosal repair and barrier enhancement component were mixed at a mass ratio of 12:1, added to the above sodium alginate solution containing a pH buffer pair, stirred evenly, and then injected into a 5.0% (w / v) calcium chloride solution. Ionic crosslinking was carried out at 30°C for 60 min to form a calcium alginate gel layer.

[0087] S4. Preparation of the outer responsive shell: A mixture of methacrylic acid-ethyl acrylate copolymer and methacrylic acid-methyl methacrylate copolymer (mass ratio 1:1) was used as the pH responsive material. This mixture was then combined with a solution of ethanol and water (volume ratio 3:1), and 2.0% (mass fraction) of diethyl phthalate was added as a plasticizer. The mixture was stirred and dissolved to obtain a 15% (mass fraction) coating solution. Fluidized bed coating technology was used, with the coating temperature set at 80℃ and the air inlet volume at 50m³. 3 / h, atomization pressure 0.3MPa, coating weight gain 40%, to obtain three-layer structured Chinese medicine granules.

[0088] S5. Formulation: Mix the Chinese herbal medicine granules with pharmaceutical excipients (mannitol accounts for 30% of the total mass of the preparation and steviol glycosides account for 0.3% of the total mass of the preparation), granulate and dry, with a particle size distribution of D90=480μm and D50=180μm, a sweet taste, and good dispersibility.

[0089] Comparative Example 1: Without mucosal repair and barrier enhancement components Compared with Example 1, step S2 was omitted, and the mucosal repair and barrier enhancement components in the intermediate functional buffer layer were removed. All other steps were the same as in Example 1, and tablets were prepared.

[0090] Comparative Example 2: No outer response shell Compared with Example 1, step S4 is omitted, there is no outer response shell, only the core layer and the intermediate functional buffer layer are retained, and the rest is the same as in Example 1, and tablets are prepared.

[0091] Comparative Example 3: Traditional Decoction According to the traditional Chinese medicine composition formula in Example 1, the decoction was prepared by traditional decoction method: 10 parts of Codonopsis pilosula, 10 parts of Poria cocos, 10 parts of Pinellia ternata, 10 parts of prepared Glycyrrhiza uralensis, 10 parts of Citrus reticulata peel, 20 parts of raw Atractylodes macrocephala, 5 parts of Coptis chinensis, 30 parts of Taraxacum mongolicum, 20 parts of Eupatorium fortunei, 10 parts of Magnolia officinalis, 10 parts of Citrus aurantium, 10 parts of Aucklandia lappa, 20 parts of Cuttlebone, and 15 parts of stir-fried chicken gizzard lining were pulverized, added to 10 times the amount of water, soaked for 30 minutes, brought to a boil over high heat, and then simmered twice over low heat (40 minutes each time). The decoctions were combined and concentrated under reduced pressure at 65℃ and -0.09MPa until each milliliter contained 1g of raw herbs, thus obtaining the traditional Chinese medicine composition decoction.

[0092] Performance testing: 1. In vitro release performance test Using the USP basket method, the formulations prepared in Examples 1-3 and Comparative Examples 1-3 were subjected to release tests in simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 6.8), respectively. The temperature was 37±0.5℃, and the rotation speed was 100 rpm. Sampling was performed periodically to determine the cumulative release rate. The results are shown in Table 1 and... Figure 1 As shown.

[0093] Table 1. Results of in vitro release performance tests for different formulations

[0094] From Table 1 and Figure 1It can be seen that the formulations of Examples 1-3 all had a 2-hour release rate of <10% in gastric juice, indicating that the outer pH-responsive shell layer can effectively protect the active ingredients of traditional Chinese medicine from gastric acid degradation; the cumulative release rate in intestinal juice was >82% in 6 hours, achieving targeted intestinal release, which meets the design expectations. Comparative Example 2, lacking an outer responsive shell layer, had a 2-hour release rate of 42.6% in gastric juice, with a large amount of active ingredients released in the stomach, which are easily destroyed; Comparative Example 3 had a 2-hour release rate as high as 68.3% in gastric juice, lacking targeting and having low bioavailability. Comparative Example 1, lacking mucosal repair and barrier enhancement components, had a lower 6-hour cumulative release rate in intestinal juice than Example 1, indicating that the addition of mucosal repair components changed the microstructure of the intermediate functional buffer layer (such as increasing hydrophilicity or porosity), thereby optimizing the drug release behavior and helping to achieve a more stable and efficient intestinal release.

[0095] A damage model was constructed using human intestinal mucosal epithelial cells (Caco-2). After the preparations of Examples 1-3 and Comparative Examples 1-3 were applied to the damaged cells, the relative expression level of tight junction protein ZO-1 was detected by Western Blot (with β-actin as an internal reference). The results are shown in Table 2 below.

[0096] Table 2. Test results of mucosal repair performance of different formulations

[0097] As shown in Table 2, the relative expression levels of ZO-1 protein in Examples 1-3 were significantly higher than those in the model control group (P<0.01), with Example 3 showing the highest ZO-1 expression level. This indicates that the formulation of the present invention can effectively upregulate the expression of tight junction proteins and repair the intestinal mucosal barrier. Comparative Example 1, lacking mucosal repair and barrier enhancement components, had a ZO-1 expression level of only 0.45±0.07, significantly lower than that of Example 1 (P<0.05), confirming that mucosal repair and barrier enhancement components are key to improving mucosal repair function. The ZO-1 expression level in Comparative Example 3 (0.58±0.08) was lower than all other examples, indicating that the three-layer structure of the formulation can promote the targeted release of active ingredients in the intestine and enhance the mucosal repair effect.

[0098] The formulations of Examples 1-3 and Comparative Examples 1-3 were placed under accelerated stability test conditions (40°C, 75% relative humidity) for 6 months, and the retention rates of the active ingredients (berberine and Codonopsis polysaccharide) were detected. The results are shown in Table 3 below.

[0099] Table 3. Accelerated stability test results for different formulations

[0100] As shown in Table 3, after 6 months of accelerated stability testing, the retention rates of berberine and Codonopsis pilosula polysaccharides in Examples 1-3 were all >88%, with no significant changes in appearance, indicating that the three-layer structure formulation effectively protects the active ingredients and has good stability. Comparative Example 2, lacking an outer responsive shell, showed a significant decrease in the retention rate of the active ingredients and exhibited slight discoloration, indicating that the outer coating can improve the stability of the formulation. Comparative Example 3 showed an extremely low retention rate of the active ingredients and exhibited turbidity and precipitation, confirming the poor stability of traditional dosage forms and their inability to be stored for long periods.

[0101] 150 patients with functional dyspepsia of spleen deficiency and qi stagnation combined with spleen and stomach damp-heat were randomly divided into 5 groups (30 patients in each group). They were given the drugs of Examples 1-3, Comparative Example 1, and Comparative Example 3, respectively. The treatment course was 4 weeks, and the patients were followed up for 8 weeks after stopping the drug. The clinical comprehensive efficacy rate, TCM syndrome score and recurrence rate were evaluated. The results are shown in Table 4 below.

[0102] Table 4 Clinical trial results of different formulations

[0103] As shown in Table 4, the overall clinical efficacy of Examples 1-3 was >86%, with Example 1 exhibiting the highest efficacy, the lowest TCM syndrome score after treatment (3.2±1.8), and an 8-week recurrence rate of only 6.7%, significantly superior to Comparative Examples 1 and 3 (P<0.05). Comparative Example 1, lacking mucosal repair and barrier enhancement components, had a lower clinical efficacy and recurrence rate than Examples 1-3, indicating that mucosal repair function is crucial for improving clinical efficacy and reducing recurrence. Comparative Example 3 had the worst clinical efficacy, TCM syndrome score, and recurrence rate, and the highest incidence of adverse reactions, confirming that the formulation process of this invention can improve efficacy and reduce adverse reactions.

[0104] Therefore, this invention employs the aforementioned traditional Chinese medicine composition for treating functional dyspepsia, its formulation, and its preparation method. Through scientific formulation of principal, assistant, and adjuvant herbs and a three-layer intelligent response structure, it achieves comprehensive coverage of the complex pathogenesis of spleen deficiency, damp-heat, qi stagnation, and mucosal damage. The test results of Examples 1-3 demonstrate that the formulation of this invention possesses excellent intestinal targeted release performance, mucosal repair function, and stability. Its clinical efficacy is significantly superior to traditional dosage forms and comparative formulations lacking key components, and it exhibits good safety, making it suitable for long-term treatment and conditioning of patients with functional dyspepsia.

[0105] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can still be made to the technical solutions of the present invention, and these modifications or equivalent substitutions cannot cause the modified technical solutions to deviate from the spirit and scope of the technical solutions of the present invention.

Claims

1. A traditional Chinese medicine composition for treating functional dyspepsia, characterized in that: The traditional Chinese medicine composition, by weight, includes 8-12 parts of Codonopsis pilosula, 8-12 parts of Poria cocos, 8-12 parts of Pinellia ternata, 8-12 parts of prepared Glycyrrhiza uralensis, 8-12 parts of Citrus reticulata peel, 15-25 parts of raw Atractylodes macrocephala, 3-6 parts of Coptis chinensis, 25-35 parts of Taraxacum mongolicum, 15-25 parts of Eupatorium fortunei, 8-12 parts of Magnolia officinalis, 8-12 parts of Citrus aurantium, 9-12 parts of Aucklandia lappa, 15-25 parts of Cuttlebone, and 10-20 parts of stir-fried chicken gizzard lining.

2. A traditional Chinese medicine preparation for treating functional dyspepsia, characterized in that: The invention comprises a traditional Chinese medicine composition for treating functional dyspepsia as described in claim 1, wherein the dosage form of the traditional Chinese medicine preparation is tablets, capsules or granules, and the traditional Chinese medicine preparation is made from traditional Chinese medicine granules with a three-layer structure, wherein the traditional Chinese medicine granules are, from the inside out, a core layer, an intermediate functional buffer layer and an outer responsive shell layer; the core layer is made from a composite extract of the traditional Chinese medicine composition as described in claim 1, the intermediate functional buffer layer is a calcium alginate gel layer containing mucosal repair and barrier enhancement components and pH buffer pairs, and the outer responsive shell layer is a coating layer containing pH responsive material.

3. A traditional Chinese medicine preparation for treating functional dyspepsia according to claim 2, characterized in that: The mucosal repair and barrier enhancement component is composed of Bletilla striata polysaccharide, glutamine, and L-arginine in a mass ratio of (2.5~3.5):(1.5~2.5):(0.8~1.2).

4. A traditional Chinese medicine preparation for treating functional dyspepsia according to claim 2, characterized in that: The pH buffer pair is sodium dihydrogen phosphate-disodium hydrogen phosphate, with a buffer capacity of 10~50 mmol / L.

5. A traditional Chinese medicine preparation for treating functional dyspepsia according to claim 2, characterized in that: The pH-responsive material is one or more of the following: methacrylic acid-ethyl acrylate copolymer and methacrylic acid-methyl methacrylate copolymer.

6. A method for preparing a traditional Chinese medicine preparation for treating functional dyspepsia as described in any one of claims 2-5, characterized in that: Includes the following steps: S1. Extraction of compound extract of traditional Chinese medicine: Codonopsis pilosula, Poria cocos, prepared licorice root, tangerine peel, Pinellia ternata, raw Atractylodes macrocephala, Magnolia officinalis, Citrus aurantium, Aucklandia lappa, cuttlebone, and stir-fried chicken gizzard lining are decocted in water to obtain an aqueous extract. Coptis chinensis, Taraxacum mongolicum, and Eupatorium fortunei are extracted by ethanol reflux to obtain an alcoholic extract. The aqueous extract and alcoholic extract are combined and spray-dried to obtain a dry powder of compound extract of traditional Chinese medicine. S2. Preparation of mucosal repair and barrier enhancement components: Mix and grind Bletilla striata polysaccharide, glutamine, and L-arginine, add dispersant, and obtain mucosal repair and barrier enhancement component powder; S3. Constructing an intermediate functional buffer layer: Prepare a sodium alginate solution containing pH buffer pairs, mix the dry powder of the traditional Chinese medicine compound extract of S1 and the powder of the mucosal repair and barrier enhancement component of S2 with the sodium alginate solution containing pH buffer pairs, and inject it into the calcium chloride solution for ionic cross-linking to form a calcium alginate gel layer. S4. Preparation of outer responsive shell: Prepare a coating solution containing pH responsive material. Using fluidized bed coating technology, spray the coating solution onto the surface of the calcium alginate gel layer in S3 to obtain traditional Chinese medicine granules. S5. Formulation: Mix Chinese herbal granules with pharmaceutical excipients and compress them into tablets, fill capsules, or granulate them to obtain granules.

7. The method for preparing a traditional Chinese medicine preparation for treating functional dyspepsia according to claim 6, characterized in that: In S1, the spray drying conditions are: inlet air temperature 170~190℃, outlet air temperature 75~85℃, and feed rate 5~10mL / min.

8. The method for preparing a traditional Chinese medicine preparation for treating functional dyspepsia according to claim 6, characterized in that: In S2, the dispersant includes one of polyethylene glycol 4000, polyethylene glycol 8000 or Tween 80, and the mass of the dispersant accounts for 0.5% to 12% of the mucosal repair and barrier enhancement component powder.

9. The method for preparing a traditional Chinese medicine preparation for treating functional dyspepsia according to claim 6, characterized in that: In S3, the sodium alginate solution containing a pH buffer pair is prepared by mixing sodium alginate with a 2%~8% (w / w) sodium dihydrogen phosphate-disodium hydrogen phosphate buffer solution, stirring and dissolving to obtain a sodium alginate solution containing a pH buffer pair with a sodium alginate mass fraction of 1.5%~3.0%; the calcium chloride solution has a mass-volume percentage of 0.5%~5.0%, and the ion crosslinking time is 10~60 min.

10. A method for preparing a traditional Chinese medicine preparation for treating functional dyspepsia according to claim 6, characterized in that: In S4, the coating solution containing the pH-responsive material is prepared by mixing the pH-responsive material with a mixed solution of ethanol and water, adding a plasticizer with a mass fraction of 0.5% to 2.0%, stirring to dissolve, and obtaining a coating solution with a mass fraction of 5% to 15%.

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