Pharmaceutical composition for protecting gastric mucosa, gastric floating buoyant raft system of pharmaceutical composition and preparation method of gastric floating buoyant raft system

Abstract

The invention discloses a pharmaceutical composition for protecting gastric mucosa, a gastric floating buoyant raft system of the pharmaceutical composition and a preparation method of the gastric floating buoyant raft system. The mass ratio of the proton pump inhibitor to the traditional Chinese medicine extract is (1: 2)-(1: 4), and the traditional Chinese medicine extract is prepared from gingerol oil and pogostemon cablin essential oil according to the mass ratio of (0.5-3): 1. The pharmaceutical composition is prepared into a gastric floating raft system, and the dosage form is in a solution state under preparation and in-vitro conditions; after being orally taken and entering the stomach, the gel buoyant raft is rapidly subjected to phase transformation in the environment of low-pH gastric juice and expands to form a layer of light gel buoyant raft which is low in density, compact in structure and certain in mechanical strength. The gel raft can stay on the surface of gastric juice for a long time, so that retention and slow release of the medicine in the stomach are realized, and the local action effect is enhanced. Compared with a single chemical medicine, the compound preparation is mild in medicine property, the irritation is obviously reduced, the curative effect is enhanced through the synergistic effect of multiple components, and the adverse reaction is reduced.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, specifically to a pharmaceutical composition for protecting the gastric mucosa, its gastric floating raft system, and its preparation method. Background Technology

[0002] Gastric inflammation and ulcers are among the most common digestive system diseases in clinical practice. Essentially, they result from a disruption of the balance between defensive and offensive factors in the gastric mucosa. The gastric mucosa is constantly exposed to various offensive factors, including but not limited to high concentrations of gastric acid, pepsin, Helicobacter pylori infection, nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, and stress. Under physiological conditions, the gastric mucosa maintains its integrity through a sophisticated defense system comprised of the mucus-bicarbonate barrier, tight junctions of epithelial cells, adequate mucosal blood flow, and prostaglandin-mediated cell protection mechanisms. However, when the offensive factors are too strong or the defensive factors are impaired, gastric mucosal inflammation and erosion can occur, progressing to acute or chronic gastritis or peptic ulcers. In severe cases, complications such as bleeding, perforation, and even obstruction can arise, posing a serious threat to the patient's quality of life and health.

[0003] The current core treatment strategy revolves around balancing the attack and defense systems, primarily employing three classes of drugs: acid suppressants (such as proton pump inhibitors), which strongly inhibit gastric acid and reduce its attack intensity; antibacterial drugs, used in combination to eradicate Helicobacter pylori; and mucosal protectants (such as bismuth preparations), which form a protective film on the mucosal surface to enhance its defense capabilities.

[0004] However, existing treatment options still have many limitations. First, long-term or high-dose use of proton pump inhibitors may increase the risk of fractures, intestinal infections, and malabsorption of nutrients. Second, the antibiotic resistance rate of Helicobacter pylori is increasing year by year, leading to a decline in the eradication success rate of standard triple or quadruple therapy. Third, while existing mucosal protectants have some efficacy, their effects are often short-lived and difficult to maintain long-term protection after gastric emptying, and their effect on promoting the active repair and regeneration of damaged mucosa is limited. In addition, most treatment options focus on "symptomatic treatment," and their role in regulating the complex inflammatory and immune microenvironment of the gastric mucosa, clearing excess oxygen free radicals, and fundamentally promoting tissue repair and regeneration is still insufficient.

[0005] Therefore, there is an urgent need in this field to develop a novel gastric-targeted therapeutic agent. Conventional oral dosage forms (such as tablets and capsules) are typically designed to release drugs in the intestines, resulting in short retention times in the stomach and an inability to maintain effective drug concentrations at sites of gastric inflammation and ulceration, leading to insufficient efficacy. An ideal new therapeutic agent should be able to specifically retain or release in the stomach, not only effectively neutralizing attacking agents but also actively enhancing the gastric mucosa's self-defense and repair capabilities, providing more durable and comprehensive local protection, particularly demonstrating superior efficacy in regulating inflammatory responses and promoting tissue healing, thereby overcoming the aforementioned shortcomings of existing technologies. Summary of the Invention

[0006] Therefore, it is necessary to provide a composition that ensures efficacy in treating gastric inflammation and ulcers while having relatively simple components. By developing gastric retention-targeting agents and prolonging their duration of action in the stomach, a stable local drug concentration can be maintained, significantly enhancing therapeutic efficacy while reducing the dosage and frequency of administration. This invention aims to provide a pharmaceutical composition for protecting the gastric mucosa, its gastric floating raft system, and a method for its preparation.

[0007] This invention provides a pharmaceutical composition for protecting the gastric mucosa, comprising a proton pump inhibitor and a traditional Chinese medicine extract.

[0008] Proton pump inhibitors include one or more of omeprazole, lansoprazole, pantoprazole, esomeprazole, dexlansoprazole, rabeprazole, and esomeprazole.

[0009] The Chinese herbal extract is a cellulose inclusion complex of gingerol oil and patchouli essential oil prepared by mixing them in a certain mass ratio, using ethyl cellulose as the packaging material, and then using purified water as the antisolvent method.

[0010] In some embodiments, the preparation method of the ethyl cellulose inclusion complex of the traditional Chinese medicine extract includes the following steps: (1) Preparation of ethyl cellulose solution; (2) Forming a homogeneous drug-containing emulsion: The Chinese herbal extract composition is added to an ethyl cellulose solution and stirred until homogeneous. An emulsifier solution is then added to form a homogeneous and stable emulsion, wherein the emulsifier solution is an aqueous solution of sodium dodecyl sulfate. (3) The target analyte is precipitated by antisolvent method; the antisolvent is purified water.

[0011] As a preferred embodiment, in step (1), the mass concentration of the ethyl cellulose solution is 10%.

[0012] As a preferred embodiment, in step (2), the herbal extract composition is 30-40% of the total weight of the ethyl cellulose.

[0013] As a preferred embodiment, in step (2), the mass concentration of the sodium dodecyl sulfate aqueous solution of the emulsifier is 0.5%.

[0014] As a preferred embodiment, in step (2), the stirring speed during emulsification is 600 r / min and the emulsification time is 30 min.

[0015] In some embodiments, the mass ratio of gingerol oil and patchouli essential oil in the herbal extract is 0.5 to 3:1, preferably 2:1.

[0016] In some embodiments, the mass ratio of the proton pump inhibitor to the traditional Chinese medicine extract is 1:2 to 4.

[0017] This invention also provides an oral gastric floating raft system, comprising a solid inclusion complex of gingerol oil and patchouli extract prepared using the above method. The dosage form is in solution state under preparation and in vitro conditions; after oral administration into the stomach, it rapidly undergoes a phase transition in the low pH gastric juice environment, swelling to form a low-density, dense, and mechanically strong lightweight gel raft. It can float on gastric juice for an extended period.

[0018] In some embodiments, the oral gastric flotation raft system comprises an active pharmaceutical ingredient, a hydrophilic gel matrix, a gelling agent, a flotation agent, a sustained-release agent, and an optional solvent.

[0019] In some embodiments, the weight ratio of the herbal extract to the excipients in the gastric floating raft system is 1:2 to 1:10, and the excipients include the following components in parts by weight: 1 to 8 parts of hydrophilic gel matrix, 1 to 3 parts of auxiliary gel forming agent, 1 to 5 parts of flotation agent, and 1 to 3 parts of sustained-release agent.

[0020] In some embodiments, the hydrophilic gel matrix in the gastric floating raft system includes one or more of gelatin, gum arabic, chitosan, sodium alginate, and gellan gum.

[0021] In some embodiments, the auxiliary gel-forming agent in the gastric floating raft system includes one or more of the following: Carbopol 940, Carbopol 941, Carbopol 974P, Carbopol 980, Carbopol 981, Carbopol 5984, carbopol homopolymer (Type A), carbopol homopolymer (Type B), and carbopol homopolymer (Type C).

[0022] In some embodiments, the flotation agent in the gastric flotation raft system includes one or more of cetyl alcohol, octadecanol, stearic acid, glyceryl monostearate, glyceryl sorbate, sodium bicarbonate, sodium carbonate, calcium carbonate, sodium alginate, carrageenan, guar gum, xanthan gum, pectin, carbomer, chitosan, and polyvinylpyrrolidone (PVP).

[0023] In some embodiments, the sustained-release agent in the gastric floating raft system includes one or more of the following: hydroxypropyl methylcellulose HPMC E3, hydroxypropyl methylcellulose HPMC K4M, hydroxypropyl methylcellulose HPMC E5, hydroxypropyl methylcellulose HPMC E6, hydroxypropyl methylcellulose HPMC E15, hydroxypropyl methylcellulose HPMC K15M, hydroxypropyl methylcellulose HPMC F50, hydroxypropyl methylcellulose HPMC K100M, polyvinyl chloride SG-3, polyvinyl chloride S-700, polyvinyl chloride SG-5, polyvinyl chloride S-800, ethyl cellulose ETHOCEL Standard45, ethyl cellulose ETHOCEL Standard100, ethyl cellulose HS-45, and ethyl cellulose 100.

[0024] The preparation method of the gastric floating raft system includes the following steps: (1) Mixing: The therapeutically effective amount of proton pump inhibitor is mixed with the traditional Chinese medicine composition, hydrophilic gel matrix, auxiliary gel forming agent, flotation agent and sustained-release agent to obtain a homogeneous mixture; (2) Preparation of gastric floating raft system: Add the mixture obtained in step (1) to the prescribed amount of purified water and stir at a constant temperature and speed until a homogeneous solution is obtained.

[0025] The mixing step was performed using a V-type mixer at a speed of 30 rpm for 30 minutes.

[0026] The step of preparing the gastric floating raft system uses a magnetic stirrer to mix at 800 rpm for 12 hours, with the temperature controlled at 30°C.

[0027] In some embodiments, the density of the gastric floating raft, which is a lightweight gel raft formed after phase transformation in a gastric juice environment, is 0.1-1.0 g / cm³. 3 The preferred concentration is 0.2-0.8 g / cm³. 3 The optimal value is 0.3-0.7 g / cm³. 3 .

[0028] The present invention further provides the application of the above-mentioned pharmaceutical composition or oral gastric floating raft system in the preparation of gastric mucosal protective drugs.

[0029] The aforementioned gastric mucosa protectant can inhibit gastric acid secretion and assist in the treatment of digestive disorders such as gastroesophageal reflux disease, as well as peptic ulcer diseases such as gastric and duodenal ulcers, stress ulcers, and Zollinger-Ellison syndrome. Therefore, this invention also provides the application of the above-mentioned pharmaceutical composition or oral gastric floating raft system in the preparation of drugs for the prevention and treatment of gastric inflammation or ulcers.

[0030] This invention first discovered a traditional Chinese medicine composition that has a therapeutic effect on gastric ulcers, and further combined it with traditional proton pump inhibitors, which significantly improved the therapeutic effect and reduced the dosage of proton pump inhibitors, thus lowering the risk of side effects.

[0031] The gastric floating raft system designed in this invention, after oral administration, rapidly undergoes a phase transition in the low-pH gastric juice environment, expanding to form a low-density, dense, and mechanically strong lightweight gel raft. This gel raft can remain on the gastric juice surface for an extended period, achieving gastric retention and sustained release of the drug, thus enhancing local efficacy. Compared to single chemical drugs, this compound preparation is milder, significantly less irritating, and enhances efficacy and reduces adverse reactions through the synergistic effect of its multiple components. Attached Figure Description

[0032] To more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0033] Figure 1 It represents the cumulative release rate of the proton pump inhibitor-Chinese herbal extract raw material control formulation at each time point.

[0034] Figure 2 It represents the cumulative release rate of a proton pump inhibitor-TCM extract gastric floating raft formulation at various time points. Detailed Implementation

[0035] The specific embodiments of the present invention will be described in more detail below with reference to the accompanying drawings and examples, so as to better understand the solution of the present invention and its advantages in various aspects. However, the specific embodiments and examples described below are for illustrative purposes only and are not intended to limit the present invention.

[0036] In one aspect, the present invention provides a pharmaceutical composition for treating gastric inflammation and ulcers, comprising a proton pump inhibitor and a traditional Chinese medicine extract.

[0037] Proton pump inhibitors include one or more of omeprazole, lansoprazole, pantoprazole, esomeprazole, dexlansoprazole, rabeprazole, and esomeprazole.

[0038] Proton pump inhibitors work by irreversibly inhibiting H2 on gastric parietal cells. + / K + -ATPase (i.e., proton pump) effectively blocks the final stage of gastric acid secretion, thereby significantly reducing gastric acidity and creating a favorable environment for gastric mucosal repair. However, its function is mainly focused on acid suppression, with limited anti-inflammatory and protective effects on the mucosa.

[0039] Patchouli essential oil and gingerol oil are both active extracts derived from traditional Chinese medicine. Patchouli essential oil contains patchouli alcohol, patchouli ketone, or patchoulene; it has anti-inflammatory, antibacterial, and gastrointestinal motility-promoting effects. Gingerol oil contains gingerol or shogaol compounds; it can inhibit the release of inflammatory factors, has antioxidant properties, inhibits the growth of Helicobacter pylori, and stimulates the synthesis of protective mucus in the gastric mucosa. The combination of these two extracts can synergistically exert anti-inflammatory, antibacterial, gastrointestinal function-regulating, and mucosal barrier-enhancing effects. Furthermore, in the treatment of gastric ulcers and related gastric diseases, this extract combination can compensate for the shortcomings of proton pump inhibitors in mucosal protection and anti-infection.

[0040] The traditional Chinese medicine extract was prepared by mixing patchouli essential oil and gingerol oil in a certain weight ratio, using ethyl cellulose as the packaging material, and using the antisolvent method with purified water as the antisolvent. The resulting powder was a mixture of gingerol oil and patchouli essential oil with ethyl cellulose.

[0041] The pharmaceutical composition of this application, through the combined use of a proton pump inhibitor and a traditional Chinese medicine extract, can reduce mucosal inflammation by inhibiting gastric acid, thereby achieving the effects of treating and preventing gastric inflammation and ulcers.

[0042] In some embodiments, the mass ratio of gingerol oil and patchouli essential oil in the herbal extract is 1:2 to 3:1, preferably 2:1.

[0043] In some embodiments, the mass ratio of the proton pump inhibitor to the traditional Chinese medicine extract is 1:2 to 1:4.

[0044] Another aspect of the present invention provides an oral gastric floating raft system for the compound preparation, wherein the oral gastric floating raft system is a gel-like liquid that, upon oral administration, expands upon contact with gastric juice to form a solid state of a continuous and dense lightweight gel raft, which floats on the gastric juice for a long time.

[0045] In some embodiments, the oral gastric flotation raft system comprises an active pharmaceutical ingredient, a hydrophilic gel matrix, an auxiliary gel-forming agent, a flotation agent, a sustained-release agent, and a solvent; and is manufactured by thoroughly mixing the contents in purified water.

[0046] In some embodiments, after the oral gastric floating raft system forms a lightweight gel raft, the proton pump inhibitor and the traditional Chinese medicine complex are evenly dispersed in the lightweight gel raft. As the lightweight gel raft is dissolved by gastric juice, the drug is gradually released to achieve sustained release and targeted effects.

[0047] In some embodiments, the hydrophilic gel matrix material includes one or more of gelatin, gum arabic, chitosan, sodium alginate, and gellan gum.

[0048] In some embodiments, the auxiliary gelling agent material includes one or more of Carbopol 940, Carbopol 941, Carbopol 974P, Carbopol 980, Carbopol 981, Carbopol 5984, carbopol homopolymer (Type A), carbopol homopolymer (Type B), and carbopol homopolymer (Type C).

[0049] In some embodiments, the flotation agent material includes one or more of cetyl alcohol, octadecanol, stearic acid, glyceryl monostearate, glyceryl sorbate, sodium bicarbonate, sodium carbonate, calcium carbonate, sodium alginate, carrageenan, guar gum, xanthan gum, pectin, carbomer, chitosan, and polyvinylpyrrolidone (PVP).

[0050] In some embodiments, the sustained-release agent comprises one or more of the following: hydroxypropyl methylcellulose HPMC E3, hydroxypropyl methylcellulose HPMC K4M, hydroxypropyl methylcellulose HPMC E5, hydroxypropyl methylcellulose HPMC E6, hydroxypropyl methylcellulose HPMC E15, hydroxypropyl methylcellulose HPMC K15M, hydroxypropyl methylcellulose HPMC F50, hydroxypropyl methylcellulose HPMC K100M, polyvinyl chloride SG-3, polyvinyl chloride S-700, polyvinyl chloride SG-5, polyvinyl chloride S-800, ethyl cellulose ETHOCEL Standard45, ethyl cellulose ETHOCEL Standard100, ethyl cellulose HS-45, and ethyl cellulose 100.

[0051] Experimental Example 1: Preparation of EC Granules from Traditional Chinese Medicine Extracts

[0052] (1) Preparation of organic phase solution: Weigh 2.0g of ethyl cellulose (model EC-N50), place it in a 500mL beaker, add 100mL of anhydrous ethanol, place it on a magnetic stirrer, and stir at 600rpm for 30min at room temperature until the ethyl cellulose is completely dissolved to form an organic phase solution.

[0053] (2) Preparation of the drug-containing organic phase solution: Slowly add 1.0g of the mixed essential oil, which is a blend of gingerol oil and patchouli essential oil in an optimized mass ratio (1:2), to the above organic phase solution, and continue stirring at 600rpm for 30min to ensure that it is fully mixed.

[0054] (3) Emulsification: The resulting mixture is poured into a 100 mL aqueous solution of sodium dodecyl sulfate (SDS) with a mass-volume concentration of 0.5% under continuous stirring, and then subjected to high-speed shear emulsification to form a primary emulsion.

[0055] (4) Preparation of the target compound by antisolvent method: Under constant stirring, the primary emulsion was slowly added dropwise to 1 L of purified water at a rate of approximately 2 mL / min. After the addition was complete, stirring was continued for 30 min to ensure complete solvent diffusion. The product was then allowed to precipitate by standing, filtered, and then freeze-dried to obtain the target compound, denoted as EC. 1:2 .

[0056] The mass ratios of gingerol oil and patchouli essential oil were adjusted to 1:1, 2:1, and 3:1, respectively, to prepare 1.0g of mixed essential oil. EC granules of the herbal extract were then prepared using the same method and denoted as EC. 1:1 EC 2:1 EC 3:1 .

[0057] Example 2: Protective effect of gingerol oil and patchouli oil in different mass ratios on an ethanol-induced gastric injury model.

[0058] Male rats, weighing approximately 200g, were randomly divided into 8 groups of 5 rats each. After fasting for 24 hours, the rats were anesthetized intraperitoneally with 0.1mL of 20% urethane followed by ethanol injection to induce a gastric lesion. The normal control group received no treatment. The model control group was administered physiological saline by gavage, followed by anhydrous ethanol at 5mL / kg body weight after 30 minutes. The drug-treated groups were administered the corresponding drugs by gavage, followed by anhydrous ethanol at 5mL / kg body weight after 30 minutes. One day later, the rats were sacrificed, and the stomach and duodenum were removed. The stomach and duodenum were cut open along the greater curvature, flattened, and scored according to the size of the ulcer or erosion area: 1 for punctate erosion, 2 for erosion <1mm, 3 for erosion 1–2mm, 4 for erosion 2–4mm, and 5 for erosion >4mm. The average gastric lesion index score for each group was calculated, and the results are shown in Table 1 below.

[0059] Table 1. Effects of different mass ratios of gingerol oil and patchouli oil on ethanol-induced gastric injury.

[0060] The gastric injury index showed that the rats in the model control group had the most severe gastric injury compared to the normal control group. Drug administration provided varying degrees of protection against gastric mucosal damage, with the most significant protective effect against ethanol-induced gastric injury in rats achieved when the mass ratio of gingerol oil to patchouli essential oil was 2:1. Therefore, a mass ratio of gingerol oil to patchouli essential oil of 2:1 was selected for subsequent experiments.

[0061] Examples 3-9: Preparation of oral gastric floating raft system

[0062] EC, a traditional Chinese medicine extract prepared in Example 1, was used as a proton pump inhibitor (omeprazole). 2:1 The drug consists of granules as the main ingredient, sodium alginate as the hydrophilic gel matrix, calcium carbonate as the crosslinking and flotation agent, hydroxypropyl methylcellulose (SH-K100M (2208)) as the sustained-release agent, carbomer 940 as the auxiliary gel-forming agent, and purified water for the preparation of an oral gastric flotation raft system.

[0063] Table 2. Prescriptions for the oral gastric flotation raft systems in Examples 3-8

[0064] Preparation process of oral gastric flotation raft system: (1) Mixing: The prescribed amount of proton pump inhibitor combined with traditional Chinese medicine, hydroxypropyl methylcellulose, sodium alginate, calcium carbonate and carbomer were placed into a V-type mixer and mixed at 30 rpm for 30 minutes to obtain a uniform dry powder mixture.

[0065] (2) Preparation of a homogeneous solution: Add the prescribed amount of purified water to the above mixture, mix with a magnetic stirrer at 800 rpm for 12 h, control the temperature at 30℃, and the target solution viscosity is less than 2000 mPa·s to obtain the gastric floating raft system.

[0066] Control formulation: Weigh 0.1g of proton pump inhibitor and 0.3g of the traditional Chinese medicine extract prepared in Example 3 into a V-type mixer, mix at 30 rpm for 30 min, and then fill into a gastric-soluble capsule shell to make a capsule.

[0067] In vitro flotation performance experiment: 900 mL of 0.1 mol / L hydrochloric acid solution was used as the release medium, the temperature was (37.0±0.5)℃, the rotation speed was 100 r / min, and the time was recorded with a stopwatch. The time from when the gastric flotation raft system was placed in the dissolution vessel to when the tablet floated to the surface of the liquid was defined as the initial floating time T1, and the time from the start of the initial floating to the end of the experiment was defined as the continuous floating time T2. The experimental results are shown in Table 3.

[0068] Table 3. Floating time of each group of gastric floating raft systems

[0069] Table 3 shows that the floating time of each group of samples exceeded 12 hours, achieving good results. The floating times of Examples 3-9 were significantly shorter than those of the control preparation, with Examples 8-9 having the shortest floating times, followed by Examples 5 and 7. This indicates that the gastric floating raft system provided by this invention can all float in gastric fluid within 1 minute, and after forming a gel raft, it can float and remain in gastric fluid for more than 12 hours, thereby improving drug utilization. Comparing Examples 3-5 reveals that sodium alginate and calcium carbonate have some influence on the floating time and drift time of the gastric floating raft system. Too high or too low alginate dosage will prolong the floating time, while too low a calcium carbonate dosage will prolong the floating time.

[0070] In vitro release of the oral gastric flotation raft system: A quantitative sample obtained in Example 5 was weighed, and a control formulation containing the same amount of drug as the sample obtained in Example 5 was weighed as a control. Dissolution experiments were conducted according to the second method (paddle method) of the 2025 edition of the Pharmacopoeia of the People's Republic of China, using 250 mL of pH 1.2 HCl solution as the dissolution medium, at a temperature of 37 ± 0.5 °C, and a rotation speed of 50 r / min. -1 Samples (5 mL) were taken at 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 14, 18, and 24 hours, respectively. An equal volume of blank dissolution medium at the same temperature was added simultaneously. The sample solutions were filtered through a 0.45 μm microporous membrane, and the initial filtrate was discarded. Subsequent filtrates were analyzed under chromatographic conditions. The cumulative dissolution rate of Example 5 and the control formulation at each time point was calculated using the external standard method. Detailed results of the cumulative dissolution rate of the sample obtained from Control Example 1 at each time point are shown in [link to relevant documentation]. Figure 1 Detailed results of the cumulative dissolution at each time point in Example 5 can be found in [link to example]. Figure 2 .

[0071] Conclusion: From Figure 1 and Figure 2 It can be seen that the sample obtained in Example 5 released the drug more slowly than the control formulation, and the cumulative dissolution rate was significantly higher than that of the control formulation. This indicates that the gastric floating raft system obtained in Example 5 achieved a significant sustained-release effect in vitro, with an in vitro cumulative release rate as high as 99%.

[0072] Dissolution comparison experiment: According to the second method (paddle method) for dissolution determination in the 2025 edition of the Pharmacopoeia of the People's Republic of China, the formulation was placed in 900 mL of 0.1 mol / L simulated gastric fluid (pH 1.2) at 37℃ with a stirring rod speed of 50 rpm. Samples of 5 mL were taken at 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, and 24 h, and buffer solution of the same temperature and volume was added simultaneously. The samples were filtered through a 0.45 μm microporous membrane, and the filtrate was analyzed under chromatographic conditions. The cumulative release rate was determined using the external standard method. The release times of the proton pump inhibitor and the traditional Chinese medicine extract are shown in Tables 4 and 5 below.

[0073] Table 4. Complete dissolution time of omeprazole in the gastric floating raft system

[0074] Table 5. Complete dissolution time of traditional Chinese medicine extracts in the gastric floating raft system

[0075] As shown in Tables 4 and 5, this product rapidly expands and remains in simulated gastric fluid, with Example 5 exhibiting the longest gastric retention time and the highest cumulative release rate. In Example 5, the cumulative release rates of the proton pump inhibitor (omeprazole) at 2, 6, 12, and 24 hours were approximately 42%, 68%, 98%, and 98%, respectively; the cumulative release rates of the traditional Chinese medicine extract at 2, 6, 12, and 24 hours were approximately 6%, 31%, 63%, and 99%, respectively. This demonstrates good sustained-release properties. The dissolution times of Examples 3-9 were significantly longer than the control formulation, indicating that the dissolution rate of the gastric floating raft system was significantly lower than that of the control formulation. The sustained-release raft slowly releases the active ingredient in the release medium, maintaining the content of the active ingredient in the body at a certain level for a certain period of time.

[0076] Example 10: Proton pump inhibitors with different mass ratios and traditional Chinese medicine extract EC 2:1 Protective effect of particles on an ethanol-induced gastric injury model

[0077] 1. Drug preparation

[0078] Proton pump inhibitor solution: Accurately weigh 10g of proton pump inhibitor omeprazole, dissolve it in 10mL of physiological saline, vortex on a vortex apparatus for 10min to prepare a homogeneous solution.

[0079] Proton pump inhibitor + EC 2:1 (1:2) Solution: Accurately weigh omeprazole and EC (a traditional Chinese medicine extract) separately. 2:1 10g of granules (mass ratio 1:2) were dissolved in 10mL of physiological saline and vortexed for 10min to prepare a homogeneous solution.

[0080] Proton pump inhibitor + EC 2:1 (1:3) Solution: Accurately weigh omeprazole and EC (a traditional Chinese medicine extract) separately. 2:1 10g of granules (mass ratio 1:3) were dissolved in 10mL of physiological saline and vortexed for 10min to prepare a homogeneous solution.

[0081] Proton pump inhibitor + EC 2:1 (1:4) Solution: Accurately weigh omeprazole and EC (a traditional Chinese medicine extract) separately. 2:110g of granules (mass ratio 1:4) were dissolved in 10mL of physiological saline and vortexed for 10min to prepare a homogeneous solution.

[0082] Stomach floating raft system: The sample prepared in Example 5 was selected.

[0083] 2. Experimental Methods

[0084] Male rats, weighing approximately 200g, were randomly divided into 8 groups of 5 rats each. After fasting for 24 hours, the rats were anesthetized intraperitoneally with 0.1mL of 20% urethane followed by ethanol injection to induce a gastric lesion. The normal control group received no treatment. The model control group was administered physiological saline by gavage, followed by anhydrous ethanol at 5mL / kg body weight after 30 minutes. The drug-treated groups were administered the corresponding drugs by gavage, followed by anhydrous ethanol at 5mL / kg body weight after 30 minutes. One day later, the rats were sacrificed, and the stomach and duodenum were removed. The stomach and duodenum were cut open along the greater curvature, flattened, and scored according to the size of the ulcer or erosion area: 1 for punctate erosion, 2 for erosion <1mm, 3 for erosion 1–2mm, 4 for erosion 2–4mm, and 5 for erosion >4mm. The average gastric lesion index score for each group was calculated, and the results are shown in Table 6 below.

[0085] Table 6. Effects of different mass ratios of gingerol oil and patchouli oil on ethanol-induced gastric injury.

[0086] It is evident that all treatment groups experienced varying degrees of reduction in gastric damage, with the proton pump inhibitor + EC showing the most significant improvement. 2:1 The therapeutic effect of the group (1:3) was significantly better than that of the 1:2 and 1:4 combinations, and the gastric floating raft system can further reduce the gastric damage index, and has a significant effect on reducing gastric damage and protecting the gastric mucosa.

[0087] The embodiments described above are merely examples of several implementations of the present invention, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these modifications and improvements all fall within the scope of protection of the present invention.

Claims

1. A pharmaceutical composition for protecting the gastric mucosa, characterized in that, The application relates to a medicine composition and a preparation method thereof.

2. The pharmaceutical composition of claim 1, wherein, The medicine composition is an ethyl cellulose inclusion compound of the traditional Chinese medicine composition; the ethyl cellulose inclusion compound of the traditional Chinese medicine composition is prepared by mixing gingerol oil and patchouli oil in a mass ratio, taking ethyl cellulose as a packing material, and taking purified water as an anti-solvent.

3. The pharmaceutical composition of claim 2, wherein, The preparation method of the ethyl cellulose inclusion compound of the traditional Chinese medicine composition comprises the following steps: adding traditional Chinese medicine extracts into an ethyl cellulose solution, stirring and mixing uniformly, adding an emulsifier solution to form a uniform and stable emulsion, taking purified water as an anti-solvent to precipitate a target product, and filtering and drying to obtain the ethyl cellulose inclusion compound of the traditional Chinese medicine composition; the weight of the traditional Chinese medicine composition accounts for 30-40% of the total weight of ethyl cellulose and the traditional Chinese medicine composition.

4. An oral gastric floating raft system characterized by, The application relates to a medicine composition and a preparation method thereof.

5. The oral gastric floating raft system of claim 4, wherein, The preparation method of the ethyl cellulose inclusion compound of the traditional Chinese medicine composition comprises the following steps: adding traditional Chinese medicine extracts into an ethyl cellulose solution, stirring and mixing uniformly, adding an emulsifier solution to form a uniform and stable emulsion, taking purified water as an anti-solvent to precipitate a target product, and filtering and drying to obtain the ethyl cellulose inclusion compound of the traditional Chinese medicine composition; the weight of the traditional Chinese medicine composition accounts for 30-40% of the total weight of ethyl cellulose and the traditional Chinese medicine composition.

6. An oral gastric floating raft system according to claim 4 or 5, characterised in that, The application relates to a medicine composition and a preparation method thereof.

7. The oral gastric floating raft system of claim 4, wherein, The density of the gastric floating raft formed by phase inversion of the gastric floating raft in gastric juice environment is 0.1-1.0 g / cm 3 .

8. A process for the preparation of a gastric floating raft system according to any one of claims 4-6, characterized in that, The preparation method of the ethyl cellulose inclusion compound of the traditional Chinese medicine composition comprises the following steps: adding traditional Chinese medicine extracts into an ethyl cellulose solution, stirring and mixing uniformly, adding an emulsifier solution to form a uniform and stable emulsion, taking purified water as an anti-solvent to precipitate a target product, and filtering and drying to obtain the ethyl cellulose inclusion compound of the traditional Chinese medicine composition; the weight of the traditional Chinese medicine composition accounts for 30-40% of the total weight of ethyl cellulose and the traditional Chinese medicine composition. The application relates to a medicine composition and a preparation method thereof. The preparation method of the ethyl cellulose inclusion compound of the traditional Chinese medicine composition comprises the following steps: adding traditional Chinese medicine extracts into an ethyl cellulose solution, stirring and mixing uniformly, adding an emulsifier solution to form a uniform and stable emulsion, taking purified water as an anti-solvent to precipitate a target product, and filtering and drying to obtain the ethyl cellulose inclusion compound of the traditional Chinese medicine composition; the weight of the traditional Chinese medicine composition accounts for 30-40% of the total weight of ethyl cellulose and the traditional Chinese medicine composition. The application relates to a medicine composition and a preparation method thereof. The preparation method of the ethyl cellulose inclusion compound of the traditional Chinese medicine composition comprises the following steps: adding traditional Chinese medicine extracts into an ethyl cellulose solution, stirring and mixing uniformly, adding an emulsifier solution to form a uniform and stable emulsion, taking purified water as an anti-solvent to precipitate a target product, and filtering and drying to obtain the ethyl cellulose inclusion compound of the traditional Chinese medicine composition; the weight of the traditional Chinese medicine composition accounts for 30-40% of the total weight of ethyl cellulose and the traditional Chinese medicine composition. The application relates to a medicine composition and a preparation method thereof. The preparation method of the ethyl cellulose inclusion compound of the traditional Chinese medicine composition comprises the following steps: adding traditional Chinese medicine extracts into an ethyl cellulose solution, stirring and mixing uniformly, adding an emulsifier solution to form a uniform and stable emulsion, taking purified water as an anti-solvent to precipitate a target product, and filtering and drying to obtain the ethyl cellulose inclusion compound of the traditional Chinese medicine composition; the weight of the traditional Chinese medicine composition accounts for 30-40% of the total weight of ethyl cellulose and the traditional Chinese medicine composition.

9. Use of the pharmaceutical composition according to any one of claims 1 to 3, or the gastric floating raft system according to any one of claims 4 to 6, for the manufacture of a medicament for gastric mucosa protection.

10. Use of the pharmaceutical composition according to any one of claims 1 to 3, or the gastric floating raft system according to any one of claims 4 to 6, for the manufacture of a medicament for preventing or treating gastric inflammation or ulcer.

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