Medicament for treating atrophic gastritis and its preparation method

Abstract

This invention discloses a traditional Chinese medicine drug for treating atrophic gastritis and its preparation method. The drug is composed of herbs including Salvia miltiorrhiza, chicken gizzard lining, Aucklandia lappa, Amomum villosum, Taraxacum mongolicum, Shenqu (medicated leaven), Citrus aurantium, Corydalis yanhusuo, Coix lacryma-jobi, Viola yedoensis, Angelica sinensis, and Astragalus membranaceus. In preparation, about half of the herbal mixture is pulverized into a fine powder for later use; the remaining herbs are decocted twice with water, and the filtrate is concentrated into a thick paste using vacuum low-temperature concentration technology. The thick paste is mixed with the fine herbal powder, ethanol is added, and wet microcapsules are prepared using an extrusion and spheronization method. The wet microcapsules are finally dried in stages using a fluidized bed and polished to obtain the finished product. This method, by combining extraction with the use of raw powder, and employing key processes such as low-temperature concentration and staged drying, can maximize the retention of water-soluble and heat-sensitive volatile components in the herbs, significantly improving the drug's dissolution rate, active ingredient content, and long-term storage stability, thereby more effectively exerting its comprehensive therapeutic effects of invigorating the spleen and replenishing qi, promoting blood circulation and removing blood stasis, and relieving pain.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, specifically to a drug for treating atrophic gastritis and its preparation method. Background Technology

[0002] Atrophic gastritis, a common chronic gastric disease, is characterized by the atrophy or even disappearance of the gastric mucosal glands, often accompanied by intestinal metaplasia or dysplasia. It is considered a precancerous condition and poses a long-term threat to patients' quality of life and health. In clinical treatment, modern medicine often employs comprehensive approaches such as eradicating Helicobacter pylori, protecting the gastric mucosa, supplementing with vitamins, and symptomatic treatment. However, these methods often focus on controlling symptoms or eliminating a single pathogenic factor, limiting their comprehensive therapeutic effects on improving the overall microenvironment of the gastric mucosa and promoting glandular repair. Furthermore, long-term medication may be accompanied by certain side effects. Therefore, exploring treatment strategies that can address multiple targets and aspects holistically, while also offering greater safety, has always been an important direction in medical research.

[0003] Against this backdrop, Traditional Chinese Medicine (TCM), with its holistic approach and unique theoretical system of syndrome differentiation and treatment, has demonstrated significant advantages and potential in the treatment of chronic gastritis. Traditional TCM often categorizes this disease under terms such as "stomach fullness" and "stomach pain," believing its pathogenesis is often intertwined with factors such as spleen and stomach weakness, qi stagnation and blood stasis, and internal damp-heat. Treatment emphasizes the synergistic application of multiple methods, including strengthening the spleen and replenishing qi, promoting blood circulation and removing blood stasis, regulating qi and relieving stagnation, and clearing heat and removing dampness. Currently, many TCM compound formulas or preparations are used to treat this disease, but they generally have some shortcomings that urgently need improvement: for example, while traditional decoctions have the advantage of flexible syndrome differentiation, their preparation is cumbersome and inconvenient to carry, making them difficult to meet the needs of modern fast-paced lifestyles; and the preparation processes of common solid preparations such as pills, powders, and tablets are often relatively crude, such as whole-formula water extraction or whole-formula pulverization, which may lead to insufficient extraction or destruction of effective components, or significant loss of volatile components in the medicinal materials during high-temperature processing, affecting the full exertion and stability of the efficacy. In addition, outdated formulation technology can also lead to poor performance of the final product in terms of disintegration time, dissolution rate and bioavailability, which restricts further improvement of clinical efficacy.

[0004] Faced with the aforementioned challenges, the development of modern TCM formulation technology has provided new insights into overcoming these bottlenecks. The industry has gradually recognized that combining traditional TCM formulas with modern, refined preparation processes is key to developing new TCM products that are effective, of controllable quality, and convenient to take. This is particularly evident in how to handle complex compound formulas while considering the characteristics of each herb and preserving the essence of the entire formula; and how to maximize the retention of active ingredients and ensure the formulation possesses good physical properties and stable chemical attributes through innovative extraction, concentration, molding, and drying technologies. Therefore, developing a TCM preparation method that targets the core pathogenesis of atrophic gastritis, scientifically combines ingredients, and integrates advanced preparation processes to overcome the shortcomings of traditional formulations has significant practical importance and application value for improving the treatment level in this field. Summary of the Invention

[0005] The purpose of this invention is to provide a drug for treating atrophic gastritis and its preparation method, which solves the technical problem of obtaining modern Chinese medicine micro-pellet formulations with excellent dissolution performance and high stability while maximizing the retention of all active ingredients.

[0006] The present invention achieves the above objectives through the following technical solutions: A method for preparing a drug for treating atrophic gastritis, comprising the following steps: S1. Mix Salvia miltiorrhiza, chicken gizzard lining, costus root, amomum villosum, dandelion, medicated leaven, immature bitter orange, corydalis rhizome, coix seed, violet cress, angelica sinensis, and astragalus membranaceus to obtain a medicinal mixture; take 40-50% of the total mass of the medicinal mixture and pulverize it into a fine powder, sieve it, mix it evenly, and obtain a fine powder of medicinal materials; place the remaining medicinal mixture in a multi-functional extraction tank, decoct it for the first time, filter and collect the filtrate; add water to the residue, decoct it for the second time, and filter it; combine the two filtrates, and concentrate the filtrate at 48-52℃ using vacuum low temperature concentration technology to a thick paste with a relative density of 1.35-1.40; S2. Mix the thick paste with the fine powder of medicinal materials from step S1; add ethanol, and prepare wet micro-pellets using an extrusion-spheronization pelletizing machine; S3. Place the wet microspheres in a fluidized bed dryer and use a segmented drying process: first dry at 44-46℃, then continue drying at 34-36℃; polish the dried microspheres.

[0007] In this invention, the preparation reaction mechanism of the drug for treating atrophic gastritis is rooted in the deep integration of traditional Chinese medicine theory and modern pharmaceutical technology. It aims to maximize the extraction, retention, and integration of the effective components of various medicinal materials in the prescription through a series of precise physical and physicochemical processes, transforming them into a modern micro-pellet dosage form with excellent stability, uniformity, and high bioavailability. Its core mechanism begins with the differentiated treatment and reconstruction of the material basis of the medicinal materials. The medicinal materials in the prescription are divided into two parts. One part is directly pulverized into fine powder. This process uses mechanical force to break down the plant cell walls, allowing the medicinal materials to be preserved intact in their original state. In particular, the rich volatile components, such as the aromatic oils of costus root and cardamom, as well as some heat-labile active substances and the original fibrous skeleton, are preserved. This original powder not only serves as a carrier of the effective components but also plays an important role in excipient formation and adsorption in subsequent molding. Meanwhile, another portion of the medicinal materials undergoes an extraction process involving decoction. This is a mass transfer process based on the principles of diffusion and dissolution. Under the influence of heat, water molecules penetrate into the tissues of the medicinal materials, selectively dissolving and transferring various water-soluble active ingredients, such as polysaccharides and saponins in Astragalus and Angelica sinensis, phenolic acids in Salvia miltiorrhiza, and chlorogenic acid in Taraxacum mongolicum and Viola yedoensis, as well as some alkaloids and glycosides, into the solvent. Through two decoctions, following the concentration gradient-driven principle, the aim is to extract the soluble substances from the solid phase of the medicinal materials as fully as possible to improve the extraction yield. Subsequently, the combined extracts are treated with vacuum low-temperature concentration technology, removing most of the water at a temperature significantly lower than the boiling point at atmospheric pressure. The mechanism of this technology is to lower the boiling point of the liquid by reducing the system pressure, allowing the concentration operation to be carried out in a mild thermal environment. This effectively avoids the oxidation, hydrolysis, or structural damage of heat-sensitive components that may be caused by prolonged high-temperature heating, ensuring the chemical integrity of the active ingredients in the concentrated paste. The high relative density of the paste also provides suitable physical properties for its subsequent use as a binder. Next, the preparation reaction enters the crucial material integration and structure building stage. The previously obtained fine medicinal powder is mixed with an aqueous thick paste. This process is not a simple physical admixture, but a complex solid-liquid mixing and dispersion process. The thick paste, as a high-viscosity aqueous extract, possesses excellent adhesive properties due to its abundant polysaccharides and pectin. When it comes into contact with the dry fine medicinal powder, through shearing and stirring, the thick paste uniformly coats the surface of the fine powder particles and penetrates into the pores between the particles. The fine powder particles, acting as the core dispersed phase, are embedded in the thick paste's binding matrix. Together, they form a semi-solid soft material with a certain degree of plasticity. The addition of an appropriate amount of ethanol further adjusts the wettability and viscosity of the mixture. The volatility of ethanol and its miscibility with water help adjust the cohesiveness and plasticity of the material during subsequent molding and create conditions for drying. The use of an extrusion-spheronization pelleting machine to prepare wet microcapsules is a key mechanism in the formation of this dosage form.The soft material is first subjected to axial pressure in an extruder, forced through a screen with a specific aperture. This extrusion process causes the material to undergo shearing and compression, further homogenizing it and resulting in a dense strip-like structure. Subsequently, these strip-like materials are subjected to multiple forces, including centrifugal force, friction, and gravity, in a rotating disc, being cut and tumbled into wet pellets with high sphericity and uniform particle size. This forming mechanism endows the pellets with a regular morphology, a dense internal structure, and a smooth surface, which directly affects the final product's bulk density, flowability, dosage accuracy, and, crucially, in vitro dissolution and in vivo release behavior. Finally, the drying and post-treatment of the wet pellets are crucial for stabilizing their structure and fixing their quality. The segmented drying process used in the fluidized bed incorporates scientific drying kinetics and heat and mass transfer mechanisms. In the initial, higher temperature stage, the surface moisture of the wet pellets vaporizes rapidly, quickly establishing a gradient for moisture migration from the interior to the surface. This stage aims to efficiently remove most of the free water. The drying process then proceeds to a lower temperature stage, gently removing residual moisture bound within the microcapsules. This prevents the formation of a hard, dense surface layer (a "hard shell") due to excessively rapid surface drying. Such a shell would hinder further evaporation of internal moisture and potentially lead to delayed disintegration of the microcapsules during subsequent storage or administration. Segmented drying, by controlling the temperature gradient, balances the surface evaporation rate with the internal diffusion rate, ensuring uniform drying from the surface inwards. This results in a porous, loose yet robust internal microstructure, facilitating rapid drug disintegration and dissolution. The final polishing process uses gentle friction to further remove burrs and dust from the microcapsule surface, making it smoother. This not only improves the product's appearance but, more importantly, reduces adhesion between microcapsules and their tendency to absorb moisture during storage, enhancing their physical stability. In summary, the reaction mechanism of the entire preparation method is a systematic project with interconnected and synergistic effects. Through intelligent segmentation and recombination of the material basis of medicinal materials, combined with the refined control principles of modern extraction, concentration, shaping and drying, it ultimately transforms the traditional compound into a modern Chinese medicine preparation with a comprehensive material basis, maximum protection of active ingredients, and superior dosage form performance. This lays a solid material and morphological foundation for exerting its comprehensive pharmacological effects of invigorating the spleen and replenishing qi, promoting blood circulation and removing blood stasis, regulating qi and relieving pain, and clearing heat and dampness to treat atrophic gastritis.

[0008] According to a preferred embodiment of the present invention, in step S1, the first decoction time is 3-4 hours.

[0009] According to a preferred embodiment of the present invention, in step S2, the high-speed shear emulsification time is 10-20 min.

[0010] The present invention also provides a method for preparing a drug for treating atrophic gastritis, comprising the following raw materials in parts by weight: 20-30 parts of Salvia miltiorrhiza; 15-20 parts of chicken gizzard lining; 8-12 parts of Aucklandia lappa; 8-12 parts of Amomum villosum; 15-20 parts of Taraxacum mongolicum; 8-12 parts of Massa fermentata; 8-12 parts of Citrus aurantium; 8-12 parts of Corydalis yanhusuo; 5-10 parts of Coix lacryma-jobi; 15-20 parts of Viola yedoensis; 8-12 parts of Angelica sinensis; and 12-18 parts of Astragalus membranaceus.

[0011] The beneficial effects of this invention are as follows: The preparation method and the resulting drug provided by this invention, through innovative process design and sophisticated dosage form selection, comprehensively produce significant and multifaceted technical effects, effectively overcoming the shortcomings of existing technologies and achieving a synergistic improvement in therapeutic efficacy and formulation quality.

[0012] Firstly, in terms of medicinal material processing and preservation of active substances, this invention employs an original strategy of "partial extraction and partial powdering." Approximately half of the medicinal materials in the prescription are directly pulverized into fine powder. This processing method maximizes the preservation of the inherent volatile components and heat-sensitive active substances in the medicinal materials, especially those easily lost during high-temperature decoction. For example, the aromatic volatile oils in costus root and cardamom, as well as some enzymes, are preserved intact. Simultaneously, the other half of the medicinal materials undergoes two water decoction extractions. This method fully dissolves the water-soluble active ingredients in the medicinal materials, such as polysaccharides and saponins in astragalus and angelica, and phenolic acids in salvia miltiorrhiza. Finally, the concentrated extract is mixed with the raw medicinal powder. This essentially scientifically integrates "extracted essence" with "all components of the medicinal materials," leveraging the advantages of thorough dissolution in traditional decoctions while incorporating the characteristics of "comprehensive efficacy and rapid onset of action" in powders. This forms a complementary material basis, providing a solid guarantee for the comprehensive efficacy of subsequent preparations.

[0013] Secondly, in the formulation and process control stages, this invention introduces modern formulation technology and optimizes key parameters to ensure the product possesses excellent physical properties and chemical stability. By using an extrusion-spheronization pelletizing machine to prepare wet pellets, spherical pellets with uniform particle size and high sphericity can be obtained. This not only results in an aesthetically pleasing appearance but, more importantly, ensures the accuracy of drug dosage and consistency in packaging. During the drying process, a segmented drying process is creatively employed. First, surface moisture is rapidly removed at a slightly higher temperature, followed by slow and thorough drying at a lower temperature. This method effectively prevents the formation of a hard shell on the surface of the pellets due to excessively rapid drying, while the internal moisture is difficult to escape—a phenomenon known as "drying trapping." This avoids delayed disintegration and impaired dissolution of active ingredients, ensuring the porous and stable internal structure of the pellets. The meticulous control of low-temperature concentration and segmented drying throughout the process constitutes a "protective system" for thermally unstable components, resulting in a higher content and more stable state of active ingredients in the final product.

[0014] Ultimately, the synergistic effects of the aforementioned technologies result in a final product that demonstrates exceptional value in clinical applications. The drug prepared using this method is in micro-pellet form, which is extremely convenient to take, carry, and store compared to traditional decoctions, leading to high patient compliance. Compared to ordinary pills or tablets, it exhibits a superior dissolution rate and improved bioavailability. More importantly, this preparation method precisely serves the formulation principles for treating atrophic gastritis. The active ingredients of various medicinal materials in the prescription, such as those that invigorate the spleen and replenish qi, promote blood circulation and remove blood stasis, regulate qi and eliminate stagnation, and clear heat and remove dampness, are maximized and their synergistic effects are enhanced through this process. The drug can act more effectively on the gastric mucosa, exerting a comprehensive therapeutic effect targeting multiple points, including improving gastric microcirculation, promoting mucosal repair and glandular function recovery, eliminating inflammation, and regulating gastrointestinal motility. This addresses the core pathogenesis of atrophic gastritis—spleen and stomach weakness, qi stagnation and blood stasis, and internal damp-heat—achieving a synergistic therapeutic effect that addresses both the symptoms and the root cause, demonstrating significant clinical application prospects and socioeconomic value. Detailed Implementation

[0015] The following detailed embodiments are only used to further illustrate this application and should not be construed as limiting the scope of protection of this application. Those skilled in the art can make some non-essential improvements and adjustments to this application based on the above application content.

[0016] The following is information on domestic suppliers of key related equipment and materials: The Danshen mentioned was purchased from Tasly Pharmaceutical Group Co., Ltd.

[0017] The chicken gizzard lining was purchased from Chengdu Senke Pharmaceutical Co., Ltd.

[0018] The costus root was purchased from Jiangxi Huiren Pharmaceutical Co., Ltd.

[0019] The cardamom was purchased from Kangmei Pharmaceutical Co., Ltd.

[0020] The dandelion was purchased from Yunnan Baiyao Group Co., Ltd.

[0021] The Liushenqu was purchased from Shandong Freda Pharmaceutical Group Co., Ltd.

[0022] The Citrus aurantium was purchased from China Resources Sanjiu Pharmaceutical Co., Ltd.

[0023] The Corydalis Rhizome was purchased from Jinling Pharmaceutical Co., Ltd.

[0024] The Job's tears were purchased from Zhejiang Conba Pharmaceutical Co., Ltd.

[0025] The Viola yedoensis was purchased from Guangzhou Baiyunshan Pharmaceutical Group Co., Ltd.

[0026] The Angelica sinensis mentioned was purchased from Gansu Longxi Qizheng Medicinal Materials Co., Ltd.

[0027] The Astragalus membranaceus was purchased from Yangtze River Pharmaceutical Group Co., Ltd. Example

[0028] Preparation of the drug for treating atrophic gastritis. First, prepare the prescription herbs: weigh 250g of Salvia miltiorrhiza, 175g of chicken gizzard lining, 100g of Aucklandia lappa, 100g of Amomum villosum, 175g of Taraxacum mongolicum, 100g of Massa fermentata, 100g of Citrus aurantium, 100g of Corydalis yanhusuo, 75g of Coix lacryma-jobi, 175g of Viola yedoensis, 100g of Angelica sinensis, and 150g of Astragalus membranaceus. Place all the above herbs in a mixing container and stir thoroughly to obtain a herbal mixture with a total mass of 1500g. Take 750g of this herbal mixture and pulverize it using a grinder. The resulting powder is sieved through a 100-mesh sieve. Collect the fine powder that passes through the sieve and mix it in a mixer for 30 minutes to obtain a uniform herbal powder. Seal it for later use. Transfer the remaining 750g of the herbal mixture to a multi-functional extraction vessel. Add 8 times the amount of purified water, i.e., 6000ml, and turn on the heat. Maintain a gentle boil and decoct for 3.5 hours. After decoction, the residue was filtered through a 200-mesh filter cloth to separate the dregs and collect the filtrate. The separated dregs were placed back into the extraction tank, and 6 times the amount of purified water (4500 ml) was added for a second decoction, maintaining a gentle boil for 2 hours. After decoction, the residue was filtered again through a 200-mesh filter cloth and the filtrate was collected. The filtrates from the two decoctions were combined and transferred to a vacuum concentration tank for low-temperature concentration at a vacuum of -0.08 MPa and a temperature of 50°C until the relative density of the concentrated material reached 1.38 (measured at 60°C). Concentration was then stopped, yielding approximately 500 g of thick paste. Subsequently, the prepared thick paste and the previously prepared 750 g of finely powdered medicinal materials were added to a granulation mixer. Stirring was started, and approximately 200 g of 85% ethanol solution was slowly added as a wetting agent during the mixing process. Stirring and high-speed shear emulsification were continued for 15 minutes until a uniform, moderately firm, and viscous material was formed. The adhesive material is fed into an extrusion-spheronization pelletizing machine. First, it is extruded through a 0.8mm sieve to form uniform strips. Then, the strips are transferred to a spherical disc and spherically rolled for 10 minutes at 800 rpm to form spherical wet pellets. The resulting wet pellets are evenly spread in the material trough of a fluidized bed dryer, and the drying program is started. The first stage is set with an inlet air temperature of 45℃ for 2 hours. Subsequently, the inlet air temperature is adjusted to 35℃, and drying continues for 3 hours until the moisture content of the pellets is below 5%. Finally, the dried pellets are transferred to a polishing machine and polished for 10 minutes to obtain the drug pellets for treating atrophic gastritis as described in this invention. Example

[0029] The specific implementation method is the same as in Example 1, except for the preparation of the drug for treating atrophic gastritis. First, prepare the prescribed medicinal materials: weigh 200g of Salvia miltiorrhiza, 150g of chicken gizzard lining, 80g of Aucklandia lappa, 80g of Amomum villosum, 150g of Taraxacum mongolicum, 80g of Massa fermentata, 80g of Citrus aurantium, 80g of Corydalis yanhusuo, 50g of Coix lacryma-jobi, 150g of Viola yedoensis, 80g of Angelica sinensis, and 120g of Astragalus membranaceus. Place all the above medicinal materials in a mixing container and mix thoroughly to obtain a medicinal mixture with a total mass of 1300g. Take 650g of this medicinal mixture and pulverize it using a pulverizer. Sift the resulting powder through a 100-mesh sieve, collect the sieved fine powder, and mix it in a mixer for 30 minutes to obtain a uniform fine powder. Seal and store for later use. Transfer the remaining 650g of the herbal mixture to a multi-functional extraction vessel. Add 9 times the volume of purified water (5850ml) for the first time, and heat until it reaches a gentle boil, simmering for 3 hours. After simmering, filter the mixture using a 200-mesh filter cloth to separate the dregs and collect the filtrate. Place the separated dregs back into the extraction vessel, add 5 times the volume of purified water (3250ml), and simmer a second time, maintaining a gentle boil for 2.5 hours. After simmering, filter again using a 200-mesh filter cloth and collect the filtrate. Combine the filtrates from both simmerings and transfer them to a vacuum concentration vessel. Concentrate at a vacuum of -0.08MPa and a temperature of 48℃ until the relative density of the concentrated material reaches 1.35 (measured at 60℃). Stop concentration to obtain approximately 450g of a thick paste. Subsequently, the prepared thick paste and the previously prepared 650g of fine medicinal powder were added to a granulation mixer. Stirring was started, and approximately 180g of an 80% ethanol solution was slowly added as a wetting agent during the mixing process. Stirring and high-speed shearing emulsification continued for 10 minutes until a uniform, moderately firm, viscous material was formed. This viscous material was fed into an extrusion-spheronization pelletizing machine. First, it was extruded through a 0.8mm sieve to form uniform strips. Then, the strips were transferred to a spheronization disc and spheronized at 800 rpm for 10 minutes to form spherical wet pellets. The resulting wet pellets were evenly spread in the material trough of a fluidized bed dryer, and the drying program was started. The first stage inlet air temperature was set at 44℃ for 2.5 hours; subsequently, the inlet air temperature was adjusted to 34℃, and drying continued for 3.5 hours until the moisture content of the pellets was below 5%. Finally, the dried microspheres are transferred to a polishing machine and polished for 10 minutes to obtain the drug microspheres for treating atrophic gastritis as described in this invention. Example

[0030] The specific implementation method is the same as in Example 1, except for the preparation of the drug for treating atrophic gastritis. First, prepare the prescribed medicinal materials: weigh 300g of Salvia miltiorrhiza, 200g of chicken gizzard lining, 120g of Aucklandia lappa, 120g of Amomum villosum, 200g of Taraxacum mongolicum, 120g of Massa fermentata, 120g of Citrus aurantium, 120g of Corydalis yanhusuo, 100g of Coix lacryma-jobi, 200g of Viola yedoensis, 120g of Angelica sinensis, and 180g of Astragalus membranaceus. Place all the above medicinal materials in a mixing container and mix thoroughly to obtain a medicinal mixture with a total mass of 1700g. Take 850g of this medicinal mixture and pulverize it using a pulverizer. Sift the resulting powder through a 100-mesh sieve, collect the sieved fine powder, and mix it in a mixer for 30 minutes to obtain a uniform fine powder. Seal and store for later use. Transfer the remaining 850g of the herbal mixture to a multi-functional extraction vessel. Add 7 times the volume of purified water (5950ml) for the first time, and heat until it reaches a gentle boil, simmering for 4 hours. After simmering, filter the mixture using a 200-mesh filter cloth to separate the dregs and collect the filtrate. Place the separated dregs back into the extraction vessel, add 7 times the volume of purified water (5950ml), and simmer a second time, maintaining a gentle boil for 1.5 hours. After simmering again, filter the mixture using a 200-mesh filter cloth and collect the filtrate. Combine the filtrates from both simmerings and transfer them to a vacuum concentration vessel. Concentrate the mixture at a vacuum of -0.08MPa and a temperature of 52℃ until the relative density of the concentrated material reaches 1.40 (measured at 60℃). Stop concentration to obtain approximately 600g of a thick paste. Subsequently, the prepared thick paste and the previously prepared 850g of fine medicinal powder were added to a granulation mixer. Stirring was started, and approximately 250g of a 90% ethanol solution was slowly added as a wetting agent during the mixing process. Stirring and high-speed shearing emulsification continued for 20 minutes until a uniform, moderately firm, viscous material was formed. This viscous material was fed into an extrusion-spheronization pelletizing machine. First, it was extruded through a 0.8mm sieve to form uniform strips. Then, the strips were transferred to a spheronization disc and spheronized for 10 minutes at 800 rpm to form spherical wet pellets. The resulting wet pellets were evenly spread in the material trough of a fluidized bed dryer, and the drying program was started. The first stage inlet air temperature was set at 46℃ for 1.5 hours; subsequently, the inlet air temperature was adjusted to 36℃, and drying continued for 4 hours until the moisture content of the pellets was below 5%. Finally, the dried microspheres are transferred to a polishing machine and polished for 10 minutes to obtain the drug microspheres for treating atrophic gastritis as described in this invention.

[0031] Comparative Example 1 The specific implementation method is the same as in Example 1, except that the same weight of all medicinal materials as in Example 1 is weighed: 250g of Salvia miltiorrhiza, 175g of chicken gizzard lining, 100g of Aucklandia lappa, 100g of Amomum villosum, 175g of Taraxacum mongolicum, 100g of Massa fermentata, 100g of Citrus aurantium, 100g of Corydalis yanhusuo, 75g of Coix lacryma-jobi, 175g of Viola yedoensis, 100g of Angelica sinensis, and 150g of Astragalus membranaceus. All 1500g of the medicinal material mixture is directly pulverized using a pulverizer. The resulting powder is sieved through a 100-mesh sieve. The sieved fine powder is collected and mixed in a mixer for 30 minutes to obtain a uniform medicinal powder. This medicinal powder is added to a granulation mixer, and stirring is started. During the mixing process, approximately 300g of an 85% ethanol solution is slowly added as a wetting agent. Stirring and high-speed shearing emulsification are continued for 15 minutes until a uniform, moderately soft, and viscous material is formed. The binder material is fed into an extrusion-spheronization pelletizing machine. First, it is extruded through a 0.8mm mesh screen to form uniform strips. Then, the strips are transferred to a spherical pelletizing disc and spherically rolled for 10 minutes at 800 rpm to form spherical wet pellets. The resulting wet pellets are then evenly spread in the material trough of a fluidized bed dryer. The drying program is started, with the first stage set at an inlet air temperature of 45℃ for 2 hours. Subsequently, the inlet air temperature is adjusted to 35℃, and drying continues for 3 hours until the moisture content of the pellets is below 5%. Finally, the dried pellets are transferred to a polishing machine and polished for 10 minutes to obtain the control drug.

[0032] Comparative Example 2 The specific implementation method is the same as in Example 1, except for the preparation of the drug for treating atrophic gastritis. The steps for preparing the fine powder and thick paste of medicinal materials are exactly the same as in Example 1. The prepared thick paste is mixed with the fine powder of medicinal materials, and about 200g of 85% ethanol solution is added. The mixture is emulsified by high-speed shearing for 15 minutes to form a binder. The steps for forming wet microspheres by extrusion-spheronization are also exactly the same as in Example 1. The difference lies in the drying process: the obtained wet microspheres are placed in a fluidized bed dryer, and the single inlet air temperature is set to 45°C. The microspheres are dried continuously for 5 hours until the moisture content of the microspheres is less than 5%. Finally, the dried microspheres are transferred to a polishing machine and polished for 10 minutes to obtain the comparative drug.

[0033] Comparative Example 3 The specific implementation method is the same as in Example 1, except for the preparation of the drug for treating atrophic gastritis. The steps for preparing the fine powder of medicinal materials are exactly the same as in Example 1. The difference lies in the concentration process: the remaining 750g of the medicinal material mixture is decocted twice with water (the amount of water added and the time are the same as in Example 1), the filtrates are combined, and then the concentration is carried out using an open-mouth concentration method under normal pressure at 90°C until the relative density of the concentrated material reaches 1.38 (measured at 60°C). Concentration is then stopped to obtain a thick paste. Subsequent steps include mixing this thick paste with the fine powder of medicinal materials, adding ethanol (85%, about 200g), high-speed shear emulsification for 15 minutes, extrusion-spheronization to form pellets, and using the same segmented drying process as in Example 1 (drying at 45°C for 2 hours, drying at 35°C for 3 hours) and polishing treatment, all of which are consistent to obtain the comparative drug.

[0034] Performance testing The drugs for treating atrophic gastritis prepared according to Examples 1-3 and Comparative Examples 1-3 were tested according to the following performance testing methods: I. Determination of active ingredient content: The contents of salvianolic acid B (representing the water-soluble active ingredient) and costunolactone (representing the volatile active ingredient) were determined by high-performance liquid chromatography (HPLC). For salvianolic acid B, the chromatographic conditions were: octadecylsilane-bonded silica gel as the stationary phase, gradient elution with methanol-0.1% phosphoric acid solution as the mobile phase, detection wavelength of 286 nm, and column temperature of 30 °C. Appropriate amounts of each sample powder were accurately weighed, extracted with 70% methanol by ultrasonication, filtered, and then injected for determination. For costunolactone, the chromatographic conditions were: octadecylsilane-bonded silica gel as the stationary phase, isocratic elution with acetonitrile-water as the mobile phase, detection wavelength of 225 nm, and column temperature of 25 °C. Appropriate amounts of each sample powder were accurately weighed, extracted with methanol by ultrasonication, filtered, and then injected for determination. Each sample was measured in triplicate. II. Dissolution Test: Following the dissolution test method II (paddle method) of the Chinese Pharmacopoeia, 900 ml of phosphate buffer solution at pH 6.8 was used as the dissolution medium, with a rotation speed of 50 r / min and a temperature of 37.0 ± 0.5℃. Samples were taken at specified time points (10, 30, and 60 minutes), filtered, and the cumulative dissolution percentage of salvianolic acid B in the solution was determined using high-performance liquid chromatography (HPLC). III. Evaluation of Microparticle Physical Properties: This included sphericity, bulk density, and moisture content. Sphericity was determined by image analysis of the aspect ratio of 100 microparticles, and the average value was calculated. Bulk density was determined using a graduated cylinder method. Moisture content was determined using a Karl Fischer moisture analyzer. IV. Accelerated Stability Test: Each sample was placed in a sealed glass bottle and stored at 40 ± 2℃ and 75 ± 5% relative humidity for 3 months. Samples were taken at the end of 0, 1, 2, and 3 months to determine the content of salvianolic acid B and costunolactone, and the results were compared with the data at 0 to calculate the content change rate.

[0035] Performance test results: Table 1: Comparison of gastric mucosal histopathological scores among different groups of rats Group Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Comparative Example 3 Danshensu B content (mg / g) 5.82 ± 0.11 5.65 ± 0.09 5.98 ± 0.13 3.41 ± 0.15 5.80 ± 0.10 4.95 ± 0.18 Costus lactone content (mg / g) 1.58 ± 0.05 1.61 ± 0.04 1.54 ± 0.06 1.72 ± 0.05 1.56 ± 0.05 1.21 ± 0.07 Cumulative dissolution (tanshinone B, 30 min) 92.5% ± 1.8% 90.8% ± 2.1% 93.1% ± 1.5% 85.2% ± 3.0% 82.4% ± 2.7% 91.0% ± 2.0% Sphericity of microspheres (mean aspect ratio) 1.08 ± 0.02 1.09 ± 0.02 1.07 ± 0.02 1.15 ± 0.03 1.06 ± 0.02 1.08 ± 0.02 Bulk density (g / ml) 0.68 ± 0.02 0.66 ± 0.02 0.70 ± 0.02 0.72 ± 0.02 0.75 ± 0.03 0.69 ± 0.02 Moisture (%) 4.2 ± 0.2 4.0 ± 0.2 4.5 ± 0.2 4.3 ± 0.2 4.8 ± 0.3 4.3 ± 0.2 Accelerated stability study - retention rate of salvianolic acid B (after 3 months) 98.1% 97.5% 98.5% 96.2% 97.8% 94.3% Accelerated stability study - retention rate of costunolide lactone (after 3 months) 95.3% 95.8% 94.9% 92.1% 93.5% 88.7% As can be seen from Table 1, the complete preparation method of the present invention used in Examples 1 to 3 effectively solves many problems in the prior art. Regarding the retention of active ingredients, the sample samples in the examples maintained a high content of salvianolic acid B (5.65 mg / g to 5.98 mg / g) and costunolide (1.54 mg / g to 1.61 mg / g), demonstrating the advantage of combining partial extraction with the use of raw powder in balancing water-soluble and heat-sensitive volatile components. Comparative Example 1, using whole powder, had a salvianolic acid B content of only 3.41 mg / g, significantly lower than expected, confirming that this process cannot effectively release water-soluble active substances. Comparative Example 3, using concentration at 90℃ and normal pressure, showed a significant decrease in the contents of salvianolic acid B and costunolide (4.95 mg / g and 1.21 mg / g, respectively), highlighting the necessity of the vacuum low-temperature concentration process (48℃ to 52℃) of the present invention for protecting heat-sensitive components.

[0036] Regarding the formulation dissolution performance, the samples in Examples 1 to 3 showed a cumulative dissolution rate of 90.8% to 93.1% for salvianolic acid B after 30 minutes, with excellent sphericity (aspect ratio 1.07 to 1.09). This was attributed to the synergistic effect of extrusion-spheronization and segmented drying processes, which resulted in microspheres with a structure conducive to dissolution. Comparative Example 1, due to the poor plasticity of whole-powder pelleting, exhibited poor sphericity (aspect ratio 1.15) and a low dissolution rate (85.2%). Comparative Example 2, dried at a single temperature (45°C), showed a significant decrease in dissolution rate to 82.4%, demonstrating the crucial role of segmented drying processes (e.g., 44-46°C to 34-36°C) in preventing surface hardening, maintaining the internal porous structure, and thus ensuring rapid dissolution.

[0037] Regarding stability, after 3 months of accelerated testing, the retention rates of salvianolic acid B and costunolide in the samples of Examples 1 to 3 remained at high levels of 97.5% to 98.5% and 94.9% to 95.8%, respectively, indicating that the complete process chain ensured the long-term stability of the product. In contrast, the retention rates of Comparative Examples 1, 2, and 3 were generally lower. Among them, Comparative Example 3, due to high-temperature concentration, had a costunolide retention rate of only 88.7%, further confirming the significant effect of the low-temperature process system of the present invention on improving product stability. In summary, the results of Examples 1 to 3 demonstrate that the present invention, through process integration and key parameter control, comprehensively achieves efficient retention of active ingredients, excellent dissolution performance of the formulation, and good long-term stability, successfully solving the defects existing in the background technology.

[0038] 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 present 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 process for the preparation of a medicament for the treatment of atrophic gastritis, characterized by the steps of include: S1. Mix Salvia miltiorrhiza, chicken gizzard lining, costus root, amomum villosum, dandelion, medicated leaven, immature bitter orange, corydalis rhizome, coix seed, violet cress, angelica sinensis, and astragalus membranaceus to obtain a medicinal mixture; take 40-50% of the total mass of the medicinal mixture and pulverize it into a fine powder, sieve it, mix it evenly, and obtain a fine powder of medicinal materials; place the remaining medicinal mixture in a multi-functional extraction tank, decoct it for the first time, filter and collect the filtrate; add water to the residue, decoct it for the second time, and filter it; combine the two filtrates, and concentrate the filtrate at 48-52℃ using vacuum low temperature concentration technology to a thick paste with a relative density of 1.35-1.40; S2. Mix the thick paste with the fine powder of medicinal materials from step S1; add ethanol, and prepare wet micro-pellets using an extrusion-spheronization pelletizing machine; S3. Place the wet microspheres in a fluidized bed dryer and use a segmented drying process: first dry at 44-46℃, then continue drying at 34-36℃; polish the dried microspheres.

2. The method of preparing a medicament for treating atrophic gastritis according to claim 1, wherein In step S1, the first simmering time is 3-4 hours.

3. The method of preparing a medicament for treating atrophic gastritis according to claim 1, wherein In step S2, the high-speed shear emulsification time is 10-20 min.

4. A medicament for treating atrophic gastritis prepared by the method for producing a medicament for treating atrophic gastritis according to any one of claims 1 to 3, characterized by, The ingredients include the following parts by weight: Salvia miltiorrhiza 20-30 parts; chicken gizzard lining 15-20 parts; Aucklandia lappa 8-12 parts; Amomum villosum 8-12 parts; Taraxacum mongolicum 15-20 parts; Shenqu (medicated leaven) 8-12 parts; Citrus aurantium 8-12 parts; Corydalis rhizome 8-12 parts; Coix seed 5-10 parts; Viola yedoensis 15-20 parts; Angelica sinensis 8-12 parts; Astragalus membranaceus 12-18 parts.