A traditional Chinese medicine composition for treating gastric ulcer and a preparation method and application thereof

Abstract

This invention discloses a traditional Chinese medicine composition for the prevention and / or treatment of gastric ulcers and / or their complications. By weight, the composition comprises: 2-6 parts of Atractylodes lancea, 2-6 parts of Poria cocos, 1-4 parts of Magnolia officinalis, 2-6 parts of Aucklandia lappa, 1-4 parts of Lindera strychnifolia, 1-4 parts of Cyperus rotundus, 1-4 parts of Alpinia officinarum, 1-4 parts of Amomum villosum, 1-4 parts of Coix lacryma-jobi, 1-4 parts of Citrus reticulata peel, 1-4 parts of Citrus medica, 1-4 parts of Crataegus pinnatifida, 1-4 parts of Massa fermentata, 1-4 parts of Hordeum vulgare, 1-4 parts of Gallus gallus domesticus gizzard lining, 1-4 parts of Bletilla striata, 2-6 parts of Paeonia lactiflora, 2-6 parts of Corydalis yanhusuo, 1-4 parts of Cinnamomum cassia, and 1-4 parts of Piper longum. The complications are selected from one or more of the following: pain, inflammation, and delayed gastric emptying. This traditional Chinese medicine composition is safe, effective, and has a simple and efficient preparation method with controllable quality. It exhibits significant anti-inflammatory, analgesic, and gastric motility-promoting effects, and can reduce the colonization of Helicobacter pylori in the stomach. It also has significant therapeutic effects on gastric ulcers induced by different factors (Helicobacter pylori infection, pyloric ligation, and nonsteroidal anti-inflammatory drugs).

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, specifically to a traditional Chinese medicine composition for treating gastric ulcers, its preparation method, and its application. Background Technology

[0002] Gastric ulcer (GU) is one of the major gastrointestinal diseases with a rising incidence and prevalence worldwide, considered a global health problem. Despite extensive research, its specific pathogenesis remains incompletely understood. The main invasive factors contributing to gastric ulcers include gastric acid and pepsin; Helicobacter pylori infection; and medications such as nonsteroidal anti-inflammatory drugs (NSAIDs); ethanol and bile salts. In addition, dysfunction of the body's own defense-repair system is a major factor leading to recurrent and persistent ulcers. Gastric ulcers are the result of a combination of physiological, psychological, and social factors; NSAID use and smoking are risk factors for ulcer recurrence. Helicobacter pylori (Hp) is a microaerophilic bacterium that colonizes the epithelial cells of the human gastric mucosa, and nearly 80%–90% of GU cases worldwide are caused by Hp infection. Since the vast majority of gastric ulcers are Hp-related ulcers, the recurrence rate significantly decreases after complete eradication. Therefore, Hp infection is the greatest risk factor for the incidence of GU.

[0003] Modern medicine primarily treats gastric ulcers by eliminating or weakening attacking factors (eradicating *Helicobacter pylori*, suppressing or antagonizing acid), and enhancing the gastric mucosa's defenses. While these treatments can achieve good short-term results, they cannot solve the problem of recurrence. Chronic diseases have a prolonged course and complex causes; relying solely on Western medicine will result in numerous side effects and unsatisfactory long-term outcomes. For example, antibiotic resistance can lead to gastrointestinal flora imbalance; acid suppressants reduce gastric acid production but also impair digestive function; and most commercially available traditional Chinese medicines for treating gastric ulcers have limited applicability, and their mechanisms of action and pharmacological effects are not fully understood.

[0004] Therefore, finding a traditional Chinese medicine with broad applicability, good efficacy, and few toxic side effects for the prevention and / or treatment of gastric ulcers has become an urgent need. Summary of the Invention

[0005] Based on this, the present invention provides a traditional Chinese medicine composition for the prevention and / or treatment of gastric ulcers and / or their complications, comprising, by weight: 2-6 parts of Atractylodes lancea, 2-6 parts of Poria cocos, 1-4 parts of Magnolia officinalis, 2-6 parts of Aucklandia lappa, 1-4 parts of Lindera strychnifolia, 1-4 parts of Cyperus rotundus, 1-4 parts of Alpinia officinarum, 1-4 parts of Amomum villosum, 1-4 parts of Coix lacryma-jobi, 1-4 parts of Citrus reticulata peel, 1-4 parts of Citrus medica, 1-4 parts of Crataegus pinnatifida, 1-4 parts of Massa fermentata, 1-4 parts of Hordeum vulgare, 1-4 parts of Gallus gallus domesticus gizzard lining, 1-4 parts of Bletilla striata, 2-6 parts of Paeonia lactiflora, 2-6 parts of Corydalis yanhusuo, 1-4 parts of Cinnamomum cassia, and 1-4 parts of Piper longum, wherein the complications are selected from one or more of the following: pain, inflammation, and delayed gastric emptying.

[0006] In this invention, when proportions, equivalents, temperatures, concentrations, times, mesh counts, parts by weight, weight ratios, or other values ​​or parameters are expressed as ranges, preferred ranges, or a series of upper and lower preferred values, this should be understood as specifically disclosing all ranges formed by any pairing of any upper or preferred value with any lower or preferred value, regardless of whether the range is disclosed individually. For example, when the range "2-6" is disclosed, the described range should be interpreted as including ranges "2-6", "2-5", "2-4", "2-3", "3-6", "3-5", "3-4", "4-6", "4-5", and "5-6", etc.; when the range "1-4" is disclosed, the described range should be interpreted as including ranges "1-4", "1-3", "1-2", "2-4", "2-3", and "3-4", etc. When numerical ranges are described herein, unless otherwise stated, the range is intended to include its endpoints and all integers and fractions within the range, and all values ​​within the range achieve the effects of this invention.

[0007] Furthermore, by weight, the traditional Chinese medicine composition includes: 3-6 parts of Atractylodes lancea, 3-6 parts of Poria cocos, 2-4 parts of Magnolia officinalis, 3-6 parts of Aucklandia lappa, 2-4 parts of Lindera strychnifolia, 1-3 parts of Cyperus rotundus, 2-4 parts of Alpinia officinarum, 2-4 parts of Amomum villosum, 2-4 parts of Coix lacryma-jobi, 2-4 parts of Citrus reticulata peel, 2-4 parts of Citrus medica, 1-4 parts of Crataegus pinnatifida, 1-4 parts of Massa fermentata, 1-4 parts of Hordeum vulgare, 1-4 parts of Gallus gallus domesticus gizzard lining, 1-4 parts of Bletilla striata, 3-6 parts of Paeonia lactiflora, 3-6 parts of Corydalis yanhusuo, 1.5-4 parts of Cinnamomum cassia, and 2-4 parts of Piper longum.

[0008] Furthermore, by weight, the traditional Chinese medicine composition includes: approximately 3 parts of Atractylodes lancea, approximately 3 parts of Poria cocos, approximately 2 parts of Magnolia officinalis, approximately 3 parts of Aucklandia lappa, approximately 2 parts of Lindera strychnifolia, approximately 3 parts of Cyperus rotundus, approximately 2 parts of Alpinia officinarum, approximately 2 parts of Amomum villosum, approximately 2 parts of Coix lacryma-jobi, approximately 2 parts of Citrus reticulata peel, approximately 2 parts of Citrus medica, approximately 1 part of Crataegus pinnatifida, approximately 1 part of Massa fermentata, approximately 1 part of Hordeum vulgare, approximately 1 part of Gallus gallus domesticus gizzard lining, approximately 1 part of Bletilla striata, approximately 3 parts of Paeonia lactiflora, approximately 3 parts of Corydalis yanhusuo, approximately 1.5 parts of Cinnamomum cassia, and approximately 2 parts of Piper longum.

[0009] In this invention, "about" refers to a value within a range of ±5% of a specific value. For example, "about 3" includes 3 ±5%, or from 2.85 to 3.15; "about 2" includes 2 ±5%, or from 1.9 to 2.1; "about 1" includes 1 ±5%, or from 0.95 to 1.05; and "about 1.5" includes 1.5 ±5%, or from 1.425 to 1.575.

[0010] Further, by weight, the traditional Chinese medicine composition comprises: Atractylodes lancea 2.85-3.15 parts, Poria cocos 2.85-3.15 parts, Magnolia officinalis 1.9-2.1 parts, Aucklandia lappa 2.85-3.15 parts, Lindera strychnifolia 1.9-2.1 parts, Cyperus rotundus 2.85-3.15 parts, Alpinia officinarum 1.9-2.1 parts, Amomum villosum 1.9-2.1 parts, and Coix lacryma-jobi 1.9-2.1 parts. 1 part of dried tangerine peel, 1.9-2.1 parts of Buddha's hand, 1.9-2.1 parts of hawthorn, 1-1.05 parts of Shenqu (medicated leaven), 1-1.05 parts of malt, 1-1.05 parts of chicken gizzard lining, 1-1.05 parts of Bletilla striata, 2.85-3.15 parts of white peony root, 2.85-3.15 parts of Corydalis yanhusuo, 1.425-1.575 parts of cinnamon, and 1.9-2.1 parts of Piper longum.

[0011] Furthermore, the Atractylodes lancea is stir-fried with wheat bran. Furthermore, the Cyperus rotundus is vinegar-processed. Furthermore, the Coix lacryma-jobi is stir-fried with wheat bran. Furthermore, the Crataegus pinnatifida is charred. Furthermore, the Shenqu (medicated leaven) is charred. Furthermore, the malt is charred. Furthermore, the chicken gizzard lining is stir-fried.

[0012] Furthermore, the traditional Chinese medicine composition is further used in combination with one or more drugs and / or extracts used for the prevention and / or treatment of gastric ulcers. Further, the drug is selected from one or more of the following: H2 receptor antagonists, proton pump inhibitors, anti-Helicobacter pylori drugs, and gastric mucosa protectants. Further, the H2 receptor antagonist is selected from one or more of the following: cimetidine, ranitidine, and famotidine. Further, the proton pump inhibitor is omeprazole. Further, the anti-Helicobacter pylori drug is selected from one or more of the following: colloidal bismuth, metronidazole, tinidazole, amoxicillin, clarithromycin, tetracycline, and furazolidone. Further, the gastric mucosa protectant is sucralfate and / or colloidal bismuth.

[0013] The one or more drugs and / or extracts for the prevention and / or treatment of gastric ulcers and / or their complications claimed in this invention are not limited to the drugs listed above, but may also include other types of drugs for the prevention and / or treatment of gastric ulcers and / or their complications, as well as effective components of traditional Chinese medicine, etc.

[0014] According to another aspect of the present invention, a formulation comprising the above-described traditional Chinese medicine composition is provided.

[0015] Further, the formulation includes one or more pharmaceutically acceptable excipients. Further, the excipients are selected from one or more of the following: anti-caking agents, preservatives, diluents, suspending agents, and flavoring agents. Further, the flavoring agent is selected from one or more of the following: stevioside, sucralose, and aspartame. Further, the flavoring agent is sucralose. Further, the weight ratio of the flavoring agent to the traditional Chinese medicine composition is 1:1000-5000, for example, about 1:2000. Further, the dosage form of the formulation is an oral preparation, such as a powder.

[0016] The excipients and formulations described above in this invention are merely illustrative examples and are not limited to those examples. Any excipient that can be mixed with the traditional Chinese medicine composition of this invention is within the scope of protection claimed by this invention.

[0017] According to another aspect of the present invention, a method for preparing the above-mentioned traditional Chinese medicine composition is provided, the method comprising: weighing appropriate amounts of Atractylodes lancea, Poria cocos, Magnolia officinalis, Aucklandia lappa, Lindera strychnifolia, Cyperus rotundus, Alpinia officinarum, Amomum villosum, Coix lacryma-jobi, Citrus reticulata peel, Citrus medica, Crataegus pinnatifida, Massa fermentata, Hordeum vulgare, Gallus gallus domesticus gizzard lining, Bletilla striata, Paeonia lactiflora, Corydalis yanhusuo, Cinnamomum cassia and Piper longum, mixing for the first time, drying for the first time, pulverizing for the first time, mixing for the second time, sterilizing, drying for the second time, pulverizing for the second time, to obtain the traditional Chinese medicine composition.

[0018] Of these, the aforementioned 20 medicinal materials were sourced from the market and have all been identified as appropriate medicinal materials. Among them, Atractylodes lancea is the principal ingredient, Poria cocos and Magnolia officinalis are the assistant ingredients, and the remaining seventeen ingredients are adjuvant ingredients.

[0019] According to another aspect of the present invention, a method for preparing the above-mentioned preparation is provided, the method comprising: mixing the above-mentioned traditional Chinese medicine composition with an appropriate amount of excipients for a third time, and optionally dispensing the mixture to obtain the preparation.

[0020] Furthermore, the method includes any one or more of the following items [1] to

[10] :

[0021] [1] The first mixing and / or the second mixing and / or the third mixing shall be carried out by sieving or stirring, for example, stirring; [2] The time for the first mixing and / or the second mixing and / or the third mixing shall be 20-40 min, for example, about 30 min; [3] The sterilization method shall be dry heat sterilization, moist heat sterilization, cobalt-60 irradiation sterilization and / or ethanol sterilization, for example, moist heat sterilization; [4] The sterilization time shall be 10-40 min, for example, about 30 min; [5] The temperature of the moist heat sterilization method shall be 110-127℃, for example, about 121℃; [6] The moist heat sterilization method shall be carried out by sieving or stirring, for example, stirring; [7] The time for the first mixing and / or the second mixing and / or the third mixing shall be 20-40 min, for example, about 30 min; [8] The temperature of the moist heat sterilization method shall be 110-127℃, for example, about 121℃; [9] The temperature of the moist heat sterilization method shall be 110-127℃, for example, about 121℃;

[10] The temperature of the moist heat sterilization method shall be 110-127℃, for example, about 121℃; [1 ... The thickness of the substrate for the fungal method is 1-3cm, for example, about 2cm; [7] The first drying is at 40-60℃ for 8-12 hours, for example, at 50-55℃ for about 10 hours; [8] The second drying is at 70-90℃ for 0.5-1.5 hours, for example, at 75-85℃ for about 1 hour; [9] The first crushing is coarsely crushed with a 60-80 mesh sieve and then crushed with a 100-150 mesh sieve, for example, coarsely crushed with a 60 mesh sieve and then crushed with a 100 mesh sieve;

[10] The second crushing is crushed with a 100-150 mesh sieve, for example, crushed with a 100 mesh sieve.

[0022] According to another aspect of the present invention, there is provided the use of the above-described traditional Chinese medicine composition or the above-described preparation in the preparation of food, medicine and / or health products for the prevention and / or treatment of gastric ulcers and / or their complications, wherein the complications are selected from one or more of the following: pain, inflammation and delayed gastric emptying.

[0023] The terms “food,” “health product,” “food product,” “health product,” “health composition,” or “food composition” in this invention mean a product or composition intended to be ingested by an animal (including a human) and to provide that animal with nutrition or health benefits.

[0024] According to another aspect of the present invention, the above-described traditional Chinese medicine composition or preparation is provided for the prevention or treatment of gastric ulcers and / or their complications in a subject.

[0025] According to another aspect of the present invention, a method for preventing or treating gastric ulcers and / or their complications in a subject is provided, comprising administering to the subject an effective amount of the above-described traditional Chinese medicine composition or the above-described preparation.

[0026] In this invention, the terms "subject," "individual," or "patient" are used interchangeably and refer to a vertebrate, preferably a mammal. The mammal may be a human, a non-human primate, a mouse, a rat, a dog, a cat, a horse, or a cow, but is not limited to these examples. Mammals other than humans can be advantageously used as subjects representing models of gastric ulcers and / or their associated symptoms. Preferably, the subject is a human. Such subjects typically suffer from or are susceptible to a condition that can be prevented or treated by administration of the above-described traditional Chinese medicine composition or preparation of this invention.

[0027] The "effective amount" of the above-described traditional Chinese medicine composition or preparation used in this invention can achieve the desired therapeutic and / or preventive effects. The effective amount for this purpose will depend on factors such as the route of delivery, the activity of the specific active substance or preparation used, the type of gastric ulcer and / or its associated symptoms, the stage and severity of the disease being treated, the individual's weight and overall health status, and the judgment of the prescribing physician. Dosage can be administered once a week, twice a week, daily, or even several times a day. Dosage units can be administered over a short period (e.g., weeks to months) or a longer period (months to years). "Effective amount" specifically refers to the amount of the above-described traditional Chinese medicine composition or preparation that imparts a therapeutic effect (e.g., control, relief, improvement, mitigation, or slowing of progression) or prevents (e.g., delaying onset or reducing the risk of development) of a disease, condition, or symptom or its symptoms to the treated subject.

[0028] Further, the gastric ulcer is selected from one or more of the following: drug-induced gastric ulcer, physical procedure-induced gastric ulcer, and bacterial-induced gastric ulcer. Further, the pain is acute or chronic. Further, the pain is peripheral or central. Further, the inflammation is specific or nonspecific. Further, the inflammation is acute or chronic. Further, the drug is selected from one or more of the following: nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and reserpine. Further, the physical procedure is pyloric ligation. Further, the bacteria is Helicobacter pylori. Further, the NSAID is selected from one or more of the following: ibuprofen, diclofenac sodium, and indomethacin.

[0029] The beneficial effects of this invention are:

[0030] The traditional Chinese medicine composition of this application is safe, effective, and has a simple and efficient preparation method with controllable quality. It exhibits significant anti-inflammatory, analgesic, and gastric motility-promoting effects, and can reduce the colonization of Helicobacter pylori in the stomach. It also has significant therapeutic effects on gastric ulcers induced by different factors (Helicobacter pylori infection, pyloric ligation, and nonsteroidal anti-inflammatory drugs). Attached Figure Description

[0031] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without exceeding the scope of protection claimed by the present invention.

[0032] Figure 1 This is a flowchart illustrating the preparation process of the formulation of this application.

[0033] Figure 2 The effect of Xiangshu Pingwei Powder on gastric tissue in a rat model of gastric ulcer. A: Normal control group; B: Model control group; C: Weikangling capsule group; D: Omeprazole enteric-coated capsule group; E: Xiangshu Pingwei Powder group.

[0034] Figure 3 The effect of Xiangshu Pingwei Powder on gastric tissue lesions in a BALB / c mouse gastric ulcer model (HE×100). A. Normal control group; B. Model control group; C. Weikangling capsule group; D. Colloidal bismuth pectin capsule group; E. Xiangshu Pingwei Powder group. Detailed Implementation

[0035] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0036] The singular forms “a,” “an,” and “the” used in the specification and appended claims include plural indicators unless the context clearly specifies otherwise.

[0037] Unless otherwise stated, all technical and scientific terms and abbreviations used herein have the meanings commonly understood by one of ordinary skill in the field of this invention or the field of application of such terms. While any methods, conditions, substances, or materials similar to or equivalent to those disclosed herein may be used in the practice of this invention, preferred methods, conditions, substances, or materials are described herein.

[0038] In this invention, the term "comprising" and "including" are synonymous. The terms "comprising," "including," "having," "containing," or any other variations thereof as used herein are intended to cover a non-exclusive inclusion. For example, a composition, step, method, article, or apparatus that includes the listed elements is not necessarily limited to those elements, but may include other elements not expressly listed or elements inherent to such a composition, step, method, article, or apparatus.

[0039] Example

[0040] Example 1: Screening of Preparation Process Route

[0041] 1.1 Processing Technology for the Preparation of Traditional Chinese Medicine Compositions

[0042] 1.1.1 First Investigation of Drying Process

[0043] Because the medicinal materials used in this application contain a large amount of fiber and sugar, direct pulverization results in high viscosity, which is not conducive to pulverization and sieving. Therefore, a mixed pulverization method is adopted to ensure that the medicinal materials can be smoothly pulverized and sieved. The medicinal materials were first dried. Considering that the medicinal materials used in this application may contain volatile and heat-sensitive components, a low-temperature drying temperature of 50–55℃ was selected. Drying was carried out for 0 h, 5 h, 10 h, and 15 h respectively, followed by pulverization, and the pulverization effect was observed. The results are shown in Table 1.

[0044] Table 1. Statistical table of drying time investigation results

[0045]

[0046] The results showed that after drying for 0 hours, pulverization and sieving were difficult, and the particle size data did not meet the requirements for powder preparation. After drying for 5 to 15 hours, pulverization and sieving were relatively smooth, and the particle size data basically met the requirements for powder preparation. However, the particle size data after drying for 5 hours had a higher risk. In view of the above, considering the impact of energy consumption, it was determined that the medicinal materials in this application should be dried at a low temperature of 50 to 55℃ for 10 hours before pulverization.

[0047] 1.1.2 Examination of the mesh size of the crushing sieve

[0048] The mesh size of the sieve affects the powder yield of medicinal slices, which in turn indirectly affects the product yield. Therefore, this study investigated the effect of sieve mesh sizes (100 mesh, 120 mesh, and 150 mesh) on the powder yield and appearance uniformity. Each single-ingredient medicinal slice was weighed according to the prescription ratio, in triplicate, and pulverized and sieved using the following methods: ① Pulverized and passed through a 100-mesh sieve; ② Pulverized and passed through a 120-mesh sieve; ③ Pulverized and passed through a 150-mesh sieve. The ease of sieving was observed, and the initial powder yield was calculated. Then, powders from ①, ②, and ③ were taken from each sample, mixed using a sieve analysis method for 30 minutes, and samples were taken to check the appearance uniformity and particle size. The results are shown in Table 2.

[0049] Table 2 Statistical Table of Grinding Screen Mesh Count Investigation Results

[0050]

[0051] Note: Powder yield (%) = Weight of powder after pulverization and sieving / Weight of medicinal slices before pulverization and sieving × 100%.

[0052] The results showed that during the sieving process, 100-mesh and 120-mesh sieves were easier to pass through than 150-mesh sieves; the powder yield was 100-mesh > 120-mesh > 150-mesh; and the uniformity and particle size of the powder after sieving met the requirements for all sieve mesh sizes. Since 100-mesh pulverization is sufficient to meet the particle size requirements for medicinal materials in this application, and considering the ease of operation and powder yield, the sieve mesh size for pulverizing medicinal materials in this application was determined to be 100-mesh.

[0053] 1.1.3 Examination of Crushing Methods

[0054] Given that the yield of each medicinal herb after single-pass pulverization is too low, and that some herbs have a high sugar content, repeated pulverization will increase their stickiness, which is not conducive to industrial production, it was considered to mix and pulverize the herbs. Each herb was weighed according to the prescription ratio, divided into triplicate portions, mixed separately, and then fed into a graded ultrafine continuous pulverizer. First, it was coarsely pulverized with a 60-mesh sieve, then pulverized with a 100-mesh sieve. The powder was then passed through a 100-mesh sieve, and the yield was calculated. The results are shown in Table 3.

[0055] Table 3 Statistical table of the results of the investigation on crushing methods

[0056]

[0057]

[0058] Note: Powder yield (%) = Weight of powder after pulverization and sieving / Weight of medicinal slices before pulverization and sieving × 100%.

[0059] The results show that, based on the analysis of the single-pass powder yield in Table 2 and the difficulty of the actual operation, the mixed pulverization operation is simple and the single-pass powder yield is significantly higher than that of single-herb pulverization. Since the medicinal materials in this application do not contain precious, rare, highly toxic, or extremely toxic medicinal materials, from the perspective of simple operation and energy saving, the pulverization method of the medicinal materials in this application is determined to be pulverization after mixing the medicinal materials.

[0060] 1.1.4 Sterilization Examination

[0061] 1.1.4.1 Investigation of sterilization methods

[0062] There are several methods for sterilizing Chinese herbal medicine powders, including dry heat sterilization, moist heat sterilization, cobalt-60 irradiation sterilization, and ethanol sterilization. Since the medicinal materials used in this application are raw powders containing a significant amount of flammable substances such as fiber, dry heat sterilization, with temperatures exceeding 160℃, is deemed unsuitable due to the risk of safety accidents. Furthermore, the medicinal materials in this application, including Lindera strychnifolia, Alpinia officinarum, Crataegus pinnatifida, Shenqu (medicated leaven), Malt, Chicken gizzard lining, Bletilla striata, Paeonia lactiflora, and Piper longum, are not listed in the Ministry of Health's "Standards for Sterilization Doses of Chinese Herbal Medicine under 60Co Irradiation." Although irradiation has a significant sterilization effect, even a small dose of 3 kGy can reduce the content of irradiation-sensitive medicinal materials by 20%–50%. Therefore, cobalt-60 irradiation sterilization is also not considered. Only the moist heat sterilization method and the ethanol sterilization method were compared. Six 100g portions of the uniformly mixed traditional Chinese medicine composition powder of this application were prepared. Three portions were placed in a moist heat sterilizer with a layer thickness of 2cm; sterilized at 121℃ for 20 minutes, followed by drying at 85℃. The other three portions were each sprayed with 25ml of 75% ethanol, stirred evenly, sealed, and left to stand for 48 hours. They were then dried in a hot air circulating drying oven at 40℃ until no alcohol odor remained, and finally dried at 85℃. The properties, characteristic chromatograms, and microbial limits of the powder were used as evaluation indicators.

[0063] Feature map:

[0064] Determined by high performance liquid chromatography (General Chapter 0512, Chinese Pharmacopoeia 2015).

[0065] Chromatographic conditions and system suitability tests were performed using octadecylsilane-bonded silica gel as the packing material (Aglient 5TC-C18(2), 4.6 mm × 250 mm, 5 μm or equivalent column); methanol-acetonitrile (20:80) as mobile phase A and 0.1% phosphoric acid solution as mobile phase B, with gradient elution as specified in Table 4; flow rate of 1.0 mL / min; column temperature of 40 °C; and detection wavelength of 240 nm. The theoretical plate number, calculated based on the piperine peak, should be no less than 100,000.

[0066] Table 4 Gradient elution conditions for feature maps

[0067] Time (minutes) Mobile phase A (%) Mobile phase B (%) 0～30 10→37 90→63 30～35 37→50 63→50 35～70 50→70 50→30 70～72 70→98 30→2 72～82 98 2 82～83 98→10 2→90 83～90 10 90

[0068] Preparation of reference solution: Take appropriate amounts of isobarbital, hesperidin, galangin, piperine, magnolol, alder, and atractylodes lancea reference standards, weigh them accurately, and add methanol to prepare a mixed solution containing 0.1 mg of each in 1 ml.

[0069] Preparation of the test solution: Take 5g of the drug powder of this application, accurately weigh it, place it in a stoppered conical flask, accurately add 50ml of methanol, stopper tightly, sonicate (power 500W, frequency 40kHz) for 60 minutes, take it out, cool it, shake it well, filter it, and take the filtrate to obtain the test solution.

[0070] For the assay, precisely pipette 10 μl each of the reference solution and the test solution, inject them into the liquid chromatograph, measure and record the chromatogram after 75 minutes.

[0071] The chromatogram of the test sample should have 12 characteristic peaks, of which 7 peaks should have the same retention time as the corresponding reference peak. The peak corresponding to the piperine reference peak is the S peak. Calculate the relative retention time of each other characteristic peak and the S peak. The relative retention time of each characteristic peak should be within ±10% of the specified value.

[0072] The results showed that the ethanol sterilization method had no effect on the detection of the characteristic peaks in the characteristic spectrum, but it could not effectively kill microorganisms in the powder. The microbial limit did not meet the requirements and was therefore not adopted.

[0073] The characteristic spectrum of the moist heat sterilization method showed 22 peaks before sterilization and 20 peaks after sterilization. Comparison of the disappeared peaks identified two as cardamom and galangal, volatile components from cardamom. Modern pharmacological studies have shown that their main pharmacological activities are inhibiting platelet aggregation and tumor formation, which have poor relevance to the therapeutic functions of the traditional Chinese medicine composition in this application, and their content is extremely low. Moist heat sterilization effectively kills microorganisms in the powder, and the microbial limits meet the regulations.

[0074] In summary, given that moist heat sterilization remains the most effective sterilization method currently available, and the decrease in characteristic chromatogram levels is within an acceptable range, for safety reasons, moist heat sterilization is still recommended as the sterilization method for the traditional Chinese medicine composition of this application.

[0075] 1.1.4.2 Investigation of sterilization temperature

[0076] The commonly used temperature for moist heat sterilization is 121℃. Therefore, 121℃ is used as the median value to investigate the effects of sterilization temperatures of 110℃, 121℃, and 127℃, with a material thickness of 2cm and a sterilization time of 20 minutes, on the properties, characteristic spectrum, and microbial limits.

[0077] The results showed that the characteristic chromatograms of the drug powder in this application remained unchanged after sterilization at different temperatures for 20 minutes, meeting all requirements and effectively killing microorganisms. Since the drug powder in this application is a whole powder without extraction, there is a significant risk of microbial contamination, especially spores. Furthermore, the sterilization equipment temperature is a range value. Considering the potential differences in material thickness and equipment performance during later production sterilization processes compared to the laboratory, and given the above circumstances, the over-sterilization method was selected according to the "Guidelines for Sterilization / Aseptic Process Validation" (Second Draft). A relatively reliable sterilization temperature of 121℃ was chosen. At a sterilization temperature of 121℃, microorganisms, especially spores, are killed more thoroughly. Considering the differences in temperature control between different equipment, the sterilization temperature for the drug powder in this application was determined to be 121±5℃.

[0078] 1.1.4.3 Examination of sterilization time

[0079] Considering the impact of sterilization time on the characteristic spectrum and microbial limits, this experiment investigated the effects of sterilization times of 10 minutes, 20 minutes, 30 minutes, and 40 minutes on the powder properties, characteristic spectrum, and microbial limits of the drug in this application at 121℃ with a material thickness of 2 cm.

[0080] The results showed that the microbial detection of different moist heat sterilization times met the requirements, indicating that the sterilization uniformity was qualified. Considering the large amount of materials in large-scale production, in order to ensure the sterilization effect, the overkill method was selected according to the "Guideline for Validation of Sterilization / Aseptic Process" (Second Draft), and the sterilization time was determined to be 30 minutes.

[0081] In summary, the sterilization process was determined to be: moist heat sterilization, with a sterilization temperature of 121±5℃ and a sterilization time of 30 minutes.

[0082] 1.1.5 Second Drying Process

[0083] Because the multi-functional Chinese medicine sterilizer has a drying function, it is used to dry the sterilized powder in order to reduce the number of process steps. In order to avoid condensation on the surface of the powder due to rapid cooling and secondary contamination, the drying temperature is set to 75℃~85℃ based on experience, and the drying time is 1 hour, with the moisture content controlled to not exceed 5%.

[0084] 1.2 Formulation Process

[0085] Since the formulation of this application is a powder, the formulation process is relatively simple. Therefore, only the drying process, the type of flavoring agent, the amount of flavoring agent added, and the total mixture are examined. The process flow diagram for the preparation of this formulation is shown below. Figure 1 .

[0086] 1.2.1 Combined Investigation

[0087] Both the premixing and the addition of flavoring agents after sterilization were performed using the same trough mixer. Therefore, the uniformity of the two mixing methods was examined, and the mixing parameters were consistent.

[0088] 1.2.1.1 Investigation of Mixed Methods

[0089] The most commonly used methods for mixing traditional Chinese medicine powders are sieving and stirring. Therefore, this study investigated the effects of sieving and stirring on the uniformity of powder mixing in this application. The preparation methods for each test sample are as follows:

[0090] Sieve analysis method: Weigh the Chinese herbal medicine slices according to the prescription ratio, crush them, sieve them, then take the prescribed amount of flavoring agent, mix them evenly with an appropriate amount of medicinal powder, stir for 30 minutes, so that the powder can completely pass through a 100-mesh sieve, and take samples from five points: top, middle, bottom, left and right.

[0091] Stirring method: Weigh the Chinese herbal medicine slices according to the prescription ratio, crush them, sieve them, then take the prescribed amount of flavoring agent, mix them evenly with an appropriate amount of herbal powder, stir for 30 minutes, and take samples from five points: top, middle, bottom, left and right.

[0092] The uniformity of appearance and characteristic spectrum were used as evaluation indicators. The results are shown in Table 5.

[0093] Table 5. Statistical Table of Investigation Results for Hybrid Methods

[0094]

[0095]

[0096] The results showed that both mixing methods resulted in uniform appearance and color, without patterns or spots, and the characteristic spectra all met the requirements. All chromatographic peaks in the characteristic spectra were consistent, indicating that both methods could mix the powder uniformly. Therefore, considering the ease of operation, the stirring method was selected as the mixing method.

[0097] 1.2.1.2 Investigation of Mixing Time

[0098] To understand the effect of time on mixing uniformity, the influence of mixing time on mixing uniformity was investigated. Chinese medicinal herbs were weighed according to the prescription ratio, pulverized, and passed through a 100-mesh sieve. A specified amount of flavoring agent was then added and mixed evenly with an appropriate amount of the powdered herbs. The powdered herbs were placed in a trough mixer and stirred for 20 minutes, 30 minutes, and 40 minutes respectively. Samples were taken from five points: top, middle, bottom, left, and right. Appearance uniformity and characteristic chromatograms were used as evaluation indicators. The results are shown in Table 6.

[0099] Table 6. Statistical Table of Mixed Time Investigation Results

[0100]

[0101] The results showed that when the mixing times were 20 minutes, 30 minutes, and 40 minutes, the appearance was uniform in color, without any patterns or spots, and the characteristic chromatograms met the requirements, indicating that mixing for 20–40 minutes was sufficient to homogenize the pharmaceutical powder of this application. To ensure consistency with production, a mixing time of 30 minutes was determined.

[0102] In summary, the mixing process is determined to be: using the stirring method and mixing for 30 minutes.

[0103] 1.2.2 Investigation of Flavoring Agents

[0104] 1.2.2.1 Investigation of the types of flavoring agents

[0105] Because traditional Chinese medicine powders have a bitter and salty taste, the types of flavoring agents were investigated to improve their taste. Stevia, sucralose, and aspartame were examined for their effects on taste improvement, with the taste (sweetness, bitterness, and saltiness) after being dissolved in warm water as the indicator. Information on the sources and applicable standards of the flavoring agents is shown in Table 7.

[0106] Table 7. Statistics on Flavoring Agent Grades, Sources, and Implementation Standards

[0107]

[0108] Weigh each single herb slice according to the prescription ratio, pulverize, pass through a 100-mesh sieve, mix well, weigh 50g, divide into 3 equal portions, add 0.05g of stevioside, sucralose, and aspartame to each portion, and mix well.

[0109] Take 4g of the powder and mix it with 100ml of warm water. A taste evaluation panel of 20 people will evaluate the sweetness, bitterness, and saltiness of the taste. The results are shown in Table 8.

[0110] Table 8. Taste Evaluation Table for Different Types of Flavoring Agents

[0111]

[0112]

[0113] Note: Sweetness is rated as "- (not sweet), + (sweet), ++ (too sweet)", bitterness as "- (mild), + (average), ++ (strong)" and saltiness as "- (mild), + (average), ++ (strong)".

[0114] The results showed that both stevioside and sucralose could improve the bitter taste of the pharmaceutical powder of this application, while aspartame had a poor improvement effect; sucralose was better than stevioside in masking the bitter taste of the powder, and its sweetness was also better than that of stevioside. Therefore, the flavoring agent of this application was determined to be sucralose.

[0115] 1.2.2.2 Investigation on the amount of flavoring agent added

[0116] Because many evaluators rated the sweetness as too sweet when 0.1% sucralose was added, the amount of flavoring agent added was investigated.

[0117] Take the thoroughly mixed test sample from section 1.2.2.1, make three parallel portions, and add 0.01 g, 0.025 g, and 0.05 g of sucralose powder to each sample, respectively, and mix well.

[0118] Take 4g of the powder, dissolve it in 100ml of warm water, and have a taste evaluation panel of 20 people assess its sweetness, bitterness, and saltiness. The results are shown in Table 9.

[0119] Table 9. Taste Evaluation Table Based on the Amount of Flavoring Agent Added

[0120]

[0121] Note: Sweetness is rated as "- (not sweet), + (sweet), ++ (too sweet)", bitterness as "- (mild), + (average), ++ (strong)" and saltiness as "- (mild), + (average), ++ (strong)".

[0122] The results showed that adding 0.01g of sucralose to 50g of the powder was insufficient to mask the bitter taste, while adding 0.025g of sucralose effectively masked the bitter taste and provided a suitable sweetness. Therefore, the amount of flavoring agent added in this application was determined to be 0.05%.

[0123] Example 2: Preparation Process Example

[0124] 2.1 Preparation process

[0125] Weigh out the following twenty medicinal slices: 74.04g of stir-fried Atractylodes lancea, 74.04g of Poria cocos, 49.36g of Magnolia officinalis, 74.04g of Aucklandia lappa, 49.36g of Lindera strychnifolia, 74.04g of vinegar-processed Cyperus rotundus, 49.36g of Alpinia officinarum, 49.36g of Amomum villosum, 49.36g of stir-fried Coix lacryma-jobi, 49.36g of Citrus reticulata peel, 49.36g of Citrus medica, 24.68g of charred Crataegus pinnatifida, 24.68g of charred Shenqu (medicated leaven), 24.68g of charred Hordeum vulgare malt, and 24.6g of stir-fried chicken gizzard lining. Mix 8g of Bletilla striata, 24.68g of Paeonia lactiflora, 74.04g of Corydalis yanhusuo, 37.02g of Cinnamomum cassia, and 49.36g of Piper longum. Dry at 50-55℃ for 10 hours. After coarse crushing, pulverize through a 100-mesh sieve. Mix for 30 minutes, sterilize by moist heat at 121±5℃ for 30 minutes, dry at 75-85℃ for 1 hour, pulverize through a 100-mesh sieve, add 0.46g of sucralose, mix for 30 minutes, and make 1000g. Package to obtain powder one.

[0126] 2.2 Preparation Process Two

[0127] Weigh out the following twenty medicinal slices: 74.04g of stir-fried Atractylodes lancea, 49.36g of Poria cocos, 49.36g of Magnolia officinalis, 49.36g of Aucklandia lappa, 49.36g of Lindera strychnifolia, 74.04g of vinegar-processed Cyperus rotundus, 24.68g of Alpinia officinarum, 49.36g of Amomum villosum, 49.36g of stir-fried Coix lacryma-jobi, 49.36g of Citrus reticulata peel, 49.36g of Citrus medica, 24.68g of charred Crataegus pinnatifida, 74.04g of charred Shenqu (medicated leaven), 24.68g of charred Hordeum vulgare malt, and 24.6g of stir-fried chicken gizzard lining. Mix 8g of Bletilla striata, 74.04g of Paeonia lactiflora, 74.04g of Corydalis yanhusuo, 49.36g of Cinnamomum cassia, and 49.36g of Piper longum. Dry at 55-60℃ for 10 hours. After coarse crushing, pulverize through a 100-mesh sieve. Mix for 20 minutes. Sterilize by moist heat at 121±5℃ for 30 minutes. Dry at 75-85℃ for 1 hour. Pulverize through a 100-mesh sieve. Add 0.46g of sucralose and mix for 30 minutes to make 1000g. Package into individual portions to obtain powder two.

[0128] 2.3 Preparation Process Three

[0129] Weigh out the following twenty medicinal slices: 49.36g of stir-fried Atractylodes lancea, 49.36g of Poria cocos, 49.36g of Magnolia officinalis, 74.04g of Aucklandia lappa, 49.36g of Lindera strychnifolia, 74.04g of vinegar-processed Cyperus rotundus, 49.36g of Alpinia officinarum, 49.36g of Amomum villosum, 49.36g of stir-fried Coix lacryma-jobi, 49.36g of Citrus reticulata peel, 49.36g of Citrus medica, 24.68g of charred Crataegus pinnatifida, 74.04g of charred Shenqu (medicated leaven), 74.04g of charred Hordeum vulgare malt, and 24.6g of stir-fried chicken gizzard lining. Mix 8g of Bletilla striata, 24.68g of Paeonia lactiflora, 49.36g of Corydalis yanhusuo, 49.36g of Cinnamomum cassia, and 49.36g of Piper longum. Dry at 50-55℃ for 10 hours. After coarse crushing, pulverize through a 100-mesh sieve. Mix for 40 minutes, sterilize by moist heat at 121±5℃ for 20 minutes, dry at 75-85℃ for 1 hour, pulverize through a 100-mesh sieve, add 0.46g of sucralose, mix for 40 minutes, and make 1000g. Package to obtain powder three.

[0130] 2.4 Preparation Process Four

[0131] Weigh out the following twenty medicinal slices: 74.04g of stir-fried Atractylodes lancea, 74.04g of Poria cocos, 24.68g of Magnolia officinalis, 74.04g of Aucklandia lappa, 24.68g of Lindera strychnifolia, 49.36g of vinegar-processed Cyperus rotundus, 49.36g of Alpinia officinarum, 49.36g of Amomum villosum, 49.36g of stir-fried Coix lacryma-jobi, 49.36g of Citrus reticulata peel, 49.36g of Citrus medica, 24.68g of charred Crataegus pinnatifida, 24.68g of charred Shenqu (medicated leaven), 24.68g of charred Hordeum vulgare malt, and 24.6g of stir-fried chicken gizzard lining. Mix 8g of Bletilla striata, 24.68g of Paeonia lactiflora, 49.36g of Corydalis yanhusuo, 37.02g of Cinnamomum cassia, and 49.36g of Piper longum. Dry at 50-55℃ for 10 hours. After coarse crushing, pulverize through a 100-mesh sieve. Mix for 30 minutes, sterilize by moist heat at 121±5℃ for 30 minutes, dry at 75-85℃ for 1 hour, pulverize through a 100-mesh sieve, add 0.46g of sucralose, mix for 30 minutes, and make 1000g. Package into powder four.

[0132] Example 3: Pharmacological Efficacy Example

[0133] 3.1 Reagents and Materials

[0134] The following powders were prepared according to "2.1 Preparation Process One" (named Xiangshu Pingwei Powder): batch number 20200428-1, supplied by Hunan Yineng Biomedical Co., Ltd.; Omeprazole enteric-coated capsules: batch number 3082002052, manufactured by Zhuhai Rundu Pharmaceutical Co., Ltd.; Famotidine tablets: batch number 20200401, manufactured by Guangdong Bidi Pharmaceutical Co., Ltd.; Weikangling capsules: batch numbers 20190802 / 20200201. Manufacturer: Jilin Songliao Pharmaceutical Co., Ltd.; Compound Acetylsalicylic Acid Tablets: Batch No. 190601, Manufacturer: Grand Pharmaceutical (China) Co., Ltd.; Domperidone Tablets: Batch No. 190701, Manufacturer: Hunan Qianjin Xiangjiang Pharmaceutical Co., Ltd.; Colloidal Bismuth Pectin Capsules: Batch No. 191103, Manufacturer: Hunan Huana Pharmaceutical Co., Ltd.; Indomethacin Enteric-coated Tablets (Indomethacin): Batch No. G190803, Manufacturer: Shanxi Yunpeng Pharmaceutical Co., Ltd. Company; Helicobacter pylori (H. pylori, HP): Product No. ATCC43504, Supplier: ATCC; CMC-Na: Batch No. 20170915, Manufacturer: Sinopharm Chemical Reagent Co., Ltd.; Concentrated Hydrochloric Acid: Batch No. 20191030, Manufacturer: Sinopharm Chemical Reagent Co., Ltd.; Sodium Hydroxide: Batch No. 20181115, Manufacturer: Sinopharm Chemical Reagent Co., Ltd.; Phenolphthalein: Batch No. 20190909, Manufacturer: Tianjin Zhiyuan Chemical Reagent Co., Ltd.; 95% Ethanol: Batch No. 20191206, Manufacturer: Sinopharm Chemical Reagent Co., Ltd.; Glacial Acetic Acid: Batch No. 20190221, Manufacturer: Sinopharm Chemical Reagent Co., Ltd.; 0.9% Sodium Chloride Injection: Batch No. 20021301D, Manufacturer: Hunan Kangyuan Pharmaceutical Co., Ltd.; Evans Blue: Batch No. RS18B233, Manufacturer: Shanghai Ruiyong Biotechnology Co., Ltd.

[0135] 3.2 Instruments and Equipment

[0136] Vernier calipers, production number: 1203A50878; manufacturer: Chengdu Sanhe Measuring Tools Co., Ltd.; 3111 CO2 incubator (Thermo, USA), RM2235 paraffin sectioner, TP1020 fully automatic dehydrator, HI1220 slide roaster, HI1210 slide spreader, EG1150H+C tissue embedding machine, CX31 biological microscope, DFC420C pathological imaging system, ASP200S automatic tissue dehydrator, DM2000 biological microscope, DM2500 fluorescence microscope, BX34 biological microscope, MD50 digital imaging system (all from Leica, Germany); UV-Power PC ultraviolet / visible spectrophotometer (Beijing Labtech Instruments Co., Ltd.), TD4 benchtop low-speed centrifuge (Hunan Keda Industrial Development Co., Ltd.); PL203 electronic balance (Mettler-Toledo Instruments (Shanghai) Co., Ltd.).

[0137] 3.3 Statistics and Analysis

[0138] The data in this experiment were rounded to the nearest whole number, and the measurement data were expressed as mean ± standard deviation. The statistical software used was SPSS. Pairwise comparisons were performed using the Independent-Samples t-test. For comparisons among multiple groups, homogeneity of variance and normality were first assessed. If both groups had homogeneous variances and were normally compliant, the LSD-t or Dunnett-t test was used; if they were not normally compliant, the Nonparametric t test was used; and if they were normally compliant but had unequal variances, Dunnett's T3 or Tamhane's T2 test was used. Statistical results were presented with α = 0.05 as the test limit, where P ≤ 0.05 indicated statistical significance, and P ≤ 0.01 indicated a highly significant difference.

[0139] 3.4 Effects of Xiangshu Pingwei Powder on Indomethacin-induced Gastric Ulcer Model in Rats

[0140] 3.4.1 Grouping and Dosing

[0141] Fifty qualified SPF-grade male SD rats (Animal Quality Certificate No.: 430727201100999427, provided by Hunan Silek Jingda Experimental Animal Co., Ltd.), weighing 181.2–234.0 g, were randomly divided into four groups: normal control group, model control group, Weikangling capsule group (0.43 g / kg), famotidine tablet group (3.6 mg / kg), and Xiangshu Pingwei powder group (2.16 g crude drug / kg), with 10 animals in each group. All groups were administered the corresponding dose of drug solution orally at 15 mL / kg via gavage. The normal control group and model control group were administered an equal volume of 0.5% CMC-Na via gavage, once daily for 7 consecutive days. On the 6th day of administration, the rats were fasted for 24 hours but allowed free access to water. One hour after the last administration, the model group and all dosage groups were administered indomethacin orally at 100 mg / kg via gavage. Five hours after modeling, rats in each group were anesthetized by intravenous injection of 20 mg / kg propofol emulsion via the tail vein, followed by euthanasia via exsanguination of the abdominal aorta. The pylorus and cardia were ligated, and 10 mL of 10% neutral formalin solution was injected for fixation. The stomach was then cut open along the greater curvature, and the gastric contents were washed away. The degree of gastric mucosal damage was observed, and the long diameter (A) and wide diameter (B) of the ulcer were measured. The ulcer area was calculated as π*A*B / 4.

[0142] 3.4.2 Dosage Design

[0143] The experimental grouping and dosage design are detailed in Table 10.

[0144] Table 10 Trial grouping and dosage design

[0145]

[0146] 3.4.3 Experimental Results

[0147] 3.4.3.1 Gross anatomical observation

[0148] In the normal control group, the gastric mucosa of rats was smooth and without erosion or bleeding points; in the model control group, the gastric mucosa of rats showed redness, swelling, erosion, multiple bleeding points, and black linear ulcers; the bleeding points and black linear ulcers in the Weikangling capsule group, famotidine tablet group, and Xiangshupingwei powder group were significantly improved compared with the model control group.

[0149] 3.4.3.2 Effect on ulcer area

[0150] As shown in Table 11, compared with the normal control group, the gastric ulcer area of ​​rats in the model control group was significantly increased (P≤0.01); compared with the model control group, the gastric ulcer area of ​​the Weikangling capsule group, famotidine tablet group, and Xiangshupingwei powder group was significantly reduced (P≤0.01).

[0151] Table 11 Effects of Xiangshu Pingwei Powder on Indomethacin-induced gastric ulcer model in rats ( n=10)

[0152]

[0153]

[0154] Note: Compared with the normal control group ++ P≤0.01; compared with the model control group ** P≤0.01.

[0155] The above results indicate that Xiangshu Pingwei Powder can significantly reduce the area of ​​gastric ulcers caused by indomethacin, suggesting that Xiangshu Pingwei Powder has a significant therapeutic effect on gastric ulcers caused by indomethacin.

[0156] 3.5 Effects of Xiangshu Pingwei Powder on a Rat Model of Gastric Ulcer Induced by Pyloric Ligation

[0157] 3.5.1 Experimental Methods

[0158] 3.5.1.1 Modeling, Grouping, and Drug Administration

[0159] Sixty qualified SPF-grade male SD rats (Animal Quality Certificate No.: 430727201100999534, provided by Hunan Silek Jingda Experimental Animal Co., Ltd.), weighing 189.0–221.6 g, were randomly divided into four groups according to body weight: normal control group, model control group, Weikangling capsule group (0.43 g / kg), omeprazole enteric-coated capsule group (3.6 mg / kg), and Xiangshu Pingwei powder group (2.16 g crude drug / kg), with 12 animals in each group. The animals in each group were administered the corresponding dose of drug solution orally at 15 mL / kg by gavage. The normal control group and model control group were administered an equal volume of 0.5% CMC-Na by gavage once a day for 7 consecutive days.

[0160] On the 5th day after administration, the animals in each group were fasted but allowed to drink water for 48 hours. Before the operation, the animals were given the drug once by oral gavage. One hour after administration, the animals were anesthetized by inhalation with isoflurane (1-4% for induction, 0.25-2% for maintenance). The abdominal wall was cut open, and a suture was threaded through the junction of the pylorus and duodenum (without damaging blood vessels) to ligate the pylorus.

[0161] 3.5.1.2 Dosage Design

[0162] The experimental grouping and dosage design are detailed in Table 12.

[0163] Table 12 Trial grouping and dosage design

[0164]

[0165]

[0166] 3.5.2 Indicator Testing

[0167] 3.5.2.1 Effects on gastric acid content and pepsin activity

[0168] Six hours after model establishment, rats in each group were anesthetized by inhalation of isoflurane (1-4% for induction, 0.25-2% for maintenance), followed by active exsanguination and euthanasia. The pylorus and cardia were ligated and cut, and gastric contents were collected. The contents were centrifuged at 3000 rpm for 10 min, and the supernatant was used as the gastric fluid volume. Gastric acid content was determined by acid-base titration, and pepsin activity was detected. The specific detection methods are as follows:

[0169] 1) Determination of gastric acid content: Pipette 1 mL of supernatant, add 1-2 drops of 0.5% phenolphthalein indicator, and slowly titrate with 0.02 mol / L NaOH until the solution turns slightly pink and remains unchanged after standing for 2 seconds. Record the volume of NaOH solution consumed. Calculate the total gastric acidity and total acid output. Total acidity = volume of NaOH solution * 20, Total acid output = Total acidity * gastric juice volume / 5.

[0170] 2) Pepsin assay: Pipette 3 mL of supernatant into a 50 mL Erlenmeyer flask, add 15 mL of 0.05 mol / L hydrochloric acid solution, shake well, add two freshly prepared protein tubes, seal the flask, and incubate at 37 °C for 24 h. Remove the protein tubes and measure the length (mm) of the transparent portion at both ends using calipers. Calculate the average value A from the four measurements. Pepsin activity units (U / mL) = A 2 ×16, Pepsin excretion = Pepsin activity units * gastric juice volume / 5.

[0171] 3.5.2.2 Effects on gastric tissue lesions

[0172] After collecting gastric fluid, the stomach was fixed in 10% neutral formalin solution, sectioned, stained with hematoxylin and eosin (HE), and the lesions in the gastric tissue were observed. The observations included the degree of gastric mucosal damage (ulcers and erosions), the degree of glandular atrophy, and the degree of inflammatory cell infiltration in the submucosa. The severity of the lesions was scored according to the following criteria: NSL (non-solubilized gastric fluid) indicates no abnormalities (0 points); "+" indicates mild lesions (1 point); "++" indicates moderate lesions (2 points); and "+++" indicates severe lesions (3 points). The pathological scores of each group of animals were statistically analyzed.

[0173] 3.5.3 Experimental Results

[0174] 3.5.3.1 Effects of gastric acid and pepsin activity

[0175] As shown in Tables 13 and 14, compared with the normal control group, the total gastric acid, gastric acid excretion, pepsin activity, and pepsin excretion of rats in the model control group were significantly increased (P≤0.01); compared with the model control group, the total gastric acid, pepsin activity, and pepsin excretion of rats in the Weikangling capsule group were significantly decreased (P≤0.05 or P≤0.01), the total gastric acid, pepsin activity, and pepsin excretion of rats in the omeprazole enteric-coated capsule group were significantly decreased (P≤0.05 or P≤0.01), and the total gastric acid, gastric acid excretion, pepsin activity, and pepsin excretion of rats in the Xiangshupingwei powder group were significantly decreased (P≤0.01). Compared with the omeprazole enteric-coated capsule group, the pepsin excretion of rats in the Xiangshupingwei powder group was significantly decreased (P≤0.05).

[0176] Table 13 Effects of Xiangshu Pingwei Powder on the pH of gastric juice in a rat model of gastric ulcer ( n=12)

[0177]

[0178] Table 14 Effects of Xiangshu Pingwei Powder on pepsin activity in a rat gastric ulcer model ( n=12)

[0179]

[0180] Note: Compared with the normal control group ++ P≤0.01; compared with the model control group * P≤0.05, ** P≤0.01; compared with the omeprazole enteric-coated capsule group & P≤0.05.

[0181] 3.5.3.2 Effects on gastric tissue lesions

[0182] like Figure 2 As shown, under microscopic examination of the gastric mucosa of rats in the normal control group, epithelial cells were neatly arranged without defects or sloughing, and no edema, hemorrhage, or inflammatory cell infiltration was observed. Under microscopic examination of the gastric mucosa of rats in the model control group, epithelial cell degeneration and necrosis, hemorrhage in the lamina propria of the mucosa, edema and hemorrhage in the submucosa, and a large number of inflammatory cells were observed. Under microscopic examination of the gastric mucosa of the Weikangling capsule group, the omeprazole enteric-coated capsule group, and the Xiangshupingwei powder group, edema and hemorrhage of varying degrees were observed, and necrosis of epithelial cells in some animals was observed, accompanied by a small amount of inflammatory cell infiltration. Xiangshupingwei powder can reduce the degree of gastric mucosal damage.

[0183] As shown in Table 15, compared with the normal control group, the pathological score of gastric mucosa tissue in the model control group was significantly increased (P≤0.01); the lesions such as gastric mucosal edema, hemorrhage and inflammatory infiltration in each drug administration group were significantly improved. Compared with the model control group, the pathological score of gastric mucosa tissue in the Xiangshupingwei powder group was significantly reduced (P≤0.01).

[0184] Table 15 Effects of Xiangshu Pingwei Powder on Gastric Tissue Pathological Scores in a Rat Gastric Ulcer Model n=12)

[0185] Group dose Gastric mucosal lesion score normal control group — 0.0±0.0 Model control group — <![CDATA[1.8±0.6 ++ ]]> Weikangling Capsule Group 0.43g / kg <![CDATA[0.9±0.7 ** ]]> Omeprazole enteric-coated capsules 3.6 mg / kg <![CDATA[1.1±0.5 * ]]> Xiangshu Pingwei Powder Group 2.16g crude drug / kg <![CDATA[0.9±0.7 ** ]]>

[0186] Note: Compared with the normal control group ++ P≤0.01; compared with the model control group * P≤0.05, ** P≤0.01.

[0187] The above results indicate that Xiangshu Pingwei Powder can significantly reduce pepsin activity and inhibit gastric acid secretion, significantly reduce the degree of gastric mucosal damage, and lower the gastric mucosal tissue lesion score, suggesting that Xiangshu Pingwei Powder has a significant therapeutic effect on gastric ulcers caused by pyloric ligation.

[0188] 3.6 Effects of Xiangshu Pingwei Powder on Helicobacter pylori-induced gastric ulcer model in mice

[0189] 3.6.1 Experimental Methods

[0190] 3.6.1.1 Modeling, Grouping, and Drug Administration

[0191] Sixty qualified SPF-grade male BALB / c mice (Animal Quality Certificate No.: 430727201101212714, provided by Hunan Silek Jingda Experimental Animal Co., Ltd.), weighing 17.0–19.2 g, were selected and divided into a model group (n=50) and a normal group (n=10). Mice were fasted for 24 hours before inoculation. The model group was administered 1.0 mL / mouse (1×10⁻⁶) of H. pylori strain via oral gavage. 9The mice were vaccinated three times a week for two weeks, with CFU / mL. Two hours after vaccination, the mice were allowed free access to water and food. The control group received no treatment. Before vaccination in the third week, three animals were randomly selected from the model group, and their stomachs were harvested for a rapid urease test and histopathological examination. The results showed a positive rapid urease test, and microscopic examination revealed gastric mucosal epithelial degeneration and necrosis, as well as inflammatory cell infiltration, indicating successful model replication. Forty model mice were randomly divided into four groups according to body weight: model control group, Weikangling capsule group (0.624 g / kg), colloidal bismuth pectin capsule group (78 mg / kg), and Xiangshu Pingwei powder group (3.12 g crude drug / kg), with 10 animals in each group. Each group received the corresponding concentration of drug solution orally at 30 mL / kg via gavage. The normal control group and model control group received an equal volume of 0.5% CMC-Na via gavage once daily for 21 consecutive days.

[0192] 3.6.1.2 Dosage Design

[0193] The experimental groups and dosages are detailed in Table 16.

[0194] Table 16 Grouping and Dosage Design

[0195]

[0196] 3.6.2 Detection Indicators

[0197] 3.6.2.1 Effect on the HP colorimetric reaction of gastric tissue

[0198] Animals in each group were fasted for 24 hours before the last administration, but allowed free access to water. One hour after the last administration, animals were euthanized by exsanguination via the abdominal aorta under isoflurane anesthesia. The abdominal cavity was opened, and a tissue sample from the lower part of the stomach was taken. The colonization of Helicobacter pylori in the stomach was examined using rapid HP test strips. The results were judged as follows: negative ("-"), weakly positive ("±"), and positive ("+"). The degree of colorimetric reaction in each group was recorded.

[0199] 3.6.2.2 Effects on gastric tissue lesions

[0200] Gastric tissue was fixed in 10% neutral formalin solution and stained with hematoxylin and eosin (HE) for histopathological examination. The lesions in the gastric tissue were observed, including the degree of gastric mucosal damage (ulcers and erosions), the degree of glandular atrophy, and the degree of inflammatory cell infiltration in the submucosa. The lesions were comprehensively graded according to the following criteria: NSL indicates no abnormalities; "+" indicates mild lesions; "++" indicates moderate lesions; and "+++" indicates severe lesions.

[0201] 3.6.3 Experimental Results

[0202] 3.6.3.1 Model Establishment

[0203] The gastric tissue of the model group animals showed a positive H. pylori staining reaction. Microscopic observation revealed significant epithelial degeneration and necrosis, atrophy of mucosal glands, vascular congestion, and submucosal edema and inflammatory cell infiltration in the gastric mucosa. This indicates that Helicobacter pylori has significant colonization in the stomach and can cause significant pathological changes in gastric tissue. These results suggest that repeated gavage administration of Helicobacter pylori can induce significant gastric ulcers in BALB / c mice, which can be used for subsequent experimental research.

[0204] 3.6.3.2 Effect on HP colorimetric reaction in gastric tissue

[0205] As shown in Table 17, compared with the normal control group, the positive frequency of the model control group was significantly increased (P = 0.000), indicating that Helicobacter pylori can colonize in the stomach; compared with the model control group, the positive frequency of the colloidal bismuth pectin capsule group and the Xiangshu Pingwei powder group was significantly reduced (P ≤ 0.05 or P ≤ 0.01), indicating that Xiangshu Pingwei powder can reduce the colonization of Helicobacter pylori in the stomach.

[0206] Table 17 Effects of Xiangshu Pingwei Powder on the HP colorimetric reaction of gastric tissue in a BALB / c mouse gastric ulcer model (n=10)

[0207]

[0208] 3.6.3.3 Effects on gastric tissue lesions

[0209] As shown in Table 18 and Figure 3 As shown, in the normal control group, the gastric mucosa of mice was intact, the glands were regular, and no inflammatory cell infiltration was observed in the submucosa. In the model control group, a large number of inflammatory cells were observed in the gastric mucosa and submucosa of mice, the degree of gastric tissue lesions was significantly increased (P≤0.01), and the number of lesion animals was significantly increased (P≤0.01). In the small stomach, a small number of inflammatory cells were scattered in the submucosa, and the inflammation was improved. Compared with the model control group, the degree of gastric tissue lesions in the Xiangshu Pingwei powder group was significantly reduced (P≤0.05), and the number of lesion animals was significantly reduced (P≤0.05).

[0210] Table 18 Effects of Xiangshu Pingwei Powder on Gastric Tissue Lesions in a BALB / c Mice Gastric Ulcer Model (n=10)

[0211]

[0212] The above results indicate that Xiangshu Pingwei Powder can reduce the colonization of Helicobacter pylori in the stomach of BALB / c mice and reduce the degree of gastric tissue lesions caused by it (mucosal damage, glandular atrophy, and submucosal inflammatory infiltration), suggesting that Xiangshu Pingwei Powder has a certain therapeutic effect on gastric ulcers caused by Helicobacter pylori.

[0213] 3.7 Effects of Xiangshu Pingwei Powder on Acetic Acid-Induced Writhing in Mice

[0214] 3.7.1 Experimental Methods

[0215] 3.7.1.1 Grouping and Dosing

[0216] Forty ICR mice (Animal Quality Certificate No.: 110726201100212354, provided by Changsha Tianqin Biotechnology Co., Ltd.), half male and half female, weighing 18.5–23.7 g, were randomly divided into four groups according to sex and weight: a model control group, a Weikangling capsule group (0.624 g / kg), a compound acetylsalicylic acid tablet group (0.17 g / kg), and a Xiangshu Pingwei powder group (3.12 g crude drug / kg), with 10 animals in each group. Each group received the corresponding concentration of the drug via oral gavage at a dose of 30 mL / kg. The model control group received an equal amount of 0.5% CMC-Na via gavage. Administration was once daily for 7 consecutive days. Thirty minutes after the last administration, each group of mice received an intraperitoneal injection of 0.2 mL of 0.6% acetic acid solution, and observation continued for 15 minutes. The number of writhing responses (abdominal concavity, hind limb extension, and hip elevation) in each mouse was observed and recorded.

[0217] 3.7.1.2 Dosage Design

[0218] The experimental groups and dosages are detailed in Table 19.

[0219] Table 19 Grouping and Dosage Design

[0220]

[0221] 3.7.2 Experimental Results

[0222] As shown in Table 20, compared with the model control group, the number of writhing movements in the Weikangling capsule group, compound acetylsalicylic acid tablet group and Xiangshupingwei powder group was significantly reduced (P≤0.01), suggesting that Xiangshupingwei powder has analgesic effects.

[0223] Table 20 Effects of Xiangshu Pingwei Powder on the analgesic effect in mice n=10)

[0224] Group dose Number of twists Model control group — 21.6±4.4 Weikangling Capsule Group 0.624g / kg <![CDATA[13.0±3.1 ** ]]> Compound acetylsalicylic acid tablets 0.17g / kg <![CDATA[6.4±3.5 ** ]]> Xiangshu Pingwei Powder Group 3.12g crude drug / kg <![CDATA[10.9±3.9 ** ]]>

[0225] Note: Compared with the model control group ** P≤0.01.

[0226] Xiangshu Pingwei Powder can significantly reduce the number of writhing movements in mice induced by acetic acid, suggesting that it has a significant peripheral analgesic effect.

[0227] 3.8 Effects of Xiangshu Pingwei Powder on Acetic Acid-Induced Capillary Permeability in Mice

[0228] 3.8.1 Experimental Methods

[0229] 3.8.1.1 Grouping and Dosing

[0230] Forty ICR mice that passed quarantine (Animal Quality Certificate No.: No. 110726201100212585, provided by Changsha Tianqin Biotechnology Co., Ltd.) were selected, with half males and half females, weighing 16.7–23.5 g. They were randomly divided into four groups according to sex and weight: a model control group, a Weikangling capsule group (0.624 g / kg), a compound acetylsalicylic acid tablet group (0.17 g / kg), and a Xiangshu Pingwei powder group (3.12 g crude drug / kg), with 10 animals in each group. Mice in each group were administered the corresponding drugs orally by gavage at a volume of 30 mL / kg. The model control group was given the same volume of 0.5% CMC-Na once daily for 7 consecutive days. One hour after the last administration, mice in each group were injected intravenously with 0.5% Evans blue solution at a dose of 10 mL / kg, followed by an intraperitoneal injection of 0.2 mL of 0.8% acetic acid solution per mouse. One hour later, the mice were euthanized by cervical dislocation and injected intraperitoneally with 4.0 mL of 0.9% sodium chloride injection. After gently massaging the abdomen, the abdominal skin and muscles were cut open, and 1.0 mL of liquid was aspirated. The mixture was centrifuged at 3000 r / min for 15 min, and the absorbance of the supernatant was measured at 590 nm.

[0231] 3.8.1.2 Dosage Design

[0232] The experimental groups and dosages are detailed in Table 21.

[0233] Table 21 Grouping and Dosage Design

[0234]

[0235] 3.8.2 Experimental Results

[0236] As shown in Table 22, compared with the model control group, the absorbance values ​​of the Weikangling capsule group, the compound acetylsalicylic acid tablet group, and the Xiangshupingwei powder group were significantly reduced (P≤0.05 or P≤0.01), suggesting that Xiangshupingwei powder has a significant inhibitory effect on acetic acid-induced peritoneal capillary permeability in mice.

[0237] Table 22 Effects of Xiangshu Pingwei Powder on Acetic Acid Permeability in Mice ( n=10)

[0238]

[0239]

[0240] Note: Compared with the model control group * P≤0.05, ** P≤0.01.

[0241] Xiangshu Pingwei Powder can significantly inhibit capillary permeability and exudation in the early stage of inflammation, suggesting that it has an anti-inflammatory effect.

[0242] 3.9 Effect of Xiangshu Pingwei Powder on Gastric Emptying in Mice

[0243] 3.9.1 Experimental Methods

[0244] 3.9.1.1 Grouping and Dosing

[0245] Forty ICR mice (Animal Quality Certificate No.: 110726201100212463, provided by Changsha Tianqin Biotechnology Co., Ltd.), half male and half female, weighing 18.3–24.0 g, were randomly divided into four groups according to sex and weight: a model control group, a Weikangling capsule group (0.624 g / kg), a domperidone tablet group (3.9 mg / kg), and a Xiangshu Pingwei powder group (3.12 g crude drug / kg), with 10 animals in each group. Mice in each group were administered the corresponding test substance by gavage at a dose of 30 mL / kg, while the model control group was administered an equal volume of 0.5% CMC-Na by gavage, once daily for 7 consecutive days. On the 6th day of administration, mice were fasted but allowed free access to water for at least 16 hours. 30 minutes after the last administration, mice in each group were administered a 3% blue paste by gavage at a dose of 20 mL / kg. Thirty minutes later, the mice in each group were euthanized by cervical dislocation. The abdomen is opened, the cardia and pylorus are ligated, the stomach is removed, and after being dried with filter paper, the total weight is measured. Then, the stomach body is cut open along the greater curvature, the stomach contents are washed away, and after being dried, the net weight is measured. The difference between the total weight of the stomach and the net weight of the stomach is the weight of the residue in the stomach.

[0246] 3.9.1.2 Dosage Design

[0247] The experimental groups and dosages are detailed in Table 23.

[0248] Table 23 Grouping and Dosage Design

[0249]

[0250]

[0251] 3.9.2 Experimental Results

[0252] As shown in Table 24, compared with the model control group, the amount of gastric residue in the animals in the Weikangling capsule group, domperidone tablet group and Xiangshupingwei powder group was significantly reduced, suggesting that Xiangshupingwei powder has the effect of promoting gastric emptying.

[0253] Table 24 Effects of Xiangshu Pingwei Powder on Gastric Emptying in Mice n=10)

[0254] Group dose Gastric residue (g) Model control group — 0.501±0.186 Weikangling Capsule Group 0.624g / kg <![CDATA[0.155±0.053 ** ]]> Domperidone tablets 3.9 mg / kg <![CDATA[0.263±0.110 * ]]> Xiangshu Pingwei Powder Group 3.12g crude drug / kg <![CDATA[0.179±0.068 ** ]]>

[0255] Note: Compared with the model control group* P≤0.05, ** P≤0.01.

[0256] Xiangshu Pingwei Powder can significantly reduce the amount of residue in the stomach of mice, suggesting that it has the effect of promoting gastric motility.

[0257] 3.10 Conclusion and Evaluation

[0258] Gastric ulcer is a term used in modern Western medicine, but it falls under the category of stomach pain within the spleen and stomach diseases of traditional Chinese medicine. Traditional Chinese medicine theory states that the spleen and stomach are the source of qi and blood production in the human body, and the foundation of acquired constitution. The most reasonable theory regarding its pathogenesis is the imbalance between attacking and defending factors. Attacking factors mainly refer to gastric acid, pepsin, and Helicobacter pylori (H. pylori), while defending factors mainly include gastric mucosal blood flow, bicarbonate and mucus secretion, cell membrane integrity, cell regeneration, prostaglandin production, and digestive hormones. Indomethacin-induced gastric mucosal damage mainly affects the mucosal prostaglandin system, weakening defending factors, while attacking factors disrupt the gastric mucosal barrier, causing acute gastric mucosal injury. Pyloric ligation-related ulcers occur because gastric juices are retained in the stomach after pyloric ligation, leading to erosion by gastric acid and pepsin, and increased digestive power. H. pylori infection is a major factor causing gastritis, gastric and duodenal ulcers, and even gastric cancer. With the widespread use of broad-spectrum antibiotics, the number of drug-resistant H. pylori strains is constantly increasing, making the development of highly effective and selective anti-H. pylori drugs a trend. Studies have reported that traditional Chinese medicine (TCM) or integrated TCM and Western medicine can improve H. pylori eradication rates, alleviate gastric mucosal inflammation, or inhibit peptic ulcers. From a modern medical perspective, the mechanism of action of effective TCM in inhibiting H. pylori infection is analyzed. Possible mechanisms by which TCM inhibits H. pylori-related gastritis include inhibiting the expression of its virulence factors, regulating infection-induced immune imbalance, and correcting gastrointestinal hormone secretion disorders.

[0259] The traditional Chinese medicine composition of this invention mainly consists of Poria cocos, stir-fried Atractylodes lancea, Magnolia officinalis, Aucklandia lappa, Lindera strychnifolia, and vinegar-processed Cyperus rotundus. An animal gastric ulcer model was established using indomethacin, Helicobacter pylori ligation, and the Xiangshu Pingwei Powder. After intervention with the powder, its efficacy against gastric ulcers induced by different factors was observed. The anti-inflammatory, analgesic, and gastric motility effects of the Xiangshu Pingwei Powder were observed using writhing, acetic acid permeability, and gastric emptying tests. The results showed that the Xiangshu Pingwei Powder significantly reduced the area of ​​gastric ulcers induced by indomethacin, alleviated the degree of gastric mucosal damage caused by Helicobacter pylori, significantly inhibited gastric acid secretion and pepsin activity, reduced the amount of gastric acid and pepsin excreted, and promoted gastric emptying. Simultaneously, it reduced the number of writhing episodes induced by acetic acid in mice and decreased capillary peritoneal permeability induced by acetic acid.

[0260] In summary, Xiangshu Pingwei Powder has significant anti-inflammatory, analgesic, and gastric motility-promoting effects, and can reduce the colonization of Helicobacter pylori in the stomach. It also has significant therapeutic effects on gastric ulcers induced by different factors (Helicobacter pylori infection, pyloric ligation, and nonsteroidal anti-inflammatory drugs).

[0261] The embodiments of the present invention have been described in detail above. Specific examples have been used to illustrate the principles and implementation methods of the present invention. The descriptions of the embodiments above are only for the purpose of helping to understand the method and core ideas of the present invention. Furthermore, any changes or modifications made by those skilled in the art based on the ideas of the present invention, its specific implementation methods, and its application scope, are all within the scope of protection of the present invention. Therefore, the content of this specification should not be construed as a limitation of the present invention.

Claims

1. A traditional Chinese medicine composition for the prevention and / or treatment of gastric ulcers and / or their complications, characterized in that, By weight, the traditional Chinese medicine composition comprises 2.85-3.15 parts of Atractylodes lancea, 2.85-3.15 parts of Poria cocos, 1.9-2.1 parts of Magnolia officinalis, 2.85-3.15 parts of Aucklandia lappa, 1.9-2.1 parts of Lindera strychnifolia, 2.85-3.15 parts of Cyperus rotundus, 1.9-2.1 parts of Alpinia officinarum, 1.9-2.1 parts of Amomum villosum, 1.9-2.1 parts of Coix lacryma-jobi, 1.9-2.1 parts of Citrus reticulata peel, 1.9-2.1 parts of Citrus medica, and 0 parts of Crataegus pinnatifida. The formula consists of 0.95-1.05 parts of Shenqu (a traditional Chinese medicine), 0.95-1.05 parts of malt, 0.95-1.05 parts of chicken gizzard lining, 0.95-1.05 parts of Bletilla striata, 2.85-3.15 parts of white peony root, 2.85-3.15 parts of Corydalis yanhusuo, 1.425-1.575 parts of cinnamon, and 1.9-2.1 parts of Piper longum, wherein the accompanying symptoms are selected from one or more of the following: pain, inflammation, and delayed gastric emptying.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The Atractylodes lancea mentioned is stir-fried with wheat bran.

3. The traditional Chinese medicine composition according to claim 1, characterized in that, The Cyperus rotundus mentioned is vinegar-processed Cyperus rotundus.

4. The traditional Chinese medicine composition according to claim 1, characterized in that, The Job's tears mentioned are stir-fried Job's tears.

5. The traditional Chinese medicine composition according to claim 1, characterized in that, The hawthorn in question is a type of charred hawthorn.

6. The traditional Chinese medicine composition according to claim 1, characterized in that, The Six Divine Songs mentioned are Jiao Six Divine Songs.

7. The traditional Chinese medicine composition according to claim 1, characterized in that, The malt is roasted malt.

8. The traditional Chinese medicine composition according to claim 1, characterized in that, The chicken gizzard lining mentioned is stir-fried chicken gizzard lining.

9. A formulation comprising the traditional Chinese medicine composition according to any one of claims 1 to 8.

10. The formulation according to claim 9, characterized in that, The formulation includes one or more pharmaceutically acceptable excipients.

11. The formulation according to claim 10, characterized in that, The excipients are selected from one or more of the following: anti-caking agents, preservatives, diluents, suspending agents, and flavoring agents.

12. The formulation according to claim 11, characterized in that, The flavoring agent is selected from one or more of the following: stevioside, sucralose, and aspartame.

13. The formulation according to claim 12, characterized in that, The flavoring agent is sucralose.

14. The formulation according to claim 11, characterized in that, The weight ratio of the flavoring agent to the traditional Chinese medicine composition is 1:1000-5000.

15. The formulation according to claim 14, characterized in that, The weight ratio of the flavoring agent to the traditional Chinese medicine composition is 1:2000.

16. The formulation according to claim 9, characterized in that, The dosage form of the preparation is an oral preparation.

17. The formulation according to claim 16, characterized in that, The dosage form of the preparation is a powder.

18. A method for preparing the traditional Chinese medicine composition according to any one of claims 1 to 8, characterized in that, The method includes: weighing appropriate amounts of Atractylodes lancea, Poria cocos, Magnolia officinalis, Aucklandia lappa, Lindera strychnifolia, Cyperus rotundus, Alpinia officinarum, Amomum villosum, Coix lacryma-jobi, Citrus reticulata peel, Citrus medica, Crataegus pinnatifida, Massa fermentata, Hordeum vulgare, Gallus gallus domesticus gizzard lining, Bletilla striata, Paeonia lactiflora, Corydalis yanhusuo, Cinnamomum cassia and Piper longum, mixing them for the first time, drying them for the first time, pulverizing them for the first time, mixing them for the second time, sterilizing them, drying them for the second time, and pulverizing them for the second time to obtain the Chinese herbal composition.

19. A method for preparing the formulation according to any one of claims 9 to 17, characterized in that, The method includes: mixing the traditional Chinese medicine composition according to any one of claims 1 to 8 with an appropriate amount of excipients for a third time to obtain the preparation.

20. The method according to claim 19, characterized in that, The method further includes: dispensing after a third mixing to obtain the formulation.

21. The method according to claim 18 or 19, characterized in that, The method includes any one or more of the following items [1] to [10]: [1] The first mixing and / or the second mixing and / or the third mixing shall be carried out by sieving or stirring. [2] The time for the first mixing and / or the second mixing and / or the third mixing is 20-40 min; [3] The sterilization method is dry heat sterilization, moist heat sterilization and / or cobalt-60 irradiation sterilization; [4] The sterilization time is 10-40 min; [5] The temperature of the moist heat sterilization method is 110-127℃; [6] The thickness of the material used in the moist heat sterilization method is 1-3 cm; [7] The first drying process is carried out at 40-60℃ for 8-12 hours; [8] The second drying process is carried out at 70-90℃ for 0.5-1.5 hours; [9] The first crushing is coarse crushing with a 60-80 mesh sieve followed by crushing with a 100-150 mesh sieve; [10] The second crushing is performed by crushing with a 100-150 mesh sieve.

22. The method according to claim 21, characterized in that, The first mixing and / or the second mixing and / or the third mixing are performed by stirring.

23. The method according to claim 21, characterized in that, The time for the first mixing and / or the second mixing and / or the third mixing is 30 minutes.

24. The method according to claim 21, characterized in that, The sterilization method is moist heat sterilization.

25. The method according to claim 21, characterized in that, The sterilization time is 30 minutes.

26. The method according to claim 21, characterized in that, The temperature for the moist heat sterilization method is 121°C.

27. The method according to claim 21, characterized in that, The thickness of the material used in the moist heat sterilization method is 1.9~2.1cm.

28. The method according to claim 21, characterized in that, The first drying process involves drying at 50-55°C for 10 hours.

29. The method according to claim 21, characterized in that, The second drying process involves drying at 75-85℃ for 0.95-1.05 hours.

30. The method according to claim 21, characterized in that, The first crushing process involves coarse crushing with a 60-mesh sieve followed by pulverizing with a 100-mesh sieve.

31. The method according to claim 21, characterized in that, The second crushing is performed using a 100-mesh sieve.

32. The use of the traditional Chinese medicine composition according to any one of claims 1 to 8 or the preparation according to any one of claims 9 to 17 in the preparation of a medicament for the prevention and / or treatment of gastric ulcers and / or their complications, characterized in that, The complications are selected from one or more of the following: pain, inflammation, and delayed gastric emptying.

33. The use according to claim 32, characterized in that, The gastric ulcer is selected from one or more of the following: drug-induced gastric ulcer, physical manipulation-induced gastric ulcer, and bacterial-induced gastric ulcer.

34. The use according to claim 32, characterized in that, The pain can be acute or chronic.

35. The use according to claim 32, characterized in that, The pain is either peripheral or central.

36. The use according to claim 32, characterized in that, The inflammation can be specific or nonspecific.

37. The use according to claim 32, characterized in that, The inflammation can be acute or chronic.

38. The use according to claim 33, characterized in that, The drug in question is a nonsteroidal anti-inflammatory drug (NSAID).

39. The use according to claim 33, characterized in that, The physical procedure is pyloric ligation.

40. The use according to claim 33, characterized in that, The bacteria in question is Helicobacter pylori.

41. The use according to claim 38, characterized in that, The nonsteroidal anti-inflammatory drug is selected from one or more of the following: ibuprofen, diclofenac sodium, and indomethacin.

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