A traditional Chinese medicine composition for treating gastric ulcers, its preparation method and application.

Abstract

This invention belongs to the field of traditional Chinese medicine and discloses a traditional Chinese medicine composition for treating gastric ulcers, mainly composed of the following components in parts by weight: 5-20 parts of white peony root, 5-20 parts of atractylodes macrocephala, 5-20 parts of tangerine peel, 5-20 parts of bupleurum root, 5-20 parts of poria cocos, 2-8 parts of licorice root, 5-20 parts of malt, 5-20 parts of codonopsis pilosula, 5-20 parts of lily bulb, 2-10 parts of perilla leaf, 5-20 parts of immature bitter orange peel, and 2-8 parts of dried ginger. This invention also discloses a method for preparing this traditional Chinese medicine composition for treating gastric ulcers and its application in the preparation of drugs for treating gastric ulcers. The combined effects of these herbs in the traditional Chinese medicine composition of this invention warm the middle jiao, strengthen the spleen, and replenish qi, effectively addressing the pathogenesis of spleen and stomach deficiency-cold syndrome, repairing mucosal damage, promoting ulcer healing, and solving the problem of prolonged and recurrent gastric ulcers in most patients with spleen and stomach deficiency-cold syndrome.

Description

Technical Field

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

[0002] Gastric ulcer (GU) is damage to the gastric mucosa caused by gastric acid and pepsin digesting the ulcer and penetrating the muscular layer. Its occurrence is closely related to factors such as stress, smoking, alcohol consumption, nonsteroidal anti-inflammatory drugs (NSAIDs), Helicobacter pylori infection, and genetics. The main clinical manifestations of GU are recurrent, rhythmic, and periodic upper abdominal pain after meals, accompanied by symptoms such as acid reflux, belching, and nausea; the condition is often chronic. Currently, Western medicine treatment for GU mainly relies on chemical drugs, but this has problems such as numerous adverse reactions, a high recurrence rate, and poor patient compliance. Clinical studies show that traditional Chinese medicine plays an important role in the treatment of GU, possessing many advantages such as multi-target, multi-level, multi-pathway, and high safety. However, there are still problems such as weak correlation between traditional efficacy and modern pharmacological activity mechanism and single evaluation index. Moreover, due to the characteristics of gastric ulcer (spleen and stomach deficiency and cold syndrome) such as recurrent attacks, diversity, protracted and difficult healing, the existing traditional Chinese medicine for treating gastric ulcer of spleen and stomach deficiency and cold syndrome is difficult to meet the treatment needs of this disease. Therefore, the problem of prolonged and recurrent attacks of gastric ulcer of spleen and stomach deficiency and cold syndrome is difficult to solve, which seriously affects the patient's quality of life and work status. Summary of the Invention

[0003] The technical problem to be solved by the present invention is to overcome the deficiencies and defects mentioned in the background art above, and to provide a traditional Chinese medicine composition for treating gastric ulcers, its preparation method and application.

[0004] To solve the above-mentioned technical problems, the technical solution proposed by this invention is as follows:

[0005] A traditional Chinese medicine composition for treating gastric ulcers mainly consists of the following components in parts by weight: 5-20 parts of white peony root, 5-20 parts of atractylodes macrocephala, 5-20 parts of tangerine peel, 5-20 parts of bupleurum root, 5-20 parts of poria cocos, 2-8 parts of licorice root, 5-20 parts of malt, 5-20 parts of codonopsis pilosula, 5-20 parts of lily bulb, 2-10 parts of perilla leaf, 5-20 parts of immature bitter orange peel, and 2-8 parts of dried ginger.

[0006] The above-mentioned traditional Chinese medicine composition for treating gastric ulcers preferably consists mainly of the following components in parts by weight: 8-20 parts of white peony root, 8-15 parts of atractylodes macrocephala, 8-15 parts of tangerine peel, 8-15 parts of bupleurum root, 8-15 parts of poria cocos, 4-8 parts of licorice root, 8-15 parts of malt, 8-15 parts of codonopsis pilosula, 8-15 parts of lily bulb, 4-10 parts of perilla leaf, 8-15 parts of immature bitter orange peel, and 4-8 parts of dried ginger.

[0007] The above-mentioned traditional Chinese medicine composition for treating gastric ulcers preferably consists mainly of the following components in parts by weight: 10 parts of white peony root, 10 parts of atractylodes macrocephala, 10 parts of tangerine peel, 10 parts of bupleurum root, 10 parts of poria cocos, 6 parts of licorice root, 10 parts of malt, 10 parts of codonopsis pilosula, 10 parts of lily bulb, 5 parts of perilla leaf, 10 parts of immature bitter orange peel, and 6 parts of dried ginger.

[0008] In the above-mentioned traditional Chinese medicine composition for treating gastric ulcers, preferably, the Bupleurum is vinegar-processed Bupleurum, the malt is stir-fried malt, and the Citrus aurantium is stir-fried Citrus aurantium with wheat bran.

[0009] The above-mentioned traditional Chinese medicine composition for treating gastric ulcers preferably includes any one of the following dosage forms: decoction, paste, tablet, capsule, pill, granule, and powder.

[0010] Based on a general inventive concept, the present invention also provides a method for preparing the above-described traditional Chinese medicine composition for treating gastric ulcers, comprising the following steps:

[0011] Weigh out the prescribed amounts of each Chinese herbal medicine component, soak and decoct them, combine the filtrates, then heat and concentrate them, and cool them to complete the preparation of the Chinese herbal medicine composition for treating gastric ulcers.

[0012] In the above preparation method, preferably, the ingredients are first soaked in cold water for 20-40 minutes, and the decoction includes at least two decoctions: the first decoction for 30-50 minutes and the second decoction for 20-40 minutes.

[0013] In the above preparation method, preferably, the heating and concentration is carried out until the concentration of the concentrate is 0.8-1.2 g / mL.

[0014] Based on a general inventive concept, the present invention also provides the application of the above-described traditional Chinese medicine composition for treating gastric ulcers in the preparation of a drug for treating gastric ulcers.

[0015] In the above application, preferably, the gastric ulcer includes gastric ulcer of the spleen and stomach deficiency-cold type, which is diagnosed as spleen and stomach deficiency-cold syndrome in traditional Chinese medicine.

[0016] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0017] In the traditional Chinese medicine composition used in the present invention, Pseudostellaria heterophylla tastes sweet and can replenish qi, strengthen the spleen, and promote fluid production. Dry ginger is pungent, greatly hot, mainly enters the middle jiao, and has the effect of warming the middle jiao and dispelling cold. The two herbs together serve as the monarch herbs and have the effect of warming the middle jiao, strengthening the spleen, and replenishing qi. Atractylodes macrocephala tastes sweet and bitter, is warm in nature, replenishes qi with its sweetness and warmth, and strengthens the spleen with its bitterness and dryness. When combined with Pseudostellaria heterophylla, it enhances the power of replenishing qi and strengthening the spleen. Poria cocos is sweet and bland, strengthening the spleen and promoting diuresis. When combined with Pseudostellaria heterophylla, it enhances the power of strengthening the spleen. Bupleurum chinense is pungent and bitter and has the effect of lifting yang qi. When combined with Pseudostellaria heterophylla, it can replenish qi and lift yang. The three herbs together serve as the minister herbs and enhance the effect of strengthening the spleen and lifting yang. Paeonia lactiflora is bitter and sour, can nourish blood, soothe the liver, and relieve pain. When combined with Glycyrrhiza uralensis, it can relieve spasm and stop the pain in the epigastrium. Aurantii Fructus Immaturus is bitter, pungent, and sour, can regulate qi and relieve fullness. When combined with Bupleurum chinense, it coordinates the liver and spleen and regulates the qi movement. Citrus reticulata Blanco is bitter and pungent, warm in nature, and has the effect of regulating qi and strengthening the spleen. Germinated Barley is sweet, neutral in nature, can promote qi movement, strengthen the spleen, and stimulate the appetite. When combined with Atractylodes macrocephala and Citrus reticulata Blanco, it enhances the effect of replenishing qi and strengthening the spleen. Perilla frutescens is pungent, warm in nature, can promote qi movement, relieve fullness, and harmonize the stomach. Lilium brownii is sweet, can regulate qi in the middle, clear the heart, and calm the mind, and can also protect the stomach yin. The above six herbs together serve as the assistant herbs and play the role of strengthening the spleen, regulating qi, and relieving spasm and stomach pain. Glycyrrhiza uralensis strengthens the spleen and harmonizes the middle, and also harmonizes the properties of various herbs, serving as the envoy herb. The combination of all herbs has the effect of warming the middle jiao, strengthening the spleen, and replenishing qi, hitting the pathogenesis of spleen and stomach yang deficiency syndrome, repairing mucosal damage, promoting ulcer healing, and solving the problems of protracted illness and repeated attacks in most patients with gastric ulcer of spleen and stomach yang deficiency syndrome. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 are the photos of the effects of each experimental group on the gastric mucosa morphology of GU rats: "→" indicates the ulcer site;

[0019] Figure 2 are the effects of each experimental group on the pathological morphological changes of the gastric mucosa of GU rats observed by HE staining (HE, ×150): "→" indicates the exfoliation site of the gastric mucosa epithelium, the marked area "a" indicates epithelial cell edema, and the marked area "b" indicates inflammatory cell infiltration;

[0020] Figure 3 are the effects of each experimental group on the mucus content of the gastric mucosa of GU rats observed by PAS staining;

[0021] Figure 4 are the protective effects of each experimental group on the gastric mucosa of GU rats observed by scanning electron microscopy (×300);

[0022] Figure 5 are the protective effects of each experimental group on the gastric mucosa of GU rats observed by transmission electron microscopy (×5000);

[0023] Figure 6 are the effects of each experimental group on the expression of phosphorylated Raf, MEK1 / 2, and ERK1 proteins in the gastric mucosa of GU rats (150×, scale bar = 100 μm);

[0024] Figure 7The effects of each experimental group on the expression of phosphorylated IkBβ, IKKβ, and NF-κB proteins in the gastric mucosa of GU rats (150×, scale bar=100μm).

[0025] Figure 1-7 In the following groups: A. Normal group; B. Model group; C. Rabeprazole group; D. Low-dose drug group of Example 1; E. Medium-dose drug group of Example 1; F. High-dose drug group of Example 1.

[0026] Figure 8 These are ultra-high performance liquid chromatography combined with high-resolution mass spectrometry (UHPLC) of the traditional Chinese medicine composition: A. Positive ion mode spectrum of the traditional Chinese medicine composition; B. Negative ion mode spectrum of the traditional Chinese medicine composition; 1. Hesperidin; 2. Poria cocos B; 3. 2-Amino-5-guanidinyl-valeric acid; 4. Saikosaponin A; 5. Paeoniflorin; 6. Naringin; 7. Paeoniflorin lactone; 8. Codonopsis pilosula cyclic peptide B; 9. Rosmarinic acid; 10. Luteolin; 11. Atractylodes macrocephala lactone I; 12. Glycyrrhizin; 13. Saikosaponin D; 14. Atractylodes macrocephala lactone III; 15. 6-Gingerol. Detailed Implementation

[0027] To facilitate understanding of the present invention, the present invention will be described more fully and in detail below with reference to the accompanying drawings and preferred embodiments, but the scope of protection of the present invention is not limited to the following specific embodiments.

[0028] Unless otherwise defined, all technical terms used herein have the same meaning as commonly understood by those skilled in the art. The technical terms used herein are for the purpose of describing particular embodiments only and are not intended to limit the scope of the invention.

[0029] Unless otherwise specified, all raw materials, reagents, instruments and equipment used in this invention can be purchased from the market or prepared by existing methods.

[0030] Example 1:

[0031] A traditional Chinese medicine composition for treating gastric ulcers consists of 10 g of white peony root, 10 g of atractylodes macrocephala, 10 g of tangerine peel, 10 g of vinegar-processed bupleurum root, 10 g of poria cocos, 6 g of licorice root, 10 g of stir-fried malt, 10 g of codonopsis pilosula, 10 g of lily bulb, 5 g of perilla leaf, 10 g of stir-fried bitter orange peel, and 6 g of dried ginger. All the medicinal materials were purchased from the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine.

[0032] The dosage form of the traditional Chinese medicine composition for treating gastric ulcers in this embodiment is a decoction. The preparation method is as follows: Weigh 10 g of white peony root, 10 g of atractylodes macrocephala, 10 g of tangerine peel, 10 g of vinegar-processed bupleurum root, 10 g of poria cocos, 6 g of licorice root, 10 g of stir-fried malt, 10 g of codonopsis pilosula, 10 g of lily bulb, 5 g of perilla leaf, 10 g of stir-fried bitter orange peel, and 6 g of dried ginger. Soak them in cold water for 30 minutes, then decoct twice. The first decoction is for 40 minutes, and the amount of water used for decoction is 8 times the weight of the traditional Chinese medicine components. The second decoction is for 30 minutes, and the amount of water used for decoction is 5 times the weight of the traditional Chinese medicine components. Filter out and combine the decoctions, heat and concentrate to 1 g / mL, cool and store at 4℃ for later use.

[0033] Example 2:

[0034] This embodiment establishes a rat model of gastric ulcer (GU) with spleen and stomach deficiency and cold, and verifies the technical efficacy of the traditional Chinese medicine composition for treating gastric ulcer in Example 1 in treating GU with spleen and stomach deficiency and cold.

[0035] I. Materials and Methods

[0036] 1. Laboratory animals

[0037] Seventy-two male SPF-grade SD rats, weighing (180±20) g, were purchased from Hunan Slack Jingda Experimental Animal Co., Ltd. (Animal License No. ZS-202310100026). They were housed at the Animal Experiment Center of Hunan University of Traditional Chinese Medicine, with an indoor temperature of 24℃~26℃ and humidity of 45%~55%. Before the formal experiment, they were given an acclimatization diet for 5 days, during which they had free access to food and water. The experiment was conducted with alternating light and darkness for 12 hours each day.

[0038] 2. Experimental drugs

[0039] Example 1 Drug: The formulation and preparation method are described in Example 1.

[0040] Senna leaves were purchased from the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine. The preparation method was as follows: 50 g of senna leaves were added to 500 mL of distilled water and decocted twice in the same manner as in Example 1. The residue was removed, the decoction was filtered and combined, and the liquid was heated and concentrated to 1 g / mL. After cooling, it was stored at 4℃ for later use.

[0041] The positive control drug was rabeprazole sodium enteric-coated capsules (Jichuan Pharmaceutical Group Co., Ltd., batch number 2305155), which was dissolved in physiological saline to form a suspension, and the dosage was 2.08 mg / kg.

[0042] The modeling drug was indomethacin (Yunpeng Pharmaceutical Group Co., Ltd., batch number 20221028), prepared using the same method as rabeprazole sodium enteric-coated capsules, with a dosage of 4 mg / kg, to be prepared and used immediately.

[0043] 3. Experimental Methods

[0044] Referring to the experimental methods of our research group in the previous study (Establishment and evaluation of a rat model of gastric ulcer disease with spleen and stomach deficiency-cold syndrome combined with indomethacin [J]. Journal of Basic Chinese Medicine, 2020, 26(04):468-473), a rat model of gastric ulcer disease with spleen and stomach deficiency-cold syndrome was established by combining the "bitter and cold purgative + fatigue" method with indomethacin. After 5 days of adaptive feeding, 72 SD rats were randomly divided into 6 groups: normal group, model group, positive drug group, and low, medium and high dose groups of the drug in Example 1, with 12 rats in each group. The normal group rats were given 1 mL / 100 g distilled water by gavage at regular intervals every day without any other treatment, while the other groups were given 1 mL / 100 g senna leaf decoction (1 g crude drug / mL) by gavage. Two hours after drug administration, rats in the model group, positive drug group, and each drug group of Example 1 were placed in a water tank filled with room temperature water and swam until they were completely submerged for 3 seconds. This was repeated for 7 days to establish a spleen and stomach deficiency-cold syndrome model. Starting on the 8th day, indomethacin suspension (4 mg / kg) was administered by gavage for 5 consecutive days to establish a GU disease model. Four hours after GU modeling, the positive drug group and the low, medium, and high doses of the drug from Example 1 were administered by gavage at doses of 2.08 mg / kg, 5.57 g / kg, 11.14 g / kg, and 22.28 g / kg, respectively, for 4 consecutive days.

[0045] II. Detection Indicators and Methods

[0046] 1. Observation of gastric mucosa morphology in rats

[0047] The differences between the gastric mucosa of rats in each group were observed by the naked eye, and whether the rats with spleen and stomach deficiency and cold type of GU showed signs of GU such as bleeding, ulceration, and erosion.

[0048] 2. Determination of gastric mucosal ulcer index (UI) and healing index (TI) in rats.

[0049] The gastric mucosal injury was scored according to the scoring method previously established by our research group: normal mucosa scored 0 points, ulcer (bleeding) length not exceeding 1 mm scored 1 point, 1-2 mm scored 2 points, 2-3 mm scored 3 points, 3-4 mm scored 4 points, and more than 4 mm scored 5 points. UI was equal to the average injury score of each group of rats, and TI / % = (1 - UI of treatment group / UI of model group) × 100%.

[0050] 3. Gastric mucosal blood flow detection

[0051] After drug administration, all rats were fasted for 24 hours. After anesthesia, gastric mucosal blood flow was measured using the laser blood flow imaging method reported by Xu Yunjiao et al. The specific method is as follows: After anesthesia, the abdomen of the rats was cut open to expose the gastric tissue. A small incision of 1.0 cm was made in the anterior wall of the pylorus. After the blood flow velocity stabilized, the gastric mucosal blood flow at the antrum of each group of rats was measured using a laser speckle blood flow imaging probe.

[0052] 4. Detection of serum inflammatory factors and oxidative stress levels in rats using ELISA.

[0053] After anesthetizing rats, blood was collected from the abdominal aorta into vacuum blood collection tubes. The blood was centrifuged at 3500 r / min at 4℃ for 5 min, and the supernatant was collected. The ELISA kit was used according to the instructions to analyze the expression levels of inflammatory factors TNF-α, IL-18, and IL-1β in serum, as well as the content or activity of oxidative stress indicators CAT, GST, and SOD.

[0054] 5. HE staining of gastric tissue

[0055] The stomach was removed and cut along the greater curvature. The stomach contents were cleaned, flattened, photographed, and the ulceration was recorded. A portion of the stomach tissue was removed, fixed with 4% paraformaldehyde, embedded, and sectioned in paraffin. The tissue sections were then rinsed sequentially in xylene-anhydrous ethanol and 75% ethanol for dehydration, followed by rinsing with tap water. The tissue sections were pretreated for 1 min, then stained with hematoxylin for 5 min, rinsed with tap water, differentiated with differentiation solution, rinsed with tap water, bluing with blue solution, rinsed with running water, dehydrated in 95% ethanol for 1 min, and stained with eosin for 15 s. The pathological changes in the gastric tissue were observed under an optical microscope and photographed.

[0056] 6. PAS staining of gastric tissue

[0057] The prepared tissue sections were stained with PAS staining solution B for 15 min, rinsed with tap water, rinsed twice with distilled water, then immersed in PAS staining solution A for 30 min, protected from light, and rinsed with running water for 5 min. Subsequently, they were stained with PAS staining solution C for 30 s, rinsed with tap water, differentiated with hydrochloric acid solution, rinsed with tap water, blued with ammonia solution, and rinsed with running water. Finally, they were dehydrated and cleared, and mounted with neutral resin. The gastric tissue sections were observed under an optical microscope, images were acquired, and the PAS staining results were statistically analyzed.

[0058] 7. Scanning electron microscopy observation

[0059] 1 mm 3After rinsing, the gastric tissue from both sides was fixed in electron microscopy fixative at room temperature for 2 h, and then transferred to 4℃ for storage. The fixed samples were rinsed three times with 0.1 mol / L phosphate-buffered saline (PBS, pH 7.4) for 15 min each time. Subsequently, the tissue was fixed in 1% osmium tetroxide (0.1 mol / L PBS, pH 7.4) at room temperature in the dark for 2 h. The tissue was then sequentially placed in 30%, 50%, 70%, 80%, 90%, 95%, and 100% ethanol for 15 min each time, followed by dehydration with isoamyl acetate for 15 min. The gastric tissue was dried using a critical point desiccator. The dried gastric tissue was then adhered tightly to a conductive carbon film double-sided adhesive and sputtered with gold for 30 s on an ion sputtering stage. Finally, the tissue was observed and images were acquired under a scanning electron microscope.

[0060] 8. Observation by transmission electron microscopy

[0061] Gastric tissue was fixed by immersing it in 2.5% glutaraldehyde at 4°C for 2 h. The fixed gastric tissue was then rinsed three times with 100 mmol / L sodium dimethylarsenate buffer. After rinsing, it was fixed again by immersing it in 1% osmium tetroxide at 4°C for 2 h. After rinsing three times with distilled water, it was dehydrated by different proportions of alcohol and acetone, embedded in epoxy resin, ultrathinly sectioned, and double-stained with lead and uranium to prepare gastric tissue sections with copper mesh. Ultramicroscopic images of the gastric tissue were observed and acquired under a transmission electron microscope.

[0062] 9. Immunofluorescence assay for the expression of phosphorylated Raf, MEK1 / 2, ERK1, IkBβ, IKKβ, and NF-κB proteins in gastric mucosa.

[0063] Immunofluorescence was used to detect the expression of phosphorylated Raf, MEK, ERK1, IkBβ, IKKβ, and NF-κB proteins in gastric mucosa. The specific method is as follows: Embedded gastric tissue blocks were dewaxed, and antigen retrieval was performed using EDTA antigen retrieval solution. After drying, the sections were circled around the tissue with an immunohistochemical pen, then placed flat in a light-protected humidified chamber and incubated at room temperature for 25 min with 3% hydrogen peroxide solution to block endogenous peroxidase. The sections were then placed flat in the light-protected humidified chamber and blocked with fetal bovine serum at room temperature for 30 min. Rabbit anti-phosphorylated Raf (Ser446) primary antibody (1:400), rabbit anti-phosphorylated MEK1 / 2 (Ser222) primary antibody (1:300), and rabbit anti-phosphorylated ERK1 (Thr197+) primary antibody were added to the samples. Rabbit anti-phosphorylated IkBβ primary antibody (1:400), rabbit anti-phosphorylated IKKβ primary antibody (1:300), rabbit anti-phosphorylated NF-κB (1:100), and rabbit anti-phosphorylated NF-κB (Ser337) primary antibody (1:400) were incubated overnight at 4°C. The primary antibodies were removed, and the gastric tissue sections were rinsed. HRP-labeled goat anti-rabbit secondary antibody was added to the samples, and the sections were incubated in the dark at room temperature for 1 h. The samples were then treated with the TSAPLus fluorescent three-label four-color staining kit to produce red, green, and yellow fluorescence. DAPI staining solution was added for counterstaining, and the sections were rinsed with PBS and mounted with anti-fluorescence quenching mounting medium. Six fields of view were randomly selected from each section, and the expression of phosphorylated Raf, MEK, ERK1, IkBβ, IKKβ, and NF-κB proteins in the gastric tissue was observed and photographed under a 100x inverted fluorescence microscope. Image Pro Plus 6.0 was used to analyze and calculate the average fluorescence intensity to evaluate the effect of the drug in Example 1 on the expression levels of various proteins in the gastric mucosa of GU rats with spleen and stomach deficiency and cold.

[0064] 10. Statistical Analysis

[0065] SPSS 24.0 software was used for statistical analysis of the data. Quantitative data conforming to a normal distribution were analyzed using... ±s represents the mean. One-way ANOVA was used for comparisons between groups, and the LSD method was used for multiple comparisons. P <0.05 indicates that the difference is statistically significant.

[0066] III. Experimental Results

[0067] 1. Effects on gastric mucosal morphology, UI, and TI in rats

[0068] The effects of each group on the gastric mucosal morphology of GU are as follows: Figure 1 As shown, by Figure 1It can be seen that the gastric mucosa of the normal group rats was smooth and intact, with no damage to the folds, and no edema, erosion, bleeding or ulceration was observed; the gastric mucosa of the model group rats was severely eroded, with multiple linear bleeding bands or patchy bleeding points, and thickened folds; compared with the model group, the degree of gastric ulceration in the rabeprazole group rats was significantly reduced; compared with the model group, the gastric mucosa of rats in each dose group of the drug in Example 1 was more intact, with fewer bleeding bands and bleeding points, among which the high dose group had the most obvious effect on repairing the damaged gastric mucosa of rats.

[0069] The effects of each group on the gastric mucosa UI and TI in rats are shown in Table 1.

[0070] Table 1. Effects of each group on UI and TI in rat gastric mucosa (i.e., +s, n=6)

[0071]

[0072] Note: ① Compared with the normal group, P <0.01; ② Compared with the model group, P <0.01. (Same as Tables 1-6)

[0073] Table 1 shows that the gastric mucosal ulcer index of the model group rats was significantly higher than that of the normal group ( P <0.01); After treatment with the drug in Example 1, the gastric mucosal ulcer index of rats was significantly reduced ( P <0.01). Further research revealed that the healing indices of the low, medium, and high dose groups of the drug in Example 1 were 77.81%, 88.02%, and 90.53%, respectively. These results indicate that the drug in Example 1 has a good therapeutic effect on GU of spleen and stomach deficiency-cold type, with the high dose group showing the most significant effect.

[0074] 2. HE staining was used to observe the effects of each group on the pathological morphological changes of the gastric mucosa in GU rats.

[0075] The results of HE staining observation on the pathological morphological changes of gastric mucosa in GU rats are shown in the figure. Figure 2As shown, the results indicated that the normal group rats had intact gastric mucosal structure and orderly glandular structure, with no epithelial cell shedding, inflammatory cell infiltration, or congestion points observed in any of the mucosal structural layers. The model group rats had incomplete gastric mucosal structure, disordered glandular arrangement, epithelial cell shedding, a large number of inflammatory cells infiltrating the submucosa, and vasodilation and congestion in the muscular layer. Compared with the model group, the rabeprazole group rats showed significantly reduced gastric mucosal structural damage, improved glandular disorder, and a small amount of inflammatory cell infiltration and reduced epithelial cell shedding. Compared with the model group, the rats in each dose group of the drug in Example 1 had relatively intact gastric mucosal structure, tightly arranged glands, and a small amount of epithelial cell shedding and inflammatory cell infiltration. Among them, the high-dose group showed almost no epithelial cell shedding, exhibiting the most significant effect.

[0076] 3. PAS staining was used to observe the effects of each group on gastric mucus secretion in GU rats.

[0077] The important protective layer of the gastric mucosal epithelium is the mucopolysaccharide in the mucus, which appears purplish-red after PAS staining. Therefore, PAS staining was used to detect the content of mucopolysaccharide on the surface of rat gastric mucosal cells, i.e., the number of purple spots. The effects of PAS staining on gastric mucus secretion in GU rats are shown in the figure below. Figure 3 As shown in Table 2, the results indicated that the mucus layer of the gastric tissue in the normal group rats showed strong positive staining with PAS; in the model group rats, a large number of epithelial cells were shed, the mucosal layer structure was severely damaged, PAS positivity basically disappeared, and the percentage of positive expression area was significantly reduced. P <0.01); Compared with the model group, the rabeprazole group and the drug dosage groups in Example 1 showed reduced epithelial cell shedding, more intact mucosal structure, and PAS staining showed a certain degree of positivity, with an increased percentage of positive expression area ( P <0.01).

[0078] Table 2. Statistical results of PAS staining of gastric tissue from GU rats in each group ( +s, n=3)

[0079]

[0080] 4. Effects of each group on gastric mucosal blood flow in GU rats

[0081] The effects of each group on gastric mucosal blood flow in GU rats are shown in Table 3. The results showed that, compared with the normal group, the gastric mucosal blood flow in the model group of GU rats was significantly reduced. P <0.01); Compared with the model group, the gastric mucosal blood flow in the rabeprazole group and each dose group of Example 1 was significantly increased, and the gastric mucosal blood flow in the low, medium and high dose groups of Example 1 gradually increased, with the high dose group showing the most significant effect ( P <0.01).

[0082] Table 3 Effects of each group on gastric mucosal blood flow in GU rats ( +s, n=6)

[0083]

[0084] 5. Effects of each group on serum oxidative stress in GU rats

[0085] The effects of each group on serum oxidative stress in GU rats are shown in Table 4. The results showed that, compared with the normal group, the serum CAT and SOD levels in the model group rats were significantly reduced. P <0.01), GST content increased significantly ( P <0.01); Compared with the model group, the CAT and SOD contents in the rabeprazole group and each dose group of the drug in Example 1 were significantly increased ( P <0.01), GST content decreased significantly ( P <0.01). The results also showed that in Example 1, the contents of CAT and SOD gradually increased and the contents of GST gradually decreased in the low, medium and high dose groups of the drug.

[0086] Table 4. Effects of each group on serum oxidative stress index levels in GU rats ( +s, n=6)

[0087]

[0088] 6. Effects of each group on serum inflammatory factor levels in GU rats

[0089] Table 5 shows that, compared with the normal group, the serum levels of inflammatory factors TNF-α, IL-18, and IL-1β in the model group rats were significantly increased. P <0.01); Compared with the model group, the levels of TNF-α, IL-18, and IL-1β in the rabeprazole group and each dose group of the drug in Example 1 were significantly reduced, and the levels of each index gradually decreased in the low, medium, and high dose groups of the drug in Example 1, with the high dose group showing the most significant effect ( P <0.01).

[0090] Table 5. Effects of each experiment on serum inflammatory factor levels in GU rats ( +s, n=6)

[0091]

[0092] 7. Scanning electron microscopy was used to observe the protective effects of each group on the gastric mucosa of GU rats.

[0093] like Figure 4Scanning electron microscopy results showed that the gastric mucosa structure of the normal group rats was intact, the epithelial cells were intact and no necrosis or shedding was observed, and the cell surface showed neatly arranged microvilli. The gastric mucosa structure of the model group rats was destroyed, the epithelial cells were extensively necrotic and shedding, and the arrangement was disordered, with no boundaries between cells and a reduction in cell surface microvilli. The gastric mucosa structure damage of the rabeprazole group and the drug dose groups of Example 1 rats was significantly reduced, the mucosal epithelial cells were intact and tightly arranged, the shedding and necrosis were reduced, and the cell surface microvilli were abundant and neatly arranged. Among them, the high dose group of drug in Example 1 showed the most obvious effect.

[0094] 8. Observe the protective effect of each group on the gastric mucosa of GU rats using transmission electron microscopy.

[0095] Figure 5 The results showed that the gastric mucosal epithelial cells of the normal group rats had intact structures, large and round nuclei, and intact mitochondrial structures; the gastric mucosal epithelial cells of the model group rats lacked integrity, mitochondria were swollen and membranes were lost, a large number of inflammatory cells and macrophages infiltrated, and local glands were destroyed; the mitochondrial damage of the rabeprazole group and the drug dose groups of Example 1 rats was reduced, the infiltration of inflammatory cells and macrophages was reduced, and the epithelial cell structure was restored to integrity, among which the high dose group of drug in Example 1 showed the most obvious effect.

[0096] 9. Effects of each group on the expression of phosphorylated Raf, MEK1 / 2, and ERK1 proteins in the gastric mucosa of GU rats

[0097] Figure 6 Immunofluorescence staining images of gastric mucosa from rats in each group are shown. Blue fluorescence indicates DAPI staining, red fluorescence indicates phosphorylated Raf protein expression, green fluorescence indicates phosphorylated MEK1 / 2 protein expression, and yellow fluorescence indicates phosphorylated ERK1 expression. Table 6 shows that compared with the normal group, the expression levels of Raf, MEK1 / 2, and ERK1 proteins in the gastric mucosa of rats in the model group were significantly increased. P <0.01); Compared with the model group, the expression levels of Raf, MEK1 / 2, and ERK1 proteins in the rabeprazole group and each dose group of the drug in Example 1 were significantly reduced ( P <0.01). The above results suggest at the protein level that the drug in Example 1 can treat GU with spleen and stomach deficiency-cold syndrome by regulating the MAPK signaling pathway.

[0098] Table 6. Effects of each group on the expression of phosphorylated Raf, MEK1 / 2, and ERK1 proteins in the gastric mucosa of GU rats ( +s, n=3)

[0099]

[0100] 10. Effects of each group on the expression of phosphorylated IkBβ, IKKβ, and NF-κB proteins in the gastric mucosa of GU rats

[0101] Figure 7 Immunofluorescence staining images of gastric mucosa from each group of rats are shown. Blue fluorescence indicates DAPI staining, red fluorescence indicates phosphorylated IkBβ protein expression, green fluorescence indicates phosphorylated IKKβ protein expression, and yellow fluorescence indicates phosphorylated NF-κB expression. Table 7 shows that, compared with the normal group, the expression levels of IkBβ, IKKβ, and p-NF-κB proteins in the gastric mucosa of rats in the model group were significantly increased. P <0.01); Compared with the model group, the expression levels of IkBβ, IKKβ, and p-NF-κB proteins in the rabeprazole group and each dose group of the drug in Example 1 were significantly reduced ( P <0.01). The above results suggest at the protein level that the drug in Example 1 can treat GU with spleen and stomach deficiency-cold syndrome by regulating the NF-κB signaling pathway.

[0102] Table 7. Effects of each group on the expression of phosphorylated IkBβ, IKKβ, and NF-κB proteins in the gastric mucosa of GU rats ( +s, n=3)

[0103]

[0104] The above results show that the expression of phosphorylated Raf, MEK1 / 2, ERK1, IkBβ, IKKβ, and NF-κB proteins in the gastric mucosa of GU rats with spleen and stomach deficiency and cold were significantly increased compared with the normal group. After intervention with the drug in Example 1, the phosphorylation of all the above proteins could be reduced, indicating that the MAPK and NF-κB signaling pathways are involved in mediating the effect of the drug in Example 1 in reducing gastric mucosal damage in GU rats with spleen and stomach deficiency and cold, mediating the effect of the drug in Example 1 in improving inflammatory response and oxidative stress in GU rats with spleen and stomach deficiency and cold, and mediating the effect of the drug in Example 1 in reversing the reduction of gastric mucosal blood flow in GU rats with spleen and stomach deficiency and cold. On the other hand, it also reveals that the repair of damaged gastric mucosa in GU rats with spleen and stomach deficiency and cold is related to the inhibition of MAPK and NF-κB signaling pathway activation.

[0105] The above method, combining "bitter and cold purgative + fatigue + indomethacin," was used to establish a GU rat model of spleen and stomach deficiency-cold type. Results showed that the model rats exhibited gastric mucosal damage including edema, hemorrhage, erosion, and ulceration, epithelial cell necrosis and shedding, extensive inflammatory cell infiltration, and reduced gastric mucosal blood flow. HE staining, PAS staining, scanning electron microscopy, and transmission electron microscopy all confirmed the successful establishment of the GU rat model of spleen and stomach deficiency-cold type. After drug intervention in Example 1, the pathological damage to the rat gastric mucosa was reduced, gastric mucosal blood flow increased, serum CAT and SOD levels increased, and GST, TNF-α, IL-18, and IL-1β levels decreased, with the most significant improvement observed in the high-dose group of Example 1. This indicates that the traditional Chinese medicine composition of the present invention can reduce the release of pro-inflammatory factors and enhance antioxidant enzyme activity, thereby inhibiting oxidative stress and inflammatory responses, and improving gastric mucosal damage and blood circulation.

[0106] In summary, the traditional Chinese medicine composition of the present invention has a significant intervention effect on GU rats with spleen and stomach deficiency and cold, reducing gastric mucosal structural damage and functional disorder in GU rats with spleen and stomach deficiency and cold, thereby promoting ulcer healing.

[0107] Example 3:

[0108] This embodiment describes the quality control of the traditional Chinese medicine composition in Example 1, and the specific methods include:

[0109] (1) Weigh out 10 g of white peony root, 10 g of atractylodes macrocephala, 10 g of tangerine peel, 10 g of vinegar-processed bupleurum root, 10 g of poria cocos, 6 g of licorice root, 10 g of stir-fried malt, 10 g of codonopsis pilosula, 10 g of lily bulb, 5 g of perilla leaf, 10 g of stir-fried bitter orange peel, and 6 g of dried ginger. Soak them in cold water for 30 minutes, then decoct them twice. The first decoction is for 40 minutes, and the amount of water used for decoction is 8 times the weight of the Chinese herbal components. The second decoction is for 30 minutes, and the amount of water used for decoction is 5 times the weight of the Chinese herbal components. Filter out and combine the decoctions.

[0110] (2) Take 20 mL of the drug solution into a centrifuge tube and centrifuge at 12,000 rpm for 10 min at 4℃. Accurately pipette 150 μL of the supernatant and add 500 μL of extract containing isotope-labeled internal standard (200 μL methanol, 200 μL acetonitrile, and 100 μL water). Centrifuge at 12,000 rpm for 10 min at 4℃, filter at 0.22 μm, and then place in a vial. The quality control of the traditional Chinese medicine composition was performed using Vanquish ultra-high performance liquid chromatography combined with Orbitrap Exploris 120 high-resolution mass spectrometry. The mobile phase was: Phase A: ultrapure water containing 0.01% acetic acid; Phase B: acetonitrile + isopropanol (volume ratio 1:1). The mass spectrometry spray voltage was 3.8 kV for positive ion mode and 3.4 kV for negative ion mode. The sheath gas flow rate and auxiliary gas flow rate were 50 and 15 Arb, respectively. The ion transmission tube temperature was 320℃. The full scan resolution was 60,000, the secondary mass spectrometry resolution was 15,000, and the collision energy was 30 V.

[0111] The results of quality control of traditional Chinese medicine compositions are as follows: Figure 8 As shown, 15 major active ingredients in the traditional Chinese medicine composition were identified by positive ion mode mass spectrometry and negative ion mode mass spectrometry. These ingredients are hesperidin, pamoate B, 2-amino-5-guanidinylvaleric acid, saikosaponin A, paeoniflorin, naringin, paeoniflorin lactone, codonopsis pilosula cyclic peptide B, rosmarinic acid, luteolin, atractylodes lactone I, glycyrrhizin, saikosaponin D, atractylodes lactone III, and 6-gingerol. Under the same conditions, the above 15 major active ingredients were identified in three repeated experiments.

[0112] The above results suggest that the traditional Chinese medicine composition in Example 1 has good stability and controllable quality.

[0113] Example 4:

[0114] This embodiment demonstrates through clinical practice that the traditional Chinese medicine composition of the present invention can effectively treat gastric ulcers of the spleen and stomach deficiency-cold type, eliminate gastric ulcer symptoms, improve the manifestations of spleen and stomach deficiency-cold syndrome, and significantly reduce the recurrence rate of ulcers, decrease the incidence of adverse reactions, and improve patient medication compliance. The traditional Chinese medicine composition of the present invention has good therapeutic effects on gastric ulcers of the spleen and stomach deficiency-cold type and has good clinical application value.

[0115] Case 1: Mr. Wang, male, 45 years old, first visit on March 13, 2012. The patient complained of intermittent stomach pain for three years. Western medicine diagnosed him with a gastric ulcer, and conventional Western medicine treatment had no significant improvement in his symptoms, so he came for consultation. Presenting with stomach pain, no acid reflux, preference for warmth and pressure, heaviness in the limbs, aversion to cold and cold extremities, fair appetite, bland taste in the mouth, loose stools, and sensitivity to spicy and cold foods. His tongue was pale with a white, slippery coating, and his pulse was deep, slow, and weak. The diagnosis was spleen and stomach deficiency-cold. Prescription: White peony root 15g, Atractylodes macrocephala 15g, Tangerine peel 10g, Vinegar-processed Bupleurum chinense 15g, Poria cocos 10g, Licorice root 8g, Fried malt 15g, Codonopsis pilosula 10g, Lilium brownii 15g, Perilla frutescens leaf 10g, Fried Citrus aurantium 12g, Dried ginger 8g. 14 doses, decocted in water, one dose per day, divided into two administrations. A year later, during a follow-up visit, all symptoms had healed and there had been no recurrence.

[0116] Case 2: Ms. Deng, female, 42 years old, first visit on February 16, 2013. The patient had been experiencing stomach pain for over a year. Western medicine diagnosed her with a gastric ulcer. After integrated traditional Chinese and Western medicine treatment, her symptoms did not improve significantly, so she sought medical attention. Symptoms included dull pain in the epigastric region, fatigue, poor appetite, abdominal distension, mild acid reflux, no heartburn, aversion to cold, cold limbs, and loose stools. Her tongue was pale with teeth marks, the coating was thin and white, and her pulse was deep, slow, and weak. Traditional Chinese medicine diagnosis was spleen and stomach deficiency-cold syndrome. Prescription: White peony root 10g, Atractylodes macrocephala 10g, Tangerine peel 10g, Vinegar-processed Bupleurum chinense 10g, Poria cocos 10g, Licorice root 6g, Fried malt 10g, Codonopsis pilosula 10g, Lilium brownii 10g, Perilla frutescens leaf 5g, Fried Citrus aurantium 10g, Dried ginger 6g. 21 doses, decocted in water, one dose per day, divided into two administrations. A follow-up visit after medication revealed that the patient's stomach pain had completely subsided and his appetite had returned to normal.

[0117] Case 3: Mr. Zhu, male, 40 years old, first visit on November 4, 2013. The patient complained of stomach pain for half a year. Western medicine diagnosed him with a gastric ulcer, but his symptoms did not improve significantly after conventional Western medicine treatment, so he came for consultation. His symptoms included stomach pain, fatigue and weakness in the limbs, cold extremities, decreased appetite, nausea and vomiting (vomitus containing clear water), abdominal distension, loose stools, and even undigested food in the stool. His tongue was pale with a white, slippery coating, and his pulse was deep, slow, and weak. The diagnosis was spleen and stomach deficiency-cold syndrome. Prescription: White peony root 15g, Atractylodes macrocephala 15g, Tangerine peel 12g, Vinegar-processed Bupleurum chinense 15g, Poria cocos 15g, Licorice root 8g, Fried malt 15g, Codonopsis pilosula 15g, Lilium brownii 15g, Perilla frutescens leaf 8g, Fried Citrus aurantium 12g, Dried ginger 8g. 14 doses, decocted in water, one dose per day, divided into two administrations. A year later, during a follow-up visit, all symptoms had healed and there was no recurrence.

[0118] Case 4: Mr. Zhang, male, 55 years old, first visit on April 23, 2014. The patient complained of epigastric pain for two and a half years, tested positive for Helicobacter pylori, and was diagnosed with gastric ulcer by Western medicine. He received conventional Western medicine treatment for over a year, but the pain continued to recur, so he came for consultation. His current symptoms included dull, persistent epigastric pain, mild acid reflux, loss of appetite, preference for warmth and pressure, heaviness and fatigue in the limbs, cold extremities, pale complexion, and a lack of taste in his mouth. His tongue was pale with a white, slippery coating, and his pulse was deep, slow, and weak. The diagnosis was spleen and stomach deficiency-cold syndrome. The prescription was: white peony root 15g, atractylodes macrocephala 12g, tangerine peel 10g, vinegar-processed bupleurum root 12g, poria cocos 10g, licorice root 8g, stir-fried malt 10g, codonopsis pilosula 10g, lily bulb 10g, perilla leaf 8g, stir-fried bitter orange peel 10g, dried ginger 6g. 14 doses, decocted in water, one dose per day, divided into two administrations. With the combined use of antibiotics and other Western medicines, the patient's Helicobacter pylori has been completely eradicated, and there is no stomach pain. The patient reported that the combination of traditional Chinese medicine and Western medicine significantly reduced adverse reactions such as nausea and vomiting.

[0119] Case 5: Ms. Lin, female, 25 years old, first visit on December 21, 2014. The patient complained of intermittent stomach pain for six months, severely affecting her daily work and life. Western medicine diagnosed her with Helicobacter pylori-associated gastric ulcer, but her symptoms did not improve significantly after treatment. She then sought medical attention. Currently, she experiences dull, persistent stomach pain that worsens with exertion, loss of appetite, fatigue, abdominal distension, accompanied by nausea and vomiting with clear phlegm. Her tongue is pale with teeth marks, and her pulse is deep, tight, and weak. The diagnosis is spleen and stomach deficiency-cold. Prescription: White peony root 10g, Atractylodes macrocephala 10g, Tangerine peel 10g, Vinegar-processed Bupleurum chinense 10g, Poria cocos 10g, Licorice root 6g, Fried malt 10g, Codonopsis pilosula 8g, Lilium brownii 8g, Perilla frutescens leaf 8g, Fried Citrus aurantium 8g, Dried ginger 5g. 14 doses, decocted in water, one dose per day, divided into two administrations, concurrently with Western medicine. One month later, during a follow-up visit, the patient's ulcer had healed, Helicobacter pylori was negative, and no adverse reactions occurred during the medication period; one year later, during a follow-up visit, the ulcer had not recurred.

[0120] Case 6: Ms. Li, female, 35 years old, first visit on November 12, 2015. The patient complained of recurrent stomach pain for a year. Western medicine diagnosed her with a gastric ulcer, but her symptoms did not improve significantly after treatment. She then sought medical attention. Current symptoms included stomach pain relieved by warmth and pressure, no acid reflux, worsening with negative emotions, abdominal distension, indigestion, weight loss, loose stools, and a pale complexion. Her tongue was pale with teeth marks, and her pulse was deep, tight, and weak. The diagnosis was spleen and stomach deficiency-cold syndrome. Prescription: White peony root 10g, Atractylodes macrocephala 10g, Tangerine peel 10g, Vinegar-processed Bupleurum chinense 10g, Poria cocos 10g, Licorice root 6g, Fried malt 10g, Codonopsis pilosula 10g, Lilium brownii 10g, Perilla frutescens leaf 5g, Fried Citrus aurantium 10g, Dried ginger 6g. 14 doses, decocted in water, one dose daily, divided into two administrations. A one-year follow-up showed that all symptoms had resolved and there was no recurrence.

[0121] Case 7: Mr. Jiang, male, 42 years old, first visit on March 7, 2016. The patient complained of recurrent stomach pain for one year. Western medicine diagnosed him with a gastric ulcer and he was given conventional Western medicine treatment, but there was no significant improvement. He then came for consultation. His current symptoms included stomach pain relieved by warmth and pressure, cold extremities, poor appetite, loose stools, and significant aggravation after consuming cold foods. His tongue was pale with a white, slippery coating, and his pulse was deep, tight, and weak. The diagnosis was spleen and stomach deficiency-cold syndrome. Prescription: White peony root 10g, Atractylodes macrocephala 10g, Tangerine peel 10g, Vinegar-processed Bupleurum chinense 10g, Poria cocos 10g, Licorice root 6g, Fried malt 10g, Codonopsis pilosula 10g, Lilium brownii 10g, Perilla frutescens leaf 5g, Fried Citrus aurantium 10g, Dried ginger 6g. 14 doses, decocted in water, one dose per day, divided into two administrations. The patient had a follow-up visit on March 21, 2016. After diagnosis, the patient was given the same prescription. A follow-up visit one year later showed that all symptoms had disappeared and there had been no recurrence.

[0122] Case 8: Mr. Chen, male, 38 years old, first visit on November 16, 2016. The patient complained of stomach pain for more than two years. Western medicine diagnosed him with a gastric ulcer. After integrated traditional Chinese and Western medicine treatment, the pain persisted, recurring frequently and severely affecting his daily work and life. He then sought medical attention. His current symptoms included cold pain in the stomach, without acid reflux or heartburn, fatigue, heaviness in the limbs, poor appetite, bland taste in the mouth without thirst, and loose stools. His tongue was pale with teeth marks, and his pulse was deep, slow, and weak. The diagnosis was spleen and stomach deficiency-cold syndrome. Prescription: White peony root 20g, Atractylodes macrocephala 15g, Tangerine peel 15g, Vinegar-processed Bupleurum chinense 15g, Poria cocos 10g, Licorice root 8g, Fried malt 15g, Codonopsis pilosula 15g, Lilium brownii 15g, Perilla frutescens leaf 10g, Fried Citrus aurantium 15g, Dried ginger 8g. 21 doses, decocted in water, one dose per day, divided into two administrations. A year later, during a follow-up visit, all symptoms had disappeared and there was no recurrence.

[0123] Case 9: Ms. Zhou, female, 47 years old, first visit on February 20, 2017. The patient complained of epigastric pain for one and a half years, with intermittent attacks. Western medicine diagnosed her with a gastric ulcer, but treatment failed to cure it, prompting her to seek medical attention. Presenting symptoms included epigastric pain relieved by warmth and pressure, cold extremities, pale complexion, abdominal distension, decreased appetite, loose stools, aversion to cold foods, and anxiety. Her tongue was pale with a white, slippery coating, and her pulse was deep, slow, and weak. The diagnosis was spleen and stomach deficiency-cold syndrome. Prescription: White peony root 15g, Atractylodes macrocephala 15g, Tangerine peel 15g, Vinegar-processed Bupleurum chinense 15g, Poria cocos 10g, Licorice root 8g, Fried malt 10g, Codonopsis pilosula 15g, Lilium brownii 15g, Perilla frutescens leaf 10g, Fried Citrus aurantium 15g, Dried ginger 8g. 21 doses, decocted in water, one dose per day, divided into two administrations. A year later, during a follow-up visit, all symptoms had subsided and did not recur.

[0124] Case 10: Ms. He, female, 33 years old, first visit on November 5, 2017. The patient complained of stomach pain for two years. Western medicine diagnosed her with a gastric ulcer. Despite conventional Western medicine treatment, the pain recurred repeatedly and was persistent. She then sought medical attention. Presenting with stomach pain, no significant acid reflux, aversion to cold, cold limbs, pale complexion, poor appetite, abdominal distension with abdominal pain, loose stools, preference for warmth and aversion to cold. Her tongue was pale with a thin white coating, and her pulse was deep, slow, and weak. The diagnosis was spleen and stomach deficiency-cold syndrome. Prescription: White peony root 15g, Atractylodes macrocephala 15g, Tangerine peel 12g, Vinegar-processed Bupleurum chinense 12g, Poria cocos 10g, Licorice root 8g, Fried malt 12g, Codonopsis pilosula 15g, Lilium brownii 15g, Perilla frutescens leaf 8g, Fried Citrus aurantium 12g, Dried ginger 8g. 21 doses, decocted in water, one dose per day, divided into two administrations. A year later, during a follow-up visit, all symptoms had healed and there was no recurrence.

[0125] The technical solutions of the present invention have been described in detail above with reference to the embodiments / drawings. However, the present invention is not limited to the above technical solutions. For those skilled in the art, after learning the contents described in the present invention, several equivalent changes and substitutions can be made without departing from the principle of the present invention. These equivalent changes and substitutions should also be considered to fall within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition for treating gastric ulcers of spleen and stomach deficiency-cold type, characterized in that, It is composed of the following components by weight: white peony root 5-20 parts, atractylodes macrocephala 5-20 parts, tangerine peel 5-20 parts, bupleurum chinense 5-20 parts, poria cocos 5-20 parts, licorice root 2-8 parts, malt 5-20 parts, codonopsis pilosula 5-20 parts, lily bulb 5-20 parts, perilla leaf 2-10 parts, immature bitter orange peel 5-20 parts, and dried ginger 2-8 parts.

2. The traditional Chinese medicine composition for treating gastric ulcers of spleen and stomach deficiency-cold type as described in claim 1, characterized in that, It is composed of the following components by weight: 8-20 parts white peony root, 8-15 parts atractylodes macrocephala, 8-15 parts tangerine peel, 8-15 parts bupleurum root, 8-15 parts poria cocos, 4-8 parts licorice root, 8-15 parts malt, 8-15 parts codonopsis pilosula, 8-15 parts lily bulb, 4-10 parts perilla leaf, 8-15 parts immature bitter orange peel, and 4-8 parts dried ginger.

3. The traditional Chinese medicine composition for treating gastric ulcers of spleen and stomach deficiency-cold type as described in claim 1, characterized in that, It is composed of the following components by weight: 10 parts white peony root, 10 parts atractylodes macrocephala, 10 parts tangerine peel, 10 parts bupleurum, 10 parts poria cocos, 6 parts licorice root, 10 parts malt, 10 parts codonopsis pilosula, 10 parts lily bulb, 5 parts perilla leaf, 10 parts immature bitter orange peel, and 6 parts dried ginger.

4. The traditional Chinese medicine composition for treating gastric ulcers of spleen and stomach deficiency-cold type as described in any one of claims 1 to 3, characterized in that, The Bupleurum is vinegar-processed Bupleurum, the malt is stir-fried malt, and the Citrus aurantium is stir-fried Citrus aurantium with wheat bran.

5. The traditional Chinese medicine composition for treating gastric ulcers of spleen and stomach deficiency-cold type as described in any one of claims 1 to 3, characterized in that, The dosage form of the traditional Chinese medicine composition includes any one of the following: decoction, paste, tablet, capsule, pill, granule, and powder.

6. A method for preparing a traditional Chinese medicine composition for treating gastric ulcers of spleen and stomach deficiency-cold type as described in any one of claims 1 to 5, characterized in that, Includes the following steps: Weigh out the prescribed amounts of each Chinese herbal medicine component, soak and decoct them, combine the filtrates, then heat and concentrate them, and cool them to complete the preparation of the Chinese herbal medicine composition for treating gastric ulcers.

7. The preparation method according to claim 6, characterized in that, Soak in cold water for 20-40 minutes. The decoction process includes at least two decoctions: the first decoction for 30-50 minutes and the second decoction for 20-40 minutes.

8. The preparation method according to claim 6, characterized in that, The process involves heating and concentrating the solution until the concentration reaches 0.8-1.2 g / mL.

9. The use of a traditional Chinese medicine composition for treating gastric ulcer of spleen and stomach deficiency-cold type as described in any one of claims 1 to 5 in the preparation of a drug for treating gastric ulcer of spleen and stomach deficiency-cold type.

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