A pharmaceutical composition for treating helicobacter pylori positive chronic atrophic gastritis and application thereof

Abstract

The application discloses a kind of drug composition for treating helicobacter pylori positive chronic atrophic gastritis and application thereof, it is related to Chinese medicine and national medicine technical field, drug composition is by Yi medicine roasted black buckwheat tea and Xiangsha Liujunzi decoction of separate packing composition, in use combined administration;Xiangsha Liujunzi decoction is made from the following weight parts of raw medicinal materials: 15 parts of Dangshen, 10 parts of Baizhu, 15 parts of Fuling, 12 parts of Chenpi, 15 parts of Zhishanxia, 10 parts of Guangmuxiang, 10 parts of Sharen, 6 parts of Zhigancao.Compared with Xiangsha Liujunzi decoction alone, the composition can significantly reduce the level of inflammatory factors (IL-6, IL-1β, TNF-α), increase the level of anti-inflammatory factor IL-10, reduce oxidative stress (MDA), improve the activity of antioxidant enzymes (SOD, GSH-Px), significantly improve the pathological inflammation of gastric mucosa, effectively promote the recovery of gastric mucosa function (serum pepsinogen ratio is significantly increased), and significantly reduce endoscopic score.

Description

Technical Field

[0001] This invention relates to the fields of traditional Chinese medicine and ethnic medicine, specifically to a composition of Yi medicine-processed black buckwheat tea and the traditional Chinese medicine compound Xiangsha Liujunzi Decoction, and its novel use in the preparation of drugs for treating Helicobacter pylori (Hp) positive chronic atrophic gastritis (CAG). Background Technology

[0002] Chronic atrophic gastritis (CAG) is a common precancerous lesion of gastric cancer, especially when combined with Helicobacter pylori (Hp) infection, the risk of cancerous transformation is significantly increased. Currently, Western medicine routinely uses quadruple therapy to eradicate Hp, but it faces problems such as high antibiotic resistance rates, intestinal flora imbalance, and high recurrence rates. For existing gastric mucosal atrophy and intestinal metaplasia, there is still a lack of universally recognized and effective drugs to reverse them.

[0003] Traditional Chinese medicine (TCM) treatment for chronic atrophic gastritis (CAG) has advantages in holistic regulation and multi-target therapy. Xiangsha Liujunzi Decoction, originating from *Ancient and Modern Famous Physicians' Prescriptions*, is a classic formula for treating stomach pain due to spleen and stomach deficiency, possessing the effects of tonifying qi and strengthening the spleen, promoting qi circulation and resolving stagnation. Clinical studies have shown that it can improve the symptoms and some pathological indicators of CAG patients and significantly reduce the levels of inflammatory factors, but there is still room for improvement in its ability to reverse atrophy, rapidly improve inflammation, and resist oxidative stress.

[0004] Black tartary buckwheat (Fagopyrum tataricum (L.) Gaertn.) is a signature medicinal and edible plant of Liangshan Yi Autonomous Prefecture. Yi medicine theory holds that it has the effects of "relieving stagnation and intestinal congestion." Modern research confirms that black tartary buckwheat is rich in flavonoids (such as rutin and quercetin), which have strong antioxidant, anti-inflammatory, and gastric mucosal protective effects. Studies have shown that under conditions of gastric mucosal damage, tartary buckwheat extract can significantly reduce oxidative stress damage to the gastric mucosa through its antioxidant activity, exerting a significant gastric mucosal protective effect; its active ingredients, such as rutin and quercetin, can be effectively released during gastric digestion, further exerting local antioxidant and mucosal protective effects.

[0005] Serum pepsinogen (PG) is an important biomarker reflecting the functional status of the gastric mucosa. PGⅠ is mainly secreted by the chief cells of the fundic glands, while PGⅡ is jointly secreted by the fundic glands (fundus and body), cardiac glands, pyloric glands, and Brunner's gland cells of the duodenum, with a more extensive secretory area than PGⅠ. When fundic glands atrophy, the number of chief cells secreting PGⅠ decreases, and PGⅠ levels drop significantly; however, because the cell population secreting PGⅡ is more dispersed, PGⅡ levels are less affected by atrophy and can still maintain relatively high levels, leading to a significant decrease in the PGⅠ / PGⅡ ratio (PGR). Therefore, PGⅠ and PGR are considered reliable markers of gastric body atrophy. The OLGA and OLGIM staging systems are currently internationally recognized important pathological evaluation standards for assessing the degree of gastric mucosal atrophy and the risk of gastric cancer. In the treatment of CAG, the recovery of gastric mucosal function is initially manifested in the structural repair of the chief cells of the fundic glands and the recovery of PGⅠ secretory function, while the overall resolution of inflammation in the gastric mucosa and the resulting further decrease in PGⅡ may require a longer intervention period.

[0006] However, there are currently no reports of combining black buckwheat with Xiangsha Liujunzi Decoction for the treatment of Hp-positive CAG and its precancerous lesions. Summary of the Invention

[0007] Given the limitations of existing drugs in terms of efficacy and the difficulty in reversing pathological changes, the present invention aims to provide a pharmaceutical composition for treating Helicobacter pylori-positive chronic atrophic gastritis and its application. This composition, through the combined use of black buckwheat and Xiangsha Liujunzi Decoction, significantly enhances the multi-dimensional efficacy of gastric mucosa, including improvement of inflammation, antioxidant capacity, pathological reversal, functional recovery, and endoscopic repair.

[0008] This invention is achieved through the following technical solution:

[0009] This application provides a pharmaceutical composition for treating Helicobacter pylori-positive chronic atrophic gastritis. The pharmaceutical composition consists of separately packaged Yi medicine roasted black buckwheat tea and Xiangsha Liujunzi Decoction, which are administered together when used. The Xiangsha Liujunzi Decoction is made from the following raw materials in parts by weight: Codonopsis pilosula 15 parts, Atractylodes macrocephala 10 parts, Poria cocos 15 parts, Citrus reticulata peel 12 parts, processed Pinellia ternata 15 parts, Aucklandia lappa 10 parts, Amomum villosum 10 parts, and processed Glycyrrhiza uralensis 6 parts.

[0010] The mechanism of action of this invention lies in the following: Xiangsha Liujunzi Decoction improves spleen and stomach weakness by invigorating qi and strengthening the spleen, and regulating systemic immune function; Yi medicinal black buckwheat tea, rich in flavonoids (rutin, quercetin, etc.), scavenges local oxygen free radicals in the gastric mucosa through its powerful antioxidant effect, reduces oxidative stress damage, and improves the inflammatory microenvironment of the gastric mucosa. The combined use of these two herbs allows Xiangsha Liujunzi Decoction to regulate immune function and improve spleen and stomach function at a systemic level, while black buckwheat tea exerts antioxidant, anti-inflammatory, and protective effects at the local gastric mucosa level, forming a synergistic treatment model of "systemic regulation + local repair." This results in a synergistic effect superior to single-drug therapy in multiple dimensions, including inflammation improvement, oxidative stress reduction, and gastric mucosal function recovery.

[0011] Furthermore, the daily dosage of the Yi medicine-processed black buckwheat tea is 3-5 grams.

[0012] Furthermore, the use of the pharmaceutical composition for treating Helicobacter pylori-positive chronic atrophic gastritis includes the preparation of a drug for treating Helicobacter pylori-positive chronic atrophic gastritis.

[0013] Furthermore, the therapeutic effect was achieved through the synergistic effect of Yi medicine-processed black buckwheat tea and Xiangsha Liujunzi Decoction.

[0014] Furthermore, the application of the pharmaceutical composition for treating Helicobacter pylori-positive chronic atrophic gastritis also includes the preparation of a drug for reducing the pathological inflammation score of the gastric mucosa.

[0015] Furthermore, the application of the pharmaceutical composition for treating Helicobacter pylori-positive chronic atrophic gastritis also includes the preparation of a drug for increasing serum pepsinogen I levels and the PG I / PG II ratio, and promoting the recovery of gastric mucosal function.

[0016] Furthermore, the application of the pharmaceutical composition for treating Helicobacter pylori-positive chronic atrophic gastritis also includes the preparation of drugs for downregulating the levels of pro-inflammatory factors IL-6, IL-1β, and TNF-α and for upregulating the level of anti-inflammatory factor IL-10.

[0017] Furthermore, the application of the pharmaceutical composition for treating Helicobacter pylori-positive chronic atrophic gastritis also includes the preparation of drugs for reducing the oxidative stress product malondialdehyde and for increasing the activities of superoxide dismutase and glutathione peroxidase.

[0018] Furthermore, the use of the pharmaceutical composition for treating Helicobacter pylori-positive chronic atrophic gastritis also includes its use in the preparation of a medicament for improving endoscopic gastric mucosal lesions; the endoscopic gastric mucosal lesions include mucosal erythema, erosion, and / or bleeding.

[0019] Furthermore, the use of the pharmaceutical composition for treating Helicobacter pylori-positive chronic atrophic gastritis also includes the preparation of a drug for reversing gastric mucosal atrophy and / or intestinal metaplasia.

[0020] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0021] (1) The combination of Yi medicine-processed black buckwheat tea and Xiangsha Liujunzi Decoction in this embodiment of the invention can significantly downregulate the levels of pro-inflammatory factors (IL-6, IL-1β, TNF-α) and upregulate the level of anti-inflammatory factor IL-10, thereby improving the inflammatory microenvironment. After treatment, the IL-10 level in the WDB group increased by 130.5%, and the TNF-α level decreased by 56.7%. Moreover, the improvement of all inflammatory indicators showed a strict gradient trend of WDB group > WD group > WMT group. This result confirms the effective improvement of gastric mucosal inflammation by combined medication at the molecular mechanism level.

[0022] (2) The Yi medicine-processed black buckwheat tea combined with Xiangsha Liujunzi Decoction in the embodiments of the present invention can significantly reduce the oxidative stress product MDA, increase the activity of antioxidant enzymes SOD and GSH-Px, and enhance antioxidant capacity (supplementary synergistic effect). The reduction value of MDA in the WDB group (4.56±1.02 nmol / mL) was significantly higher than that in the WD group (3.89±0.98 nmol / mL) and the WMT group (2.56±0.89 nmol / mL); the increase in SOD and GSH-Px also showed a gradient trend of WDB group > WD group > WMT group. This confirms that black buckwheat has a clear supplementary synergistic effect on the antioxidant function of Xiangsha Liujunzi Decoction, that is, the addition of black buckwheat further enhances the original antioxidant capacity of Xiangsha Liujunzi Decoction.

[0023] (3) The combination of Yi medicine-processed black buckwheat tea and Xiangsha Liujunzi Decoction in the embodiments of the present invention can significantly improve the pathological damage of gastric mucosa. The improvement rate of pathological inflammation score reached 75.82%, which was significantly better than that of the WD group (49.75%) and the WMT group (30.31%). In terms of OLGA / OLGIM staging, the downstaging rate of the WDB group (30% / 20%) was higher than that of the WD group (20% / 10%) and the WMT group (10% / 0%), which confirms that the combined drug has the potential to reverse gastric mucosal atrophy and intestinal metaplasia.

[0024] (4) The combination of Yi medicine-processed black buckwheat tea and Xiangsha Liujunzi Decoction in the embodiments of the present invention can promote the recovery of gastric mucosal function and significantly increase serum pepsinogen I (PGⅠ) level and PGⅠ / PGⅡ ratio (PGR). After treatment, PGⅠ in the WDB group increased by 14.16±4.90 μg / L and PGR increased by 66.2%, which was significantly better than that in the WD group (9.15±4.85 μg / L, 48.1%) and the WMT group (-6.42±4.79 μg / L, 6.7%), indicating that the combined drug can effectively promote the functional recovery of chief cells and parietal cells of the gastric mucosa.

[0025] (5) The combination of Yi medicine-processed black buckwheat tea and Xiangsha Liujunzi Decoction in the embodiments of the present invention can improve endoscopic mucosal lesions and significantly reduce endoscopic scores such as mucosal erythema, erosion, and bleeding. The differences between groups were statistically significant after Bonferroni correction (P<0.017). This result further confirms the repair effect of the combined drug on gastric mucosal damage from a macroscopic morphological perspective.

[0026] (6) The combination of Yi medicine stir-fried black buckwheat tea and Xiangsha Liujunzi Decoction in the embodiments of the present invention can produce significant effects in multiple dimensions such as inflammation, oxidative stress, histopathology, gastric mucosal function and endoscopic morphology under a short-term intervention of 1.5 months. Its overall efficacy in treating CAG is significantly better than Xiangsha Liujunzi Decoction alone. Attached Figure Description

[0027] To more clearly illustrate the technical solutions of the exemplary embodiments of the present invention, the accompanying drawings used in the embodiments will be briefly described below. It should be understood that the following drawings only show some embodiments of the present invention and should not be considered as a limitation of the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort. In the drawings:

[0028] Figure 1 This is a flowchart of the CONSORT process for clinical trials in this embodiment of the invention;

[0029] Figure 2 This is a comparative graph showing the improvement rates of gastric mucosal inflammation scores and pathological scores in different groups of patients in this embodiment of the invention. A. Inflammation score; B. Improvement rate of inflammation score; C. Pathological score; D. Improvement rate of pathological score; Compared with before treatment, a P<0.017; compared with the WMT group, b P<0.017; compared with the WD group, c P<0.017 (Bonferroni correction);

[0030] Figure 3This is a comparison chart of serum pepsinogen-related indicators in each group of patients in this embodiment of the invention; where A. Serum PGⅠ level before and after treatment (μg / L); B. Serum PGⅡ level before and after treatment (μg / L); C. PGR ratio before and after treatment; D. Percentage increase in PGR (%); compared with before treatment in this group, a P<0.017; compared with the WMT group, b P<0.017; compared with the WD group, c P<0.017 (Bonferroni correction);

[0031] Figure 4 This is a comparative graph showing the improvement of serum inflammatory cytokine indicators in different groups of patients in this invention embodiment; where A. Decrease in interleukin-6 (IL-6) (pg / mL); B. Decrease in interleukin-1β (IL-1β) (pg / mL); C. Decrease in tumor necrosis factor-α (TNF-α) (pg / mL); D. Increase in interleukin-10 (IL-10) (pg / mL); compared with the pre-treatment values ​​in this group, aP<0.017; compared with the WMT group, bP<0.017; compared with the WD group, cP<0.017 (Bonferroni correction);

[0032] Figure 5 This is a comparative graph showing the improvement of serum oxidative stress markers in different groups of patients in this invention embodiment, where A. malondialdehyde (MDA) decrease (nmol / mL); B. superoxide dismutase (SOD) increase (U / mL); C. glutathione peroxidase (GSH-Px) increase (U / mL); These values ​​represent the comparison before treatment in this group. a P<0.017; compared with the WMT group, b P<0.017; compared with the WD group, c P<0.017 (Bonferroni correction). Detailed Implementation

[0033] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the embodiments. The illustrative embodiments and descriptions of this invention are only used to explain this invention and are not intended to limit this invention.

[0034] In the following description, numerous specific details are set forth in order to provide a thorough understanding of the invention. However, it will be apparent to those skilled in the art that these specific details are not necessary to practice the invention. In other embodiments, well-known materials or methods have not been specifically described in order to avoid obscuring the invention.

[0035] Throughout this specification, references to "an embodiment," "an example," or "an example" mean that a particular feature, structure, or characteristic described in connection with that embodiment or example is included in at least one embodiment of the invention. Therefore, the phrases "an embodiment," "an example," "an example," or "an example" appearing in various places throughout the specification do not necessarily refer to the same embodiment or example. Furthermore, specific features, structures, or characteristics can be combined in one or more embodiments or examples in any suitable combination and / or sub-combination. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items. Moreover, without contradiction, those skilled in the art can combine and integrate the different embodiments or examples described herein, as well as the features of those different embodiments or examples.

[0036] The "range" disclosed in this application is defined by a lower limit and an upper limit. A given range is defined by selecting a lower limit and an upper limit, which define the boundaries of a particular range. Ranges defined in this way can include or exclude endpoints and can be arbitrarily combined; that is, any lower limit can be combined with any upper limit to form a range. For example, if ranges of 60–120 and 80–110 are listed for a specific parameter, it is understood that ranges of 60–110 and 80–120 are also expected. Furthermore, if minimum range values ​​of 1 and 2 are listed, and if maximum range values ​​of 3, 4, and 5 are listed, then the following ranges are all expected: 1–3, 1–4, 1–5, 2–3, 2–4, and 2–5. In this application, unless otherwise stated, the numerical range "a–b" represents a shortened representation of any combination of real numbers between a and b, where a and b are real numbers. For example, the numerical range "0~5" indicates that all real numbers between "0~5" have been listed in this article; "0~5" is simply a shortened representation of these numerical combinations. Furthermore, when a parameter is stated as an integer ≥2, it is equivalent to disclosing that the parameter is, for example, an integer such as 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, etc.

[0037] Unless otherwise specified, all steps in this application may be performed sequentially or randomly, preferably sequentially. For example, the method includes steps (a) and (b), indicating that the method may include steps (a) and (b) performed sequentially, or it may include steps (b) and (a) performed sequentially. For example, the method may also include step (c), indicating that step (c) may be added to the method in any order. For example, the method may include steps (a), (b), and (c), or it may include steps (a), (c), and (b), or it may include steps (c), (a), and (b), etc.

[0038] Example 1

[0039] This embodiment provides the application of a Yi medicine-processed black buckwheat tea combined with Xiangsha Liujunzi Decoction in the preparation of a drug for treating Helicobacter pylori-positive chronic atrophic gastritis. The Yi medicine-processed black buckwheat tea combined with Xiangsha Liujunzi Decoction is composed of separately packaged Yi medicine-processed black buckwheat tea and Xiangsha Liujunzi Decoction.

[0040] The preparation method of Yi medicine roasted black buckwheat tea is as follows: High-quality black buckwheat seeds from Liangshan are taken, washed, dried, and roasted (160-180℃, 5-8 minutes) until the surface turns yellowish-brown and a burnt aroma is emitted. The seeds are then pulverized through a 20-mesh sieve and packaged in 3-5 gram packets to obtain Yi medicine roasted black buckwheat tea. The inventors discovered through experiments that when the roasting temperature is below 160℃, the dissolution rate of flavonoids in black buckwheat is low, and the antioxidant activity is not fully released; when the temperature is above 180℃, some flavonoid components may undergo thermal decomposition, reducing their activity. Roasting time less than 5 minutes results in insufficient roasting, while more than 8 minutes easily produces a burnt taste and leads to the loss of active ingredients. Therefore, choosing roasting conditions of 160℃-180℃ for 5-8 minutes can ensure the effective release of active ingredients while obtaining good sensory quality.

[0041] The preparation method of Xiangsha Liujunzi Decoction is as follows: Weigh out 15g of Codonopsis pilosula, 10g of Atractylodes macrocephala, 15g of Poria cocos, 12g of Citrus reticulata peel, 15g of processed Pinellia ternata, 10g of Aucklandia lappa, 10g of Amomum villosum, and 6g of Glycyrrhiza uralensis (processed). Add 10 times the amount of water (about 1200mL), soak for 30 minutes, bring to a boil over high heat, then simmer over low heat for 30 minutes, and filter out the liquid. Add 8 times the amount of water (about 960mL) to the dregs, and simmer in the same way for 20 minutes. Combine the two liquids, concentrate to about 300mL, and take in two divided doses.

[0042] Example 2

[0043] This clinical trial is an exploratory and prospective study with a small sample size (10 cases per group), aiming to preliminarily verify the efficacy and safety of the composition of this invention. Further large-sample, multi-center randomized controlled trials will be conducted to further verify this. The clinical trial will verify the Yi medicine-processed black buckwheat tea combined with Xiangsha Liujunzi Decoction, prepared using the method of Example 1. The clinical trial procedure is as follows: Figure 1 As shown.

[0044] 1. Research Subjects

[0045] Thirty patients with spleen and stomach deficiency syndrome and Hp-positive chronic atrophic gastritis admitted to the Liangshan Prefecture Integrated Traditional Chinese and Western Medicine Hospital were included in this study. They were randomly divided into three groups of 10 patients each using a random number table. All patients signed informed consent forms.

[0046] 2. Diagnostic criteria

[0047] Western medicine diagnostic criteria: The diagnosis was confirmed by gastroscopy and pathological biopsy, referring to the "Consensus Opinion on the Diagnosis and Treatment of Chronic Atrophic Gastritis by Integrated Traditional Chinese and Western Medicine (2017)".

[0048] Traditional Chinese Medicine diagnostic criteria: Spleen and stomach deficiency syndrome, main symptoms: abdominal distension or dull stomach pain, fatigue and weakness, and discomfort in the stomach after meals; accompanying symptoms: poor appetite, loose stools, cold limbs, and lethargy.

[0049] Hp infection criteria: 14 C-urea breath test positive (no antibiotics, PPIs, or bismuth preparations used in the two weeks prior to the test).

[0050] 3. Grouping and Treatment Methods

[0051] WMT group (control group): Received standard quadruple therapy (amoxicillin + clarithromycin + proton pump inhibitor + bismuth, 14 days) and oral placebo (200 mL warm water, bid) for 1.5 months.

[0052] WD group (Xiangsha Liujunzi Decoction group): On the basis of quadruple therapy, Xiangsha Liujunzi Decoction (prepared according to Example 1, 1 dose per day, orally divided into 2 doses) was added for continuous treatment for 1.5 months.

[0053] WDB group (the composition group of the present invention): Based on the WD group, Yi medicine stir-fried black buckwheat tea (prepared according to Example 1, 1 bag per day, brewed with 200mL of warm water) was added for continuous treatment for 1.5 months.

[0054] 4. Observation indicators and results

[0055] Statistical analysis: SPSS 26.0 software was used for statistical analysis. Quantitative data were expressed as mean ± standard deviation (x̄±s). One-way ANOVA was used for comparisons between groups, and LSD-t test was used for pairwise comparisons. Due to the involvement of multiple comparisons among three groups (WDB vs WMT, WD vs WMT, WDB vs WD), the Bonferroni method was used to adjust for significance; after adjustment, α = 0.017. P < 0.017 was considered statistically significant. Chi-square test was used for categorical data, and Mann-Whitney U test was used for ordinal data.

[0056] 4.1. Comparison of Hp eradication rates

[0057] As shown in Table 1, the eradication rate of the WDB group was 100% (10 / 10), which was higher than that of the WMT group (70%, P=0.026), but after Bonferroni correction (α=0.017), the difference was not statistically significant; the eradication rate of the WD group was 90% (9 / 10), which was not significantly different from that of the WDB group and the WMT group (P=0.500, P=0.291).

[0058] Table 1 Comparison of Hp eradication rates (eradication rate, %)

[0059]

[0060] Note: After Bonferroni correction, α = 0.017, and P ≥ 0.017 is considered not statistically significant.

[0061] 4.2. Comparison of Kimura-Takemoto classification and endoscopic scoring

[0062] The extent of gastric mucosal atrophy (Kimura-Takemoto classification) did not show a significant improvement trend in the three groups of patients. Endoscopic scores in all three groups were significantly lower after treatment than before treatment (P<0.017). The WD group showed a significantly higher reduction than the WMT group; the WDB group showed the most significant reduction, and the differences between groups remained statistically significant after Bonferroni correction (P<0.017). See Table 2 for details.

[0063] Table 2 Comparison of endoscopic scores (x̄±s, points)

[0064]

[0065] Note: Bonferroni correction was used, and P < 0.017 was considered statistically significant; aP < 0.017 vs. pre-treatment in this group; bP < 0.017 vs. WMT group; cP < 0.017 vs. WD group.

[0066] 4.3. Comparison of improvements in gastric mucosal pathology

[0067] After 1.5 months of treatment, the three groups showed differences in the dimensions and extent of improvement in gastric mucosal pathological changes. Regarding pathological inflammatory markers (Table 3 and...),... Figure 2 Compared with pre-treatment levels, the inflammation scores of all three groups decreased after treatment, with statistically significant differences (P<0.017). The improvement rate of inflammation score in the WDB group (75.82±2.345%) was significantly higher than that in the WD group (49.75±2.456%, P=0.002) and the WMT group (30.31±2.567%, P<0.001). The WD group was also significantly better than the WMT group (P=0.002). These differences remained significant after Bonferroni correction (α=0.017). See Table 3 and... Figure 2 As shown, the improvement in total pathological score exhibited a ranking between groups that was completely consistent with inflammatory changes, with statistically significant differences (P<0.017). These results suggest that the combination of buckwheat and Xiangsha Liujunzi Decoction can significantly enhance the anti-inflammatory efficacy of quadruple therapy, and is superior to the independent therapeutic value of Xiangsha Liujunzi Decoction.

[0068] Regarding the indicators of pathological structural changes in the gastric mucosa (atrophy and intestinal metaplasia), the efficacy showed a similar trend, but did not reach a statistically significant level (Table 4). The OLGA downstaging rate in the WDB group was 30%, which was higher than that in the WD group (20%) and the WMT group (10%); the OLGIM downstaging rates were 20%, 10%, and 0%, respectively. Although the differences among the three groups did not reach a statistically significant level (P>0.017), the numerical trends were completely consistent with the ranking of inflammation improvement among the groups, suggesting that the combination of buckwheat and Xiangsha Liujunzi Decoction may bring better early pathological improvement.

[0069] This result is in line with clinical expectations: reversing atrophy and intestinal metaplasia requires a longer treatment period, and 1.5 months of intervention is not enough to achieve significant histological remodeling, but the significant improvement in inflammation has laid the necessary foundation for its subsequent reversal.

[0070] Table 3 Comparison of improvement in inflammation score and pathological score between groups (x̄±s, points)

[0071]

[0072] Note: Bonferroni correction was used; P < 0.017 was considered statistically significant; vs. pre-treatment levels in this group. a P<0.017; vsWMT group, b P<0.017; vsWD group, c P<0.017.

[0073] Table 4 Comparison of OLGA and OLGIM staging improvements between groups (downstaging rate, %)

[0074]

[0075] Note: Bonferroni correction was used; for the vsWD group, aP=1.00; for the vsWMT group, bP=0.58; for the vsWMT group, cP=1.00; for the vsWD group, dP=1.00; for the vsWMT group, eP=0.47; for the vsWMT group, fP=1.00.

[0076] 4.4. Comparison of TCM syndrome scores

[0077] Compared with pre-treatment scores, the scores of primary and secondary symptoms of TCM syndromes decreased in all groups after treatment, with statistically significant differences (P<0.017). Intergroup comparisons: The WDB group was significantly better than the WD and WMT groups in reducing primary and secondary symptom scores (P<0.017), and the WD group was also significantly better than the WMT group (P<0.017). See Table 5 for details.

[0078] Table 5 Comparison of TCM syndrome scores before and after treatment (x̄±s, points)

[0079]

[0080] Note: Bonferroni correction was used; aP<0.017 vs. pre-treatment in this group; bP<0.017 vs. WMT group; cP<0.017 vs. WD group.

[0081] 4.5. Comparison of Overall Effectiveness

[0082] As shown in Table 6, the total effective rate of the WDB group was 100%, which was higher than that of the WD group (90%) and the WMT group (70%). The Mann-Whitney U test was used for intergroup comparisons: WDB vs WMT P < 0.001, WDB vs WD P = 0.003, and WD vs WMT P = 0.041. After Bonferroni correction, α = 0.017, and the P of WD vs WMT (0.041 > 0.017) was no longer statistically significant. Therefore, the conclusion is that the total effective rate of the WDB group was significantly higher than that of the WMT and WD groups (P < 0.017), while there was no statistically significant difference between the WD and WMT groups (P = 0.041).

[0083] Table 6 Comparison of overall effectiveness between groups (%)

[0084]

[0085] Note: The Mann-Whitney U test was used. a P<0.001 vs WMT group; b P=0.003 vs WD group; P=0.041 between WD group and WMT group, after Bonferroni correction (α=0.017), there was no statistically significant difference.

[0086] 4.6. Comparison of pepsinogen

[0087] As shown in Table 7 and Figure 3 As shown:

[0088] 1. Before treatment, the baseline values ​​of PGⅠ, PGⅡ and PGR were equal in the three groups (P>0.05);

[0089] 2. 1.5 months after treatment: Intra-group comparisons: Compared with pre-treatment levels, the WMT group showed a significant decrease in PGⅠ (−6.42±4.79 μg / L, P=0.002), a significant decrease in PGⅡ (2.67±1.94 μg / L, P=0.001), and a slight increase in PGR (6.7±10.2%, P=0.048). Both the WD and WDB groups showed significant increases in PGⅠ (9.15±4.85 μg / L and 14.16±4.90 μg / L, respectively, both P<0.001), significant decreases in PGⅡ (4.29±2.03 μg / L and 5.03±2.07 μg / L, respectively, both P<0.001), and significant increases in PGR (48.1±11.9% and 67.7±13.0%, respectively, both P<0.001).

[0090] Intergroup comparison: The changes in PGⅠ values ​​in the three groups showed a gradient of WDB > WD > WMT. After Bonferroni correction, the differences in WDB vs WMT (P<0.001), WD vs WMT (P=0.002), and WDB vs WD (P=0.008) were all statistically significant (α=0.017).

[0091] PGⅡ reduction value: WDB group was better than WMT group (P=0.023, not significant after correction), and there was no significant difference with WD group (P=0.435).

[0092] Percentage increase in PGR: WDB group (66.2%) > WD group (46.0%) > WMT group (7.2%), with significant differences between each pair (P<0.017).

[0093] The above results suggest that the combination of black buckwheat and Xiangsha Liujunzi Decoction can more effectively promote the recovery of gastric mucosal function, as evidenced by a significant increase in PGⅠ levels and a significant increase in the PGR ratio, and the degree of improvement is completely consistent with the intergroup ranking of inflammation and pathological scores (see Tables 3 and 4). This further confirms that the WDB regimen is superior to Xiangsha Liujunzi Decoction alone in repairing gastric mucosal damage.

[0094] It should be noted that the variation patterns of PGⅠ and PGⅡ differ:

[0095] 1. Different biological origins: PGⅠ is secreted only by the chief cells of the gastric fundic glands and is highly sensitive to oxidative stress; PGⅡ originates from the entire gastric mucosa (fundic glands, cardia glands, pyloric glands, etc.), and the secretory cell population is dispersed and changes relatively slowly.

[0096] 2. The effect of black buckwheat first targets the gastric fundic glands: The strong antioxidant effect of black buckwheat is first manifested by a significant increase in PGⅠ (WDB vs WD, P=0.008), while a further decrease in PGⅡ may require a longer intervention period.

[0097] 3. Limitations of short-term intervention: Under a 1.5-month short-term intervention, although the PGII level in the WDB group showed a decreasing trend compared to the WD group (5.03 μg / L vs 4.29 μg / L), it did not reach a statistically significant level. This phenomenon is consistent with the pathophysiological law of gastric mucosal repair: the recovery of gastric fundic gland function precedes the resolution of overall inflammation of the gastric mucosa.

[0098] The intergroup differences in PGII do not negate the synergistic effect of supplementation: the trend of PGII values ​​still shows that the WDB group is better than the WD group, which is consistent with the improvement trend of overall inflammation and oxidative stress indicators.

[0099] Table 7 Comparison of serum pepsinogen levels and improvement indicators among different groups (x̄±s)

[0100]

[0101] Note: ΔPGⅠ (μg / L) = post-treatment - pre-treatment; ΔPGⅡ (μg / L) = pre-treatment - post-treatment; PGR increase rate (%) = (post-treatment PGR - pre-treatment PGR) / pre-treatment PGR × 100; Bonferroni correction used; vs. pre-treatment in this group. a P<0.017; vs WMT group, b P<0.017; vs WD group, c P<0.017.

[0102] 4.7. Comparison of serum inflammatory cytokines

[0103] As shown in Table 8 and Figure 4As shown, the baseline levels of serum IL-6, IL-1β, TNF-α, and IL-10 were similar across the three groups before treatment. After treatment, the levels of pro-inflammatory factors in all three groups were significantly lower than before treatment (P<0.017), while the levels of anti-inflammatory factor IL-10 were significantly higher (P<0.017). Intergroup comparisons showed that the decrease in IL-6 in the WDB group was significantly higher than that in the WD group (P=0.008) and the WMT group (P<0.001); the difference between the WD group and the WMT group was P=0.027 (>0.017), but there was no statistically significant difference after adjustment. The changes in IL-1β, TNF-α, and IL-10 showed a completely consistent intergroup ranking (WDB group > WD group > WMT group), with both WDB vs WMT and WDB vs WD showing P<0.017. The differences between WD and WMT were significant: IL-1β P=0.013 (significant), TNF-α P=0.009 (significant), and IL-10 P=0.005 (significant). The above results indicate that combining black buckwheat can further enhance the anti-inflammatory effect, especially in the comparison between the WDB group and the WD group, where most indicators reached a significant level after correction. IL-6, IL-1β, and TNF-α are currently recognized core indicators for evaluating inflammatory status in CAG clinical studies. Related studies have shown that traditional Chinese medicine intervention can effectively downregulate the levels of these pro-inflammatory factors and upregulate the level of the anti-inflammatory factor IL-10.

[0104] Table 8. Comparison of serum inflammatory cytokines and improvement indicators among groups (x̄±s)

[0105]

[0106] Note: ΔIL-6, ΔIL-1β, ΔTNF-α = pre-treatment - post-treatment (decreased value); ΔIL-10 = post-treatment - pre-treatment (increased value); Bonferroni correction was used; vs. pre-treatment in this group, aP<0.017; vs. WMT group, bP<0.017; vs. WD group, cP<0.017.

[0107] 4.8. Comparison of serum oxidative stress markers

[0108] As shown in Table 9 and Figure 5As shown, the baseline levels of MDA, SOD, and GSH-Px were balanced in all three groups before treatment. After treatment, MDA levels significantly decreased in all three groups (P<0.017), while SOD and GSH-Px levels significantly increased (P<0.017). Intergroup comparisons: The decrease in MDA in the WDB group was significantly higher than that in the WD group (P=0.009) and the WMT group (P<0.001); the difference between the WD group and the WMT group was P=0.024 (>0.017), but there was no statistically significant difference after adjustment. The increase in SOD and GSH-Px showed a gradient trend of WDB group > WD group > WMT group, with P<0.017 for both WDB vs WMT and WDB vs WD, and significant P=0.015 for SOD and 0.011 for GSH-Px in WD vs WMT. These results suggest that the combination of black buckwheat and wheat can significantly enhance the body's antioxidant capacity. MDA, SOD, and GSH-Px are classic indicators for assessing the body's oxidative stress state and are widely used in CAG (Chronic Acid Glucose) efficacy evaluation studies.

[0109] Table 9. Comparison of serum oxidative stress markers and improvement indicators among groups (x̄±s)

[0110]

[0111] Note: ΔMDA = pre-treatment - post-treatment (decreased value); ΔSOD = post-treatment - pre-treatment (increased value); ΔGSH-Px = post-treatment - pre-treatment (increased value). Bonferroni correction was used, α = 0.017; vs pre-treatment in this group, aP < 0.017; vs WMT group, bP < 0.017; vs WD group, cP < 0.017.

[0112] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention, and they should all be covered within the scope of the claims and specification of the present invention.

Claims

1. A pharmaceutical composition for treating Helicobacter pylori-positive chronic atrophic gastritis, characterized in that, The pharmaceutical composition consists of separately packaged Yi medicine roasted black buckwheat tea and Xiangsha Liujunzi Decoction, which are administered together when used. Xiangsha Liujunzi Decoction is made from the following raw materials in parts by weight: Codonopsis pilosula 15 parts, Atractylodes macrocephala 10 parts, Poria cocos 15 parts, Citrus reticulata peel 12 parts, processed Pinellia ternata 15 parts, Aucklandia lappa 10 parts, Amomum villosum 10 parts, and Glycyrrhiza uralensis 6 parts.

2. The pharmaceutical composition according to claim 1, characterized in that, The daily dosage of the Yi medicine-processed black buckwheat tea is 3-5 grams.

3. The use of the pharmaceutical composition according to claim 1 or 2 in the preparation of a drug for treating Helicobacter pylori-positive chronic atrophic gastritis.

4. The application according to claim 3, characterized in that, The therapeutic effect of the drug composition is achieved through the synergistic effect of Yi medicine-processed black buckwheat tea and Xiangsha Liujunzi Decoction.

5. The application according to claim 3, characterized in that, The pharmaceutical composition is used in the preparation of a medicament for reducing the pathological inflammation score of the gastric mucosa.

6. The application according to claim 3, characterized in that, The pharmaceutical composition is used in the preparation of a drug for increasing serum pepsinogen I levels and the PG I / PG II ratio, and promoting the recovery of gastric mucosal function.

7. The application according to claim 3, characterized in that, The pharmaceutical composition is used in the preparation of drugs for downregulating the levels of pro-inflammatory factors IL-6, IL-1β, and TNF-α and for upregulating the level of anti-inflammatory factor IL-10.

8. The application according to claim 3, characterized in that, The pharmaceutical composition is used in the preparation of drugs for reducing the oxidative stress product malondialdehyde and for increasing the activity of superoxide dismutase and glutathione peroxidase.

9. The application according to claim 3, characterized in that, The pharmaceutical composition is used in the preparation of a medicament for improving endoscopic gastric mucosal lesions, including mucosal erythema, erosion, and / or bleeding.

10. The application according to claim 3, characterized in that, The use of the pharmaceutical composition in the preparation of a medicament for reversing gastric mucosal atrophy and / or intestinal metaplasia.

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