A traditional Chinese medicine composition and application thereof in preparation of a drug for treating reflux esophagitis

Abstract

The application provides a traditional Chinese medicine composition and application thereof in preparation of a drug for treating reflux esophagitis, and relates to the technical field of traditional Chinese medicine pharmacy.The traditional Chinese medicine composition takes Fritillaria thunbergii Miq., Evodia rutaecarpa, Citrus medica L. as monarch drugs, Inula japonica, Terminalia chebula Retz., Nardostachys chinensis, Syzygium aromaticum, Amomum subulatum, Phoenix tree as minister drugs, mother-of-pearl, Cortex Fraxini, Gentiana scabra Bunge, Osmanthus fragrans as auxiliary drugs, and Glycyrrhiza uralensis as a servant drug, and the drugs are combined to have the effects of dispersing the liver and harmonizing the stomach, reducing adverse and acid, and regulating cold and heat.The traditional Chinese medicine composition can significantly improve the esophagitis index of RE rats, has obvious inhibitory effect on inflammatory damage, can significantly improve the pathological morphology of the esophageal tissue of the RE rats, and realizes better anti-inflammatory and therapeutic effect on the RE rats.Meanwhile, the traditional Chinese medicine composition can significantly improve and alleviate the clinical symptoms of the patients with reflux esophagitis, such as acid reflux, heartburn, abdominal distension and belching, and reduce the frequency of the clinical symptoms.The traditional Chinese medicine composition is expected to be further developed and popularized as a drug for treating reflux esophagitis.

Description

Technical Field

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

[0002] Reflux esophagitis (RE) refers to the reflux of stomach and duodenal contents into the esophagus, causing damage to esophageal tissue. Endoscopic findings show esophageal mucosal damage. It is a subtype of gastroesophageal reflux disease (GERD), and endoscopy is the gold standard for diagnosing RE. Acid reflux and heartburn are typical symptoms of RE. Other atypical symptoms include bloating, belching, nausea, chest pain, upper abdominal pain, and even angina-like symptoms. Extraesophageal symptoms include respiratory and pharyngeal symptoms such as cough, pharyngitis, asthma, and dysphagia, severely impacting patients' quality of life. In recent years, with the steady and continuous development of the social economy, people's pace of life has gradually accelerated, and corresponding dietary structures and lifestyles have changed significantly. At the same time, the incidence of reflux esophagitis has continued to rise, especially among the elderly. Reflux esophagitis has a long course and is prone to recurrence. Common complications include upper gastrointestinal bleeding that causes hematemesis and melena, esophageal stricture that causes difficulty swallowing, Barrett's esophagus as a precancerous lesion that can cause aspiration pneumonia with cough and fever, and esophageal ulcers that cause severe retrosternal pain, all of which significantly reduce the patient's quality of life.

[0003] Currently, the main medications used in clinical practice to treat reflux esophagitis include potent proton pump inhibitors (PPIs) that suppress acid, potassium-competitive acid blockers (P-CABs) that offer rapid onset and stable acid suppression, H2 receptor antagonists (H2RAs) used for patients with mild to moderate symptoms, prokinetic agents that enhance esophageal and gastric motility to reduce reflux, and mucosal protectants that form a protective film on the esophageal mucosa to promote healing. Among these, PPIs and P-CABs are commonly used first-line drugs for treating reflux esophagitis. However, while Western medicine treatment can alleviate symptoms to some extent, relapse is highly likely once medication is discontinued, and long-term use can lead to dependence and drug resistance, affecting subsequent treatment outcomes.

[0004] Traditional Chinese medicine (TCM) does not have a specific disease name for reflux esophagitis. However, based on its symptoms such as acid reflux, vomiting, heartburn, and belching, it can be categorized under TCM terms like "acid vomiting," "esophageal discomfort," "heartburn," and "hiccups." In modern medicine, many practitioners use TCM to treat reflux esophagitis. TCM adheres to a holistic approach, following the principles of syndrome differentiation and treatment, regulating the body's Qi, blood, Yin, and Yang to restore balance. Clinical practice shows that TCM treatment has demonstrated good results in relieving symptoms such as heartburn and acid reflux, reducing the side effects of Western medicine, effectively shortening the course of the disease, improving patients' quality of life, and reducing the recurrence rate. Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention provides a traditional Chinese medicine composition and its application in the preparation of drugs for treating reflux esophagitis.

[0006] To achieve the above objectives, the present invention provides the following technical solution:

[0007] First, the present invention provides a traditional Chinese medicine composition, which is composed of the following traditional Chinese medicine raw materials in parts by weight: 5-20 parts of Inula japonica, 5-20 parts of Amomum tsao-ko, 5-20 parts of Salvia miltiorrhiza, 5-20 parts of Evodia rutaecarpa, 5-20 parts of Fritillaria thunbergii, 5-20 parts of eggshell membrane, 5-20 parts of pearl powder, 5-20 parts of Gentiana scabra, 5-20 parts of Fraxinus chinensis, 5-20 parts of Citrus medica, 5-20 parts of Nardostachys jatamansi, 5-20 parts of Phragmites communis, 5-20 parts of Syzygium aromaticum, 5-20 parts of Osmanthus fragrans, and 5-20 parts of Glycyrrhiza uralensis.

[0008] Furthermore, the traditional Chinese medicine composition comprises the following traditional Chinese medicine raw materials in parts by weight: 5-15 parts of Inula japonica, 5-15 parts of Amomum tsao-ko, 5-15 parts of Salvia miltiorrhiza, 5-15 parts of Evodia rutaecarpa, 5-15 parts of Fritillaria thunbergii, 5-15 parts of eggshell membrane, 5-15 parts of pearl powder, 5-15 parts of Gentiana scabra, 5-15 parts of Fraxinus chinensis, 5-15 parts of Citrus medica, 5-15 parts of Nardostachys jatamansi, 5-15 parts of Phragmites communis, 5-15 parts of Syzygium aromaticum, 5-15 parts of Osmanthus fragrans, and 5-15 parts of Glycyrrhiza uralensis.

[0009] Furthermore, the traditional Chinese medicine composition comprises the following traditional Chinese medicine raw materials in parts by weight: 12 parts of Inula japonica, 9 parts of Amomum tsao-ko, 12 parts of Salvia miltiorrhiza, 12 parts of Evodia rutaecarpa, 12 parts of Fritillaria thunbergii, 9 parts of eggshell membrane, 9 parts of pearl powder, 9 parts of Gentiana scabra, 9 parts of Fraxinus chinensis, 12 parts of Citrus medica, 9 parts of Nardostachys jatamansi, 9 parts of Phragmites communis rhizome, 9 parts of Syzygium aromaticum, 9 parts of Osmanthus fragrans, and 9 parts of Glycyrrhiza uralensis.

[0010] Furthermore, the present invention also provides the application of the above-mentioned traditional Chinese medicine composition in the preparation of a drug for treating reflux esophagitis. The drug is made from the above-mentioned parts by weight of traditional Chinese medicine as raw materials, supplemented with medically acceptable excipients, and prepared into an oral dosage form, wherein the dosage form is granules, oral liquid, powder, decoction, soup, tablets, capsules, or paste.

[0011] In traditional Chinese medicine, reflux esophagitis is often considered to be caused by factors such as improper diet, emotional imbalance, and weakness of the spleen and stomach, leading to dysfunction of the liver and stomach, and the stomach qi failing to descend and instead rising upwards. Over time, it is accompanied by symptoms of mixed cold and heat, and phlegm obstruction, falling under the categories of acid regurgitation, heartburn, and stomach pain. This invention starts with the dialectical treatment of liver and stomach disharmony, upward rebellion of stomach qi, and mixed cold and heat, and scientifically and rationally combines a traditional Chinese medicine composition for the treatment of reflux esophagitis, which has the effects of soothing the liver and stomach, descending rebellious qi and inhibiting acid, and balancing cold and heat.

[0012] In the herbal composition of this invention, Fritillaria thunbergii is bitter and cold in nature, and enters the lung and stomach meridians. It has the effects of clearing heat and resolving stagnation, neutralizing acid and relieving pain. It can clear the heat stagnation in the liver and stomach, relieve heartburn and burning pain, and effectively neutralize stomach acid, making it an important herb for neutralizing acid. Evodia rutaecarpa is pungent, bitter and hot in nature, and enters the liver, spleen, stomach and kidney meridians. It has the effects of dispelling cold and relieving pain, suppressing nausea and vomiting, and neutralizing acid. It can disperse liver stagnation, guide liver qi downward, and allow stomach qi to descend accordingly. Together with Fritillaria thunbergii, one is cold and the other is hot, clearing stomach heat and warming stomach cold, achieving a balance of cold and heat. Citrus medica is pungent, bitter, sour and warm in nature, and enters the liver, spleen, stomach and lung meridians. It can soothe the liver and relieve stagnation, and relieve stomach pain caused by stomach qi stagnation. At the same time, it can balance the coldness of Fritillaria thunbergii and the heat of Evodia rutaecarpa, achieving the purpose of regulating the liver and stomach. The three ingredients work together as the principal herbs, enabling the liver qi to flow smoothly, the stomach qi to descend freely, and the stagnant heat to be cleared away.

[0013] Inula japonica, salty and warm in nature, enters the lung, stomach, and large intestine meridians. It can lower qi, resolve phlegm, and relieve nausea and vomiting, thus enhancing the overall nausea and vomiting effect of the principal herb, Evodia rutaecarpa. Salvia miltiorrhiza, sweet and warm in nature, enters the liver and stomach meridians. It has the effects of soothing the liver, regulating qi, harmonizing the stomach, and relieving pain. Nardostachys jatamansi, pungent, sweet, and warm in nature, enters the spleen and stomach meridians. It can regulate qi, relieve pain, and invigorate the spleen. Together, they assist the principal herb, Citrus medica, in soothing the liver and regulating qi. Clove, pungent and warm in nature, enters the spleen, stomach, lung, and kidney meridians. It can warm the middle jiao, relieve nausea and vomiting, dispel cold, relieve pain, and warm the kidneys and tonify yang. It assists Evodia rutaecarpa in enhancing its effects of warming the stomach, dispelling cold, and relieving nausea and vomiting. Amomum tsao-ko, pungent and warm in nature, enters the spleen and stomach meridians. It can dry dampness, warm the middle jiao, stop malaria, and eliminate phlegm. It can effectively dry dampness and remove turbidity, clear dampness from the stomach, restore the spleen and stomach's digestive function, and assist Fritillaria thunbergii in enhancing its phlegm-resolving and pathogen-eliminating effects. Phoenix skin is sweet and bland in taste, and neutral in nature. It enters the lung and stomach meridians, and can nourish yin and clear the lungs, promote wound healing and tissue regeneration. It can nourish the yin of the esophageal mucosa, replenish the body fluids consumed by stomach heat, and promote mucosal repair. The above are all assistant herbs, which assist the principal herbs from multiple angles such as lowering adverse qi, soothing the liver, regulating qi, protecting the membrane, and warming and transforming.

[0014] Mother-of-pearl is salty and cold in nature, and enters the liver and heart meridians. It can calm the liver and subdue yang, and soothe the mind and calm fright. Gentian root is bitter and cold in nature, and enters the liver and gallbladder meridians. It can clear heat and dry dampness, and purge liver and gallbladder fire. Fraxinus bark is bitter, astringent, and cold in nature, and enters the liver, gallbladder, and large intestine meridians. It can clear heat and dry dampness, and astringe and stop dysentery. All three are cold in nature. Gentian root and Fraxinus bark clear and purge liver and gallbladder fire, while mother-of-pearl calms the liver and subdues yang, preventing liver fire from attacking the stomach again. It assists the principal drug, Buddha's Hand, and the assistant drug, Sal atractylodes, in enhancing the liver-soothing and calming effects. At the same time, it can restrain the warm and drying properties of the principal drug, Evodia rutaecarpa, and the assistant drugs, Clove, Amomum tsao-ko, and Nardostachys jatamansi, preventing excessive consumption of stomach yin by warming drugs and avoiding the overall formula from being too warm and promoting heat. It is an adjuvant drug. Osmanthus is pungent and warm in nature, and enters the spleen, stomach, and lung meridians. It can warm the lungs, resolve phlegm, dispel cold, and relieve pain. It can assist the principal herb Evodia rutaecarpa and the assistant herb Clove in enhancing the warming and cold-dispelling effects on the stomach. It can also clear small amounts of phlegm between the lungs and stomach, and assist the assistant herb Amomum villosum and the principal herb Fritillaria thunbergii in enhancing the phlegm-removing effects. Reed rhizome is sweet and cold in nature, and enters the lung and stomach meridians. It can clear heat, generate fluids, and stop vomiting. Its cold nature can further balance the dryness of the warm herbs in the formula, and its fluid-generating effect can alleviate the potential for the cold herbs in the formula to damage yin. Its anti-vomiting effect further enhances the overall antiemetic effect of the formula. Both are adjuvant herbs. Finally, licorice root, which is sweet and neutral in nature, is used as the guiding herb to tonify the spleen and replenish qi, clear heat and detoxify, relieve spasms and pain, guide the medicine into the meridians, and harmonize the effects of the other herbs.

[0015] The herbal composition of this invention has a significant therapeutic effect on rats with esophagitis, significantly improving the esophagitis index and inhibiting inflammatory damage. It also significantly improves the pathological morphology of esophageal tissue in rats with esophagitis. This herbal composition achieves good anti-inflammatory and therapeutic effects on rats with esophagitis by upregulating plasma motilin levels and downregulating the levels of inflammatory factors IL-6, IL-17, and TNF-α.

[0016] The herbal composition of this invention achieves a high overall effective rate in treating reflux esophagitis, significantly improving and alleviating clinical symptoms such as acid reflux, heartburn, bloating, and belching, and effectively reducing the frequency of symptom attacks. This herbal composition holds promise for further development and promotion as a treatment for reflux esophagitis. Attached Figure Description

[0017] Figure 1 The results of esophageal inflammation index (A) and damage inhibition rate (B) in each group of rats are shown; compared with the model group, **P<0.01.

[0018] Figure 2 The histopathological scores of the esophageal mucosa tissue of rats in each group are shown; compared with the model group, **P<0.01.

[0019] Figure 3 The results show the plasma motilin content in rats of each group; compared with the model group, *P<0.05, **P<0.01.

[0020] Figure 4Results of the levels of inflammatory factors IL-6, IL-17 and TNF-α in the esophageal tissue of rats in each group; compared with the model group, ***P<0.001, ****P<0.0001. Detailed Implementation

[0021] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0022] Example 1

[0023] A traditional Chinese medicine composition comprising the following parts by weight of traditional Chinese medicine raw materials: 12 parts of Inula japonica, 9 parts of Amomum tsao-ko, 12 parts of Salvia miltiorrhiza, 12 parts of Evodia rutaecarpa, 12 parts of Fritillaria thunbergii, 9 parts of eggshell membrane, 9 parts of pearl powder, 9 parts of Gentiana scabra, 9 parts of Fraxinus chinensis, 12 parts of Citrus medica, 9 parts of Nardostachys jatamansi, 9 parts of Phragmites communis rhizome, 9 parts of Syzygium aromaticum, 9 parts of Osmanthus fragrans, and 9 parts of Glycyrrhiza uralensis.

[0024] The above-mentioned traditional Chinese medicine composition is used to prepare a drug for treating reflux esophagitis. The drug is made from the above-mentioned proportions of traditional Chinese medicinal materials by weight, supplemented with medically acceptable excipients, and prepared into an oral dosage form, which is granules, oral liquid, powder, decoction, soup, tablets, capsules, or paste.

[0025] Example 2

[0026] The difference between this embodiment and Embodiment 1 is that the traditional Chinese medicine composition is composed of the following traditional Chinese medicine raw materials in parts by weight: 8 parts of Inula japonica, 6 parts of Amomum tsao-ko, 6 parts of Salvia miltiorrhiza, 6 parts of Evodia rutaecarpa, 8 parts of Fritillaria thunbergii, 6 parts of eggshell membrane, 8 parts of pearl powder, 6 parts of Gentiana scabra, 6 parts of Fraxinus chinensis, 8 parts of Citrus medica, 6 parts of Nardostachys jatamansi, 6 parts of Phragmites communis, 6 parts of Syzygium aromaticum, 6 parts of Osmanthus fragrans, and 6 parts of Glycyrrhiza uralensis.

[0027] Example 3

[0028] The difference between this embodiment and Embodiment 1 is that the traditional Chinese medicine composition is composed of the following traditional Chinese medicine raw materials in parts by weight: 16 parts of Inula japonica, 16 parts of Amomum tsao-ko, 16 parts of Salvia miltiorrhiza, 16 parts of Evodia rutaecarpa, 18 parts of Fritillaria thunbergii, 16 parts of eggshell membrane, 18 parts of pearl powder, 16 parts of Gentiana scabra, 16 parts of Fraxinus chinensis, 16 parts of Citrus medica, 16 parts of Nardostachys jatamansi, 16 parts of Phragmites communis, 16 parts of Syzygium aromaticum, 16 parts of Osmanthus fragrans, and 16 parts of Glycyrrhiza uralensis.

[0029] Example 4

[0030] The difference between this embodiment and Embodiment 1 is that the traditional Chinese medicine composition is composed of the following traditional Chinese medicine raw materials in parts by weight: 6 parts of Inula japonica, 6 parts of Amomum tsao-ko, 6 parts of Salvia miltiorrhiza, 8 parts of Evodia rutaecarpa, 8 parts of Fritillaria thunbergii, 5 parts of eggshell membrane, 6 parts of pearl powder, 55 parts of Gentiana scabra, 5 parts of Fraxinus chinensis, 5 parts of Citrus medica, 5 parts of Nardostachys jatamansi, 5 parts of Phragmites communis, 5 parts of Syzygium aromaticum, 5 parts of Osmanthus fragrans, and 5 parts of Glycyrrhiza uralensis.

[0031] Example 5

[0032] The difference between this embodiment and Embodiment 1 is that the traditional Chinese medicine composition is composed of the following traditional Chinese medicine raw materials in parts by weight: 12 parts of Inula japonica, 10 parts of Amomum tsao-ko, 12 parts of Salvia miltiorrhiza, 14 parts of Evodia rutaecarpa, 14 parts of Fritillaria thunbergii, 10 parts of eggshell membrane, 12 parts of pearl powder, 12 parts of Gentiana scabra, 10 parts of Fraxinus chinensis, 12 parts of Citrus medica, 10 parts of Nardostachys jatamansi, 12 parts of Phragmites communis, 10 parts of Syzygium aromaticum, 10 parts of Osmanthus fragrans, and 10 parts of Glycyrrhiza uralensis.

[0033] Example 6

[0034] The difference between this embodiment and Embodiment 1 is that the traditional Chinese medicine composition is composed of the following traditional Chinese medicine raw materials in parts by weight: 10 parts of Inula japonica, 6 parts of Amomum tsao-ko, 10 parts of Salvia miltiorrhiza, 12 parts of Evodia rutaecarpa, 14 parts of Fritillaria thunbergii, 6 parts of eggshell membrane, 12 parts of pearl powder, 8 parts of Gentiana scabra, 8 parts of Fraxinus chinensis, 8 parts of Citrus medica, 8 parts of Nardostachys jatamansi, 8 parts of Phragmites communis, 8 parts of Syzygium aromaticum, 8 parts of Osmanthus fragrans, and 8 parts of Glycyrrhiza uralensis.

[0035] Example 7

[0036] The difference between this embodiment and Embodiment 1 is that the traditional Chinese medicine composition is composed of the following traditional Chinese medicine raw materials in parts by weight: 8 parts of Inula japonica, 8 parts of Amomum tsao-ko, 8 parts of Salvia miltiorrhiza, 12 parts of Evodia rutaecarpa, 12 parts of Fritillaria thunbergii, 6 parts of eggshell membrane, 10 parts of pearl powder, 6 parts of Gentiana scabra, 6 parts of Fraxinus chinensis, 8 parts of Citrus medica, 8 parts of Nardostachys jatamansi, 6 parts of Phragmites communis, 6 parts of Syzygium aromaticum, 6 parts of Osmanthus fragrans, and 6 parts of Glycyrrhiza uralensis.

[0037] Test case

[0038] Investigation on the effects of the traditional Chinese medicine composition of this invention on rats with reflux esophagitis

[0039] 1. Materials

[0040] 1.1 Laboratory Animals

[0041] Sixty SPF-grade male SD rats, weighing 220-250g, were acclimatized for one week before the experiment.

[0042] 1.2 Test Drugs

[0043] The herbal decoction of this invention is prepared by weighing the following herbal ingredients according to the following weights: 12g of Inula japonica, 9g of Amomum tsao-ko, 12g of Salvia miltiorrhiza, 12g of Evodia rutaecarpa, 12g of Fritillaria thunbergii, 9g of eggshell membrane, 9g of pearl powder, 9g of Gentiana scabra, 9g of Fraxinus chinensis, 12g of Citrus medica, 9g of Nardostachys jatamansi, 9g of Phragmites communis, 9g of Syzygium aromaticum, 9g of Osmanthus fragrans, and 9g of Glycyrrhiza uralensis. After washing, the ingredients are decocted and concentrated using an automatic decoction machine to a decoction volume of 1g / mL of raw herbs. The decoction is then refrigerated for later use.

[0044] Positive control drugs: Pantoprazole sodium enteric-coated tablets (40mg / tablet) and Mosapride citrate tablets (5mg / tablet).

[0045] 2 methods

[0046] 2.1 Establishment of a rat model of reflux esophagitis (RE)

[0047] Sixty male SD rats were randomly selected, with 10 rats assigned to the sham-operated group. The remaining 50 rats underwent a modeling procedure using forestomach ligation combined with partial pyloric ligation. The specific method was as follows: all rats were fasted for 24 hours prior to surgery, but had free access to water. Except for the sham-operated group, rats in all other groups underwent anesthesia and skin preparation. An incision of approximately 2 cm was made along the midline of the abdomen to enter the abdominal cavity. The stomach tissue was located and pulled downwards, allowing for thorough dissection of the stomach and surrounding pyloric tissue. First, a 3-0 suture was used to ligate the forestomach. Then, another 3-0 suture was used to ligate the pylorus. A 0.38 mm diameter glass rod was placed on the pylorus and ligated together with the rod. The rod was then removed, and the stomach was returned to its original position before the abdomen was closed. Rats in the sham-operated group underwent the same anesthesia and abdominal incision. The stomach tissue was exposed for approximately 5 minutes before being returned to its original position and the abdomen closed. After modeling, all rats were routinely disinfected and returned to the animal room. On the first postoperative day, all rats were kept on a restricted diet but allowed free access to water. On the second postoperative day, they were given small amounts of food, and on the third postoperative day, they resumed their normal diet. Two weeks after modeling, all rats survived.

[0048] 2.2 Drug administration

[0049] Fifty rats that successfully developed the model were randomly divided into a model group, a western medicine group, a high-dose traditional Chinese medicine group, and a low-dose traditional Chinese medicine group. The western medicine group was administered pantoprazole sodium distilled water suspension (8.5 mg / kg / d) + mosapride distilled water suspension (2 mg / kg / d) by gavage. The high-dose and low-dose traditional Chinese medicine groups were administered the traditional Chinese medicine decoction of this invention by gavage (1.5 g / kg / d and 0.75 g / kg / d, respectively). The model group and sham-operated group were administered an equal volume of distilled water by gavage. Administered once daily for 14 consecutive days.

[0050] 2.3 Collection of materials

[0051] After 14 days of gavage, the rats were kept on a fasting diet but allowed free access to water for 24 hours. Once all rats were satisfactorily anesthetized, blood was collected via the abdominal aorta, centrifuged, and the supernatant was stored at -80°C for later analysis. Tissue from the cardia and 2 cm above the esophagus was collected and divided into three parts. One part was stored in 4% paraformaldehyde at 4°C, and the other two parts were stored at -80°C.

[0052] 2.4 Observation Indicators and Methods

[0053] 2.4.1 General Condition Observation

[0054] Observe the general condition of rats in each group, such as hair color and shedding, activity level, food and water intake, stool volume and characteristics, and body weight.

[0055] 2.4.2 Detection of esophagitis index and inhibition rate in rats

[0056] During tissue collection, the esophagus was longitudinally cut, rinsed with physiological saline, laid flat on cardboard, and the degree of lesion was observed visually while scoring was performed. The esophagitis index and inhibition rate were calculated. The esophagitis index was based on the diagnostic and treatment guidelines, as shown in Table 1.

[0057] Damage inhibition rate = (Esophagitis index of model group - Esophagitis index of treatment group) / Esophagitis index of model group × 100%

[0058] Table 1. Gross visual grading and scoring criteria for esophagitis

[0059]

[0060] 2.4.3 Esophageal mucosal pathological score

[0061] Esophageal tissue was routinely fixed at 4℃ in 4% paraformaldehyde, dehydrated, embedded in paraffin, sectioned, stained with hematoxylin and eosin, and examined under a light microscope. Respiratory esophageal (RE) tissue sections were then graded pathologically, with normal, mild, moderate, and severe grades assigned scores of 0, 1, 2, and 3, respectively. The pathological grading followed the RE pathological grading criteria in the "Guidelines for the Diagnosis and Treatment of RE" issued by the Chinese Society of Digestive Endoscopy in 2003, as detailed in Table 2.

[0062] Table 2 Pathological Scoring Criteria

[0063]

[0064] 2.4.4 Determination of plasma motilin content

[0065] Centrifuged plasma was tested step by step according to the instructions for use of the Genemei rat MTL kit.

[0066] 2.4.5 Detection of the levels of inflammatory factors IL-6, IL-17 and TNF-α in esophageal tissue

[0067] Pretreatment of esophageal tissue samples: Accurately weigh the esophageal tissue and add PBS at a ratio of weight (g):volume (mL) = 1 g:18 mL. Place the PBS in a grinding bead and grind the tissue in a cryogenic grinder. Centrifuge at 3500 r / min for 20 min at 4 ℃. Aliquot the supernatant into EP tubes to obtain esophageal tissue homogenate.

[0068] The levels of IL-6, IL-17, and TNF-α in colon tissue homogenate were detected according to the ELISA kit instructions.

[0069] 2.5 Statistical Methods

[0070] Statistical analysis was performed using Prism 8.0.2, and one-way ANOVA was used for comparisons between groups. Results are expressed as mean ± standard deviation. The results were analyzed using a t-test. P < 0.05 was considered statistically significant.

[0071] 3 Results

[0072] 3.1 General Case

[0073] During the modeling and gavage treatment, rats in all groups exhibited varying degrees of changes in fur color, reduced activity, decreased food and water intake, watery stools, and weight loss. The sham-operated group recovered to normal the fastest, while the model group recovered the slowest and even experienced worsening of these symptoms.

[0074] 3.2 Comparison of esophagitis index and damage inhibition rate among different groups of rats

[0075] Compared with the sham surgery group, the esophagitis index in the model group was significantly increased (P<0.01); compared with the model group, the esophagitis index in the Western medicine group and the high- and low-dose traditional Chinese medicine groups was significantly decreased (P<0.01), and the damage inhibition rate was significantly increased. Results are as follows. Figure 1 As shown.

[0076] 3.3 Comparison of esophageal mucosal pathological scores among different groups of rats

[0077] No obvious inflammatory response was observed in the esophageal mucosa of rats in the sham-operated group; in the model group, thickening of the esophageal squamous epithelium and a small amount of basal cell hyperplasia were observed, with partial mucosal erosion, and the esophageal histopathological score was significantly increased compared with the sham-operated group (P<0.01); compared with the model group, the squamous epithelial hyperplasia and inflammatory cell infiltration of the esophageal mucosa in the low- and high-dose traditional Chinese medicine groups and the Western medicine group were all improved, with no obvious erosion or ulceration, and the esophageal histopathological scores were all significantly reduced (P<0.01). Results are as follows. Figure 2 As shown.

[0078] 3.4 Comparison of plasma motilin levels in rats of different groups

[0079] Compared with the sham-operated group, the plasma motilin content in the model group rats was significantly decreased (P<0.05); compared with the model group, the plasma motilin content in the Western medicine group and the high- and low-dose traditional Chinese medicine groups was significantly increased (P<0.01). Results are as follows. Figure 3 As shown.

[0080] 3.5 Comparison of the levels of inflammatory factors IL-6, IL-17 and TNF-α in the esophageal tissue of rats in different groups

[0081] Compared with the sham-operated group, the levels of inflammatory factors IL-6, IL-17, and TNF-α in the esophageal tissue of rats in the model group were significantly increased (P<0.001, P<0.0001); compared with the model group, the levels of inflammatory factors IL-6, IL-17, and TNF-α in the esophageal tissue of rats in the Western medicine group and the high- and low-dose traditional Chinese medicine groups were significantly decreased (P<0.001, P<0.0001). Results are as follows. Figure 4 As shown.

[0082] 4. Conclusion

[0083] The herbal composition of this invention has a significant therapeutic effect on rats with esophagitis, significantly improving the esophagitis index and inhibiting inflammatory damage. It also significantly improves the pathological morphology of esophageal tissue in rats with esophagitis (RE). This herbal composition may achieve its anti-inflammatory and therapeutic effects on RE rats by upregulating plasma motilin levels and downregulating the levels of inflammatory factors IL-6, IL-17, and TNF-α.

[0084] Application examples

[0085] 1. Materials and Methods

[0086] 1.1 General Information

[0087] Ninety-eight patients diagnosed with reflux esophagitis and admitted to our outpatient or inpatient department between January 2024 and June 2025 were randomly divided into two groups of 49 each. In the control group, there were 28 males and 21 females, with a mean age of (42.91±8.41) years and a mean disease duration of (3.98±0.97) months. In the observation group, there were 26 males and 23 females, with a mean age of (44.09±9.16) years and a mean disease duration of (4.09±1.12) months. There were no statistically significant differences in general characteristics between the two groups (P>0.05).

[0088] 1.2 Case Criteria

[0089] Inclusion criteria: (1) The symptoms met the criteria for clinical symptoms of reflux esophagitis. The Western medicine diagnostic criteria were based on the "2020 Chinese Expert Consensus on Gastroesophageal Reflux Disease"; the TCM diagnostic criteria were based on the "Expert Consensus on TCM Diagnosis and Treatment of Gastroesophageal Reflux Disease" issued by the Spleen and Stomach Disease Branch of the Chinese Academy of Traditional Chinese Medicine in 2017; the symptoms were mainly acid reflux, heartburn, etc.; (2) No abnormalities in mental state, consciousness, or language communication; (3) Age 18-65 years; (4) No allergic reactions or contraindications to the medications used; (5) High clinical cooperation and good compliance; (6) No history of medical or surgical treatment; (7) Informed consent from the patient or their family.

[0090] Exclusion criteria: (1) dysfunction or serious lesions of vital organs and tissues such as heart, liver, and kidney; (2) drug-induced esophagitis; (3) special groups such as pregnant or lactating women; (4) primary diseases of blood, immune system, etc.; (5) malignant tumors; (6) other digestive tract diseases, such as peptic ulcers or gastrointestinal bleeding.

[0091] 1.3 Methods

[0092] Control group: Pantoprazole, 40 mg / tablet, once a day, orally, for 4 consecutive weeks.

[0093] Observation group: Inula japonica 12g, Amomum tsao-ko 9g, Salvia miltiorrhiza 12g, Evodia rutaecarpa 12g, Fritillaria thunbergii 12g, Eggshell membrane 9g, Mother-of-pearl 9g, Gentiana scabra 9g, Fraxinus chinensis 9g, Citrus medica 12g, Nardostachys jatamansi 9g, Phragmites communis 9g, Syzygium aromaticum 9g, Osmanthus fragrans 9g, Glycyrrhiza uralensis 9g. The herbs were decocted in water, and 400mL of the decoction was taken twice daily, morning and evening, 200mL each time, for 4 weeks.

[0094] 1.4 Observation Indicators

[0095] 1.4.1 Efficacy assessment

[0096] A cure is defined as the absence of clinical symptoms of reflux esophagitis, a symptom score reduction of ≥95%, and endoscopic restoration of the esophageal mucosa to normal. A marked effect is defined as significant improvement in clinical symptoms compared to before treatment, with 70% ≤ symptom score reduction <95% and endoscopic improvement of the esophageal mucosa by 2 grades compared to before treatment. An effective effect is defined as some improvement in clinical symptoms compared to before treatment, with 30% ≤ symptom score reduction <70% and endoscopic improvement of the esophageal mucosa by 1 grade compared to before treatment. Failure to meet the above criteria, or even worsening of the condition, is defined as ineffective. Total effective rate = cure + marked effect + effective rate.

[0097] 1.4.2 Clinical Symptom Score

[0098] The symptoms of acid reflux, heartburn, abdominal distension, and belching in the two groups of patients before and after treatment were quantitatively scored. 0 points were asymptomatic, 2 points were mild, 4 points were moderate, and 6 points were severe. The score range was 0-24 points, with higher scores indicating more severe symptoms.

[0099] 1.4.3 Scoring of the Reflux Diagnostic Questionnaire (RDQ)

[0100] The scores were calculated based on the frequency of reflux esophagitis symptoms before and after treatment in both groups, totaling 20 points; and based on the severity of reflux esophagitis symptoms, totaling 20 points; for a total score of 40 points, the higher the score, the more severe the condition.

[0101] 1.5 Statistical Methods

[0102] Statistical analysis was performed using Prism 8.0.2. Quantitative data were expressed as mean ± standard deviation. Independent samples t-tests were used between groups, and paired samples t-tests were used within groups. Categorical data were expressed as percentages. Chi-square tests were used for comparisons between groups. 2 The test showed that P < 0.05 was statistically significant.

[0103] 2 Results

[0104] 2.1 Comparison of clinical efficacy between the two groups

[0105] The total effective rate of treatment in the control group was 80.95%, while that in the observation group was 95.92%. The difference between the two groups was statistically significant (P < 0.05).

[0106] Table 3 Comparison of clinical efficacy between the two groups

[0107]

[0108] 2.2 Comparison of clinical symptom scores before and after treatment in the two groups

[0109] Before treatment, there was no statistically significant difference in clinical symptom scores between the two groups (P>0.05). After treatment, the clinical symptom scores in both groups decreased significantly compared to before treatment (P<0.05); after treatment, the clinical symptom score in the observation group was significantly lower than that in the control group (P<0.05).

[0110] Table 4 Comparison of clinical symptom scores before and after treatment in the two groups

[0111]

[0112] Note: Within the group, the comparison between post-treatment and pre-treatment levels is as follows. # P<0.05; After treatment, compared with the control group, *P<0.05

[0113] 2.3 Comparison of RDQ scores before and after treatment in the two groups

[0114] Before treatment, there was no statistically significant difference in RDQ scores between the two groups (P>0.05). After treatment, RDQ scores in both groups decreased significantly compared to before treatment (P<0.05); after treatment, the RDQ score in the observation group was significantly lower than that in the control group (P<0.05).

[0115] Table 5 Comparison of RDQ scores before and after treatment in the two groups

[0116]

[0117] Note: Within the group, the comparison between post-treatment and pre-treatment levels is as follows. # P<0.05; After treatment, compared with the control group, *P<0.05

[0118] 3 Discussion

[0119] This invention's traditional Chinese medicine composition is based on the principle of syndrome differentiation and treatment, with scientific and rational formulation. Fritillaria thunbergii clears heat and dissipates nodules, neutralizes acid and relieves pain, clearing heat stagnation in the liver and stomach, alleviating heartburn and burning pain, and neutralizing stomach acid. Evodia rutaecarpa has the effects of dispelling cold, relieving pain, suppressing nausea and vomiting, and neutralizing acid. Together with Fritillaria thunbergii, one is cold and the other hot, clearing stomach heat and warming stomach cold, achieving a balance of cold and heat. Citrus medica can soothe the liver and relieve stagnation, venting stagnant liver qi, harmonizing the stomach and relieving pain caused by stagnant stomach qi, while balancing the cold of Fritillaria thunbergii and the heat of Evodia rutaecarpa, achieving the goal of harmonizing the liver and stomach. These three herbs together serve as the principal herbs, allowing liver qi to flow smoothly, stomach qi to descend, and stagnant heat to be cleared. Inula japonica can lower qi and eliminate phlegm, relieve nausea and vomiting, and assist the principal herb Evodia rutaecarpa in enhancing the overall effect of the formula in relieving nausea and vomiting. Salvia miltiorrhiza has the effects of soothing the liver and regulating qi, harmonizing the stomach and relieving pain. Nardostachys jatamansi can regulate qi and relieve pain, relieve depression and invigorate the spleen. Together, they assist the principal herb Citrus medica in soothing the liver and regulating qi. Clove warms the middle jiao, lowers nausea and vomiting, dispels cold and relieves pain, warms the kidneys and invigorates yang, and assists Evodia rutaecarpa in enhancing its effects of warming the stomach, dispelling cold, lowering nausea and vomiting. Amomum tsao-ko dries dampness, warms the middle jiao, stops malaria and eliminates phlegm, and assists Fritillaria thunbergii in enhancing its effects of resolving phlegm and eliminating pathogens. Ephedra sinica can nourish yin and clear the lungs, astringe sores and promote tissue regeneration. It can nourish the yin of the esophageal mucosa, replenish the fluids lost due to stomach heat, and promote mucosal repair. These six herbs together serve as assistant herbs, assisting the principal herb from multiple angles: lowering nausea and vomiting, soothing the liver, regulating qi, protecting the mucosa, and warming and transforming. Mother-of-pearl calms the liver and suppresses yang, soothes the mind and calms the nerves; gentian clears heat and dries dampness, drains liver and gallbladder fire; fraxinus bark clears heat and dries dampness, astringes and stops dysentery. All three are cold in nature. Gentian and fraxinus bark clear liver and gallbladder fire, while mother-of-pearl calms the liver and suppresses yang, preventing liver fire from attacking the stomach again. It assists the principal herb, citron, and the assistant herb, salsa, in enhancing the liver-soothing and calming effects. At the same time, it can restrain the warming and drying properties of the principal herb, evodia, and the assistant herbs, clove, cardamom, and nardostachys, preventing excessive consumption of stomach yin by warming herbs and avoiding the overall formula becoming too warm and heat-inducing. It is thus an adjuvant herb. Osmanthus warms the lungs, resolves phlegm, dispels cold and relieves pain, and can assist evodia and clove. This formula enhances the warming and stomach-dispersing effects, clears small amounts of phlegm between the lungs and stomach, and assists the principal herbs, Amomum villosum and Fritillaria thunbergii, in strengthening their phlegm-removing power. Reed rhizome clears heat, generates fluids, and stops vomiting; its cold nature further balances the dryness of the warming herbs in the formula, and its fluid-generating effect alleviates the potential for the cold herbs to damage yin. Its anti-vomiting effect further enhances the overall formula's antiemetic effect. These two herbs serve as adjuvants. Finally, licorice root is used as the guiding herb to tonify the spleen and replenish qi, clear heat and detoxify, relieve spasms and pain, guide the herbs into the meridians, and harmonize the effects of all the herbs. Together, these herbs work to soothe the liver and stomach, reduce nausea and vomiting, and balance the effects of cold and heat.

[0120] The above results demonstrate that the herbal composition of this invention achieves a high overall effective rate in treating reflux esophagitis, significantly improving and alleviating clinical symptoms such as acid reflux, heartburn, bloating, and belching, and effectively reducing the frequency of symptom attacks. This herbal composition provides a new approach and method for the treatment of reflux esophagitis.

[0121] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. 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 of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A traditional Chinese medicine composition for treating reflux esophagitis, characterized in that, The traditional Chinese medicine composition is made from the following traditional Chinese medicine raw materials in parts by weight: 5-20 parts of Inula japonica, 5-20 parts of Amomum tsao-ko, 5-20 parts of Salvia miltiorrhiza, 5-20 parts of Evodia rutaecarpa, 5-20 parts of Fritillaria thunbergii, 5-20 parts of eggshell membrane, 5-20 parts of pearl powder, 5-20 parts of Gentiana scabra, 5-20 parts of Fraxinus chinensis, 5-20 parts of Citrus medica, 5-20 parts of Nardostachys jatamansi, 5-20 parts of Phragmites communis, 5-20 parts of Syzygium aromaticum, 5-20 parts of Osmanthus fragrans, and 5-20 parts of Glycyrrhiza uralensis.

2. The traditional Chinese medicine composition for treating reflux esophagitis according to claim 1, characterized in that, The traditional Chinese medicine composition is made from the following traditional Chinese medicine raw materials in parts by weight: 5-15 parts of Inula japonica, 5-15 parts of Amomum tsao-ko, 5-15 parts of Salvia miltiorrhiza, 5-15 parts of Evodia rutaecarpa, 5-15 parts of Fritillaria thunbergii, 5-15 parts of eggshell membrane, 5-15 parts of pearl powder, 5-15 parts of Gentiana scabra, 5-15 parts of Fraxinus chinensis, 5-15 parts of Citrus medica, 5-15 parts of Nardostachys jatamansi, 5-15 parts of Phragmites communis, 5-15 parts of Syzygium aromaticum, 5-15 parts of Osmanthus fragrans, and 5-15 parts of Glycyrrhiza uralensis.

3. The traditional Chinese medicine composition for treating reflux esophagitis according to claim 1, characterized in that, The traditional Chinese medicine composition is made from the following traditional Chinese medicine raw materials in parts by weight: 12 parts of Inula japonica, 9 parts of Amomum tsao-ko, 12 parts of Salvia miltiorrhiza, 12 parts of Evodia rutaecarpa, 12 parts of Fritillaria thunbergii, 9 parts of eggshell membrane, 9 parts of pearl powder, 9 parts of Gentiana scabra, 9 parts of Fraxinus chinensis, 12 parts of Citrus medica, 9 parts of Nardostachys jatamansi, 9 parts of Phragmites communis rhizome, 9 parts of Syzygium aromaticum, 9 parts of Osmanthus fragrans, and 9 parts of Glycyrrhiza uralensis.

4. The use of the traditional Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a medicament for treating reflux esophagitis, characterized in that, The drug is made from the above-mentioned proportions of Chinese medicinal herbs by weight, supplemented with medically acceptable excipients, and prepared into oral dosage forms, including granules, oral liquids, powders, decoctions, tablets, capsules, and pastes.

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