Traditional Chinese medicine granules for treating esophageal high-grade intraepithelial neoplasia as well as preparation method and application of traditional Chinese medicine granules

Abstract

The invention relates to traditional Chinese medicine granules for treating esophageal high-grade intraepithelial neoplasia as well as a preparation method and application of the traditional Chinese medicine granules, which can be used for remarkably relieving clinical symptoms such as unsmooth choking of a patient and safely and effectively treating esophageal high-grade intraepithelial neoplasia. The traditional Chinese medicine composition is prepared from the following raw material medicines by weight: 10-20g of rabdosia rubescens, 10-20g of radix ophiopogonis, 10-20g of inula flower, 10-20g of turmeric, 3-9g of ginseng and 1-5g of coptis chinensis, the whole formula has the effects of tonifying qi, clearing heat, reducing phlegm and removing stasis, and the traditional Chinese medicine composition is convenient to carry and store; the traditional Chinese medicine preparation for treating esophageal high-grade intraepithelial neoplasia is simple in preparation process, convenient to take and capable of remarkably improving the pathological process of esophageal high-grade intraepithelial neoplasia, is a great innovation of the traditional Chinese medicine preparation for treating esophageal high-grade intraepithelial neoplasia, and has practical clinical significance and popularization and application value.

Description

I. Technical Field

[0001] The present invention relates to the field of medicine, in particular to a traditional Chinese medicine granule (also known as Esophageal Qing Granule) for treating high-grade intraepithelial neoplasia of the esophagus, and its preparation method and application. II. Background Art

[0002] High-grade intraepithelial neoplasia of the esophagus (HGIN), as a key stage of esophageal precancerous lesions, is the last intervention opportunity to reduce the cancer conversion rate. According to the recommendations of the "2024 CSCO Esophageal Cancer Diagnosis and Treatment Guidelines", the preferred treatment method for high-grade intraepithelial neoplasia is endoscopic submucosal dissection (ESD). When the long diameter of the lesion is ≤ 10 mm, endoscopic mucosal resection (EMR) can also be considered if complete resection can be ensured. However, clinical studies have found that reflux, esophagitis, etc. are the main reasons for recurrence and are also common problems after endoscopic mucosal resection for the treatment of esophageal precancerous lesions and early cancer. Therefore, how to improve the quality of life of patients has become an urgent medical problem to be solved.

[0003] Esophageal cancer belongs to the category of "dysphagia" in the field of traditional Chinese medicine. "Ye" means that the food is blocked when swallowed; "Ge" indicates that the food is difficult to swallow smoothly, and even shows a phenomenon of rejection. Past medical experts have elaborated on its etiology and pathogenesis in depth and detail. It is recorded in "Jingyue Quanshu·Dysphagia": "The syndrome of dysphagia must be caused by sorrow, worry, overwork, depression, or excessive indulgence in alcohol and sex, resulting in damage." "Taiping Shenghui Fang" also points out: "Improper cold and warmth, improper diet, or anger and qi reversal, excessive thinking and worry that damage the heart, resulting in disharmony between yin and yang, and stuffiness in the chest and diaphragm, so it is called diaphragmatic qi." Thus, it can be seen that the etiology of dysphagia mainly includes emotional discomfort, improper diet, old age and weakness, and deficiency of vital qi. Its pathogenesis is complex and involves many factors such as "phlegm coagulation, qi stagnation, heat accumulation, blood stasis, and deficiency of vital qi". Due to qi stagnation, phlegm coagulates, blood circulation is blocked to form blood stasis, and heat is generated after a long time of stagnation, which further consumes body fluids, resulting in dryness of body fluids and blood, dryness and stenosis of the esophagus, and obstruction of food passage. In the initial stage of the disease, it is mainly manifested as excess syndromes of qi, stasis, and phlegm; after a long illness, it is mainly manifested as deficiency of vital qi with yin deficiency and body fluid injury. If the condition persists, it will progress from yin deficiency to yang deficiency, eventually leading to deficiency of both yin and yang.

[0004] The precancerous lesion state is an insurmountable stage in the development process of esophageal cancer. After reviewing relevant domestic and foreign research, it is found that there is currently no effective drug that can improve the quality of life of patients. Through long-term clinical observation, practice, and research, it has been shown that traditional Chinese medicine has unique advantages and potential in the treatment of esophageal precancerous lesions, especially high-grade esophageal intraepithelial neoplasia. Traditional Chinese medicine can not only effectively relieve the clinical symptoms of patients and alleviate pain, but also significantly improve the quality of life of patients and prolong their survival period. It can not only improve the treatment effect but also effectively improve the symptoms of patients. Traditional Chinese medicine has a unique mechanism of action in the treatment of high-grade esophageal intraepithelial neoplasia. On the one hand, various traditional Chinese medicine components can regulate the immune function of the body, enhance the body's ability to recognize and eliminate tumor cells, activate immune cells such as T lymphocytes and NK cells, and enable them to better play the roles of immune surveillance and immune killing, thereby inhibiting the growth and proliferation of neoplastic cells. On the other hand, traditional Chinese medicine can also affect the processes of cell proliferation, apoptosis, and differentiation by regulating relevant signaling pathways. For example, some traditional Chinese medicines can intervene in the Wnt / β-catenin signaling pathway, inhibit abnormal cell proliferation signal transduction, induce neoplastic cells to differentiate into normal cells, or cause them to undergo apoptosis, thereby preventing the further development of neoplasia. In addition, the anti-inflammatory effect of traditional Chinese medicine cannot be ignored. The inflammatory microenvironment plays an important role in the occurrence and development of tumors. Traditional Chinese medicine can reduce the levels of inflammatory factors, alleviate local inflammatory reactions, reduce the damage and stimulation of inflammation to esophageal epithelial cells, and reduce the risk of neoplasia from the root cause. However, currently, the number of traditional Chinese medicine preparations specifically used for the treatment of esophageal precancerous lesions on the market is scarce and far from meeting the clinical needs. Therefore, it is urgent to develop a safe, effective, and highly targeted traditional Chinese medicine preparation. III. Summary of the Invention

[0005] In view of the above situation, to solve the defects of the prior art, the purpose of the present invention is to provide a traditional Chinese medicine granule for the treatment of high-grade esophageal intraepithelial neoplasia, its preparation method, and application, which can significantly relieve clinical symptoms such as patients' dysphagia when eating, and safely and effectively treat high-grade esophageal intraepithelial neoplasia.

[0006] The first technical solution provided by the present invention is a traditional Chinese medicine granule for the treatment of high-grade esophageal intraepithelial neoplasia, which is made from the following raw materials by weight: Rabdosia rubescens 10 - 20 g, Ophiopogon japonicus 10 - 20 g, Inula japonica 10 - 20 g, Curcuma longa 10 - 20 g, Panax ginseng 3 - 9 g, and Coptis chinensis 1 - 5 g.

[0007] Preferably, the traditional Chinese medicine granule for the treatment of high-grade esophageal intraepithelial neoplasia is made from the following raw materials by weight: Rabdosia rubescens 15 g, Ophiopogon japonicus 15 g, Inula japonica 15 g, Curcuma longa 15 g, Panax ginseng 6 g, and Coptis chinensis 3 g.

[0008] The second technical solution provided by the present invention is a preparation method of traditional Chinese medicine granules for treating high-grade intraepithelial neoplasia of the esophagus. The above raw materials are crushed and percolated with ethanol, concentrated under reduced pressure to prepare an extract, dried, pulverized into fine powder, added with excipients, wetted with a wetting agent, uniformly made into soft material, passed through a sieve to obtain wet granules, dried, sized through a sieve, and then the fine powder is sieved out with a sieve, and packaged to obtain the granule agent.

[0009] Preferably, the ethanol percolation is that the raw materials are added with 4 - 6 times the volume of ethanol with a volume concentration of 60% - 80%.

[0010] Preferably, the extract is prepared into an extract with a relative density of 1.2 by concentrating under reduced pressure at 60°C.

[0011] Preferably, the wetting agent is ethanol with a volume concentration of 90% - 95%.

[0012] Preferably, the wet granules pass through a 16 - mesh sieve, and the sizing is through a 14 - mesh sieve to screen out agglomerated lumps and coarse particles, and the fine powder is sieved out through a 60 - mesh sieve to make the granules uniform.

[0013] Preferably, the subsequent drying temperature of the wet granules is 50 - 60°C.

[0014] Preferably, the ratio of the medicinal powder to the excipients is 1:2.

[0015] Preferably, the composition of the excipients is dextrin:sugar powder = 1:1.

[0016] The third technical solution provided by the present invention is the application of the active ingredients of the traditional Chinese medicine granules for treating high - grade intraepithelial neoplasia of the esophagus as described in the first technical solution in the preparation of drugs for treating high - grade intraepithelial neoplasia of the esophagus.

[0017] The beneficial technical effects of the present invention are:

[0018] Taking replenishing qi and clearing heat, resolving phlegm and removing stasis as the core treatment principle. Selecting Rabdosia rubescens and Ginseng as the monarch drugs, aiming to play the roles of clearing heat and resolving phlegm, replenishing qi and strengthening the foundation for the common symptoms of patients with high - grade intraepithelial neoplasia of the esophagus such as dysphagia, expectoration, anorexia, endogenous phlegm - heat accumulation, and weakness of the spleen and stomach.

[0019] Inula japonica Thunb. and Ophiopogon japonicus (Thunb.) Ker - Gawl. are used as ministerial drugs together, playing a synergistic therapeutic role for the symptoms of anorexia due to heat in the stomach yin and hiccups of the patients.

[0020] Curcuma longa L. is used as an adjuvant drug, which can effectively relieve the symptoms such as burning discomfort behind the sternum and fullness in the chest and epigastrium, and can enhance the effects of soothing the liver and regulating qi, promoting blood circulation and removing stasis when combined with other drugs.

[0021] Coptis chinensis, as an adjuvant drug, has a significant effect of clearing heat, reducing adverse qi and stopping vomiting on symptoms such as fullness and discomfort in the epigastric and abdominal regions, nausea and vomiting caused by damp-heat blocking the middle-jiao and qi stagnation.

[0022] The whole formula together exerts the effects of supplementing qi and clearing heat, resolving phlegm and removing stasis, which is convenient for carrying and storing; it can be taken immediately after being brewed, with convenient administration, and can significantly improve the pathological process of high-grade intraepithelial neoplasia of the esophagus. It is a major innovation in traditional Chinese medicine preparations for the treatment of high-grade intraepithelial neoplasia of the esophagus, and has practical clinical significance and value for popularization and application. IV. Specific Embodiments

[0023] The following further elaborates on the specific embodiments of the present invention in conjunction with the examples.

[0024] Example 1

[0025] A traditional Chinese medicine granule for treating high-grade intraepithelial neoplasia of the esophagus is prepared from the following raw materials by weight: Rabdosia rubescens 10 g, Ophiopogon japonicus 10 g, Inula japonica 10 g, Curcuma longa 10 g, Panax ginseng 3 g, and Coptis chinensis 1 g.

[0026] Its preparation method is as follows: The raw materials are pulverized, percolated with 4 times the volume of 60% ethanol by volume, concentrated under reduced pressure at 60 °C to prepare an extract with a relative density of 1.2, dried, pulverized into fine powder, and auxiliary materials are added. The ratio of the medicinal powder to the auxiliary materials is 1:2, and the auxiliary material composition is dextrin:sugar powder = 1:1. Using 90% ethanol by volume as the wetting agent, it is uniformly made into soft material, wet granules are obtained by passing through a 16-mesh sieve, dried at 50 °C, sized through a 14-mesh sieve, the agglomerated lumps and coarse granules are screened out, and then the fine powder is screened out through a 60-mesh sieve to make the granules uniform, and then packaged to obtain the granule agent.

[0027] Example 2

[0028] A traditional Chinese medicine granule for treating high-grade intraepithelial neoplasia of the esophagus is prepared from the following raw materials by weight: Rabdosia rubescens 15 g, Ophiopogon japonicus 15 g, Inula japonica 15 g, Curcuma longa 15 g, Panax ginseng 6 g, and Coptis chinensis 3 g.

[0029] Its preparation method is as follows: The raw materials are pulverized, percolated with 5 times the volume of 70% ethanol by volume, concentrated under reduced pressure at 60 °C to prepare an extract with a relative density of 1.2, dried, pulverized into fine powder, and auxiliary materials are added. The ratio of the medicinal powder to the auxiliary materials is 1:2, and the auxiliary material composition is dextrin:sugar powder = 1:1. Using 95% ethanol by volume as the wetting agent, it is uniformly made into soft material, wet granules are obtained by passing through a 16-mesh sieve, dried at 55 °C, sized through a 14-mesh sieve, the agglomerated lumps and coarse granules are screened out, and then the fine powder is screened out through a 60-mesh sieve to make the granules uniform, and then packaged to obtain the granule agent.

[0030] Example 3

[0031] A traditional Chinese medicine granule for treating high-grade intraepithelial neoplasia of the esophagus, which is made from the following raw materials by weight: 20 g of Rabdosia rubescens, 20 g of Ophiopogon japonicus, 20 g of Inula japonica, 20 g of Curcuma longa, 9 g of Panax ginseng, and 5 g of Coptis chinensis.

[0032] The preparation method is as follows: The raw materials are crushed, percolated with 6 times the volume of ethanol with a concentration of 80%, concentrated under reduced pressure at 60°C to prepare an extract with a relative density of 1.2, dried, pulverized into fine powder, and auxiliary materials are added. The ratio of the medicine powder to the auxiliary materials is 1:2, and the auxiliary material composition is dextrin:sugar powder = 1:1. Using ethanol with a volume concentration of 95% as a wetting agent, it is uniformly made into soft material, passed through a 16-mesh sieve to obtain wet granules, dried at 60°C, granulated through a 14-mesh sieve, the agglomerated lumps and coarse granules are screened out, and then passed through a 60-mesh sieve to screen out the fine powder to make the granules uniform, and then packaged to obtain the granule agent.

[0033] The traditional Chinese medicine granule of the present invention is precisely aimed at patients with high-grade intraepithelial neoplasia of the esophagus belonging to the syndrome of weakness of the spleen and stomach and the intermingling of phlegm and stasis, and takes replenishing qi and clearing heat, resolving phlegm and removing stasis as the core treatment principle. Rabdosia rubescens was first recorded in "Shennong Ben Cao Jing" and was listed as a top-grade medicine in "Compendium of Materia Medica". It is often used to treat symptoms such as asthma and chest tightness. "Supplementary Records of Materia Medica" also records that it can treat persistent cough, blood in sputum, chest pain, etc. Rabdosia rubescens is bitter, sweet, and slightly cold in nature, and belongs to the lung, stomach, and liver meridians. It has the effects of clearing heat and detoxifying, promoting blood circulation and relieving pain. "Chinese Herbal Medicine" records that it "clears heat and detoxifies, promotes blood circulation and relieves pain. It is mainly used for sore throat, headache due to cold, tracheitis, chronic hepatitis, rheumatic joint pain, snake and insect bites."

[0034] According to the record in "Shennong Ben Cao Jing", Panax ginseng "tonifies the five internal organs, calms the mind, stabilizes the soul, stops palpitation, eliminates pathogenic factors, improves eyesight, and promotes intelligence and happiness." "Summary of Medical Herbs" also points out that it "tonifies primordial qi, quenches thirst, and promotes the production of body fluid." Panax ginseng is sweet, slightly bitter, and flat in nature, and belongs to the lung, spleen, and heart meridians. It greatly tonifies primordial qi, invigorates the spleen and benefits the lung, promotes the production of body fluid, and soothes the mind and promotes intelligence. It is a precious tonic commonly used in traditional Chinese medicine. Its medicinal properties are mild, neither dry nor wet, neither cold nor hot, and it is a mild tonic. Therefore, Rabdosia rubescens and Panax ginseng are selected as the monarch drugs to aim at the common symptoms of patients with high-grade intraepithelial neoplasia of the esophagus, such as difficulty in swallowing, expectoration of phlegm, poor appetite, internal accumulation of phlegm-heat, and weakness of the spleen and stomach, and play the roles of clearing heat and resolving phlegm, replenishing qi and consolidating the root.

[0035] According to the record in "Shennong Ben Cao Jing", Inula japonica "maintains qi stagnation and fullness under the hypochondrium, and palpitations. Removes water, eliminates cold and heat among the five internal organs, supplements the middle, and lowers qi." "Treatise on Medical Properties" states that it "treats qi in the costal region, eliminates cold, heat, and edema, mainly treats retained water in the bladder, expels water from the large abdomen, improves appetite, and stops vomiting and refusal to eat." It is bitter, pungent, salty, and slightly warm in nature, and belongs to the lung and stomach meridians. It has the effects of descending qi, promoting diuresis and resolving phlegm, and suppressing the adverse rising of qi and stopping vomiting, and can effectively improve the symptoms of patients with precancerous lesions of esophageal cancer, such as difficulty in eating, vomiting phlegm, and belching.

[0036] Ophiopogon japonicus, as recorded in *Huayan of Materia Medica*, is "a medicine for clearing the heart and moistening the lungs. It mainly treats insufficient heart qi, palpitations, forgetfulness, mental derangement; or lung heat and dryness, continuous cough, withered lungs, shortness of breath and weakness, internal heat in the lungs, hemoptysis; or consumptive fever, dryness of body fluids; or dryness of the spleen and stomach, constipation due to deficiency." Ophiopogon japonicus is sweet, slightly bitter, and slightly cold, and enters the stomach, lung, and heart meridians. It has the effects of nourishing yin and promoting fluid production, moistening the lungs and clearing the heart. Together with Inula japonica, it serves as the ministerial drugs, playing a synergistic therapeutic role in treating symptoms such as anorexia due to stomach yin heat and hiccups in patients.

[0037] Curcuma longa, as recorded in *Supplementary Records of Materia Medica*, "has a pungent taste, is warm in nature, non-toxic, yellow in color, and mainly promotes blood circulation to remove blood stasis, lowers qi, and is warm without being cold." *Searching for the Origin of Materia Medica* states: "Curcuma longa benefits the fire and promotes qi. With its pungent and warm nature, it reaches the fire to promote qi transformation. When qi transformation occurs, body fluids flow in the three yin and three yang meridians. The clear ones are infused into the lungs, and the turbid ones are infused into the meridians and flow into the sea, and then the blood moves on its own. This is to regulate qi and disperse stagnation and promote blood circulation to remove stasis." It is hot in nature, with a pungent and bitter taste, promoting blood circulation to remove blood stasis, regulating qi and activating collaterals, and promoting menstruation and relieving pain. As an assistant drug, it can effectively relieve symptoms such as burning discomfort behind the sternum and fullness and stuffiness in the chest and epigastric region. When combined with other drugs, it can enhance the effects of soothing the liver and regulating qi, promoting blood circulation to remove blood stasis.

[0038] Coptis chinensis, as recorded in *Shennong's Classic of Materia Medica*, "mainly treats heat in the eyes, lacrimation due to injury to the canthi, abdominal pain and diarrhea due to intestinal carbuncle, and swelling and pain in the vagina of women." *Justification of Materia Medica* records: "Coptis chinensis is extremely bitter and cold. Its bitterness dries dampness, and its coldness subdues heat. It can purge and descend all excessive damp-heat, and there is no heat in the heart, spleen, liver, kidney, gallbladder, stomach, large and small intestines that it cannot treat." Coptis chinensis is extremely bitter and cold, clearing heat and drying dampness, purging fire and detoxifying, especially good at clearing damp-heat in the middle jiao. As a guiding drug, it has a significant effect of clearing heat, reducing adverse qi, and stopping vomiting on symptoms such as fullness and stuffiness in the epigastric region and nausea and vomiting caused by damp-heat blocking the middle jiao and qi stagnation.

[0039] Through experiments and applications, the traditional Chinese medicine granules of the present invention have achieved very good beneficial technical effects. The relevant experimental data are as follows:

[0040] 1. Diagnostic criteria:

[0041] Referring to the *Expert Consensus on the Diagnosis and Treatment Strategies of Precancerous States and Precancerous Lesions of Esophageal Squamous Cell Carcinoma in China 2020*: Histopathology is the gold standard for diagnosing esophageal intraepithelial neoplasia. Esophageal high-grade intraepithelial neoplasia is defined as the range of atypical cells exceeding half of the epithelial layer but not breaking through the basement membrane.

[0042] 2. Case inclusion criteria:

[0043] All those who meet the following conditions can be selected as cases: meeting the diagnostic criteria of esophageal high-grade intraepithelial neoplasia and undergoing endoscopic resection within ≤1 month; being diagnosed as having the syndrome of phlegm stasis and weakness of the spleen and stomach in traditional Chinese medicine; being aged between 18 and 80 years old (both men and women); having good general conditions and stable vital signs; not participating in other clinical trials observing the clinical efficacy of insomnia; the patients being fully informed, voluntarily participating, willing to receive treatment and taking medicine according to the regulations to complete the course of treatment.

[0044] 3. Exclusion criteria:

[0045] Pregnant or lactating women; patients with mental disorders; those with language expression disorders and lacking the ability to judge their own symptoms; patients with allergic constitutions or those known to be allergic to the ingredients of this medicine; those with severe primary diseases involving the heart, liver, lungs, kidneys, hematopoietic system, etc.

[0046] 4. Treatment plan:

[0047] Take one dose daily on the basis of symptomatic supportive treatment. Take it in two divided doses, each dose melted with 150 - 200 ml of boiling water and taken 1 hour after meals. The treatment duration is 6 months, and the treatment effect is evaluated after the treatment ends.

[0048] 5. Efficacy evaluation criteria:

[0049] Refer to the "Guiding Principles for Clinical Research of New Chinese Medicines" to score the main clinical symptoms, such as the frequency and degree of symptoms like dysphagia, retrosternal pain, acid reflux, heartburn, etc. Score 0 points, 2 points, 4 points, and 6 points for none, mild, moderate, and severe respectively. The curative effect is judged according to the integral reduction rate. The higher the integral reduction rate, the more obvious the treatment effect.

[0050] Marked effect: The clinical symptoms and signs are significantly improved, and the symptom integral decreases by ≥ 70%;

[0051] Effective: The clinical symptoms and signs are somewhat improved, and the symptom integral decreases by ≥ 30% and < 70%;

[0052] Ineffective: The clinical symptoms and signs have no obvious change or even worsen, and the symptom integral decreases by ≤ 30%.

[0053] Total effective rate = [(marked effect + effective) / n] × 100%.

[0054] The scoring criteria refer to "Oncology" edited by Sun Yan. Each time the patient is admitted to the hospital, the symptoms of esophageal cancer patients are evaluated by the same deputy chief traditional Chinese medicine doctor and the traditional Chinese medicine symptom integral form is filled out for integral calculation and recording.

[0055] (3) Safety indicators

[0056] 1) Routine blood test, routine urine test, routine stool test;

[0057] 2) Electrocardiogram, chest DR, liver function, kidney function;

[0058] 3) Coagulation function test.

[0059] Each is detected once at 0, 3, and 6 months.

[0060] 6. Statistical processing:

[0061] Perform a preliminary analysis on the baseline data to describe and infer characteristics first. For measurement data that conforms to a normal distribution, describe it using the mean ± standard deviation (x±s) and perform a t-test. If it does not conform to a normal distribution, represent it using the median and perform a rank sum test. Categorical variables are represented using frequencies and constituent ratios, and the chi-square test X 2 。

[0062] 7. Results:

[0063] Table 1 Statistical results of the curative effect

[0064] Number of people Marked effect Effective Ineffective Total effective rate 52 15 30 7 86.54％

[0065] As can be seen from the above table, a total of 52 people used the Esophageal Qing Granules in Example 2 of the present invention. Among them, 15 cases were markedly effective, 30 cases were effective, 7 cases were ineffective, and the total effective rate was 86.54%.

[0066] No adverse reactions were found in this trial, indicating that the medication of the present invention is safe and the curative effect is stable and reliable.

[0067] To describe the treatment situation in more detail, the following gives typical cases and the curative effect of the treatment:

[0068] Case 1 Wang XX, male, 63 years old, from Changzhi City, Shanxi Province. First diagnosis on September 15, 2024

[0069] Chief complaint: More than 5 months after ESD for high-grade squamous intraepithelial neoplasia of the esophagus

[0070] History of present illness: In May 2023, due to weight loss, the patient underwent gastroscopy at Henan Cancer Hospital, which showed high-grade intraepithelial neoplasia of the esophagus. Subsequently, endoscopic submucosal dissection (ESD) of the esophagus was performed. The postoperative pathology showed: (ESD of the esophagus) high-grade intraepithelial neoplasia of squamous epithelium, with focal glandular involvement, and negative resection margins (lateral and basal). Gastroscopy showed: after ESD of the esophagus, superficial gastritis. The pathology on March 11, 2024 showed: (35 cm of the esophagus) chronic mucosal inflammation, focal low-grade intraepithelial neoplasia of squamous epithelium, and a small focus considered high-grade intraepithelial neoplasia in combination with immunohistochemistry. Immunohistochemistry A: P53(+), Ki-67(+). The pathology on March 22, 2024 showed: (cardia) chronic mucosal inflammation with glandular dilation. So, on March 27, 2024, "endoscopic submucosal dissection (ESD) for early esophageal cancer" was performed. The postoperative pathology showed: (esophagus) low-grade intraepithelial neoplasia of squamous epithelium, and a small focus considered high-grade intraepithelial neoplasia of squamous epithelium in combination with immunohistochemistry. Immunohistochemistry A / B / D: P53 (focal +), Ki-67 (upward shift of focal expression). The pathological consultation at the Cancer Hospital of the Chinese Academy of Medical Sciences showed: (ESD of the esophagus on May 26, 2023) high-grade intraepithelial neoplasia of squamous epithelium, no tumor at the basal resection margin, and the situation of the lateral resection margin should be combined with the original unit's pathological specimen collection record and report. pTNM stage: pTis. (ESD of the esophagus on March 27, 2024) low-grade intraepithelial neoplasia of squamous epithelium, focal high-grade intraepithelial neoplasia, and focal considered mucosal squamous cell carcinoma invading the lamina propria mucosae, no vascular tumor thrombus or nerve invasion seen. No tumor at the lateral and basal resection margins. pTNM stage: pT1a. Immunohistochemistry of the original unit: p53 (diffuse strong +, indicating a missense mutant expression pattern). The gastroscopy on July 10, 2024 showed: after ESD for high-grade intraepithelial neoplasia of the esophagus. Currently taking: Ruanjian Sanjie Capsule, traditional Chinese medicine decoction. Symptoms seen in the outpatient clinic: dysphagia, occasional retrosternal pain, fatigue, dry mouth, often hoarse voice; abdominal distension after eating, occasional acid reflux, heartburn, hiccups, relieved after passing gas; normal appetite; poor sleep, light sleep and easy to wake up, difficult to fall asleep again after waking up; normal defecation, yellow urine. The weight has decreased by about 6 Kg in the past 4 months.

[0071] After communicating with the patient and their family members, an informed consent form was signed, and the patient began taking the traditional Chinese medicine (Esophageal Qing) granules prepared in Example 2 of the present invention orally. After taking the above prescription for more than one month, the effect was acceptable, and the patient's sleep improved compared to before. On October 23, 2024, the patient had a review at the Cancer Hospital of the Chinese Academy of Medical Sciences. The pathology report (dated October 24, 2024) showed: "(1) Mild chronic inflammation of the squamous epithelial tissue in the esophagus (about 33 cm from the incisors at the esophagus) after ESD at an external hospital for esophageal cancer." "(2) High-grade intraepithelial neoplasia of the squamous epithelium (about 35 cm from the incisors at the esophagus)." On November 19, 2024, endoscopic submucosal dissection (ESD) of the esophagus was performed, and the operation process was smooth. During the review on December 29, 2024, the current symptoms were as follows: Smooth swallowing, significant relief of pain behind the sternum, slightly dry mouth, often hoarse voice; abdominal distension after eating, occasional acid reflux, heartburn, and hiccups relieved; normal appetite, good appetite; normal sleep; dry stools sometimes, yellow urine. The patient's weight decreased by about 3 kg in the past three months.

[0072] 8. Conclusion:

[0073] The Esophageal Qing granules of the present invention are exquisitely formulated with the above six traditional Chinese medicines. The medication is precise and sophisticated, and each medicine synergizes with and complements each other. The whole prescription exerts the effects of replenishing qi, clearing heat, resolving phlegm, and removing stasis. Verified by a large number of clinical trials and practical applications, the clinical efficacy is remarkable, effectively improving the clinical symptoms of patients. The traditional Chinese medicine granule is convenient to carry abroad and meets the entry requirements of some countries; its quality is stable and controllable, and it has high safety; it is small in volume and light in weight, convenient to carry and store; it can be taken immediately after brewing, and the administration is convenient, providing a brand-new and highly valuable treatment option for patients with high-grade intraepithelial neoplasia of the esophagus, and is expected to benefit more patients in clinical promotion and application.

Claims

1. A Chinese medicine granule for treating high-grade esophageal intraepithelial neoplasia, characterized in that: The drug is prepared from the following raw materials by weight: 10-20 g of Rubescens herb, 10-20 g of Radix Ophiopogonis, 10-20 g of Flos Inulae, 10-20 g of Curcuma longa, 3-9 g of Radix Ginseng and 1-5 g of Rhizoma Coptidis.

2. The Chinese medicine granules for treating high-grade esophageal intraepithelial neoplasia according to claim 1, characterized in that: The drug is prepared from the following raw materials by weight: 15 g of Rubescens rubescens, 15 g of Ophiopogon japonicus, 15 g of Inula frutescens, 15 g of Curcuma longa, 6 g of Ginseng and 3 g of Coptis chinensis.

3. The method for preparing the Chinese medicine granules for treating high-grade esophageal intraepithelial neoplasia according to claim 1, characterized in that: The raw material drug is crushed and percolated with ethanol, concentrated under reduced pressure to prepare an extract, dried, crushed into fine powder, added with auxiliary materials, moistened with a wetting agent, uniformly made into a soft material, sieved to obtain wet granules, dried, sieved through a sieve to obtain whole granules, and then sieved with a sieve to remove fine powder and packaged to obtain granules.

4. The method for preparing the Chinese medicine granules for treating high-grade esophageal intraepithelial neoplasia according to claim 3, characterized in that: The ethanol percolation is prepared by adding 4-6 times the volume of ethanol with a concentration of 60%-80% to the raw material.

5. The method for preparing the Chinese medicine granules for treating high-grade esophageal intraepithelial neoplasia according to claim 3, characterized in that: The extract is prepared by concentrating under reduced pressure at 60° C. to obtain an extract with a relative density of 1.

2.

6. The method for preparing the Chinese medicine granules for treating high-grade esophageal intraepithelial neoplasia according to claim 3, characterized in that: The wetting agent is ethanol with a volume concentration of 90%-95%.

7. The method for preparing the Chinese medicine granules for treating high-grade esophageal intraepithelial neoplasia according to claim 3, characterized in that: The wet granules are passed through a 16-mesh sieve, the whole granules are passed through a 14-mesh sieve, the sticky lumps and coarse particles are screened out, and the fine powder is screened out through a 60-mesh sieve to make the particles uniform.

8. The method for preparing the Chinese medicine granules for treating high-grade esophageal intraepithelial neoplasia according to claim 3, characterized in that: The subsequent drying temperature of the wet granules is 50-60°C.

9. The method for preparing the Chinese medicine granules for treating high-grade esophageal intraepithelial neoplasia according to claim 3, characterized in that: The ratio of the medicine powder to the auxiliary material is 1:2, and the auxiliary material composition is dextrin: powdered sugar = 1:

1.

10. The Chinese medicine granules for treating high-grade esophageal intraepithelial neoplasia according to claim 1 or 2, and use of the active ingredients thereof in the preparation of a drug for treating high-grade esophageal intraepithelial neoplasia.