A traditional Chinese medicine composition for treating upper gastrointestinal cancer and its preparation method

Abstract

The application provides a traditional Chinese medicine composition and a preparation method thereof, which is used for treating the symptom of water and rice not entering of upper gastrointestinal cancer, and is mainly made of eaglewood, borax, green malachite, white vine, belamcanda, ginseng, mint, wintergreen, mountain bittercress, Sichuan fritillary and borneol, and is characterized by that: white vine, belamcanda, ginseng, mint, wintergreen, mountain bittercress and Sichuan fritillary medicinal materials are extracted to obtain an extract; the extract is filtered and concentrated after being combined to obtain a clear paste; the eaglewood and the borax and the green malachite are crushed into fine powder; the fine powder, the borneol and the clear paste are uniformly mixed to obtain a medicinal paste. The traditional Chinese medicine composition has the effect of treating the symptom of water and rice not entering of esophageal cancer, is green, low in cost, low in side effect and the like, fills the blank of water and rice not entering of advanced esophageal cancer at home and abroad at present, combines the traditional Chinese medicine concept and the modern pharmaceutical technology, can become a new type of medicine for treating the symptom of water and rice not entering caused by digestive system cancer, has wide market prospect and application value.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and in particular to a traditional Chinese medicine composition and its preparation method. Background Technology

[0002] Esophageal cancer, gastric cancer, and cardia cancer are common malignant tumors of the digestive tract, with high global incidence and mortality rates. Currently, treatments for upper gastrointestinal cancers mainly include surgery, radiotherapy, and chemotherapy. However, these treatments often come with severe side effects, causing not only immense physical suffering but also significant impacts on patients' mental health and social lives. Especially in the late stages of the disease, patients often experience severe symptoms such as difficulty swallowing and vomiting immediately after eating, clinically known as "unable to eat or drink," which greatly reduces their quality of life.

[0003] Current clinical treatments for these symptoms include esophageal stent placement, oral feeding, or nasogastric feeding (for patients unable to eat orally, a feeding tube is inserted into the esophagus through the mouth or nose, passing through the pharynx and reaching the stomach). However, these treatments are all physical therapies, failing to address the root cause and having limitations such as limited efficacy, significant side effects, high cost, and patient discomfort. Furthermore, their effectiveness is limited for late-stage patients. In addition, these methods are often expensive, placing a financial burden on patients' families. While modern medicine offers some symptomatic treatments for symptoms like loss of appetite, such as feeding tube placement and pain medication, these methods do not fundamentally improve the patient's swallowing function.

[0004] Traditional Chinese medicine (TCM), a medical system with thousands of years of history, offers unique treatment options for many intractable diseases through its holistic approach and the principle of syndrome differentiation and treatment. Traditional Chinese medicine, due to its multi-component, multi-target characteristics, low side effects, and good patient tolerability, has become an important choice for adjuvant cancer therapy. However, existing TCM preparations still suffer from unstable efficacy, weak targeting, and unclear mechanisms of action. Therefore, there is an urgent need for a safe, effective, and economical treatment method to alleviate the loss of appetite in patients with upper gastrointestinal cancer. Summary of the Invention

[0005] In response to the problem of loss of appetite and other symptoms in patients with upper gastrointestinal cancer, this invention proposes a method for preparing a traditional Chinese medicine composition and the traditional Chinese medicine composition itself, which can improve the quality of life of patients with loss of appetite caused by upper gastrointestinal cancer and has a good therapeutic effect on upper gastrointestinal cancer.

[0006] To achieve the above objectives, the technical solution of the present invention is implemented as follows: A traditional Chinese medicine composition, by weight, is mainly made from the following components: 5-10 parts agarwood 5-10 parts of borax 5-10 parts of Qingmeng stone 10-20 parts of white peony root 10-20 parts of Belamcanda chinensis 10-20 portions of ginseng 5-15 servings of mint 10-20 parts of *Isodon japonicus* 10-20 servings of Pseudobulbus Cremastrae 10-20 parts of Fritillaria cirrhosa 10-20 servings of borneol.

[0007] Furthermore, the dosage form of the traditional Chinese medicine composition is decoction, powder, granule or ointment, preferably ointment.

[0008] Furthermore, the preparation method includes the following steps: (1) Boil the medicinal materials, including white peony root, belamcanda chinensis, ginseng, mint, scutellaria barbata, cremastra appendiculata and fritillaria cirrhosa, in water to obtain an extract; (2) Filter and concentrate the extract to obtain a clear extract; (3) Grind agarwood, borax and chlorite into fine powder; (4) Mix the fine powder, borneol and clear paste evenly to obtain the Chinese medicine composition ointment.

[0009] Furthermore, in step (1), the temperature for adding water and decocting is 80-100℃, and the time is 45-90 minutes; the number of times of decocting is 2-3.

[0010] Furthermore, in step (2), the concentration is carried out under reduced pressure, and the relative density of the extract is 1.15-1.20 at 50-60℃.

[0011] Furthermore, in step (3), the solid powder is further subdivided into solid powder that passes through a sieve of 100 mesh or higher.

[0012] Furthermore, in step (4), pharmaceutically acceptable excipients are added, which help to better exert the efficacy, improve stability, or improve taste, flavor or properties.

[0013] Furthermore, the pharmaceutically acceptable excipients include one or more of honey, refined honey, sucrose, microcrystalline cellulose, povidone, or maltodextrin.

[0014] Furthermore, the aforementioned traditional Chinese medicine composition is used to treat symptoms of upper gastrointestinal cancer such as loss of appetite.

[0015] The upper gastrointestinal cancers mentioned are esophageal cancer, cardia cancer, or gastric cancer.

[0016] Peppermint and *Isodon japonicus* are used medicinally as the whole plant, and their production process is not suitable for pulverization; therefore, extraction is used before medicinal use. *Ampelopsis japonica*, *Belamcanda chinensis*, ginseng, *Cremastra appendiculata*, and *Fritillaria cirrhosa* are often extracted before medicinal use, so extraction is also used for these purposes. Agarwood is a precious medicinal material and is best used by pulverization. Borax and chlorite are mineral-based medicines; extraction does not retain most of their active ingredients. To maximize their efficacy, and because both are relatively easy to pulverize, borax and chlorite are also pulverized before medicinal use.

[0017] In this invention, *Ampelopsis japonica* clears heat and detoxifies, reduces swelling and dissipates nodules, promotes wound healing and tissue regeneration; *Belamcanda chinensis* clears heat and detoxifies, dissipates nodules and reduces inflammation, reduces swelling and relieves pain, stops cough and resolves phlegm; *Imperata cylindrica* clears heat and detoxifies, invigorates blood and relieves pain; and *Cremastra appendiculata* clears heat and detoxifies, resolves phlegm and dissipates nodules. These four herbs are commonly used in traditional Chinese medicine for treating abdominal masses and are also recognized by modern medicine as having significant anti-cancer effects. Therefore, these four herbs, clearing heat and detoxifying, reducing swelling and dissipating nodules, serve as the principal herbs.

[0018] The formula contains peppermint to dispel wind and heat, clear the throat and soothe the throat; borax to clear heat and detoxify, reduce swelling and soothe the throat; chlorite to expel phlegm and lower qi; borneol to open the orifices, refresh the mind, reduce swelling and relieve pain; fritillaria to clear heat and moisten the lungs, resolve phlegm and stop coughing, disperse nodules and reduce swelling; and agarwood to regulate qi, relieve pain, stop vomiting and relieve asthma. All six herbs work together to reduce swelling and soothe the throat, resolve phlegm and disperse nodules, and are considered assistant herbs.

[0019] Ginseng greatly replenishes vital energy, restores pulse and consolidates the body, generates fluids and nourishes blood. It replenishes both qi and blood, supports the body's resistance and eliminates pathogens, preventing the above ten herbs from being too cold and excessive in eliminating pathogens, which could damage the body's resistance, leading to depletion of qi and blood and insufficient vital energy.

[0020] In addition, honey can nourish the body, moisturize dryness, relieve pain, and detoxify.

[0021] Modern pharmacological, efficacy, and clinical research: Modern pharmacological studies have shown that white peony has anti-cancer effects: in vitro experiments have shown that it has an inhibitory effect on the human cervical cancer cell culture line JTC-26, with an inhibition rate of over 90%.

[0022] Belamcanda chinensis extract can inhibit tumor growth and has anti-cancer effects. Using tumor-bearing mouse S180 as a model, its anti-tumor effect was observed, and the tumor inhibition rate of Belamcanda chinensis extract reached 44.74%.

[0023] *Rabdosia rubescens* is a traditional Chinese medicine used in Henan province to treat esophageal and gastric cardia cancer. Anticancer active substances extracted from *Rabdosia rubescens*, such as Rubescensine A, have significant antitumor effects against various transplanted animal tumors. Clinically, it has shown some efficacy in treating esophageal and liver cancer. A clinical observation of 76 elderly patients with advanced esophageal cancer by Zhou Li et al. indicated that *Rabdosia rubescens* is effective in treating this condition, with the 6-month and 12-month survival rates in the treatment group being 66.7% and 31.5%, respectively, significantly higher than the 40.9% and 9.1% in the control group.

[0024] Modern medicine has confirmed that Cremastra appendiculata is a highly effective drug for treating cancer, capable of treating various cancers, and is often used as a basic medicine in cancer treatment.

[0025] Researchers at Stanford University in the UK have discovered that peppermint leaves can inhibit blood vessel growth at the site of cancerous lesions, depriving the tumor of blood supply and ultimately causing the cancer cells to die.

[0026] Agarwood volatile oil has pharmacological activities such as antioxidation, antibacterial, analgesic and sedative, anti-inflammatory and anticancer effects.

[0027] Ginseng, a precious medicinal herb, is known for its anti-tumor effects, particularly the rare ginsenosides Rg3 and Rh2 among its total ginsenosides. Studies have found that Rg3 and Rh2 not only possess anti-tumor pharmacological effects but also regulate and enhance the body's immunity.

[0028] The monomeric compounds in the total alkaloids of Fritillaria cirrhosa, such as Fritillaria cirrhosa ketone, Fritillaria cirrhosa alkaloid, Fritillaria cirrhosa nitrate, Isoflavone, Isoflavone nitrate, and Fritillaria cirrhosa alkaloid, can inhibit the proliferation of eukaryotic tumor cells and have a therapeutic effect on tumors.

[0029] The therapeutic mechanism of this invention for treating upper gastrointestinal cancer is as follows: It primarily clears the throat and relieves sore throat, eliminates carbuncles and dissipates nodules, thus removing the root cause of cancer—heat toxins; secondarily, it regulates qi and resolves phlegm, dissolving masses and accumulations; and it also simultaneously nourishes both qi and yin to achieve the effect of eliminating pathogens and supporting the body's resistance. The entire formula has a clear primary and secondary component, combining both attacking and tonifying effects.

[0030] The *Neijing* states, "To treat disease, one must seek its root cause," meaning that when treating illness, one must target the underlying cause. The inventor has made further progress in the research of upper gastrointestinal cancers. Based on the etiology and pathogenesis of esophageal cancer, the treatment principles can be summarized as: strengthening the body's resistance and nourishing its foundation; clearing heat and detoxifying; and resolving phlegm and removing blood stasis.

[0031] (1) Strengthening the body's resistance and promoting its fundamental health: It can enhance the body's cellular immunity and humoral immunity, improve bone marrow hematopoietic function, regulate the body's endocrine metabolism and material metabolism, reduce the toxic side effects of radiotherapy and chemotherapy, and some prescriptions also have the effects of inhibiting tumors and controlling the infiltration and metastasis of cancer cells.

[0032] (2) Heat-clearing and detoxifying method: It can directly or indirectly inhibit cancer cells. It is not the same as the antibacterial and antipyretic effects of Western medicine. While removing cancer toxins, heat-clearing and detoxifying also plays a role in protecting the body's vital energy.

[0033] (3) Phlegm-clearing and blood-stasis-removing method: This method mainly improves the body's microcirculation, increases vascular permeability, improves blood hypercoagulability, and has certain anti-inflammatory and immune effects. It eliminates accumulations and tumors, resolves phlegm and softens hard masses, inhibits the growth and metastasis of tumors, and inhibits the expression of adhesion molecules in cancer cells. It has a synergistic effect when combined with radiotherapy and chemotherapy. Huang Shiwen et al. believed that the phlegm-clearing and blood-stasis-removing method is the main treatment for mid-to-late stage esophageal cancer. By clearing phlegm and dispersing nodules, the tumors remaining in the esophagus are dispersed, and symptoms such as vomiting phlegm and pharyngeal obstruction are relieved. Phlegm can dissipate local tumors, thereby improving the symptoms caused by tumors.

[0034] The present invention has the following beneficial effects: 1. This invention provides a novel traditional Chinese medicine preparation aimed at treating severe symptoms in patients with advanced esophageal and gastric cardia cancer, including dysphagia, vomiting after eating, and difficulty swallowing water or rice. According to traditional Chinese medicine theory, dysphagia caused by esophageal and gastric cardia cancer is related to local phlegm and blood stasis, and impaired Qi circulation. Therefore, this invention utilizes a carefully selected combination of Chinese medicinal herbs, leveraging their unique effects of clearing the throat, relieving sore throat, and dispersing nodules and swellings, to open the esophagus, relieve pain, dissipate local masses, and restore the normal function of the throat and esophagus, thereby improving the patient's ability to eat, enhancing their quality of life, and alleviating pain.

[0035] 2. The traditional Chinese medicine composition of the present invention effectively improves the symptoms of esophageal cancer and cardia cancer patients who cannot eat or drink, opens the esophagus, allows patients to eat, and improves the quality of life of patients; at the same time, it can also promote the shrinkage of lesions in the esophagus and cardia; the present invention provides a traditional Chinese medicine treatment drug that is low in cost, easy to popularize and has few side effects, as a supplement or alternative to existing treatment options.

[0036] 3. The traditional Chinese medicine composition of this invention is specifically formulated to address the etiology and pathogenesis of malignant tumors of the upper gastrointestinal tract. The formula is scientifically rigorous, combining the principles of strengthening the body's resistance, clearing heat and detoxifying, and resolving phlegm and removing blood stasis. It enhances the body's cellular and humoral immunity, improves bone marrow hematopoietic function, regulates endocrine metabolism and material metabolism, and reduces the toxic side effects of radiotherapy and chemotherapy. Some of the formulas also have the effects of inhibiting tumors and controlling the infiltration and metastasis of cancer cells, which can be an effective adjuvant treatment for upper gastrointestinal cancer.

[0037] 4. The herbal composition of the present invention is made into an ointment, which overcomes the problem of difficulty in taking ordinary pills, tablets and capsules. The medicine slowly passes through the esophagus and can directly act on the lesion site. The human body absorbs it quickly and the effect is good. Moreover, it is convenient to carry and has good clinical effect.

[0038] 5. The preparation method of the pharmaceutical composition of this invention is scientific and reasonable. Peppermint and *Rabdosia rubescens* are used as the whole herb, and their production process is not suitable for pulverization; therefore, extraction is used. *Ampelopsis japonica*, *Belamcanda chinensis*, ginseng, *Cremastra appendiculata*, and *Fritillaria cirrhosa* are often extracted before use; therefore, extraction is also used. Agarwood is a precious medicinal material and is best pulverized. Borax and chlorite are mineral-based medicines; extraction cannot retain most of the active ingredients. To maximize efficacy, and because both are relatively easy to pulverize, borax and chlorite are also pulverized before use. Attached Figure Description

[0039] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0040] Figure 1 This is a schematic diagram of the preparation process of the traditional Chinese medicine composition in Example 1 of the present invention.

[0041] Figure 2 The traditional Chinese medicine composition of this invention was designed to be used in an experiment to treat esophageal cancer cells (Eca109) at a concentration of 24 hours. Figure 2 a) and 48h Figure 2 b) Curve graph.

[0042] Figure 3 The traditional Chinese medicine composition of this invention was designed to be used for 24 hours of treatment in an experiment to study the proliferation and toxicity of esophageal cancer cells TE-1. Figure 3 a) and 48h Figure 3 b) Curve graph.

[0043] Figure 4 The traditional Chinese medicine composition of this invention was designed to be used in a 24-hour treatment concentration experiment to investigate its effect on the proliferation and toxicity of KYSE-450 esophageal cancer cells. Figure 4 a) and 48h Figure 4 b) Curve graph.

[0044] Figure 5 The traditional Chinese medicine composition of this invention was designed to be used in the proliferation-toxicity experiment of KYSE-5100 esophageal cancer cells at a concentration of 24 hours. Figure 5 a) and 48h Figure 5 b) Curve graph.

[0045] Figure 6 The diagram shows the detection of cancer marker proteins by the traditional Chinese medicine composition of this invention. The marker proteins are LC3-b, Bc1-2, Bax, and c-PARP, an indicator of apoptosis.

[0046] Figure 7 Diagnostic reports for esophageal cancer patients before and after taking the traditional Chinese medicine composition of this invention.

[0047] Figure 8 Diagnostic reports for esophageal cancer patients before and after taking the traditional Chinese medicine composition of this invention.

[0048] Figure 9 Diagnostic reports for patients with gastric cardia cancer before and after taking the traditional Chinese medicine composition of this invention.

[0049] Figure 10 Diagnostic reports for patients with gastric cardia cancer before and after taking the traditional Chinese medicine composition of this invention.

[0050] Figure 11 Diagnostic reports for esophageal cancer patients before and after taking the traditional Chinese medicine composition of this invention. Detailed Implementation

[0051] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and 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.

[0052] The IC50 value refers to the concentration of a drug at a certain concentration that induces 50% apoptosis in tumor cells. This concentration is called the 50% inhibitory concentration, which is the concentration at which the ratio of apoptotic cells to the total number of cells is equal to 50%.

[0053] In addition, the IC50 value can be used to measure the ability of a drug to induce apoptosis; the stronger the induction ability, the lower the value. Conversely, the IC50 value can also indicate the tolerance of a certain cell type to a drug. Generally speaking, the smaller the IC50 value, the stronger the antibody's specificity.

[0054] Example 1 This embodiment provides a traditional Chinese medicine composition and its preparation method. Specifically, the prescription of the traditional Chinese medicine preparation is as follows: 7.5 parts agarwood 10 parts of borax 5 portions of Qingmeng stone 15 portions of white peony root 20 portions of Belamcanda chinensis 10 portions of ginseng 5 servings of mint 10 parts of *Isodon japonicus* 15 servings of Pseudobulbus Cremastrae 20 portions of Fritillaria cirrhosa 20 servings of borneol The preparation method includes the following steps: a. Boil the following herbs twice in water: white peony root, belamcanda chinensis, ginseng, mint, scutellaria barbata, cremastra appendiculata, and fritillaria cirrhosa. The boiling temperature is 80-100℃, and each time it lasts for 1 hour. b. After combining the decoctions, filter and concentrate to obtain a clear extract with a relative density of 1.15-1.20 (50-60℃); c. Grind agarwood, borax, and chlorite into a fine powder, and pass the fine powder through a 100-mesh sieve; d. Add the fine powder to the clear paste, along with borneol and refined honey, and stir until evenly mixed; e. The ointment prepared by dispensing. The drug preparation process in this embodiment is as follows: Figure 1 As shown.

[0055] Example 2 This embodiment provides a traditional Chinese medicine composition, specifically, the raw materials of the traditional Chinese medicine preparation are, by weight, as follows: 10 portions of agarwood 5 parts borax 7 portions of Qingmengshi 20 portions of white peony root 15 portions of Belamcanda chinensis 15 portions of ginseng 10 servings of mint 15 portions of *Isodon japonicus* 20 servings of Pseudobulbus Cremastrae 10 portions of Fritillaria cirrhosa 15 servings of borneol The preparation method includes the following steps: a. Boil the following herbs twice in water: white peony root, belamcanda chinensis, ginseng, mint, scutellaria barbata, cremastra appendiculata, and fritillaria cirrhosa. The boiling temperature is 80-100℃, and each time it lasts for 1 hour. b. After combining the decoctions, filter and concentrate to obtain a clear extract with a relative density of 1.15-1.20 (50-60℃); c. Grind agarwood, borax, and chlorite into fine powder, and pass the fine powder through a 150-mesh sieve; d. Add the fine powder to the clear paste, along with borneol and refined honey, and stir until evenly mixed; e. Ointments prepared by repackaging.

[0056] Example 3 This embodiment provides a traditional Chinese medicine composition, specifically, the prescription of the traditional Chinese medicine preparation is as follows: 5 portions of agarwood 7.5 parts borax 10 portions of Qingmeng stone 10 portions of white peony root 10 portions of Belamcanda chinensis 20 portions of ginseng 15 servings of mint 20 portions of *Isodon japonicus* 10 servings of Pseudobulbus Cremastrae 15 portions of Fritillaria cirrhosa 10 servings of borneol The preparation method includes the following steps: a. Boil the following herbs twice in water: white peony root, belamcanda chinensis, ginseng, mint, scutellaria barbata, cremastra appendiculata, and fritillaria cirrhosa. The boiling temperature should be 95-100℃, and each time the decoction should last for 1 hour. b. After combining the decoctions, filter and concentrate to obtain a clear extract with a relative density of 1.15-1.20 (50-60℃); c. Grind agarwood, borax, and chlorite into fine powder, and pass the fine powder through a 200-mesh sieve; d. Add the fine powder to the clear paste, add borneol, and stir until evenly mixed; e. Ointments prepared by repackaging.

[0057] Example 4 This embodiment provides a traditional Chinese medicine composition, specifically, the prescription of the traditional Chinese medicine preparation is as follows: 5 portions of agarwood 7.5 parts borax 10 portions of Qingmeng stone 10 portions of white peony root 10 portions of Belamcanda chinensis 20 portions of ginseng 15 servings of mint 20 portions of *Isodon japonicus* 10 servings of Pseudobulbus Cremastrae 15 portions of Fritillaria cirrhosa 10 servings of borneol The preparation method includes the following steps: a. Weigh the above-mentioned medicinal materials, add water and decoct twice, at a temperature of 95-100℃, for 1 hour each time; b. After combining the decoctions, filter and concentrate them to obtain a clear extract with a relative density of 1.15–1.20 (50–60℃); c. Grind agarwood, borax, and chlorite into a fine powder, and pass the fine powder through a 100-mesh sieve; d. Add the fine powder to the clear paste, along with borneol and an appropriate amount of honey, and stir until well mixed; e. Ointments prepared by repackaging.

[0058] Example 5 This embodiment provides a traditional Chinese medicine composition, specifically, the raw materials of the traditional Chinese medicine preparation are, by weight, as follows: 10 portions of agarwood 5 parts borax 7 portions of Qingmengshi 20 portions of white peony root 15 portions of Belamcanda chinensis 15 portions of ginseng 10 servings of mint 15 portions of *Isodon japonicus* 20 servings of Pseudobulbus Cremastrae 10 portions of Fritillaria cirrhosa 15 servings of borneol The preparation method includes the following steps: a. Boil the following herbs twice in water: white peony root, belamcanda chinensis, ginseng, mint, scutellaria barbata, cremastra appendiculata, and fritillaria cirrhosa. The boiling temperature is 80-100℃, and each time it lasts for 45 minutes. b. After combining the decoctions, filter and concentrate to obtain a clear extract with a relative density of 1.15-1.20 (50-60℃); c. Grind agarwood, borax, and chlorite into a fine powder, and pass the fine powder through a 100-mesh sieve; d. Add the fine powder to the clear paste, along with borneol and an appropriate amount of refined honey, and stir until evenly mixed; e. Ointments prepared by repackaging.

[0059] Example 6 This embodiment provides a traditional Chinese medicine composition, specifically, the prescription of the traditional Chinese medicine preparation is as follows: 8 portions of agarwood 10 parts of borax 5 portions of Qingmeng stone 15 portions of white peony root 15 portions of Belamcanda chinensis 20 portions of ginseng 15 servings of mint 20 portions of *Isodon japonicus* 10 servings of Pseudobulbus Cremastrae 15 portions of Fritillaria cirrhosa 15 servings of borneol The preparation method includes the following steps: a. Boil the following herbs twice in water: white peony root, belamcanda chinensis, ginseng, mint, scutellaria barbata, cremastra appendiculata, and fritillaria cirrhosa. The boiling temperature is 95-100℃, and each time it lasts for 90 minutes. b. After combining the decoctions, filter and concentrate them; c. Grind agarwood, borax, and chlorite into fine powder, and pass the fine powder through a 150-mesh sieve; d. Add the fine powder to the decoction, along with borneol and an appropriate amount of maltodextrin, and stir until evenly mixed; e. Ointments prepared by repackaging.

[0060] Clinical data Cases: From 2013 to 2023, a total of 2,365 patients with upper gastrointestinal cancer were treated, aged 35-80 years, including 1,155 females and 1,210 males.

[0061] Diagnostic criteria: (1) Western medicine diagnostic criteria (refer to GUT:2018 Asian consensus on endoscopic diagnostic criteria for upper gastrointestinal tumors) Gastrointestinal tumors are divided into esophageal squamous cell carcinoma (esophageal cancer); Barrett's adenocarcinoma, cardia cancer, and gastric cancer; clinical manifestations include indigestion, dysphagia, abdominal pain, weight loss and other symptoms; (2) Traditional Chinese Medicine syndrome diagnosis criteria (see the "Guidelines for the Diagnosis and Treatment of Gastric Cancer with Integrated Traditional Chinese and Western Medicine" and the "Guidelines for the Diagnosis and Treatment of Esophageal Cancer with Integrated Traditional Chinese and Western Medicine") are divided into phlegm and qi stagnation, blood stasis obstruction, yin deficiency and heat resolution, qi deficiency and yang deficiency, spleen and kidney yang deficiency, liver and kidney yin deficiency, qi and blood deficiency, phlegm and dampness retention, and blood stasis and toxin obstruction. Clinical manifestations include, but are not limited to, difficulty in swallowing, vomiting after eating, chest pain, acid reflux, belching, nausea, vomiting, difficulty swallowing, abdominal pain, and abdominal distension.

[0062] Treatment and assessment of efficacy: Based on the principle of voluntariness, 370 patients with advanced upper gastrointestinal cancer from the admitted cases were selected and randomly assigned to the following groups. Group 1 One hundred patients with esophageal squamous cell carcinoma who were unable to eat or drink were given the herbal composition ointment of Example 1 of this invention. For the first three days, 3-5g of the ointment was taken every hour; thereafter, 3-5g was taken every two hours. After taking the ointment, patients were prohibited from eating or drinking. If food or water was consumed, an additional dose was required. Spicy and irritating foods were avoided. One course of treatment consisted of seven consecutive days; two courses of treatment were administered consecutively.

[0063] Group 2 Eighty patients who underwent radical resection for esophageal squamous cell carcinoma and experienced dysphagia, food obstruction, expectoration of large amounts of phlegm, and were only able to consume small amounts of liquid food were treated with the herbal composition ointment of Example 1 of this invention. For the first three days, 3-5g of the ointment was taken every hour; thereafter, 3-5g was taken every two hours. After taking the ointment, patients were prohibited from eating or drinking. If food or water was consumed, an additional dose was required. Spicy and irritating foods were avoided. One course of treatment consisted of seven consecutive days; two courses of treatment were administered consecutively.

[0064] Group 3 Eighty patients with gastric cardia cancer who could not eat or drink were given the herbal composition ointment of Example 1 of this invention. For the first three days, 3-5g of the ointment was taken every hour; thereafter, 3-5g was taken every two hours. Patients were prohibited from eating or drinking after taking the ointment. If food or water was consumed, an additional dose was required. Spicy and irritating foods were avoided. One course of treatment consisted of seven consecutive days; two courses of treatment were required.

[0065] Group 4 Fifty patients who underwent radical resection for gastric cardia cancer and subsequently experienced dysphagia, food obstruction, and were only able to consume small amounts of liquid food were treated with the herbal composition ointment of Example 1 of this invention. For the first three days, 3-5g of the ointment was taken every hour; thereafter, 3-5g was taken every two hours. After taking the ointment, patients were prohibited from eating or drinking. If food or water was consumed, an additional dose was required. Spicy and irritating foods were avoided. One course of treatment consisted of seven consecutive days; two courses of treatment were administered consecutively.

[0066] Group 5 Thirty patients who underwent radical gastrectomy for gastric cancer and subsequently experienced dysphagia, food obstruction, and were only able to consume small amounts of liquid food were treated with the herbal composition ointment of Example 1 of this invention. For the first three days, patients took 3-5g every hour; thereafter, they took 3-5g every two hours. After taking the ointment, patients were prohibited from eating or drinking. If food or water was consumed, an additional dose was required. Spicy and irritating foods were avoided. One course of treatment consisted of seven consecutive days; two courses of treatment were administered consecutively.

[0067] Control group: Based on the principle of voluntariness, 30 patients who underwent radical surgery for gastric cardia cancer were not given traditional Chinese medicine intervention after completing adjuvant chemotherapy, and were followed up regularly.

[0068] After the patients receive treatment with the drug of this invention for 1-2 weeks and their diet improves, they can undergo further treatment, such as chemotherapy or surgery, as well as anti-tumor drug treatment.

[0069] Efficacy assessment of dietary status within 2 treatment courses: Significant effect: Clinical symptoms and appetite improved significantly and returned to normal levels.

[0070] Effective: Clinical symptoms and appetite improved, returning to half of their original normal levels.

[0071] Ineffective: Clinical symptoms and signs show no significant improvement or even worsen; dietary condition does not improve or even worsens; endoscopic diagnosis of tumor masses shows no tendency to improve or worsens.

[0072] Treatment effect: Clinical trials involving multiple groups of patients with upper gastrointestinal cancer who could not eat or drink showed that treatment with this drug significantly improved swallowing function, effectively alleviating symptoms of inability to eat or drink, with no significant adverse reactions. Among these, patients with upper gastrointestinal cancer (Groups 2 and 4) had a lower effective rate of improvement in dietary status after surgery due to wound placement compared to patients without surgery (Groups 1 and 3). Furthermore, due to limited contact between the stomach and the drug, the effective rate of gastric cancer patients (Group 5) after taking this ointment was lower than that of esophageal and cardia cancer patients. A comparison was made between the control group and Group 4, with Group 4 showing a significantly higher effective rate than the control group. This indicates that the drug has better efficacy and safety for patients with advanced upper gastrointestinal cancer experiencing inability to eat or drink, and the differences were statistically significant (P < 0.05).

[0073] Drug cell proliferation toxicity test Regarding the cell proliferation and toxicity experiment and subsequent experimental design of the "Water and Rice Not Entering" ointment for treating upper gastrointestinal cancers, this study aimed to verify the drug's tumor-killing effect at the cellular level. Therefore, a cell proliferation-toxicity experiment was designed to evaluate its killing effect on esophageal squamous cell carcinoma cell lines. Four human esophageal cancer cell lines—Eca109, TE-1, KYSE450, and KYSE510—were selected and treated with the ointment from Example 1 at the designed concentration for 24 and 48 hours, respectively, before data were measured. After sterilizing the drug stock solution, it was diluted 1 / 2 with PBS to reduce viscosity; cells were treated with final concentrations of 0.1, 0.05, 0.025, and 0.00625 times the stock solution.

[0074] The proliferation-toxicity experiment of esophageal cancer cells Eca109, with the action curve after 24 hours of treatment at the designed concentration, is shown in the figure below. Figure 2 As shown in a, cell proliferation-toxicity was determined using CCK-8 assay, with an IC50 of 0.030 times the original concentration.

[0075] Assay for the proliferation-toxicity of esophageal cancer cells Eca109, the action curve after 48 hours of treatment at the designed concentration is as follows: Figure 2 As shown in b: Cell proliferation-toxicity was determined using CCK-8 assay, IC50 = 0.028 times the original concentration.

[0076] Assay for TE-1 esophageal cancer cells, the effect curve after 24 hours of treatment at the designed concentration is shown below. Figure 3 As shown in a: Cell proliferation-toxicity was determined using CCK-8 assay, IC50 = 0.023 times the original solution concentration.

[0077] Assay for TE-1 esophageal cancer cells, the effect curve after 48 hours of treatment at the designed concentration is shown below. Figure 3 As shown in b: Cell proliferation-toxicity was determined using CCK-8 assay, IC50 = 0.014 times the original concentration.

[0078] Assay for the proliferation-toxicity of esophageal cancer cells KYSE450, the action curve after 24 hours of treatment at the designed concentration is shown below. Figure 4 As shown in a: Cell proliferation-toxicity was determined using CCK-8 assay, IC50 = 0.024 times the original solution concentration.

[0079] Assay for the proliferation-toxicity of esophageal cancer cells KYSE450, the action curve after 48 hours of treatment at the designed concentration is shown below. Figure 4 As shown in b: Cell proliferation-toxicity was determined using CCK-8 assay, IC50 = 0.015 times the original concentration.

[0080] Assay for esophageal cancer cell proliferation-toxicity, the action curve after 24 hours of treatment at the designed concentration is shown below. Figure 5 As shown in Figure a: Cell proliferation-toxicity was measured using CCK-8 assay, and the interaction curve is shown in the figure. IC50 = 0.027 times the original solution concentration.

[0081] Assay for esophageal cancer cell proliferation-toxicity, the action curve after 48 hours of treatment at the designed concentration is shown below. Figure 5 As shown in b: Cell proliferation-toxicity was measured using CCK-8 assay, and the interaction curve is shown in the figure. IC50 = 0.021 times the original solution concentration.

[0082] The results of the cell proliferation-toxicity experiment show that the drug can inhibit cell proliferation and induce cell death in a concentration-dependent manner. Cell death occurs through various mechanisms, including active cell death (programmed cell death), apoptosis, and passive cell death (necrosis). Apoptosis induced through the mitochondrial pathway is one of the most common ways drugs kill tumor cells.

[0083] In addition, autophagy-mediated cell death is another major pathway by which drugs kill tumor cells. Therefore, to detect these two pathways, we used Western blotting to detect the marker proteins LC3-b, Bc1-2, Bax, and the apoptosis indicator c-PARP. The results are as follows: Figure 6 It was found that the drug can indeed induce apoptosis and autophagy. The drug exerts its effect by causing cell death. However, its action on cells is not time-dependent, but exhibits a good concentration-dependent effect. Therefore, we designed a gradient treatment of cells for 24 hours with drug concentrations of 0.025, 0.0125, 0.00625, and 0 times the original drug concentration, and extracted proteins to verify apoptosis- and autophagy-related proteins (such as c-PARP, Bcl-2, Bax, etc.) at the protein level. These results will provide preliminary theoretical support for evaluating the efficacy of the herbal composition of this invention in nude mice and for identifying the active ingredients using mass spectrometry / liquid chromatography-mass spectrometry.

[0084] Clinical Cases (1) Case 1: On June 10, 2019, the patient experienced chest discomfort and dysphagia. After a pathological examination at the Second People's Hospital of Fuyang City, Zhejiang Province, the patient was diagnosed with "grade II squamous cell carcinoma of the esophagus, esophageal mass, 1.0cm x 1.0cm mass in the esophagus".

[0085] The patient presented for treatment on July 16, 2019, unable to eat or drink anything, vomiting immediately after consuming any food. After taking the ointment containing the pharmaceutical composition described in this application, the patient was able to consume liquids within 3 days and noodles within 5 days, resuming a normal diet. The pharmaceutical composition was discontinued, and other medications were prescribed. After two months of traditional Chinese medicine treatment, a follow-up electronic gastroscopy and pathological examination revealed "chronic esophageal mucosal inflammation." Pre-treatment pathology result: esophageal squamous cell carcinoma (June 12, 2019); Post-treatment pathology result: chronic mucosal inflammation (August 27, 2019); Diagnostic results before and after medication are as follows. Figure 7 As shown.

[0086] (2) Case 2: A patient with advanced esophageal cancer had been unable to eat or drink for over a month at the time of consultation. After taking the drug composition described in this application, the patient was able to drink milk on the third day of treatment and eat noodles and dumplings on the fifth day. After one course of treatment, the patient resumed a normal diet, was in good spirits, and all indicators tended to return to normal. After treatment with the drug described in this application and traditional Chinese medicine, the pathological examination results before treatment were: lower esophageal cancer (March 15, 2019); the pathological examination results after treatment were: reflux esophagitis (April 28, 2020). The diagnostic results before and after taking the drug are as follows. Figure 8 As shown.

[0087] (3) Case 3: The patient presented with dysphagia, difficulty swallowing, and expectoration of large amounts of phlegm in March 2018. Pathology showed: gastric cardia adenocarcinoma, moderately differentiated. After taking the ointment of the drug composition of this invention for 7 days, the patient was able to eat and drink normally, had a good appetite, and was in good spirits. The treatment plan was adjusted to include the drug of this application, anticancer drugs, and traditional Chinese medicine. After 3 months, all indicators tended to normalize. On March 2, 2022, a follow-up examination showed mild to moderate dysplasia of the gastric cardia glands. Pathological results before treatment: gastric cardia adenocarcinoma (February 2, 2018); gastroscopy results after treatment: mild to moderate dysplasia (March 2, 2022); diagnostic results before and after medication are as follows. Figure 9 As shown.

[0088] (4) Case 4: The patient presented on March 15, 2019, with difficulty swallowing, chest and back pain, and expectoration of large amounts of phlegm. Pathological examination revealed lower esophageal-cardia atrophic gastritis; chronic superficial gastritis with erosion and duodenitis. After taking the ointment of the drug composition of this invention for 5 days, the patient was able to consume liquids, and after half a month, was able to eat noodles and dumplings. After treatment with the drug and traditional Chinese medicine, a follow-up examination 4 months later (July 16, 2019) showed that the nature of the chronic atrophic gastritis and cardia mucosal lesions was undetermined. Figure 10 As shown.

[0089] (5) Case 5: Before visiting the hospital on August 30, 2017, the patient experienced difficulty swallowing and was unable to eat. Pathology showed: mass-like proliferative lesions in the esophagus, missing surface mucosa, rigid esophageal wall, severe narrowing of the lumen from the incisors, and hard biopsy material. The diagnosis was esophageal cancer with stricture, squamous cell carcinoma. After taking the ointment of the drug composition of this invention for 7 days, the patient was able to drink milk, and after half a month of medication, normal diet was restored. After treatment with the drug of this application, anticancer drugs, and traditional Chinese medicine, all indicators returned to normal. Three years later, a follow-up gastroscopy showed: chronic esophagitis, and the diagnosis was as follows. Figure 11 As shown.

[0090] This invention provides a traditional Chinese medicine preparation for treating esophageal obstruction and an inability to eat or drink due to esophageal cancer, along with its preparation process. This preparation has a significant effect in treating esophageal cancer with an inability to eat or drink, and it has the advantages of being green, low-cost, and having few side effects. It fills the current gap in the domestic and international treatment of advanced esophageal cancer patients who cannot eat or drink anything. This drug combines traditional Chinese medicine concepts with modern pharmaceutical technology and is expected to become a new type of drug in the field of treating advanced esophageal cancer with an inability to eat or drink. It is the first targeted drug of traditional Chinese medicine in China and has broad market prospects and application value.

[0091] The above examples illustrate the process of preparing the traditional Chinese medicine composition of the present invention into a paste form and its application. However, those skilled in the art should understand that the traditional Chinese medicine composition of the present invention is not limited to this convenient and portable paste form, but can be prepared into any suitable form, such as decoction, or traditional Chinese medicine granules or powders. Therefore, those skilled in the art should understand that the above embodiments are only for explaining and illustrating the present invention and are not intended to limit it in any way.

Claims

1. A traditional Chinese medicine composition for treating loss of appetite symptoms in patients with upper gastrointestinal cancer, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 5-10 parts agarwood 5-10 parts of borax 5-10 parts of Qingmeng stone 10-20 parts of white peony root 10-20 parts of Belamcanda chinensis 10-20 portions of ginseng 5-15 servings of mint 10-20 parts of *Isodon japonicus* 10-20 servings of Pseudobulbus Cremastrae 10-20 parts of Fritillaria cirrhosa 10-20 servings of borneol.

2. The traditional Chinese medicine composition according to claim 1, characterized in that: The dosage form of the traditional Chinese medicine composition is decoction, powder, or ointment.

3. The method for preparing the traditional Chinese medicine composition according to claim 1, characterized in that, Includes the following steps: (1) Boil the medicinal materials, including white peony root, belamcanda chinensis, ginseng, mint, scutellaria barbata, cremastra appendiculata and fritillaria cirrhosa, in water to obtain an extract; (2) Filter and concentrate the extract to obtain a clear extract; (3) Grind agarwood, borax and chlorite into fine powder; (4) Mix the clear paste, fine powder and borneol evenly to obtain the Chinese medicine composition ointment.

4. The method for preparing the traditional Chinese medicine composition according to claim 3, characterized in that, In step (1), the temperature for adding water and decocting is 80-100℃, and the time is 45-90 minutes; the number of times to decoct is 2-3.

5. The method for preparing the traditional Chinese medicine composition according to claim 3 or 4, characterized in that, In step (2), the concentration is carried out under reduced pressure, and the relative density of the extract is 1.15-1.20 at 50-60℃.

6. The method for preparing the traditional Chinese medicine composition according to claim 5, characterized in that, In step (3), the fine powder is a solid powder that has passed through a sieve of 100 mesh or higher.

7. The method for preparing the traditional Chinese medicine composition according to claim 5, characterized in that, In step (4), pharmaceutically acceptable excipients are added.

8. The method for preparing the traditional Chinese medicine composition according to claim 7, characterized in that, Pharmaceutically acceptable excipients include one or more of refined honey, sucrose, honey, microcrystalline cellulose, povidone, and maltodextrin.

9. The use of the traditional Chinese medicine composition according to claim 1 or 2 in the preparation of a medicine for treating the symptoms of loss of appetite in patients with upper gastrointestinal cancer.

10. The application according to claim 9, characterized in that, The upper gastrointestinal cancers mentioned are esophageal cancer, cardia cancer, or gastric cancer.

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