Compound preparation for invigorating spleen, regulating qi and removing blood stasis, preparation method and application in preparation of medicine for improving gastrointestinal function disorder caused by chemotherapy

Abstract

The application belongs to the technical field of biological medicine, and discloses a compound preparation for invigorating the spleen, regulating qi and removing blood stasis and application thereof in preparation of a medicine for improving gastrointestinal function disorder caused by chemotherapy. The compound preparation is composed of radix pseudostellariae, fried atractylodes, poria cocos, fried liquorice, fried pinellia, dried tangerine or orange peel, fried coix seed, fried rice sprout, fried wheat germ, fried chicken gizzard, inula flower, fig, root of actinidia, root of syzygium buxifolium, and turmeric. The scheme improves and develops the theory system of combination of traditional Chinese medicine and western medicine in colorectal cancer, and is applied in clinic. The whole prescription has the effects of invigorating the spleen, regulating qi, removing blood stasis, and resisting cancer, and the compatibility of the medicines shows a significant synergistic effect. The comprehensive curative effect is better than that of single type of medicine or simple combination, especially in improving the nutritional metabolism index and maintaining the skeletal muscle mass, and the prescription has unique advantages, thereby improving the immune function of the body, effectively improving the life quality of patients, and improving the chemotherapy tolerance.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, specifically relating to a compound preparation for invigorating the spleen, regulating qi and removing blood stasis, its preparation method, and its application in the preparation of drugs to improve gastrointestinal dysfunction caused by chemotherapy. Background Technology

[0002] Colorectal cancer (CRC), a common gastrointestinal malignancy worldwide, has seen a significant increase in incidence and mortality in my country in recent years, ranking second among malignant tumors and seriously threatening public health. In clinical treatment, chemotherapy regimens based on 5-fluorouracil (5-FU) (such as the CAPOX regimen) are widely used. However, domestic and international studies have confirmed that while chemotherapy drugs kill tumor cells, they also non-selectively damage actively proliferating gastrointestinal mucosal epithelial cells, leading to gastrointestinal barrier disruption, reduced digestive enzyme secretion, gastrointestinal motility disorders, and intestinal flora imbalance. This, in turn, triggers a series of gastrointestinal reactions, including nausea, vomiting, loss of appetite, abdominal distension, diarrhea, or constipation. These symptoms directly lead to reduced food intake and malabsorption, resulting in weight loss, muscle loss, and decreased immunity, creating a vicious cycle of chemotherapy damage, gastrointestinal dysfunction, malnutrition, decreased chemotherapy tolerance, and poor prognosis.

[0003] Clinical observations indicate that the core pathogenesis of colorectal cancer patients undergoing chemotherapy in Traditional Chinese Medicine (TCM) is primarily spleen qi deficiency and blood stasis, belonging to a mixed deficiency-excess syndrome characterized by "deficiency of vital qi as the root and excess of pathogenic factors as the manifestation." Spleen qi deficiency leads to impaired digestion and insufficient production of qi and blood; blood stasis leads to stagnation of qi and obstruction of the meridians. These two factors interact and jointly cause a series of clinical manifestations in patients, such as fatigue, poor appetite, diarrhea, and weight loss.

[0004] Chemotherapy-induced gastrointestinal dysfunction is a key factor contributing to malnutrition. Its clinical manifestations are complex and diverse, mainly including nausea, vomiting, loss of appetite, or diarrhea. These symptoms not only directly lead to impaired digestion and absorption but also trigger or exacerbate metabolic disorders, ultimately severely impacting the patient's nutritional status, quality of life, treatment tolerance, and clinical prognosis.

[0005] Currently, the routine clinical management of chemotherapy-induced gastrointestinal dysfunction mainly involves symptomatic and supportive treatment. Common methods include using 5-HT3 receptor antagonists or NK-1 receptor antagonists to prevent and control chemotherapy-related acute and delayed nausea and vomiting; using montmorillonite powder or loperamide to relieve diarrhea; using prokinetic drugs (such as mosapride) to relieve abdominal distension; and using digestive enzyme preparations (such as enteric-coated pancreatic enzyme capsules) to help the breakdown and absorption of nutrients. Oral nutritional supplements, enteral or parenteral nutrition support can directly improve the patient's energy and nutrient intake. However, these methods can only temporarily and partially relieve specific symptoms, and long-term or combined use of these drugs may cause new adverse reactions. For example, strong antiemetics may cause headaches and constipation; overuse of antidiarrheal drugs can cause abdominal distension and intestinal obstruction; and prokinetic drugs may cause abdominal pain and diarrhea. These drug-related side effects overlap with the primary toxicity of chemotherapy, increasing patient suffering and treatment complexity, and sometimes even forcing adjustments to the chemotherapy regimen, affecting the anti-tumor efficacy. Furthermore, none of the aforementioned drugs can improve the skeletal muscle loss, decreased immune function, and long-term nutritional and metabolic disorders caused by chemotherapy, making it difficult to achieve a comprehensive cure. Long-term combined use may also increase the metabolic burden on the liver and kidneys, posing additional safety risks. Therefore, relying solely on symptomatic treatment in modern medicine is insufficient to meet the long-term, holistic, and safe supportive care needs of colorectal cancer chemotherapy patients.

[0006] Modern medicine's symptomatic treatment model is "divide and conquer," lacking a holistic approach to regulating gastrointestinal dysfunction caused by chemotherapy. Therefore, there is an urgent clinical need for an innovative intervention strategy that can overcome the limitations of existing treatment models. An ideal approach should be based on a comprehensive and in-depth understanding of the gastrointestinal toxicities caused by chemotherapy, enabling multi-level holistic regulation. Its goal should not be limited to temporarily controlling symptoms, but should comprehensively improve the body's nutritional status. Against this backdrop, fully leveraging the advantages of traditional Chinese medicine's holistic concept and syndrome differentiation and treatment, and developing a scientifically formulated, modernized, and standardized quality control traditional Chinese medicine preparation, has significant clinical value and application prospects. This will provide colorectal cancer chemotherapy patients with a safe, effective, and comprehensive supportive treatment option that addresses both the symptoms and the root cause, and is of great significance for improving patients' tolerance and completion rate of the entire chemotherapy course, ultimately enhancing their quality of life and treatment efficacy. Summary of the Invention

[0007] To address the above technical problems, the purpose of this invention is to provide a compound preparation for strengthening the spleen, regulating qi, and removing blood stasis. This compound preparation is composed of Codonopsis pilosula, stir-fried Atractylodes macrocephala, Poria cocos, prepared Glycyrrhiza uralensis, ginger-processed Pinellia ternata, Citrus reticulata peel, stir-fried Coix lacryma-jobi, stir-fried Oryza sativa sprouts, stir-fried Hordeum vulgare sprouts, stir-fried chicken gizzard lining, Inula japonica, Fig, Actinidia chinensis root, Myrica rubra root, and Curcuma longa. This formula is an innovative modification of the traditional Liu Jun Zi Tang (Six Gentlemen Decoction), integrating multiple medicinal materials with functions such as strengthening the spleen and replenishing qi, regulating qi and harmonizing the stomach, relieving nausea and vomiting, promoting digestion and eliminating food stagnation, promoting blood circulation and removing blood stasis, and detoxifying and fighting cancer. It forms a highly effective combination that supports the body's resistance without causing adverse reactions and eliminates adverse reactions without harming the body's resistance, comprehensively targeting gastrointestinal damage and malnutrition caused by chemotherapy. The proposal of this solution improves and develops the theoretical system of integrated traditional Chinese and Western medicine for colorectal cancer and promotes its clinical application. This formula has the effects of strengthening the spleen and removing dampness, regulating qi and stomach, and removing blood stasis and detoxifying. It can significantly improve gastrointestinal dysfunction caused by chemotherapy, including nausea, vomiting or diarrhea, thereby comprehensively improving the body's nutritional status and immune function, and enhancing the patient's quality of life and chemotherapy tolerance.

[0008] To achieve the above objectives, the present invention adopts the following technical solution: A compound preparation for invigorating the spleen, regulating qi, and removing blood stasis, wherein the preparation is prepared from the following raw materials in parts by weight: Codonopsis pilosula 10-20 parts, stir-fried Atractylodes macrocephala 6-18 parts, Poria cocos 10-20 parts, prepared Glycyrrhiza uralensis 4-10 parts, ginger-processed Pinellia ternata 6-12 parts, Citrus reticulata 6-12 parts, stir-fried Coix lacryma-jobi 6-50 parts, stir-fried rice sprouts 6-30 parts, stir-fried malt 6-30 parts, stir-fried chicken gizzard lining 6-30 parts, Inula japonica 8-15 parts, Fig 6-15 parts, Actinidia chinensis root 10-50 parts, Myrica rubra root 10-30 parts, and Curcuma longa 3-10 parts.

[0009] This formula follows five major treatment principles: strengthening the spleen and replenishing qi, regulating qi flow, promoting blood circulation and removing blood stasis, detoxifying and fighting cancer, and promoting digestion and harmonizing the stomach. The principal, assistant, adjuvant, and guiding herbs have clearly defined roles and synergistic effects. Principal herb: Codonopsis pilosula: strengthens the spleen and replenishes qi, generates fluids and nourishes the stomach, tonifying without causing dryness, targeting spleen and stomach qi deficiency and qi and yin deficiency after chemotherapy. Stir-fried Atractylodes macrocephala: strengthens the spleen and dries dampness, enhances digestion, and improves spleen deficiency with loose stools and abdominal distension. Poria cocos: strengthens the spleen and eliminates dampness, calms the mind and soothes the nerves, and improves dampness obstructing the middle jiao, poor appetite, and fatigue. Assistant herbs: Ginger-processed Pinellia ternata: relieves nausea and vomiting, dries dampness and harmonizes the stomach, specifically treating chemotherapy-induced nausea and vomiting. Tangerine peel: regulates qi and strengthens the spleen, dries dampness and resolves phlegm, eliminating qi stagnation and abdominal distension. Stir-fried Coix lacryma-jobi: strengthens the spleen and eliminates dampness, detoxifies and fights cancer, improving spleen deficiency with excessive dampness. Inula japonica: lowers qi and stops vomiting, synergistically enhancing the antiemetic effect. Adjuvant herbs: Fried rice sprouts, fried wheat sprouts, and fried chicken gizzard lining: aid digestion, relieve stagnation, invigorate the spleen and stomach, and significantly improve appetite. Fig: invigorates the spleen and stomach, detoxifies and moistens the intestines, and relieves dry mouth and constipation. *Actinidia chinensis* root and *Myrica rubra* root: clear heat and detoxify, invigorate blood and remove blood stasis. Turmeric: invigorates blood and qi, unblocks meridians and relieves pain, and improves blood stasis and qi stagnation. Guiding herb: Prepared licorice root: tonifies qi and strengthens the middle jiao, harmonizes the effects of all herbs, and makes the overall formula mild.

[0010] Characteristics of the formula: Nourishing without causing stagnation: It benefits qi and regulates qi without causing bloating; It relieves nausea without harming the stomach: It stops vomiting without depleting qi; It resolves blood stasis without harming blood: It invigorates blood without causing bleeding; It detoxifies without being cold.

[0011] Preferably, the formulation is prepared from the following raw materials in parts by weight: Codonopsis pilosula 12-18 parts, stir-fried Atractylodes macrocephala 8-15 parts, Poria cocos 12-18 parts, prepared Glycyrrhiza uralensis 5-9 parts, ginger-processed Pinellia ternata 8-10 parts, Citrus reticulata 8-10 parts, stir-fried Coix lacryma-jobi 10-40 parts, stir-fried rice sprouts 10-25 parts, stir-fried malt 10-25 parts, stir-fried chicken gizzard lining 10-25 parts, Inula japonica 10-13 parts, Fig 8-14 parts, Actinidia chinensis root 20-40 parts, Myrica rubra root 12-25 parts, and Curcuma longa 5-8 parts.

[0012] Preferably, the formulation is prepared from the following raw materials in parts by weight: Codonopsis pilosula 15 parts, stir-fried Atractylodes macrocephala 12 parts, Poria cocos 15 parts, prepared Glycyrrhiza uralensis 6 parts, ginger-processed Pinellia ternata 9 parts, Citrus reticulata 9 parts, stir-fried Coix lacryma-jobi 30 parts, stir-fried rice sprouts 15 parts, stir-fried barley sprouts 15 parts, stir-fried chicken gizzard lining 12 parts, Inula japonica 12 parts, Fig 12 parts, Actinidia chinensis root 30 parts, Myrica rubra root 15 parts, and Curcuma longa 6 parts.

[0013] A method for preparing a compound preparation for strengthening the spleen, regulating qi, and removing blood stasis includes the following steps: According to the corresponding mass proportions, select Codonopsis pilosula, stir-fried Atractylodes macrocephala, Poria cocos, prepared Glycyrrhiza uralensis, ginger-processed Pinellia ternata, Citrus reticulata peel, stir-fried Coix lacryma-jobi, stir-fried rice sprouts, stir-fried malt, stir-fried chicken gizzard lining, Inula japonica, fig, Actinidia chinensis root, Myrica rubra root, and Curcuma longa, mix, soak, decoct, and filter to obtain the final product.

[0014] Preferably, the formulation is an oral liquid formulation.

[0015] A method of using a compound preparation for strengthening the spleen, regulating qi, and removing blood stasis: the preparation obtained by the preparation method is administered at 100 mL / time, twice a day.

[0016] Application of a compound preparation for invigorating the spleen, regulating qi, and removing blood stasis in the preparation of drugs to improve gastrointestinal dysfunction caused by chemotherapy.

[0017] The above-mentioned drugs are to be taken from the first day of chemotherapy until the end of chemotherapy, and the duration of drug treatment during chemotherapy shall not be less than 2 months.

[0018] The above instructions for use and application of compound preparations are for illustrative purposes only and do not involve the treatment of diseases.

[0019] Preferably, the drug is composed of the compound preparation and other pharmaceutically acceptable excipients.

[0020] Preferably, the improvement of chemotherapy-induced gastrointestinal dysfunction includes improving nutritional and metabolic indicators, maintaining skeletal muscle mass, improving nausea, and reducing the frequency of vomiting.

[0021] Preferably, the chemotherapy is any one of FOLFIRI, FOLFOX, CAPOX, or FOLFOXIRI.

[0022] Compared with the prior art, the present invention has at least the following technical effects: This invention clarifies the TCM pathogenesis of "spleen qi deficiency and blood stasis" in colorectal cancer patients undergoing chemotherapy. This pathogenesis aligns with the characteristics of "internal deficiency of vital energy and accumulation of pathogenic factors," with "spleen qi deficiency accompanied by blood stasis" as its symptom profile. For the first time, it establishes "strengthening the spleen, activating blood circulation, and regulating qi" as the primary treatment principle. It creatively integrates and recombines the classic spleen-strengthening formula (Liu Jun Zi Tang) with various medicinal materials possessing functions such as promoting digestion, relieving nausea and vomiting, clearing heat and detoxifying, anti-tumor effects, and activating blood circulation and removing blood stasis. This results in a novel compound preparation for strengthening the spleen, regulating qi, and removing blood stasis. This compound preparation consists of Codonopsis pilosula, stir-fried Atractylodes macrocephala, Poria cocos, prepared Glycyrrhiza uralensis, ginger-processed Pinellia ternata, Citrus reticulata peel, stir-fried Coix lacryma-jobi, stir-fried Oryza sativa sprouts, stir-fried Hordeum vulgare sprouts, stir-fried chicken gizzard lining, Inula japonica, Fig, Actinidia chinensis root, Myrica rubra root, and Curcuma longa. This approach refines and develops the integrated TCM and Western medicine theory of colorectal cancer and promotes its clinical application.

[0023] This formula, while strengthening the spleen and consolidating the body's foundation, also regulates Qi, invigorates blood circulation, removes blood stasis, and detoxifies and fights cancer. The combination of herbs exhibits a significant synergistic effect, resulting in a comprehensive therapeutic effect superior to single-category herbs or simple combinations. It demonstrates unique advantages, particularly in improving nutritional and metabolic indicators and maintaining skeletal muscle mass. This comprehensively improves the body's immune function, effectively enhancing patients' quality of life and chemotherapy tolerance.

[0024] This formula is used in conjunction with chemotherapy, starting with the first course of treatment to strengthen the spleen, regulate qi, and remove blood stasis. It is prepared by the pharmacies of Zhejiang Cancer Hospital and the Second Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine, decocted to 100mL per packet, with two packets taken daily. Oral administration of this traditional Chinese medicine during chemotherapy should last for at least two months. Attached Figure Description

[0025] Figure 1 This is a schematic diagram of the high-resolution mass spectrometry results of the decoction of the spleen-strengthening, qi-regulating, and blood-stasis-removing formula prepared in Example 1. Detailed Implementation

[0026] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the present invention will be briefly introduced below in conjunction with the accompanying drawings and descriptions of the embodiments or the prior art. Obviously, the following description of the structure of the accompanying drawings is 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. It should be noted that the description of these embodiments is for the purpose of helping to understand the present invention, but does not constitute a limitation of the present invention.

[0027] One specific embodiment of the present invention is as follows: A compound preparation for strengthening the spleen, regulating qi, and removing blood stasis was provided by the decoction preparation center of the Second Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine. The dosage of Chinese medicine is the same as above, one dose per day, decocted into two packets, each packet containing 100mL.

[0028] Usage: 100mL each time, twice a day, orally, starting from the first day of chemotherapy until the end of chemotherapy. Patients who have used traditional Chinese medicine for no less than 2 months during chemotherapy.

[0029] Example 1: A compound preparation for invigorating the spleen, regulating qi, and removing blood stasis, wherein the preparation is prepared from the following raw materials in parts by weight: Codonopsis pilosula 15g, stir-fried Atractylodes macrocephala 12g, Poria cocos 15g, prepared Glycyrrhiza uralensis 6g, ginger-processed Pinellia ternata 9g, Citrus reticulata 9g, stir-fried Coix lacryma-jobi 30g, stir-fried rice sprouts 15g, stir-fried barley sprouts 15g, stir-fried chicken gizzard lining 12g, Inula japonica 12g, Fig 12g, Actinidia chinensis root 30g, Myrica rubra root 15g, Curcuma longa 6g.

[0030] The preparation and use method involves decoction, with the decoction prepared by the pharmacies of Zhejiang Cancer Hospital and the Second Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine to a concentration of 100mL per packet. Two packets are taken daily. Oral administration of this traditional Chinese medicine during chemotherapy should last for at least two months.

[0031] Example 2: A compound preparation for invigorating the spleen, regulating qi, and removing blood stasis, wherein the preparation is prepared from the following raw materials in parts by weight: Codonopsis pilosula 10g, stir-fried Atractylodes macrocephala 6g, Poria cocos 10g, prepared Glycyrrhiza uralensis 4g, ginger-processed Pinellia ternata 6g, Citrus reticulata peel 6g, stir-fried Coix lacryma-jobi 6g, stir-fried rice sprouts 6g, stir-fried barley sprouts 6g, stir-fried chicken gizzard lining 6g, Inula japonica 8g, fig 6g, Actinidia chinensis root 10g, Myrica rubra root 10g, and Curcuma longa 3g.

[0032] The preparation and usage methods are the same as in Example 1.

[0033] Example 3: A compound preparation for invigorating the spleen, regulating qi, and removing blood stasis, wherein the preparation is prepared from the following raw materials in parts by weight: 20g of Codonopsis pilosula, 18g of stir-fried Atractylodes macrocephala, 20g of Poria cocos, 10g of prepared Glycyrrhiza uralensis, 12g of ginger-processed Pinellia ternata, 12g of Citrus reticulata peel, 50g of stir-fried Coix lacryma-jobi, 30g of stir-fried rice sprouts, 30g of stir-fried barley sprouts, 30g of stir-fried chicken gizzard lining, 15g of Inula japonica, 15g of Fig, 50g of Actinidia chinensis root, 30g of Myrica rubra root, and 10g of Curcuma longa.

[0034] The preparation and usage methods are the same as in Example 1.

[0035] Example 4: A compound preparation for invigorating the spleen, regulating qi, and removing blood stasis, wherein the preparation is prepared from the following raw materials in parts by weight: Codonopsis pilosula 12g, stir-fried Atractylodes macrocephala 8g, Poria cocos 12g, prepared Glycyrrhiza uralensis 5g, ginger-processed Pinellia ternata 8g, Citrus reticulata 8g, stir-fried Coix lacryma-jobi 10g, stir-fried rice sprouts 10g, stir-fried barley sprouts 10g, stir-fried chicken gizzard lining 10g, Inula japonica 10g, fig 8g, Actinidia chinensis root 20g, Myrica rubra root 12g, and Curcuma longa 5g.

[0036] The preparation and usage methods are the same as in Example 1.

[0037] Example 5: A compound preparation for invigorating the spleen, regulating qi, and removing blood stasis, wherein the preparation is prepared from the following raw materials in parts by weight: Codonopsis pilosula 18g, stir-fried Atractylodes macrocephala 15g, Poria cocos 18g, prepared Glycyrrhiza uralensis 9g, ginger-processed Pinellia ternata 10g, Citrus reticulata peel 10g, stir-fried Coix lacryma-jobi 40g, stir-fried rice sprouts 25g, stir-fried barley sprouts 25g, stir-fried chicken gizzard lining 25g, Inula japonica 13g, fig 14g, Actinidia chinensis root 40g, Myrica rubra root 25g, and Curcuma longa 8g.

[0038] The preparation and usage methods are the same as in Example 1.

[0039] Experimental example: The efficacy of the spleen-strengthening, qi-regulating, and blood-stasis-removing compound preparation in Example 1 above is illustrated through the following clinical efficacy cases: 1. Identify the main chemical components of the decoction of the spleen-strengthening, qi-regulating, and blood-stasis-removing formula. like Figure 1 The figure shows a schematic diagram of the high-resolution mass spectrometry results for chemical composition analysis of the decoction of Jianpi Tiaoqi Huayu Fang (prepared in Example 1) based on Q-Orbitrap high-resolution liquid chromatography-mass spectrometry. In the figure, a is the characteristic spectrum of anionic components in the formula; b is the characteristic spectrum of cationic components.

[0040] Results combined Figure 1The overall spectrum and Table 1 show that the main active ingredients of this formula are, in order, zedoarondiol, tangeritin, inulicin, DL-Stachydrine, and psoralen. These are sesquiterpenoids, flavonoids, lactones, alkaloids, and coumarins, respectively.

[0041] Table 1. Top 10 Main Effective Components of the Spleen-Strengthening, Qi-Regulating, and Blood-Stasis-Removing Decoction

[0042] 2: Typical medical cases 1. Mr. He, male, 67 years old. On March 29, 2024, he underwent a 3D laparoscopic-assisted radical resection of rectal cancer via laparotomy (Dixon procedure) at Shanghai Changhai Hospital. Starting May 5, 2024, he began CAPOX chemotherapy. During chemotherapy, he experienced fatigue, poor appetite, and diarrhea. In the past month, he lost 2 kg, his appetite decreased by 51% compared to before the illness, and he had watery stools 4-5 times / day. His total score for nutritional risk screening (NRS-2002) was 4 points, and his Patient-Generated Subjective Global Assessment (PG-SGA) score was 9 points, indicating severe malnutrition. His serum prealbumin was 254 mg / L, albumin was 36.4 g / L, and hemoglobin was 103 g / L. His tongue was pale with a greasy coating, and his pulse was thready and hesitant.

[0043] Diagnosis: Malignant rectal tumor (pT4aN2bMx), intestinal tumor (spleen qi deficiency with blood stasis syndrome).

[0044] Prescription: The spleen-strengthening, qi-regulating, and blood-stasis-removing traditional Chinese medicine decoction was prepared using the formula and preparation method in Example 1. It was taken orally twice a day, with 21 doses constituting one course of treatment.

[0045] Follow-up observation: After 3 courses of treatment, a follow-up examination was conducted. The nutritional status had significantly improved, with an NRS2002 score of 3, a PG-SGA score of 5, and formed stools 1-2 times / day. Serum prealbumin was 378 mg / L, albumin was 43.6 g / L, hemoglobin was 115 g / L, the tongue was pale red with a thin white coating, and the pulse was thready.

[0046] 2. Mr. Wu, male, 65 years old. On May 14, 2025, he underwent laparoscopic radical resection of rectal cancer and adhesiolysis under general anesthesia. Starting June 18, 2025, he began CAPOX chemotherapy. During chemotherapy, he experienced fatigue, poor appetite, nausea, and vomiting. He lost 1.3 kg in 2 weeks, and his appetite decreased by 51% compared to before the illness. His nutritional risk screening total score (NRS-2002) was 3, his PG-SGA score was 9, his serum prealbumin was 235 mg / L, albumin was 38.6 g / L, and hemoglobin was 115 g / L. His tongue was pale with a greasy coating, and his pulse was weak and thready.

[0047] Diagnosis: Malignant tumor of the rectum (pT2N1bMx), intestinal tumor (spleen qi deficiency with blood stasis syndrome).

[0048] Prescription: The spleen-strengthening, qi-regulating, and blood-stasis-removing traditional Chinese medicine decoction was prepared using the formula and preparation method in Example 1. It was taken orally twice a day, with 21 doses constituting one course of treatment.

[0049] Follow-up observation: After 3 courses of treatment, a follow-up examination was conducted. The nutritional status was significantly improved, the nausea symptoms were better than before, there was no vomiting, the NRS2002 score was 3, the PG-SGA score was 6, the serum prealbumin was 275mg / L, the albumin was 41.4g / L, the hemoglobin was 131g / L, the tongue was pale red, the coating was thin and white, and the pulse was thready.

[0050] III: Clinical Research Data The team initially conducted a small-sample clinical study based on a systematic analysis of relevant records. They comprehensively summarized the characteristics of colorectal cancer chemotherapy patients from three dimensions: TCM syndrome differentiation, treatment based on syndrome differentiation, and application of specific formulas. They proposed that chemotherapy patients often have qi stagnation and blood stasis on the basis of spleen qi deficiency, and found that the syndrome of "spleen qi deficiency with blood stasis" is most common in these patients. The core pathogenesis in TCM is: chemotherapy damages spleen qi, leading to impaired spleen function, which in turn causes or aggravates malnutrition, resulting in symptoms of deficiency such as weight loss and fatigue; as spleen qi deficiency worsens, qi becomes insufficient to propel qi, leading to poor blood circulation and ultimately internal obstruction of blood stasis.

[0051] Therefore, considering the characteristics of spleen deficiency with blood stasis in colorectal cancer patients undergoing chemotherapy, and adhering to the principle of "strengthening the body's resistance and eliminating pathogenic factors," the team proposed a treatment principle combining traditional Chinese and Western medicine, with strengthening the spleen, regulating qi, and resolving blood stasis as its core. The formula for strengthening the spleen, regulating qi, and resolving blood stasis consists of Codonopsis pilosula, stir-fried Atractylodes macrocephala, Poria cocos, prepared Glycyrrhiza uralensis, ginger-processed Pinellia ternata, Citrus reticulata peel, stir-fried Coix lacryma-jobi, stir-fried Oryza sativa sprouts, stir-fried Hordeum vulgare sprouts, stir-fried chicken gizzard lining, Inula japonica, Fig, Actinidia chinensis root, Myrica rubra root, and Curcuma longa. This approach refines and develops the theoretical system of combining traditional Chinese and Western medicine for colorectal cancer and has been widely applied in clinical practice.

[0052] To clarify the effectiveness of the spleen-strengthening, qi-regulating, and blood-stasis-removing formula in improving gastrointestinal dysfunction caused by chemotherapy in colorectal cancer patients, a clinical study was conducted. The specific protocol and results are as follows: The case originated from a patient hospitalized in the Department of Oncology at the Second Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine who was diagnosed with stage II or III colorectal cancer and was expected to complete at least 4 cycles of CAPOX chemotherapy.

[0053] (a) Diagnostic criteria and inclusion / exclusion criteria 1. Diagnostic criteria: (1) The diagnostic criteria for colorectal malignant tumors refer to the "Chinese Guidelines for the Diagnosis and Treatment of Colorectal Cancer (2020 Edition)" and the staging criteria refer to the TMN staging of colorectal cancer (AJCC 8th Edition).

[0054] (2) Traditional Chinese Medicine (TCM) Diagnostic Criteria: Referring to the "Standards for Diagnosis and Efficacy of TCM Diseases" issued by the State Administration of Traditional Chinese Medicine, the diagnostic criteria for the syndrome of "Spleen Qi Deficiency with Blood Stasis" are as follows: Main symptoms: fatigue, poor appetite, dry or loose stools, sometimes with blood in the stool, pale tongue or with ecchymosis or petechiae, greasy tongue coating, and thready or thready pulse. Secondary symptoms: abdominal pain, emaciation, and sallow complexion. A TCM four diagnostic information scale was developed to record the changes in TCM syndrome. Because the TCM four diagnostic information and nutritional scale data may be subject to subjective errors due to different surveys, 2-3 fixed personnel were selected to participate in the survey and received unified training. The determination of TCM syndrome differentiation information should be carried out by at least 2 professional TCM physicians.

[0055] 2. Inclusion criteria for cases: (1) Patients with stage II or III colorectal cancer who meet the above diagnostic criteria, have not previously undergone neoadjuvant chemotherapy, and have undergone radical resection after surgery; (2) CAPOX chemotherapy regimen (capecitabine 1000 mg / m²) 2 Bi-dose po d1-d14 + oxaliplatin 130mg / m² 2 IVGTT d1 (one cycle every 21 days) is postoperative adjuvant chemotherapy. (3) Expected survival period exceeds 3 months; (4) Karnofsky Performance Status (KPS) score ≥ 60 and no obvious abnormalities in organs such as heart, lungs, liver, and kidneys.

[0056] (5) Sign the informed consent form and agree to the trial protocol; 3. Exclusion Criteria (1) Patients with mental illness and patients who are confused or unable to communicate verbally; (2) Having severe organic or functional lesions in organs such as the liver, kidneys, heart, and brain; (3) Pregnant and lactating women; (4) Patients with a known history of other intestinal diseases within the past 3 months; (5) Patients who have taken medications related to intestinal barrier function protection within the past 3 months; (6) Patients who do not meet the above inclusion criteria; 4. Shedding Criteria (1) Patients who voluntarily request to withdraw; (2) Patients who failed to complete a full four cycles of CAPOX chemotherapy; (3) Patients who received traditional Chinese medicine treatment for less than 2 months during chemotherapy; (4) Patients who are unable to complete the entire treatment regimen due to serious adverse events; (5) Those who cannot guarantee that they will complete the required medication and follow-up procedures during the trial period; 5. Exclusion criteria (1) Patients who are found to have other serious illnesses during treatment and do not meet the inclusion criteria; (2) Patients with no follow-up records; (II) Treatment Plan 1. Grouping method Sixty-seven patients were selected from the Department of Oncology at the Second Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine according to the inclusion criteria. They were randomly divided into two groups using a random number table: a control group (n=31) and an experimental group (n=36).

[0057] 2. Treatment methods CAPOX regimen: Oxaliplatin 130 mg / m² 2 IVGTT d1 + capecitabine 1000mg / m 2 Bid po d1-d14, repeated every 21 days, for a total of 4 courses of treatment.

[0058] Formula for Strengthening the Spleen, Regulating Qi, and Removing Blood Stasis: Codonopsis pilosula 15g, stir-fried Atractylodes macrocephala 12g, Poria cocos 15g, prepared Glycyrrhiza uralensis 6g, ginger-processed Pinellia ternata 9g, Citrus reticulata peel 9g, stir-fried Coix lacryma-jobi 30g, stir-fried rice sprouts 15g, stir-fried barley sprouts 15g, stir-fried chicken gizzard lining 12g, Inula japonica 12g, Fig 12g, Actinidia chinensis root 30g, Myrica rubra root 15g, Curcuma longa 6g. Preparation: Decocted in water and taken orally twice daily.

[0059] (1) Control group: 4 cycles of CAPOX chemotherapy.

[0060] (2) Experimental group: In addition to the CAPOX chemotherapy regimen, the patient began taking the spleen-strengthening, qi-regulating, and blood-stasis-removing formula during the first course of treatment. The formula was prepared by the pharmacies of Zhejiang Cancer Hospital and the Second Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine, and was decocted to 100ml / packet, with 2 packets per day. The patient took the Chinese medicine orally for no less than 2 months during chemotherapy, and no less than 15 days during each course of treatment.

[0061] (III) Evaluation Indicators 1. Nausea severity assessment: Nausea severity was graded according to CTCAE v5.0, covering the acute phase (0-24h after chemotherapy) and the delayed phase (24-72h and 72-168h after chemotherapy). 2. Nutritional status assessment: (1) Assess the nutritional status of patients according to the Nutritional Risk Screening Scale (NRS2002) and the Patient Subjective Overall Nutritional Assessment Scale (PG-SGA); (2) Body mass index (BMI), weight, serum albumin (ALB), serum prealbumin (PAB), and transferrin (TRF) in peripheral venous blood. 3. Skeletal Muscle Assessment: L3 Layer Skeletal Muscle Area Index (L3 SMI): Reflects the skeletal muscle content at the L3 layer (L3 SMI = L3 layer skeletal muscle area (cm²)). 2 ) / height squared (m) 2 (males <38.5cm) 2 / m 2 , women <38.6cm 2 / m 2 Defined as sarcopenia). 4. Safety evaluation: A retrospective analysis was conducted on the three routine tests and biochemical tests of enrolled patients before and after each cycle of chemotherapy to assess the degree of bone marrow suppression, liver and kidney function, and common clinical toxic side effects.

[0062] (iv) Statistical methods SPSS 27.0 software was used for statistical analysis. Baseline analysis was performed on the general characteristics of the subjects. Continuous variables that conformed to or were approximately normally distributed were expressed as mean ± standard deviation. The mean (±s) is used to represent the variances, while the median (interquartiles) M (P25, P75) is used for non-normal distributions. For datasets that conform to a normal distribution and whose variances are confirmed to be equal through a homogeneity of variance test, an independent samples t-test is used. However, when the data do not conform to the preconditions of normality or homogeneity of variance, the non-parametric Wilcoxon rank-sum test is chosen. A p-value less than 0.05 is considered statistically significant, i.e., the difference is meaningful.

[0063] IV. Research Results 4.1 Statistical Analysis of General Data Sixty-seven patients diagnosed with colorectal cancer at the Second Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine between 2022 and 2024, who received CAPOX chemotherapy and were diagnosed with spleen deficiency with blood stasis according to traditional Chinese medicine, were selected as the study subjects. They were divided into an experimental group and a control group, with 31 patients in the control group and 36 patients in the experimental group.

[0064] As shown in Table 2, the control group received four cycles of adjuvant CAPOX chemotherapy after surgery, while the experimental group, in addition to CAPOX chemotherapy, began taking the spleen-strengthening, qi-regulating, and blood-stasis-removing formula from the first cycle of treatment. There were no statistically significant differences between the two groups in terms of age, height, and affected area (P>0.05), indicating comparability.

[0065] Table 2 Comparison of general information between the two groups of patients

[0066] 4.2 Evaluation of Clinical Efficacy (1) Evaluation of nausea level The results, combined with the comparison of the nausea severity grading after chemotherapy in Table 3, showed that there was a statistically significant difference in the nausea severity grading during the acute and delayed phases after chemotherapy between the two groups (P<0.05).

[0067] Table 3 Comparison of Nausea Severity Grading After Chemotherapy

[0068] (2) Evaluation of nutritional indicators (2.1) Results: Based on the changes in PG-SGA scores during treatment in the two groups as shown in Table 4, there was no statistically significant difference in PG-SGA scores between the two groups during the first course of treatment (P>0.05). During the second to fourth courses of treatment, the scores in the control group increased significantly compared to the first course of treatment (P<0.05), while the scores in the experimental group showed a decreasing trend; in the fourth course of treatment, the PG-SGA score in the experimental group decreased significantly compared to the first course of treatment and the control group (P<0.05).

[0069] Table 4. Changes in PG-SGA scores during treatment in the two groups of patients.

[0070] Note: a: P<0.05 compared with the first course of treatment within the group; b: P<0.05 compared with the control group. (2.2) Results: Based on the changes in nutritional indicators during the treatment of the two groups of patients in Table 5, it can be seen that there were no statistically significant differences in albumin, transferrin, and prealbumin levels in either group during the first course of treatment (P>0.05). With the increase of chemotherapy sessions, albumin, transferrin, and prealbumin levels in the experimental group generally showed an upward trend, while in the control group, the three indicators generally showed a downward trend.

[0071] Table 5 Changes in nutritional indicators during treatment in the two groups of patients.

[0072] (2.3) Results: Combined with the changes in BMI and weight after 4 cycles of chemotherapy in Table 6, it was found that there were no statistically significant differences in weight and BMI between the two groups during the first cycle of chemotherapy (P>0.05). In the control group, weight and BMI showed a decreasing trend with increasing chemotherapy cycles, with significant decreases in the third and fourth cycles compared to the first cycle (P<0.05). In the experimental group, weight and BMI showed an increasing trend with increasing chemotherapy cycles, with a significant increase in the fourth cycle compared to the control group (P<0.05).

[0073] Table 6. Changes in BMI and weight after 4 cycles of chemotherapy

[0074] (3) Evaluation of skeletal muscle content As shown in Table 7, the skeletal muscle area index at the L3 layer in the experimental group increased compared to the control group after treatment (P<0.05). Conversely, the skeletal muscle area index at the L3 layer in the control group decreased after treatment (P<0.05), while there was no significant change in the skeletal muscle area index at the L3 layer in the experimental group (P>0.05).

[0075] Table 7. Changes in skeletal muscle area index at the L3 layer before and after treatment in the two groups of patients.

[0076] Note: a: P<0.05 compared with pre-treatment levels within the group; b: P<0.05 compared with the control group.

[0077] Finally, it should be noted that the above description is merely a preferred embodiment of the present invention and is not intended to limit the scope of protection of the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A compound preparation for invigorating the spleen, regulating qi, and removing blood stasis, characterized in that, The formulation is prepared from the following raw materials in parts by weight: Codonopsis pilosula 10-20 parts, stir-fried Atractylodes macrocephala 6-18 parts, Poria cocos 10-20 parts, prepared Glycyrrhiza uralensis 4-10 parts, ginger-processed Pinellia ternata 6-12 parts, Citrus reticulata 6-12 parts, stir-fried Coix lacryma-jobi 6-50 parts, stir-fried rice sprouts 6-30 parts, stir-fried malt 6-30 parts, stir-fried chicken gizzard lining 6-30 parts, Inula japonica 8-15 parts, Fig 6-15 parts, Actinidia chinensis root 10-50 parts, Myrica rubra root 10-30 parts, and Curcuma longa 3-10 parts.

2. The compound preparation for invigorating the spleen, regulating qi, and removing blood stasis according to claim 1, characterized in that, The formulation is prepared from the following raw materials in parts by weight: Codonopsis pilosula 12-18 parts, stir-fried Atractylodes macrocephala 8-15 parts, Poria cocos 12-18 parts, prepared Glycyrrhiza uralensis 5-9 parts, ginger-processed Pinellia ternata 8-10 parts, Citrus reticulata 8-10 parts, stir-fried Coix lacryma-jobi 10-40 parts, stir-fried rice sprouts 10-25 parts, stir-fried malt 10-25 parts, stir-fried chicken gizzard lining 10-25 parts, Inula japonica 10-13 parts, Fig 8-14 parts, Actinidia chinensis root 20-40 parts, Myrica rubra root 12-25 parts, and Curcuma longa 5-8 parts.

3. The compound preparation for invigorating the spleen, regulating qi, and removing blood stasis according to claim 2, characterized in that, The formulation is prepared from the following raw materials in parts by weight: Codonopsis pilosula 15 parts, stir-fried Atractylodes macrocephala 12 parts, Poria cocos 15 parts, prepared Glycyrrhiza uralensis 6 parts, ginger-processed Pinellia ternata 9 parts, Citrus reticulata 9 parts, stir-fried Coix lacryma-jobi 30 parts, stir-fried rice sprouts 15 parts, stir-fried barley sprouts 15 parts, stir-fried chicken gizzard lining 12 parts, Inula japonica 12 parts, Fig 12 parts, Actinidia chinensis root 30 parts, Myrica rubra root 15 parts, and Curcuma longa 6 parts.

4. A method for preparing a compound preparation for invigorating the spleen, regulating qi, and removing blood stasis as described in any one of claims 1 to 3, characterized in that, Includes the following steps: According to the corresponding mass proportions, select Codonopsis pilosula, stir-fried Atractylodes macrocephala, Poria cocos, prepared Glycyrrhiza uralensis, ginger-processed Pinellia ternata, Citrus reticulata peel, stir-fried Coix lacryma-jobi, stir-fried rice sprouts, stir-fried malt, stir-fried chicken gizzard lining, Inula japonica, fig, Actinidia chinensis root, Myrica rubra root, and Curcuma longa, mix, soak, decoct, and filter to obtain the final product.

5. The preparation method of the compound preparation for strengthening the spleen, regulating qi, and removing blood stasis according to claim 4, characterized in that, The preparation is an oral liquid preparation.

6. A method of using a compound preparation for invigorating the spleen, regulating qi, and removing blood stasis, characterized in that, The preparation obtained by the preparation method as described in claim 4 or 5 shall be administered at a dose of 100 mL twice daily.

7. The use of a compound preparation for invigorating the spleen, regulating qi, and removing blood stasis as described in any one of claims 1 to 3 in the preparation of a drug for improving gastrointestinal dysfunction caused by chemotherapy.

8. An application according to claim 7, characterized in that, The drug is composed of a compound preparation as described in any one of claims 1 to 3 and other pharmaceutically acceptable excipients.

9. An application according to claim 7, characterized in that, The improvement of chemotherapy-induced gastrointestinal dysfunction includes improving nutritional and metabolic indicators, maintaining skeletal muscle mass, reducing nausea, and reducing the frequency of vomiting.

10. An application according to claim 9, characterized in that, The chemotherapy regimen is any one of FOLFIRI, FOLFOX, CAPOX, or FOLFOXIRI.

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