A traditional Chinese medicine composition for treating colorectal cancer crisis and a preparation method thereof

Abstract

The present application relates to the technical field of anticancer pharmaceutical compositions, and discloses a traditional Chinese medicine composition for treating colorectal cancer cachexia and a preparation method thereof, wherein the traditional Chinese medicine composition comprises the following components by weight: Taizishen, Baizhu, Yiyiren, Jiangbanxia, Chenpi, Sharen, Qixie, Daxueteng, Bagen, Yeguteng, Mihetao, Xiakucao, Muli, Ezu, and Binglang; the present application can, on the one hand, support the healthy qi by using Taizishen, Baizhu, Yiyiren, Chenpi, and Ganzao to benefit qi and invigorate the spleen and supplement the root of acquired constitution; on the other hand, the present application can attack and eliminate the real evil by using Qixie, Daxueteng, Jiangbanxia, Bagen, Sharen, Yeguteng, Mihetao, Xiakucao, Muli, Ezu, and Binglang to clear heat and resolve toxicity, disperse knots, and remove blood stasis; in the tumor microenvironment, the present application can effectively inhibit the activation of the JAK / STAT3 signal pathway of colorectal cancer cachexia, thereby solving the problem that colorectal cancer cachexia is difficult to be effectively treated in clinical practice.

Description

Technical Field

[0001] This invention belongs to the field of anticancer drug composition technology, specifically relating to a traditional Chinese medicine composition for treating cachexia in colorectal cancer and its preparation method. Background Technology

[0002] Cachexia is a term used to describe a state of generalized malnutrition and emaciation, associated with various chronic diseases, cancer, organ failure, and infections. Cancer cachexia (CC) is a common clinical syndrome in patients with various malignant tumors, characterized by an involuntary decrease in fat and skeletal muscle mass. Cachexia occurs in up to 80% of cancer patients and is considered a direct cause of reduced quality of life, leading to at least 20% of cancer-related deaths and limiting treatment options for cancer patients. The pathogenesis of CC is very complex, and it is currently believed to be due to systemic metabolic disorders caused by tumor cell products and the release of excessive inflammatory mediators, resulting in insufficient protein synthesis, excessive catabolism, increased skeletal muscle consumption, and progressive organ failure. Due to its complex pathogenesis, current treatment strategies for CC mainly focus on improving immune function, enhancing resistance, and stimulating appetite, but effective treatment methods are still lacking.

[0003] Traditional Chinese medicine (TCM) does not have a specific disease name for "tumor cachexia." The *Suwen* (Plain Questions) chapter "On the True Organs and Viscera" describes cachexia as "the bones wither and decay, the flesh sinks, the chest is full of qi, breathing is difficult, and the qi moves the body," and "loss of nourishment occurs before and after the ears and on the shoulders and neck…it is difficult to cure over time, the body gradually weakens, and the muscles become emaciated," all of which describe the emaciation and malnutrition of patients with cachexia. Currently, cancer-related cancer (CC) is widely considered to fall under the categories of "atrophy syndrome" and "debilitating weakness," with "deficiency" referring to a deficiency of qi, blood, yin, and yang, and "exhaustion" referring to the depletion of the essence and qi of the internal organs. TCM believes that "cancer toxins causing deficiency" is the basic etiology and pathogenesis of CC, with deficiency of vital energy being the pathological basis of cachexia, and cancer toxins being the pathogenic cause of cachexia. Numerous studies have shown that TCM can not only alleviate symptoms in cancer patients (such as fatigue, chronic pain, anorexia, cachexia, and insomnia) and improve their quality of life (QOL), but also reduce adverse reactions and complications caused by chemotherapy, radiotherapy, or targeted therapy.

[0004] Colorectal cancer (CRC) is a common digestive system tumor. Cachexia is a wasting syndrome caused by multiple factors, including tumors or other chronic diseases such as organ failure, neurological diseases, sepsis, AIDS, and rheumatoid arthritis. It is accompanied by weight loss and energy and protein metabolism imbalance. It is characterized by loss of appetite, weight loss and skeletal muscle loss, leading to fatigue, dysfunction, increased treatment-related toxicity, and poor quality of life. It is a common complication and a major cause of death from malignant tumors.

[0005] The persistent weight loss in cancer cachexia is primarily caused by skeletal muscle atrophy. The loss of skeletal muscle mass results from an imbalance between protein synthesis and degradation, mainly regulated by lysosomes and UPS. MURF1 and MAFbx belong to the muscle-specific E3 ubiquitin ligase family; they are highly expressed in disease states such as cancer cachexia and heart failure, leading to muscle protein degradation via the proteasome. Therefore, in the treatment of colorectal cancer cachexia, formulating an effective drug to treat it has become a pressing problem in this field.

[0006] Therefore, this invention designs a traditional Chinese medicine composition that can effectively treat cachexia in colorectal cancer by inhibiting the activation of the JAK / STAT3 signaling pathway, thereby reducing protein degradation, treating muscle atrophy and insulin synthesis, and thus solving the problems existing in the prior art. Summary of the Invention

[0007] (a) Technical problems to be solved

[0008] To address the shortcomings of existing technologies, this invention provides a traditional Chinese medicine composition for treating colorectal cancer cachexia and its preparation method. This composition effectively inhibits the activation of the JAK / STAT3 signaling pathway, thereby reducing protein degradation, treating muscle atrophy, and promoting insulin synthesis. It solves the problem of colorectal cancer cachexia being difficult to treat effectively in clinical practice, leading to muscle atrophy in patients.

[0009] (II) Technical Solution

[0010] To achieve the aforementioned objective of effectively inhibiting the activation of the JAK / STAT3 signaling pathway in colorectal cancer cachexia, the present invention provides the following technical solution:

[0011] A traditional Chinese medicine composition for treating cachexia in colorectal cancer, the composition comprising the following traditional Chinese medicines in parts by weight: Codonopsis pilosula 5-25 parts, Atractylodes macrocephala 5-15 parts, Coix lacryma-jobi 10-27 parts, Pinellia ternata 5-15 parts, Citrus reticulata 5-15 parts, Amomum villosum 2-10 parts, Gecko 2-10 parts, Sargentodoxa cuneata 20-40 parts, Smilax china 20-40 parts, Grapevine 20-40 parts, Actinidia chinensis root 20-40 parts, Prunella vulgaris 5-25 parts, Ostrea gigas 20-40 parts, Curcuma zedoaria 5-25 parts, Areca catechu 5-15 parts, Glycyrrhiza uralensis 2-10 parts.

[0012] Preferably, the traditional Chinese medicine composition comprises the following traditional Chinese medicines in parts by weight: 10-20 parts of Codonopsis pilosula, 8-12 parts of Atractylodes macrocephala, 15-22 parts of Coix lacryma-jobi, 8-12 parts of Pinellia ternata, 8-12 parts of Citrus reticulata peel, 4-8 parts of Amomum villosum, 4-8 parts of Gecko, 25-35 parts of Sargentodoxa cuneata, 25-35 parts of Smilax china, 25-35 parts of Grapevine, 25-35 parts of Actinidia chinensis root, 10-20 parts of Prunella vulgaris, 25-35 parts of Ostrea gigas, 10-20 parts of Curcuma zedoaria, 8-12 parts of Areca catechu, and 4-8 parts of Glycyrrhiza uralensis.

[0013] Preferably, the traditional Chinese medicine composition comprises the following traditional Chinese medicines in parts by weight: 15 parts of Codonopsis pilosula, 10 parts of Atractylodes macrocephala, 18 parts of Coix lacryma-jobi, 10 parts of Pinellia ternata, 10 parts of Citrus reticulata peel, 6 parts of Amomum villosum, 6 parts of Gecko, 30 parts of Sargentodoxa cuneata, 30 parts of Smilax china, 30 parts of Grapevine, 30 parts of Actinidia chinensis root, 15 parts of Prunella vulgaris, 30 parts of Ostrea gigas, 15 parts of Curcuma zedoaria, 10 parts of Areca catechu, and 6 parts of Glycyrrhiza uralensis.

[0014] A method for preparing a traditional Chinese medicine composition for treating cachexia in colorectal cancer, comprising:

[0015] Step 1: Grind the prescribed amounts of Codonopsis pilosula, Amomum villosum, and gecko powder into a fine powder;

[0016] Step 2: Add water to the prescribed amounts of the following thirteen Chinese herbs: Atractylodes macrocephala, Coix lacryma-jobi, Pinellia ternata, Citrus reticulata peel, Sargentodoxa cuneata, Smilax china, Grapevine, Actinidia chinensis root, Prunella vulgaris, Ostrea gigas, Curcuma zedoaria, Areca catechu, and Glycyrrhiza uralensis. Decoction is carried out three times, one hour each time. The decoction is filtered, and the filtrates are combined. The mixture is then concentrated at 80°C to form a clear paste with a relative density of 1.20-1.28. The fine powder from Step 1 is added, mixed well, and dried at low temperature to prepare a solid preparation.

[0017] Preferably, the solid dosage form is one of tablets, capsules, or granules.

[0018] Application of a traditional Chinese medicine composition for treating cachexia in colorectal cancer in the preparation of drugs for treating cachexia in colorectal cancer.

[0019] (III) Beneficial Effects

[0020] Compared with the prior art, the present invention provides a traditional Chinese medicine composition for treating cachexia in colorectal cancer and its preparation method, which has the following beneficial effects:

[0021] The traditional Chinese medicine composition for treating colorectal cancer cachexia described in this invention has the main effects of invigorating the spleen and replenishing qi, resolving phlegm, removing blood stasis and dispersing nodules. The treatment of this formula requires, on the one hand, strengthening the body's resistance, using herbs such as Codonopsis pilosula, Atractylodes macrocephala, Coix lacryma-jobi, Citrus reticulata peel, and Glycyrrhiza uralensis to invigorate qi and strengthen the spleen, replenishing the acquired constitution; on the other hand, it also requires expelling pathogenic factors, using herbs such as Gecko, Sargentodoxa cuneata, Pinellia ternata, Smilax china, Amomum villosum, Grapevine, Actinidia chinensis root, Prunella vulgaris, Ostrea gigas, Curcuma zedoaria, and Areca catechu to clear heat, detoxify, disperse nodules and remove blood stasis. In the tumor microenvironment, IL-6 in this formula has been shown to be a key mediator of cancer-related angina pectoris (CC) in different mouse cancer models. Simultaneously, IL-6 induces weight loss by activating muscle STAT3 and blocks insulin synthesis by pancreatic β cells, effectively inhibiting the activation of the JAK / STAT3 signaling pathway in colorectal cancer cachexia, thus solving the problem of colorectal cancer cachexia being difficult to treat effectively in clinical practice and causing muscle atrophy in patients. Attached Figure Description

[0022] Figure 1 The diagram shows the effect of the traditional Chinese medicine composition for treating colorectal cancer cachexia of the present invention on the general condition and IL-6 of cachectic mice.

[0023] Figure 2 This is a diagram showing the pathological effects of the traditional Chinese medicine composition for treating colorectal cancer cachexia of the present invention on the skeletal muscle of cachectic mice.

[0024] Figure 3 This is an electrophoresis diagram showing the expression of key proteins in skeletal muscle atrophy after the application of the traditional Chinese medicine composition for treating colorectal cancer cachexia according to the present invention.

[0025] Figure 4 This figure shows the effect of the traditional Chinese medicine composition for treating colorectal cancer cachexia of the present invention on the expression of skeletal muscle atrophy-related proteins in cachectic mice.

[0026] Figure 5 This diagram illustrates the effect of the traditional Chinese medicine composition for treating colorectal cancer cachexia of the present invention on the expression of genes related to skeletal muscle atrophy in cachectic mice.

[0027] Among them: Figure 1 In the figure, Figure A shows the weight of the cachectic mouse after tumor removal, Figure B shows the skeletal muscle mass, Figure C shows the food intake, and Figure D shows the serum IL-6 content of the cachectic mouse.

[0028] exist Figure 2 In the diagram, Figure A is the normal group, Figure B is the model group, Figure C is the low-dose group of traditional Chinese medicine compositions for treating colorectal cancer cachexia, Figure D is the medium-dose group of traditional Chinese medicine compositions for treating colorectal cancer cachexia, and Figure E is the high-dose group of traditional Chinese medicine compositions for treating colorectal cancer cachexia.

[0029] exist Figure 4In the figure, Figure A shows the effect of a traditional Chinese medicine composition for treating colorectal cancer cachexia on the nitration level of STAT3 in cachectic mice; Figure B shows the effect of the traditional Chinese medicine composition for treating colorectal cancer cachexia on the expression level of MAFbx protein in cachectic mice; and Figure C shows the effect of the traditional Chinese medicine composition for treating colorectal cancer cachexia on the expression level of MURF1 protein in cachectic mice. Figure 4 A- Figure 4 In C, TreatA: low-dose group; TreatB: medium-dose group; TreatC: high-dose group; △: compared with the normal group, P < 0.05; *: compared with the model group, P < 0.05;

[0030] exist Figure 5 Figure A shows the effect of a traditional Chinese medicine composition for treating colorectal cancer cachexia on the expression level of MURF1 RNA gene in cachectic mice; Figure B shows the effect of the traditional Chinese medicine composition for treating colorectal cancer cachexia on the expression level of Myog RNA gene in cachectic mice; and Figure C shows the effect of the traditional Chinese medicine composition for treating colorectal cancer cachexia on the expression level of STAT3 RNA gene in cachectic mice. Figure 5 A- Figure 5 In C, Treat A: low-dose group; Treat B: medium-dose group; Treat C: high-dose group; △: compared with the normal group, P < 0.05; *: compared with the model group, P < 0.05. Detailed Implementation

[0031] 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.

[0032] Please see Figure 1-5 This invention provides a technical solution: a traditional Chinese medicine composition that can effectively treat cachexia in colorectal cancer, the composition comprising the following traditional Chinese medicines in parts by weight: Codonopsis pilosula, Atractylodes macrocephala, Coix lacryma-jobi, Pinellia ternata, Citrus reticulata peel, Amomum villosum, Gecko, Sargentodoxa cuneata, Smilax china, Grapevine, Actinidia chinensis root, Prunella vulgaris, Ostrea gigas, Curcuma zedoaria, Areca catechu, and Glycyrrhiza uralensis; The common pharmacological effects of these traditional Chinese medicine ingredients in this field are as follows:

[0033] Prince Ginseng: The dried tuberous root of *Pseudostellaria heterophylla* (Miq.) Pax ex Paxet Hoffm., a plant in the Caryophyllaceae family. It has a sweet and slightly bitter taste, and is neutral in nature. It enters the spleen and lung meridians. It has the effects of invigorating qi and strengthening the spleen, promoting body fluid production and moistening the lungs. It is used for spleen deficiency with fatigue, loss of appetite, weakness after illness, qi and yin deficiency, spontaneous sweating and thirst, and dry cough due to lung dryness.

[0034] Atractylodes macrocephala: The dried rhizome of Atractylodes macrocephala Koidz., a plant in the Asteraceae family. It has a bitter and sweet taste, and is warm in nature. It enters the spleen and stomach meridians. It has the effects of strengthening the spleen and replenishing qi, drying dampness and promoting diuresis, stopping sweating, and calming the fetus. It is used for spleen deficiency with poor appetite, abdominal distension and diarrhea, phlegm retention with dizziness and palpitations, edema, spontaneous sweating, and threatened abortion.

[0035] Job's tears (Coix lacryma-jobi) L. var. mayuen (Roman.) Stapf, a plant of the Poaceae family, are dried, mature seeds. They are sweet, bland, and cool in nature. They enter the spleen, stomach, and lung meridians. They have the effects of promoting diuresis and eliminating dampness, strengthening the spleen and stopping diarrhea, relieving numbness, draining pus, and detoxifying and resolving lumps. They are used for edema, beriberi, dysuria, spleen deficiency diarrhea, dampness-induced arthralgia, lung abscess, intestinal abscess, warts, and tumors.

[0036] Ginger-processed Pinellia: This is a processed product of Pinellia ternata. Pinellia ternata is the dried tuber of Pinellia ternata (Thunb.) Breit., a plant in the Araceae family. It has a pungent and warm flavor. It enters the spleen, stomach, and lung meridians. It has the effects of warming the middle jiao (spleen and stomach), resolving phlegm, and relieving nausea and vomiting. It is used for vomiting due to phlegm retention and abdominal distension.

[0037] Dried tangerine peel (Citrus reticulata Blanco) is the dried, mature peel of the citrus fruit and its cultivated varieties, belonging to the Rutaceae family. It has a bitter and pungent taste, and is warm in nature. It enters the lung and spleen meridians. It has the effects of regulating qi and strengthening the spleen, drying dampness and resolving phlegm. It is used for abdominal distension, poor appetite, vomiting and diarrhea, and cough with excessive phlegm.

[0038] Amomum villosum Lour. (Zingiberaceae) or Amomum longiligulare TLWu (Zingiberaceae) are dried, mature fruits. They are pungent and warm in nature. They enter the spleen, stomach, and kidney meridians. They have the effects of resolving dampness and invigorating the stomach, warming the spleen and stopping diarrhea. They are used for dampness obstructing the middle jiao, abdominal distension and lack of appetite, spleen and stomach deficiency and cold, vomiting and diarrhea.

[0039] Gecko: The dried whole body of the gecko *Gekko swinhoana* Gunther or *Gekkojapinicus* (Dumeril et Bibron), both belonging to the Gekkonidae family. It is salty and cold in nature, and slightly toxic. It enters the liver meridian. It has the effects of dispelling wind and calming convulsions, dispersing nodules and detoxifying. It is used for stroke paralysis, wind-phlegm epilepsy, joint pain, scrofula, and malignant sores.

[0040] Sargentodoxa cuneata (Oliv.) Rehd. et Wils, a plant in the Lardizabalaceae family, is a dried vine. It has a bitter taste and neutral properties. It enters the large intestine and liver meridians. It has the effects of clearing heat and detoxifying, promoting blood circulation, dispelling wind and relieving pain. It is used for intestinal abscesses and abdominal pain, carbuncles and sores caused by heat toxins, amenorrhea, dysmenorrhea, traumatic swelling and pain, and rheumatic pain.

[0041] Smilax china L. (Liliaceae): The dried rhizome of the plant. It has a sweet, slightly bitter, and astringent taste, and is neutral in nature. It enters the liver and kidney meridians. It has the effects of promoting diuresis and removing turbidity, dispelling wind and relieving numbness, and detoxifying and dispersing blood stasis. It is used for urinary tract infections with cloudy urine, excessive leukorrhea, rheumatic pain, boils, and carbuncles.

[0042] Wild grapevine: The dried aerial parts of *Ampelopsis sinica* (Miq.) W. Wang, a plant in the Vitaceae family. It is bitter and cold in nature. It enters the stomach and liver meridians. It has the effects of dispelling wind, promoting diuresis, relieving pain, and reducing swelling. It is used for rheumatism, gonorrhea, leukorrhea, urinary retention, swelling due to wind, boils, erysipelas, tooth decay, and swollen gums.

[0043] Kiwi root: The dried root of *Actinidia chinensis* Planconh, a plant in the Actinidiaceae family. It has a slightly sweet, astringent, and cool taste. It is slightly toxic. It enters the kidney and stomach meridians. It has the effects of clearing heat and detoxifying, dispelling wind and dampness, promoting blood circulation and reducing swelling. It is used for hepatitis, dysentery, indigestion, urinary tract infections, leukorrhea, rheumatic joint pain, traumatic injuries, boils, and scrofula.

[0044] Prunella vulgaris L. (also known as selfheal or purgative): The dried fruit spike of the plant Prunella vulgaris L. (Lamiaceae family). It has a pungent, bitter, and cold nature. It enters the liver and gallbladder meridians. It has the effects of clearing liver heat, improving eyesight, and reducing swelling. It is used for red, swollen, and painful eyes, nighttime eye pain, headache, dizziness, elk disease, emaciation, mastitis, breast lumps, and breast distension and pain.

[0045] Oyster: The shell of the oyster species *Ostrea gigas* Thunberg, *Ostrea salina* Crosse, or *Ostrea rivularis* Gould. It has a salty taste and is slightly cold in nature. It enters the liver, gallbladder, and kidney meridians. It has the effects of calming the mind, nourishing yin and yang, and softening and dispersing masses. It is used for palpitations, insomnia, dizziness, tinnitus, tuberculosis with phlegm nodules, and abdominal masses.

[0046] Curcuma zedoaria: The dried rhizome of Curcuma phaeocaulis Vai., Curcuma wangsiensis SG Lee et C F. Liang, or Curcuma wenyujin Y.H.Chen et C.Ling (all belonging to the ginger family). It has a sweet and astringent taste, and is neutral in nature. It enters the heart and kidney meridians. It has the effect of strengthening the kidneys and astringing semen. It is used for seminal emission, leukorrhea, and frequent urination.

[0047] Areca catechu L., a plant in the palm family (Arecaceae), is the dried, mature seed. It has a bitter and pungent taste, and is warm in nature. It enters the stomach and large intestine meridians. It possesses insecticidal, digestive, qi-regulating, diuretic, and antimalarial properties. It is used for tapeworm infection, ascariasis, fascioliasis, abdominal pain due to intestinal parasites, diarrhea due to food stagnation, tenesmus, edema, beriberi, and malaria.

[0048] Licorice: The dried root and rhizome of *Glycyrrhiza uralensis* Fisch., *Glycyrrhiza inflata* Bat., or *Glycyrrhiza glabra* L. (all belonging to the Fabaceae family). It has a sweet and neutral flavor. It enters the heart, lung, spleen, and stomach meridians. It tonifies the spleen and stomach, replenishes qi, and restores the pulse. It is used for spleen and stomach weakness, fatigue, palpitations, and irregular pulse.

[0049] Example 1: A traditional Chinese medicine composition that can effectively treat cachexia in colorectal cancer, the traditional Chinese medicine composition comprising the following traditional Chinese medicines in parts by weight: Codonopsis pilosula 5 parts, Atractylodes macrocephala 5 parts, Coix lacryma-jobi 10 parts, Pinellia ternata 5 parts, Citrus reticulata 5 parts, Amomum villosum 2 parts, Gecko 2 parts, Sargentodoxa cuneata 20 parts, Smilax china 20 parts, Grapevine 20 parts, Actinidia chinensis root 20 parts, Prunella vulgaris 5 parts, Ostrea gigas 20 parts, Curcuma zedoaria 5 parts, Areca catechu 5 parts, Glycyrrhiza uralensis 2 parts;

[0050] Example 2: A traditional Chinese medicine composition that can effectively treat cachexia in colorectal cancer, the traditional Chinese medicine composition comprising the following traditional Chinese medicines in parts by weight: 10 parts of Codonopsis pilosula, 8 parts of Atractylodes macrocephala, 15 parts of Coix lacryma-jobi, 8 parts of Pinellia ternata, 8 parts of Citrus reticulata peel, 4 parts of Amomum villosum, 4 parts of Gecko, 25 parts of Sargentodoxa cuneata, 25 parts of Smilax china, 25 parts of Grapevine, 25 parts of Actinidia chinensis root, 10 parts of Prunella vulgaris, 25 parts of Ostrea gigas, 10 parts of Curcuma zedoaria, 8 parts of Areca catechu, and 4 parts of Glycyrrhiza uralensis.

[0051] In preparation, weigh the above-mentioned Chinese herbal raw materials separately, and grind the Codonopsis pilosula, Amomum villosum, and gecko powder into fine powder; add water to the remaining thirteen herbs such as Atractylodes macrocephala and decoct three times. The first time, add 10 times the amount of water and decoct for 60 minutes. The second and third times, add 8 times the amount of water and decoct for 60 minutes. Filter, combine the filtrates, concentrate to a clear extract with a relative density of 1.20 to 1.28 (80℃), add the above-mentioned fine powder (Codonopsis pilosula, Amomum villosum, and gecko powder), mix well, and dry at low temperature.

[0052] Example 3: A traditional Chinese medicine composition that can effectively treat cachexia in colorectal cancer, the traditional Chinese medicine composition comprising the following traditional Chinese medicines in parts by weight: 15 parts of Codonopsis pilosula, 10 parts of Atractylodes macrocephala, 18 parts of Coix lacryma-jobi, 10 parts of Pinellia ternata, 10 parts of Citrus reticulata peel, 6 parts of Amomum villosum, 6 parts of Gecko, 30 parts of Sargentodoxa cuneata, 30 parts of Smilax china, 30 parts of Grapevine, 30 parts of Actinidia chinensis root, 15 parts of Prunella vulgaris, 30 parts of Ostrea gigas, 15 parts of Curcuma zedoaria, 10 parts of Areca catechu, and 6 parts of Glycyrrhiza uralensis (optimal ratio).

[0053] In preparation, weigh the above-mentioned Chinese herbal raw materials separately, and grind the Codonopsis pilosula, Amomum villosum, and gecko powder into fine powder; add water to the remaining thirteen herbs such as Atractylodes macrocephala and decoct three times. The first time, add 10 times the amount of water and decoct for 60 minutes. The second and third times, add 8 times the amount of water and decoct for 60 minutes. Filter, combine the filtrates, concentrate to a clear extract with a relative density of 1.20 to 1.28 (80℃), add the above-mentioned fine powder (Codonopsis pilosula, Amomum villosum, and gecko powder), mix well, and dry at low temperature.

[0054] Example 4: A traditional Chinese medicine composition that can effectively treat cachexia in colorectal cancer, the traditional Chinese medicine composition comprising the following traditional Chinese medicines in parts by weight: 20 parts of Codonopsis pilosula, 12 parts of Atractylodes macrocephala, 22 parts of Coix lacryma-jobi, 12 parts of Pinellia ternata, 12 parts of Citrus reticulata peel, 8 parts of Amomum villosum, 8 parts of Gecko, 35 parts of Sargentodoxa cuneata, 35 parts of Smilax china, 35 parts of Grapevine, 35 parts of Actinidia chinensis root, 20 parts of Prunella vulgaris, 35 parts of Ostrea gigas, 20 parts of Curcuma zedoaria, 12 parts of Areca catechu, and 8 parts of Glycyrrhiza uralensis.

[0055] In preparation, weigh the above-mentioned Chinese herbal raw materials separately, and grind the Codonopsis pilosula, Amomum villosum, and gecko powder into fine powder; add water to the remaining thirteen herbs such as Atractylodes macrocephala and decoct three times. The first time, add 10 times the amount of water and decoct for 60 minutes. The second and third times, add 8 times the amount of water and decoct for 60 minutes. Filter, combine the filtrates, concentrate to a clear extract with a relative density of 1.20 to 1.28 (80℃), add the above-mentioned fine powder (Codonopsis pilosula, Amomum villosum, and gecko powder), mix well, and dry at low temperature.

[0056] Example 5: A traditional Chinese medicine composition that can effectively treat cachexia in colorectal cancer, the traditional Chinese medicine composition comprising the following traditional Chinese medicines in parts by weight: 25 parts of Codonopsis pilosula, 15 parts of Atractylodes macrocephala, 27 parts of Coix lacryma-jobi, 15 parts of Pinellia ternata, 15 parts of Citrus reticulata peel, 10 parts of Amomum villosum, 10 parts of Gecko, 40 parts of Sargentodoxa cuneata, 40 parts of Smilax china, 40 parts of Grapevine, 40 parts of Actinidia chinensis root, 25 parts of Prunella vulgaris, 40 parts of Ostrea gigas, 25 parts of Curcuma zedoaria, 15 parts of Areca catechu, and 10 parts of Glycyrrhiza uralensis.

[0057] In preparation, weigh the above-mentioned Chinese herbal raw materials separately, and grind the Codonopsis pilosula, Amomum villosum, and gecko powder into fine powder; add water to the remaining thirteen herbs such as Atractylodes macrocephala and decoct three times. The first time, add 10 times the amount of water and decoct for 60 minutes. The second and third times, add 8 times the amount of water and decoct for 60 minutes. Filter, combine the filtrates, concentrate to a clear extract with a relative density of 1.20 to 1.28 (80℃), add the above-mentioned fine powder (Codonopsis pilosula, Amomum villosum, and gecko powder), mix well, and dry at low temperature.

[0058] The preparation methods of the traditional Chinese medicine compositions described in Examples 1-5 above all include the following steps:

[0059] Step 1: Grind the prescribed amount of the following sixteen Chinese herbs into a fine powder: Codonopsis pilosula, Atractylodes macrocephala, Coix lacryma-jobi, Pinellia ternata, Citrus reticulata peel, Amomum villosum, Gecko, Sargentodoxa cuneata, Smilax china, Grapevine, Actinidia chinensis root, Prunella vulgaris, Ostrea gigas, Curcuma zedoaria, Areca catechu, and Glycyrrhiza uralensis. Among them, Codonopsis pilosula, Amomum villosum, and Gecko are ground into a fine powder.

[0060] Step 2: The remaining thirteen ingredients, including Atractylodes macrocephala, are decocted three times with water, one hour each time. The decoction is filtered, the filtrates are combined, and concentrated into a clear extract with a relative density of 1.20-1.28 (80℃). The above-mentioned fine powder is added, mixed well, and dried at low temperature. It can be made into various dosage forms such as capsules, granules, and tablets.

[0061] Example 6: Study on the therapeutic effect on CRC

[0062] 1. Materials

[0063] Animal SPF grade male BALB / c mice, 6-8 weeks old, weighing 20-22g.

[0064] CT26 cells were cultured routinely in a 37°C, 5% CO2 incubator.

[0065] 2. Methods

[0066] 2.1. After one week of acclimatization, mice were randomly divided into 6 groups using a random number table: a blank control group, a model group, a megestrol acetate group, a low-dose group of the traditional Chinese medicine composition for treating colorectal cancer cachexia, a medium-dose group of the traditional Chinese medicine composition for treating colorectal cancer cachexia, and a high-dose group of the traditional Chinese medicine composition for treating colorectal cancer cachexia. Each group consisted of 10 mice, and the weights of the mice in each group were kept similar. All mice were numbered after grouping.

[0067] 2.2. Model Preparation

[0068] Logarithmic growth phase CT26 cells were collected, digested with 0.25% trypsin, washed and resuspended with PBS for counting, and the cell concentration was adjusted to 1×10⁻⁶. 6 / 0.1ml, for later use. A mouse model of colorectal cancer cachexia was established. In the cachexia group, after skin disinfection, each mouse received a subcutaneous injection of 0.1ml of cell suspension into the right axilla using a 1mL syringe. Before injection, the needle was first punctured subcutaneously, and the syringe was held horizontally to allow the needle to penetrate a short distance (approximately 1cm deep) before injection. The blank control group received a single injection of 0.1ml of 0.9% sodium chloride injection. The mice's average body weight decreased by 5% compared to the normal group, and they exhibited reduced activity, weakness, and lethargy. Different interventions were administered according to the grouping.

[0069] 2.3. Administration

[0070] Once the mice entered a cachectic state, drug intervention was initiated. The treatment groups included: medroxyprogesterone acetate group (24 mg / kg / d), low-dose group (0.75 g / kg / d), medium-dose group (1.5 g / kg / d), and high-dose group (3 g / kg / d). Each mouse was administered 0.01 mL / g via gavage for 15 consecutive days, once daily. The blank group and model group served as controls, administered purified water via gavage. Mice were anesthetized by intraperitoneal injection of 1% sodium pentobarbital at 5 mL / kg body weight. Blood was collected from the eyeballs, and the mice were euthanized by cervical dislocation. The intact gastrocnemius muscles from both sides were harvested and immediately weighed using an electronic balance. The tumor was removed, and surrounding muscles, skin, and other non-tumor tissues were eliminated. A portion of the skeletal muscle was fixed in 4% paraformaldehyde, and the remaining portion was frozen at -80°C for subsequent analysis.

[0071] 2.4. Indicator Testing

[0072] 2.4.1. General situation:

[0073] During the experiment, the mice's mental state, fur, activity level, food intake, and water intake were closely observed. Mice mortality and body weight changes were also observed and recorded. The long and short diameters of the tumor were measured every two days using a vernier caliper. Tumor volume was estimated using the formula V = a × b. 2 / 2 (a and b are the length and width of the tumor, respectively). The tumor weight was estimated by subtracting the tumor weight from the body weight using the formula M = V × F (F is the ratio of the actual tumor weight to the volume at the end of the experiment). The weight of the mice was measured using an electronic balance at a fixed time each day. Each group of mice was housed together and provided with the same feed and drinking water. Starting from day 1 after inoculation, the total amount of food and water consumed by each group of mice was recorded.

[0074] 2.4.2. Skeletal muscle pathological examination

[0075] Skeletal muscle tissue fixed in 4% paraformaldehyde was embedded in paraffin, paraffin sections were prepared, and hematoxylin and eosin (HE) staining was performed using conventional methods. Pathological changes were observed under a microscope, and images were collected to observe changes in the cross-sectional area of ​​skeletal muscle fibers.

[0076] 2.4.3. Detection of serum IL-6 by enzyme-linked immunosorbent assay (ELISA)

[0077] Collect serum and store it at -80°C. Perform testing strictly according to the instructions of the enzyme-linked immunosorbent assay (ELISA) kit.

[0078] 2.4.4. Western Blot Detection

[0079] Proteins were extracted from the collected muscle tissue, and the expression levels of proteins MURF1, MAFbx, and related pathway targets in the muscle tissue were detected by Western blotting. A portion of mouse skeletal muscle stored at -80℃ was used for total protein extraction, and protein concentration was measured using the BCA method and leveled. Proteins were separated by 10% SDS-PAGE electrophoresis, electroporated onto PVDF membranes, blocked with 5% skim milk powder for 1 h, and then incubated overnight at 4℃ using primary antibody. The following day, the membranes were washed four times with TBST for 5 min each time, and the corresponding secondary antibody was added. After incubation at room temperature for 1 h, the membranes were washed three times with TBST for 5 min each time, and then imaged using ECL chemiluminescence. Images were collected, and grayscale values ​​were calculated using ImageJ software. The ratio of the grayscale value of the target protein to that of the internal control was used as its expression level.

[0080] 2.4.5. Real-time PCR detection of STAT3, MuRF1, and Myog mRNA expression in gastrocnemius muscle

[0081] Gastrocnemius muscle tissue was weighed, ground, lysed, and RNA was extracted using the TRIzol method. RNA concentration and purity were measured. Reverse transcription was performed at 25℃ for 5 min, 42℃ for 30 min, and 85℃ for 5 s. RNA was reverse transcribed into cDNA, which was then amplified by PCR. The reaction volume was 10 μL. Amplification conditions were: 95℃ pre-denaturation for 30 s for one cycle; 95℃ for 15 s denaturation, and 60℃ for 30 s annealing / extension for 40 cycles. GAPDH was used as an internal reference gene, and the relative fold change in target gene expression was calculated using 2-ΔΔCt. Primers were synthesized by Wuhan Saiwei Biotechnology Co., Ltd. (see Table 1).

[0082] Table 1: Primer Table

[0083]

[0084] 2.5. Statistical Analysis

[0085] Experimental data were collected and analyzed using SPSS statistical software to test for normality and homogeneity of variance. Results are expressed as mean ± standard deviation. If the data conformed to a normal distribution, one-way ANOVA was used. For comparisons between groups with homogeneous variances, the LSD method was used; for comparisons between groups with unequal variances, Dunnett's 3 method was used. If the data did not conform to a normal distribution, nonparametric tests were used. A p-value < 0.05 was considered statistically significant.

[0086] 3. Results

[0087] 3.1. Effects of the Traditional Chinese Medicine Composition for Treating Colorectal Cancer Cachexia on General Condition: Compared with the control group, the model group mice showed significantly decreased body weight and skeletal muscle mass (P < 0.05), and a slight decrease in food intake. Compared with the model group, the mice in the traditional Chinese medicine composition group for treating colorectal cancer cachexia showed significantly increased final tumor-free weight and skeletal muscle mass after drug intervention (P < 0.05), and a slight increase in food intake, but this was not statistically significant. There was no statistically significant difference in tumor size among the different drug groups. See Table 2.

[0088] Figure 1 Table 2: Effects of a traditional Chinese medicine composition for treating colorectal cancer cachexia on the general condition and IL-6 levels in cachectic mice.

[0089]

[0090] Note: Compared with the normal group a P < 0.05; compared with the model group b P < 0.05.

[0091] 3.2. Effect of a traditional Chinese medicine composition for treating cachexia in colorectal cancer on IL-6 levels.

[0092] Compared with the blank control group, the serum IL-6 level in the model group was significantly increased (P<0.05); compared with the model group, the serum IL-6 level in the low- and medium-dose groups of the traditional Chinese medicine composition capsules for treating colorectal cancer cachexia was significantly decreased (P<0.05); see Table 1. Figure 1 .

[0093] 3.3. Effects of a traditional Chinese medicine capsule composition for treating cachexia in colorectal cancer on the pathological morphology of skeletal muscle.

[0094] Compared with the control group, the model group showed a smaller cross-sectional area of ​​gastrocnemius muscle fibers, cell atrophy, darker scleral pigmentation, fewer cell nuclei, and wider intercellular spaces. Compared with the model group, the pathological state of gastrocnemius muscle fibers in all treatment groups was improved, with increased cross-sectional area of ​​muscle fibers, more cell nuclei, and narrower intercellular spaces. See Figure 2 .

[0095] 3.4. Effects of a traditional Chinese medicine composition capsule for treating cachexia in colorectal cancer on the expression levels of STAT3, MAFbx, and MURF1 proteins in the gastrocnemius muscle.

[0096] Compared with the blank control group, the p-STAT3 / STAT3 ratio and the expression levels of MAFbx and MURF1 proteins in the skeletal muscle of mice in the model group were significantly increased (P < 0.05). Compared with the model group, the p-STAT3 / STAT3 ratio and the expression levels of MAFbx and MURF1 proteins in the skeletal muscle of mice in the medium-dose group of the traditional Chinese medicine composition capsules for treating colorectal cancer cachexia were significantly decreased (P < 0.05). See Table 3. Figure 3 and Figure 4 .

[0097] Table 3: Effects of traditional Chinese medicine composition for treating cachexia caused by colorectal cancer on the expression levels of related proteins in cachectic mice.

[0098]

[0099] 3.5. Effects of a traditional Chinese medicine capsule composition for treating cachexia in colorectal cancer on the expression levels of STAT3, MURF1, and Myog genes in the gastrocnemius muscle.

[0100] Compared with the normal control group, the expression levels of MURF1 and STAT3 RNA in the skeletal muscle of mice in the model group were significantly increased (P < 0.05), while the expression level of Myog RNA was significantly decreased (P < 0.05). Compared with the model group, the expression levels of MURF1 and STAT3 RNA in the skeletal muscle of mice in the medium-dose group of the traditional Chinese medicine composition capsules for treating colorectal cancer cachexia were significantly decreased (P < 0.05), while the expression level of Myog RNA was significantly increased (P < 0.05). See Table 4. Figure 5 .

[0101] Table 4: Effects of traditional Chinese medicine capsule composition for treating colorectal cancer cachexia on the expression levels of related genes in cachectic mice.

[0102]

[0103]

[0104] It should be noted that, in this document, relational terms such as "first" and "second" are used only to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Without further limitations, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes said element.

[0105] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A traditional Chinese medicine composition for treating colorectal cancer crisis, characterized in that: The traditional Chinese medicine composition is made of the following weight parts of traditional Chinese medicines: Taizishen 5-25 parts, Baizhu 5-15 parts, Yiyiren 10-27 parts, Jiangbanxia 5-15 parts, Chenpi 5-15 parts, Sharen 2-10 parts, Qixie 2-10 parts, Daxueteng 20-40 parts, Shengqie 20-40 parts, Yeputeng 20-40 parts, Mihetaogen 20-40 parts, Xiakucao 5-25 parts, Muli 20-40 parts, Ezu 5-25 parts, Binlang 5-15 parts, Gancao 2-10 parts. ​ 2. The traditional Chinese medicine composition for treating colorectal cancer crisis according to claim 1, characterized in that: The traditional Chinese medicine composition is made of the following weight parts of traditional Chinese medicines: Taizishen 10-20 parts, Baizhu 8-12 parts, Yiyiren 15-22 parts, Jiangbanxia 8-12 parts, Chenpi 8-12 parts, Sharen 4-8 parts, Qixie 4-8 parts, Daxueteng 25-35 parts, Shengqie 25-35 parts, Yeputeng 25-35 parts, Mihetaogen 25-35 parts, Xiakucao 10-20 parts, Muli 25-35 parts, Ezu 10-20 parts, Binlang 8-12 parts, Gancao 4-8 parts.

3. The traditional Chinese medicine composition for treating colorectal cancer cachexia as described in claim 1, characterized in that: The traditional Chinese medicine composition is made of the following weight parts of traditional Chinese medicines: Taizishen 15 parts, Baizhu 10 parts, Yiyiren 18 parts, Jiangbanxia 10 parts, Chenpi 10 parts, Sharen 6 parts, Qixie 6 parts, Daxueteng 30 parts, Shengqie 30 parts, Yeputeng 30 parts, Mihetaogen 30 parts, Xiakucao 15 parts, Muli 30 parts, Ezu 15 parts, Binlang 10 parts, Gancao 6 parts.

4. The preparation method of the traditional Chinese medicine composition for treating colorectal cancer crisis according to any one of claims 1-3, characterized in that: The application also discloses a preparation method of the traditional Chinese medicine composition. Step 1: powdering the prescribed amount of Taizishen, Sharen and Qixie; Step 2: decocting the prescribed amount of Baizhu, Yiyiren, Jiangbanxia, Chenpi, Daxueteng, Shengqie, Yeputeng, Mihetaogen, Xiakucao, Muli, Ezu, Binlang and Gancao thirteen kinds of traditional Chinese medicines with water for three times, each time for 1 hour, filtering, combining the filtrates, concentrating the combined filtrate into a clear extract with a relative density of 1.20-1.28 under the condition of 80 DEG C, adding the powder of step 1, mixing, low-temperature drying and preparing into a solid preparation.

5. The method for preparing a traditional Chinese medicine composition for treating colorectal cancer cachexia as described in claim 4, characterized in that: The solid preparation is one of a tablet, a capsule or a granule.

6. The application of the traditional Chinese medicine composition in claim 1 in the preparation of a drug for treating colorectal cancer cachexia.

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