Traditional Chinese medicine composition for treating solid tumor and preparation method thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicine compositions, and discloses a traditional Chinese medicine composition for treating solid tumors, which comprises oldenlandia diffusa, sculellaria barbata, astragalus membranaceus and glossy privet fruit. The invention also discloses a preparation method of the traditional Chinese medicine composition. The traditional Chinese medicine composition provided by the invention realizes the purpose of treating solid tumors mainly by inhibiting cancer cell respiration to cause apoptosis, and the whole formula has the effects of clearing away heat and toxic materials, supporting the healthy energy and inducing diuresis to reduce edema.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine compositions, and particularly relates to a traditional Chinese medicine composition for treating solid tumors and a preparation method thereof. Background Art

[0002] At present, in the field of tumor treatment, surgical treatment, chemotherapy and radiotherapy are the main treatment techniques. 90% of tumor patients have received one or more of these therapies, which are known as the three conventional means of tumor treatment. However, while these three conventional treatments help patients fight against tumors, due to the defects of their treatment methods, they will damage the patient's own normal tissues and organs. Many elderly and frail patients often give up active treatment because they cannot bear the toxic and side effects brought by the treatment. A large number of clinical practices have shown that the use of traditional Chinese medicine to treat tumors has definite effects, no obvious toxic and side effects, and can relieve symptoms and prolong life. According to clinical symptoms such as dizziness, difficulty in eating, fatigue, fear of cold, soreness and weakness of the waist and knees, or susceptibility to exogenous fever, traditional Chinese medicine believes that the deficiency of healthy qi and the toxic pathogens in the body are the fundamental causes of the occurrence and development of tumors, especially the coagulation of phlegm and dampness, the accumulation of fire toxin in the body, the long-term stagnation without transformation, and the transformation of depression into fire, etc., which induce the formation of tumors.

[0003] Chinese invention patent (CN103417907B): The present invention discloses the application of a traditional Chinese medicine composition in the preparation of a drug for inhibiting angiogenesis. It is made of raw materials in the following weight ratio: Astragalus membranaceus 250, Glossy privet fruit 200, Ginseng 65, Ganoderma lucidum 65, Rhizoma zedoariae 132, Atractylodes macrocephala 64, Scutellaria barbata 128, Gynostemma pentaphyllum 256, Poria cocos 65, Endothelium corneum gigeriae galli 30, Duchesnea indica 128, Solanum lyratum 128, Artemisia capillaris 128, Cynanchum paniculatum 128, Eupolyphaga seu Steleophaga 20, Hedyotis diffusa 128. This traditional Chinese medicine composition can be clinically used to treat malignant tumors, rheumatoid arthritis, diabetic retinopathy and arterial unstable plaques.

[0004] Chinese invention patent (CN102210836A) discloses the application of a traditional Chinese medicine composition in the preparation of a drug for treating gastric cancer. It is made of raw materials in the following weight ratio: Astragalus membranaceus 120 - 360, Glossy privet fruit 100 - 300, Ginseng 30 - 95, Ganoderma lucidum 30 - 95, Rhizoma zedoariae 65 - 195, Atractylodes macrocephala 30 - 90, Scutellaria barbata 65 - 195, Gynostemma pentaphyllum 120 - 360, Poria cocos 30 - 95, Endothelium corneum gigeriae galli 15 - 45, Duchesnea indica 65 - 195, Solanum lyratum 65 - 195, Artemisia capillaris 65 - 195, Cynanchum paniculatum 65 - 195, Eupolyphaga seu Steleophaga 10 - 30, Hedyotis diffusa 65 - 195. The present invention provides an effective drug for treating gastric cancer with reasonable compatibility of medicinal materials, ideal treatment effect and no toxic and side effects for clinical use.

[0005] Chinese invention patent (CN103386078B) discloses the application of a traditional Chinese medicine composition in the preparation of drugs for treating colon cancer, which is made from the following raw materials in parts by weight: Astragalus membranaceus 120 - 360, Glossy Privet Fruit 100 - 300, Ginseng 30 - 95, Ganoderma lucidum 30 - 95, Rhizoma Zedoariae 65 - 195, Atractylodes macrocephala 30 - 90, Scutellaria barbata 65 - 195, Gynostemma pentaphyllum 120 - 360, Poria cocos 30 - 95, Endothelium Corneum Gigeriae Galli 15 - 45, Duchesnea indica 65 - 195, Solanum lyratum 65 - 195, Artemisia capillaris 65 - 195, Cynanchum paniculatum 65 - 195, Eupolyphaga seu Steleophaga 10 - 30, Hedyotis diffusa 65 - 195. This invention is clinically used to treat colon cancer, especially right-sided colon cancer, and has achieved good results.

[0006] During the comprehensive treatment of tumors, cancer patients often need to simultaneously receive modern medical interventions such as combined chemotherapy, radiotherapy, targeted therapy, and immunotherapy with multiple drugs, along with frequent adjuvant medications. As a result, the body has been in a state of long-term drug metabolic load. In the prior art, traditional Chinese medicine compositions often cover 10 or more Chinese medicinal materials with different properties and effects. Some medicinal materials contain complex components such as alkaloids and glycosides, which may have pharmacokinetic interactions with Western medicines during metabolic processes such as the first-pass effect in the liver and renal excretion, thus exacerbating the metabolic burden on important organs such as the liver and kidneys and increasing the risk of adverse reactions such as drug-induced liver injury and nephrotoxicity.

[0007] Based on the principle of "simplifying medication, enhancing efficacy, and reducing toxicity" that needs to be strictly followed in clinical practice, we propose a traditional Chinese medicine composition for treating solid tumors and its preparation method. Summary of the Invention

[0008] The first object of the present invention is to provide a traditional Chinese medicine composition for treating solid tumors, including Hedyotis diffusa, Scutellaria barbata, Astragalus membranaceus, and Glossy Privet Fruit.

[0009] In the formula, Hedyotis diffusa has the effects of clearing heat and detoxifying, dissipating swelling and resolving masses. Clinically, it is mainly used to treat heat syndromes or heat-toxin accumulation, internal heat-toxin excess, or damp-heat pouring downward, and it is the monarch drug. It is combined with Glossy Privet Fruit and Astragalus membranaceus to nourish the liver and kidney, boost qi and raise yang, promote fluid production and nourish blood, promote qi movement and relieve pain, and synergistically with Scutellaria barbata to disperse stasis, resolve carbuncles, stop bleeding, and reduce swelling and promote diuresis. The whole formula has the effects of clearing heat and detoxifying, strengthening the healthy qi and consolidating the root, and reducing swelling and promoting diuresis.

[0010] Preferably, each component is proportioned by the following parts by weight: Hedyotis diffusa 10000 - 40000, Scutellaria barbata 8000 - 30000, Astragalus membranaceus 280 - 1080, and Glossy Privet Fruit 175 - 650.

[0011] Preferably, each component is proportioned by the following parts by weight: Hedyotis diffusa 14940, Scutellaria barbata 11620, Astragalus membranaceus 415, and Glossy Privet Fruit 249.

[0012] The second object of the present invention is to provide a preparation method of the above-mentioned traditional Chinese medicine composition for treating solid tumors, comprising the following steps: (1) Weigh the preparation raw materials according to the weight ratio; (2) Soak the weighed astragalus membranaceus and ligustrum lucidum, decoct twice, combine the filtrates obtained from the two filtrations and concentrate, and vacuum decompress and dry to obtain dry extract powder; (3) Decoct and filter the weighed oldenlandia diffusa and scutellaria barbata separately to obtain filtrates, adjust the pH value of the filtrates with sodium hydroxide respectively to remove acid-insoluble components, concentrate separately, dry to obtain dry extract powder and then mix evenly; (4) Crush and mix the dry extract powders prepared in steps (2) and (3) to obtain the traditional Chinese medicine composition for treating solid tumors.

[0013] Preferably, in step (2), the soaking time is 30 min; decoct twice, wherein the weight ratio of water to the preparation raw materials (astragalus membranaceus or ligustrum lucidum) for each decoction is 5:1, and the decoction time for each time is 2 h.

[0014] Preferably, in step (3), the weight ratio of water to the preparation raw materials (oldenlandia diffusa or scutellaria barbata) is 8:1, and the decoction time is 2 h.

[0015] Preferably, pharmaceutically acceptable excipients are added to make capsules or granules.

[0016] Preferably, solid tumors include various malignant tumors such as lung cancer, liver cancer, esophageal cancer, gastric cancer, intestinal cancer, stromal tumor, glioma, myeloma, laryngeal cancer, oral cancer, nasopharyngeal cancer, etc.

[0017] The present invention has the following beneficial effects: 1. In the formula of the traditional Chinese medicine composition of the present invention, oldenlandia diffusa has the effects of clearing heat and detoxifying, dissipating stasis and relieving swelling, and is mainly used to treat heat syndromes or heat-toxin accumulation, internal heat-toxin excess or damp-heat pouring downward in clinical practice, and is the monarch drug. Matched with ligustrum lucidum and astragalus membranaceus to nourish the liver and kidney, tonify qi and lift yang, promote the production of body fluid and nourish blood, promote qi circulation and relieve pain, and cooperate with scutellaria barbata to disperse stasis, resolve phlegm, stop bleeding, and reduce swelling and promote diuresis. The whole formula has the effects of clearing heat and detoxifying, strengthening healthy qi and consolidating the root, and reducing swelling and promoting diuresis.

[0018] 2. The action principle of the present invention is mainly to inhibit the respiration of cancer cells and cause their apoptosis. Specifically, it causes cancer cell apoptosis by inhibiting the DNA replication of cancer cells (DNA is the carrier of the genetic information of cells, and the continuous proliferation of cancer cells depends on the continuous replication of DNA. When the drug inhibits the DNA replication process of cancer cells, the cancer cells cannot divide and proliferate normally, and finally will initiate their own apoptosis program, that is, the programmed death of cells, so as to achieve the purpose of controlling the number of cancer cells and inhibiting tumor growth.

[0019] By down-regulating the expression of hTERT (telomerase reverse transcriptase) mRNA, reducing the synthesis of hTERT protein, and then reducing the activity of telomerase, the telomeres of cancer cells are gradually shortened, limiting their unlimited proliferation ability, and eventually leading to apoptosis. When the cell starts the apoptosis program, it can promote the expression of Cleaved caspase-3 (cysteine ​​protease) and Cleaved PARP protein (poly ADP ribose polymerase, a key execution enzyme in the cell apoptosis pathway) to induce cancer cell apoptosis. The white flower oldenlandia diffusa in the recipe can significantly reduce the activity of telomerase in human lung giant cell carcinoma cell line PG cells. After Hela cells were treated with white flower oldenlandia diffusa, the telomerase activity was significantly reduced, and the expression of TERTmRNA also showed a downward trend; the drug-containing serum of Scutellaria barbata can reduce the telomerase activity of PG cells, and combined with DDP can enhance the effect of DDP in downregulating telomerase activity; thereby activating the apoptosis signaling pathway of cancer cells, promoting the expression of these two proteins, and prompting cancer cells to apoptosis.

[0020] 3. The Chinese medicine composition of the present invention has only four components. The basic substances have been determined through pharmacological and efficacy studies. Compared with the existing Chinese medicine composition formula for treating cancer, it has fewer medicinal flavors. The Chinese medicine ingredients are relatively complex. Reducing the medicinal flavors can avoid the interaction between related substances in other Chinese medicines, thereby reducing the concentration of effective ingredients and avoiding the harm of newly generated substances to patients. The present invention adopts a special extraction process to enrich the effective material basis, disperse blood stasis and eliminate stagnation, and is compatible with Chinese medicine for strengthening the body and nourishing yin. It can effectively relieve physical fatigue during the process of solid tumor dissolution, enhance the body's immunity, and not hurt body fluids. DETAILED DESCRIPTION

[0021] Example 1 An embodiment of the Chinese medicine composition for treating solid tumors of the present invention comprises the following raw materials in parts by weight: 14940 g of Hedyotis diffusa, 11620 g of Scutellaria barbata, 415 g of Astragalus membranaceus and 249 g of Ligustrum lucidum.

[0022] The preparation method of the Chinese medicine composition for treating solid tumors comprises the following steps: (1) Weigh the raw materials according to the weight ratio; (2) Soak the weighed Astragalus and Ligustrum lucidum for 30 minutes, then add water and boil for extraction twice. For the first time, add 5 times the amount of the medicinal materials and boil for 2 hours, and filter to obtain a filtrate; for the second time, add 5 times the amount of the medicinal materials and boil for 2 hours, and filter to obtain a filtrate. The filtrates are combined, concentrated, and vacuum-dried to obtain a dry extract powder for later use; (3) Add 8 times the amount of water to the weighed Hedyotis diffusa and Scutellaria barbata, respectively, and boil for 2 hours, extract and filter them separately, adjust the pH value of the filtrate with sodium hydroxide to make the filtrate alkaline, concentrate them separately, dry them into dry extract powder, and mix them evenly; (4) The dry extract powder obtained in the above steps (2) and (3) is pulverized into fine powder and then mixed to obtain the traditional Chinese medicine composition for treating solid tumors.

[0023] The above traditional Chinese medicine composition is added with pharmaceutically acceptable excipients to prepare capsules and granules.

[0024] Example 2 An embodiment of the traditional Chinese medicine composition for treating solid tumors of the present invention, the traditional Chinese medicine composition for treating solid tumors comprises the following raw materials for preparation in parts by weight: 22410 g of Hedyotis diffusa, 18930 g of Scutellaria barbata, 622.5 g of Astragalus membranaceus, and 435 g of Glossy Privet Fruit.

[0025] The preparation method of the traditional Chinese medicine composition for treating solid tumors comprises the following steps: (1) Weigh the raw materials according to the weight ratio; (2) Soak the weighed Astragalus membranaceus and Glossy Privet Fruit for 30 min, then add water for decoction and extraction twice. For the first time, add 5 times the amount of water of the medicinal materials and decoct for 2 hours, filter to obtain the filtrate; for the second time, add 5 times the amount of water of the medicinal materials and decoct for 2 hours, filter to obtain the filtrate, combine the filtrates, concentrate, and dry under vacuum and reduced pressure to obtain dry extract powder for standby; (3) Add 8 times the amount of water to the weighed Hedyotis diffusa and Scutellaria barbata respectively and decoct for 2 hours, extract and filter respectively, adjust the pH value of the filtrate with sodium hydroxide to make the filtrate alkaline, concentrate separately, dry to obtain dry extract powder and then mix evenly; (4) The dry extract powder obtained in the above steps (2) and (3) is pulverized into fine powder and then mixed to obtain the traditional Chinese medicine composition for treating solid tumors.

[0026] The above traditional Chinese medicine composition is added with pharmaceutically acceptable excipients to prepare capsules and granules.

[0027] Example 3 An embodiment of the traditional Chinese medicine composition for treating solid tumors of the present invention, the traditional Chinese medicine composition for treating solid tumors comprises the following raw materials for preparation in parts by weight: 38800 g of Hedyotis diffusa, 23240 g of Scutellaria barbata, 830 g of Astragalus membranaceus, and 498 g of Glossy Privet Fruit.

[0028] The preparation method of the traditional Chinese medicine composition for treating solid tumors comprises the following steps: (1) Weigh the raw materials according to the weight ratio; (2) Soak the weighed Astragalus membranaceus and Glossy Privet Fruit for 30 min, then add water for decoction and extraction twice. For the first time, add 5 times the amount of water of the medicinal materials and decoct for 2 hours, filter to obtain the filtrate; for the second time, add 5 times the amount of water of the medicinal materials and decoct for 2 hours, filter to obtain the filtrate, combine the filtrates, concentrate, and dry under vacuum and reduced pressure to obtain dry extract powder for standby; (3) Weigh the Oldenlandia diffusa and Scutellaria barbata, add 8 times the amount of water, decoct for 2 hours respectively, extract and filter separately, adjust the pH value of the filtrate with sodium hydroxide to make the filtrate alkaline, concentrate separately, dry into dry extract powder and then mix well; (4) Take the dry extract powder prepared in the above steps (2) and (3), crush it into fine powder and then mix to obtain the traditional Chinese medicine composition for treating solid tumors.

[0029] Add the above traditional Chinese medicine composition to pharmaceutically acceptable excipients to prepare capsules and granules.

[0030] I. Main pharmacodynamic studies of this traditional Chinese medicine composition 1. Objective: To provide a pharmacodynamic basis for the treatment of lung cancer with "Lianbai Sanjie Capsules" through animal experiments.

[0031] 2. Method: Establish a model by injecting cancer cells into the ear vein, and continuously administer the capsule suspension of the traditional Chinese medicine composition in Examples 1-3 of the present invention for treatment.

[0032] Randomly divide 40 experimental rabbits into two groups with equal numbers, half male and half female, namely the high-dose group, medium-dose group, low-dose group of Lianbai Sanjie Capsules, blank control group, and model group, with 8 rabbits in each group. After normal feeding for seven days, the experiment starts. Except for the normal control group, the experimental rabbits in the other groups are subcutaneously inoculated with about 2 - 2.2×108 rabbit liver cancer cell lines (VX2) that have been digested with trypsin and counted in the logarithmic growth phase and dissolved in 2 ml of sodium chloride injection. To ensure that there are enough cancer cells in the rabbits' lungs to cause cancer, an additional 1 - 1.1×108 cancer cells are injected into the experimental rabbits on days 7 to 10, and the injection is continuous for 30 days. On the last day of injecting cells, perform a lung CT to observe the formation of solid tumors in the lungs. At the same time, treat with Lianbai Sanjie Capsules. The dosing doses are 0.27 mg / kg for the high dose, 0.20 mg / kg for the medium dose, and 0.13 mg / kg for the low dose. Administer the drug by gavage once a day for 30 consecutive days to stop the treatment. Check the CT to observe the lung condition and conduct gross dissection for observation.

[0033] 3. Results: After treatment, the rabbits' body weight increased, the general symptoms improved, the lung cancer shadow became smaller, and some disappeared.

[0034] 3.1 Effects on body weight: Rabbit liver cancer cells were injected into each group. During the injection period, the body weight of each group except the blank control group increased slowly, showing a significant difference compared with the blank control group. After stopping the injection of rabbit liver cancer cells, there was no significant difference in the body weight of each group of experimental rabbits compared with the blank control group before administration. In the 3rd and 4th weeks after injecting rabbit liver cancer cells, the body weight increased slowly compared with the blank control group, showing a highly significant difference. In the initial stage of administration (i.e., the 5th and 6th weeks of the experiment period), the body weight of each group of experimental rabbits increased slowly compared with the blank control group, showing a highly significant difference. In the later stage of administration (i.e., the 7th and 8th weeks of the experiment period), the body weight of each group of experimental rabbits increased normally, showing no significant difference compared with the blank control group.

[0035] 3.2 Effects on solid tumors: 30 days after injecting rabbit liver cancer cells, each group was examined by CT. In each group except the blank control group, nodules the size of mung beans and soybeans were found at the injection sites of some rabbits. When performing a lung CT, solid lesions of different sizes (lung cancer shadows) were found in the lungs of the experimental rabbits, showing a highly significant difference compared with the blank control group. Moreover, most of the experimental rabbits showed symptoms such as sneezing and running nose. After the examination was completed, each group started treatment and administration. Continuous gavage administration was carried out for 28 days. During the administration period, the body weight of the rabbits increased normally, and all symptoms such as sneezing, head shaking, and running clear nose of the experimental rabbits disappeared. 28 days after the experiment ended, the lungs of each group of animals were examined by CT. In the high, medium, and low-dose groups, the solid shadows in the lungs of 2, 1, and 1 experimental rabbits disappeared respectively, and the remaining solid shadows in the lungs were reduced to varying degrees. After continuing to observe for 1 month and then examining the solid shadows in the lungs of each group of animals by CT, the lung shadows of 6, 5, and 4 animals in the high, medium, and low-dose groups disappeared respectively (no lesions were found in the lungs of the sacrificed animals during autopsy), and the solid shadows in the lungs of the remaining animals were reduced, and the nodules at the injection sites basically disappeared, showing a highly significant difference compared with the model control group.

[0036] II. General pharmacology test 1. Laboratory tests show that it has a specific effect on the test tumor cells (solid tumors such as lung cancer and liver cancer) and has low toxicity and side effects. Laboratory cell tests confirm that as long as the drug concentration in the culture medium reaches 2 micrograms per milliliter or above, the tumor cells will completely die within 48 hours. There is no obvious difference in the growth and morphological microscopic examination between the non-tumor cell group (epithelial cells, mouse embryonic fibroblasts, vascular endothelial cells) with and without drug administration. When non-tumor cells (epithelial cells, mouse embryonic fibroblasts, vascular endothelial cells) are administered with a drug dose dozens of times higher than the lethal dose for cancer cells, there is also no obvious difference in growth compared with the non-administered group.

[0037] Compared with currently commonly used chemotherapy drugs such as vincristine, 5-fluorouracil, paclitaxel, etc., it is superior in the dose and stability of killing different cell lines.

[0038] 2. The tumor cell lines that have been tested in the laboratory are: 2.1 Cell lines with obvious killing effects: liver cancer, lung cancer, laryngeal cancer, breast cancer, colon cancer, cervical cancer, human melanoma, etc.

[0039] 2.2 Cell lines with killing effects: myeloma, mouse myeloma, lymphoma, human osteosarcoma.

[0040] 2.3 Cell lines without killing effects: human leukemia, mouse erythroleukemia, etc.

[0041] III. Acute toxicity test The acute oral toxicity test of Lianbai Sanjie Capsule in mice was entrusted to Gansu Institute for Drug Control for the test. The test methods, purposes and results are as follows.

[0042] 1. Test purpose: To observe the toxic reactions produced after a single oral gavage of the test substance at the maximum administered concentration to animals within 24 hours.

[0043] 2. Test method: Forty KM mice were randomly divided into a blank group and a dosing group. Before the test, the animals were fasted for 12 hours without water deprivation. After weighing, each mouse in the dosing group was gavaged with a concentration of 0.53 mg / ml at a volume of 0.4 ml / 10 g once within 24 hours, and the dose was 21.20 mg / kg. The blank group was given an equal volume of purified water. Immediately after dosing, the toxic reactions and death conditions of the animals were observed. From the next day after dosing, the appearance, behavior, response to stimuli, secretions, excretions, etc. and death conditions (death time, pre - dying reactions, etc.) of the animals were observed every day. During the test, the weights of each animal were measured and recorded on the 1st, 3rd, 7th, and 14th days after dosing. After the test ended, all the test animals were subjected to gross dissection. When changes in volume, color, texture, etc. of tissues and organs were found, they should be recorded and histopathological examinations were carried out.

[0044] 3. Test results: In this experiment, 40 KM strain mice weighing 18 - 22 g, with an equal number of males and females, were randomly divided into a blank group and a dosing group. After weighing, each mouse in the dosing group was gavaged with a concentration of 0.53 mg / ml at a volume of 0.40 ml / 10 g once within 24 hours, and the dose was 21.20 mg / kg. The blank group was given an equal volume of purified water. The reactions of the animals were observed immediately after dosing, such as hair, diet, drinking water, activity level, urine and feces, death conditions, etc. The body weights were continuously observed and recorded for 14 days. As a result, all the mice survived, their body weights increased, and no obvious toxic reactions were observed macroscopically. Therefore, its maximum tolerated dose is 21.2 mg / kg, which is about 706 times the clinical dosage for a 60 - kg human (the clinical dosage for humans is about 0.03 mg / kg).

[0045] IV. Long - term toxicity test The long-term toxicity test of Lianbai Sanjie Capsule on rats for six months was entrusted to Gansu Institute for Drug Control. The test methods, purposes and results are as follows.

[0046] 1. Test purpose: At 20, 40, and 60 times the clinical dosage (1.67 mg / kg), continuous repeated administration for six months. Observe the effects on indicators such as rat body weight gain, food intake, viscera-body ratio, hematological indexes, blood biochemical indexes, and pathological histological examinations. Compare the results with the normal blank control group to investigate the safety of repeated administration of Lianbai Sanjie Capsule.

[0047] 2. Test methods: 2.1 Administration method: Gavage, once a day, and the administration route is the same as that in clinical practice.

[0048] 2.2 Dose design: Three test substance administration groups were set, namely 33.4 mg / kg, 66.8 mg / kg, and 100.2 mg / kg. The powder of Lianbai Sanjie Capsule was prepared into 3.34 mg / ml, 6.68 mg / ml, and 1.002 mg / ml with distilled water. Each group was administered at a dose of 10 ml / kg, which were 20, 40, and 60 times the recommended clinical daily dose respectively. At the same time, a normal blank control group was set, and the same amount of purified water was gavaged daily.

[0049] 2.3 Test cycle: Once a day, continuous gavage administration for six months, and observe for 15 days after drug withdrawal.

[0050] 2.4 Start and end dates of the test: 2020.03.15 - 2020.09.30 2.5 Experimental procedures: The rats were randomly grouped and numbered, and continuously gavaged for six months. Observe their behavioral manifestations, fecal shapes and other symptoms and signs daily. Weigh once a week, adjust the dosage according to the body weight, measure the food intake once every two weeks. At three months and six months of administration, 10 rats (5 females and 5 males) were taken from each group to collect femoral artery blood for determination of hematological and blood biochemical indexes. Immediately dissect the heart, liver, spleen, lung, kidney, brain, spinal cord, pituitary gland, submandibular gland, thyroid gland, esophagus, trachea, thymus, pancreas, adrenal gland, stomach, duodenum, ileum, colon, uterus, ovary, bladder, testis, epididymis, mammary gland, sternum. Weigh the heart, liver, spleen, lung, kidney, stomach, adrenal gland, thymus, testis + epididymis, or uterus (uterus + ovary) precisely. At the same time, all viscera were fixed with 10% formaldehyde solution for pathological histological examination. The remaining rats were treated in the same way 15 days after drug withdrawal for various examinations.

[0051] 3. Test results: 3.1 Effects on the general condition and body weight of rats: During the 6-month dosing period, the food intake, activities, hair color, feces, and appearance behaviors of each dose group and the blank control group were basically normal, and no animals died. There were no significant differences in body weight gain between the high-dose group, medium-dose group, low-dose group, and the blank control group (P>0.05).

[0052] 3.2 Effects on food intake: There were no obvious differences in food intake between the high-dose group, medium-dose group, low-dose group, and the blank control group (P>0.05). 3.3 Effects on hematological indices of rats The peripheral blood picture was detected after three months of dosing. The results showed that the plateletcrit (PCT) was increased compared with the blank control group, and there was a significant difference in the high-dose group (P<0.05). For the other indices, including white blood cell count (WBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular hemoglobin concentration (MCHC), platelet (PLT), mean corpuscular volume (MCV), red blood cell (RBC), mean corpuscular hemoglobin (MCH), mean platelet volume (MPV), and platelet distribution width (PDW), there were no significant differences compared with the blank control group (P>0.05).

[0053] The peripheral blood picture was detected after six months of dosing. The results showed that the indices of RBC, HGB, and HCT in each dose group were decreased compared with the blank control group. Among them, there were significant differences in RBC in the high-dose, medium-dose, and low-dose groups (P<0.05); there was a very significant difference in HGB in the high-dose group (P<0.01), and significant differences in the medium-dose and low-dose groups (P<0.05); there were very significant differences in HCT in the high-dose and low-dose groups (P<0.01), and a significant difference in the medium-dose group (P<0.05); the mean corpuscular hemoglobin concentration (MCHC) was increased compared with the blank control group, and there was a significant difference in the high-dose group (P<0.05); there was a very significant difference in the low-dose group (P<0.01). For the other indices of each dose group, including plateletcrit (PCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), white blood cell count (WBC), mean platelet volume (MPV), platelet (PLT), and platelet distribution width (PDW), there were no significant differences compared with the blank control group (P>0.05).

[0054] The peripheral blood routine was detected 15 days after drug withdrawal. The results showed that the indicators of white blood cell count (WBC), platelet (PLT), plateletcrit (PCT), and platelet distribution width (PDW) in each dose group were all lower compared with the blank control group. Among them, there was a very significant difference in the high-dose group of white blood cell count (WBC) (P<0.01); there were significant differences in the high-, medium-, and low-dose groups of platelet (PLT) (P<0.05); there were very significant differences in the high- and medium-dose groups of plateletcrit (PCT) (P<0.01); there was a significant difference in the high-dose group of platelet distribution width (PDW) (P<0.05); for the indicators of red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean platelet volume (MPV) in the remaining dose groups, there were no significant differences compared with the blank control group (P>0.05).

[0055] 3.4 Effects on blood biochemical indices of rats Blood biochemical indices were detected after three months of drug administration. For the indices of total bilirubin (T-BIL), total bile acid (TBA), and triglyceride (TG) in each dose group, compared with the blank control group, the total bilirubin (T-BIL) increased in each group, with a significant difference in the low-dose group; the total bile acid (TBA) increased in each group, with a significant difference in the high-dose group and a very significant difference in the low-dose group; the triglyceride (TG) decreased in each group, with a significant difference in the low-dose group. For the remaining creatinine (CREA), gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein (TP), albumin (ALB), uric acid (UA), glucose (GLU), total cholesterol (CH), urea (UREA), potassium ion (K+), sodium ion (Na+), and calcium ion (Ca+), there were no significant differences in the indices of each dose group compared with the blank control group (P>0.05).

[0056] Blood biochemical indexes were detected after six months of drug administration. Compared with the blank control group, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), uric acid (UA), triglyceride (TG), and urea (UREA) in each dose group decreased. Among them, there were very significant differences in the high, medium, and low dose groups of alanine aminotransferase (ALT); there were very significant differences in the high and medium dose groups of aspartate aminotransferase (AST), and significant differences in the low dose group; there were very significant differences in the high and medium dose groups of alkaline phosphatase (ALP); there were very significant differences in the high and medium dose groups of uric acid (UA), and significant differences in the low dose group; there were very significant differences in the high and medium dose groups of triglyceride (TG); there were significant differences in the high and medium dose groups of urea (UREA). Compared with the blank control group, glucose (GLU) in each dose group increased, and there were very significant differences in the high and medium dose groups. For the rest, creatinine (CREA), gamma-glutamyl transpeptidase (GGT), total protein (TP), albumin (ALB), total bilirubin (T-BIL), total bile acid (TBA), total cholesterol (CH), potassium ion (K+), sodium ion (Na+), and calcium ion (Ca+) in each dose group showed no significant differences compared with the blank control group (P>0.05).

[0057] Blood biochemical indexes were detected 15 days after drug withdrawal. Compared with the blank control group, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) decreased in each dose group, and there were very significant differences in the low dose group. Uric acid (UA) decreased, and there were significant differences in the high dose group.

[0058] 3.5 Effects on the organ coefficients of rats: After three months of drug administration, each group of rats was bled from the femoral artery, carefully dissected macroscopically, and no abnormalities were found. Then, precise weighing was carried out to calculate the organ coefficients [organ weight (g) / body weight (100g)]. After statistical processing, there were no significant differences between each dose group and the blank control group (P>0.05).

[0059] 3.6 Effects on the urine indexes of rats: After 3 months of drug administration, urine was collected from each group to detect indexes such as white blood cells, ketone bodies, nitrites, bilirubin, urine protein, and occult blood, and no abnormalities were found.

[0060] 3.7 Histopathological examination: After long-term drug administration to the animals in this experiment, through histopathological examination, no obvious histopathological changes caused by the test drug were found in organs such as the heart, liver, spleen, lung, kidney, brain (cerebrum and cerebellum), adrenal gland, thyroid gland, submandibular gland, pituitary gland, thymus gland, esophagus, trachea, stomach, duodenum, ileum, colon, pancreas, testis, epididymis, ovary, uterus, mammary gland, bladder, mesenteric lymph nodes, spinal cord, and optic nerve.

[0061] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention shall be included within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition for treating solid tumors, characterized in that, It includes Oldenlandia diffusa, Scutellaria barbata, Astragalus membranaceus and Ligustrum lucidum.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The components are proportioned by weight as follows: Oldenlandia diffusa 10000 - 40000, Scutellaria barbata 8000 - 30000, Astragalus membranaceus 280 - 1080 and Ligustrum lucidum 175 - 650.

3. The traditional Chinese medicine composition according to claim 2, wherein The components are proportioned by weight as follows: Oldenlandia diffusa 14940, Scutellaria barbata 11620, Astragalus membranaceus 415 and Ligustrum lucidum 249.

4. A method for preparing a traditional Chinese medicine composition for treating solid tumors, which is used to prepare the traditional Chinese medicine composition according to any one of claims 1-3, characterized in that, It includes the following steps: (1) Weigh the preparation raw materials according to the weight ratio. (2) Soak the weighed Astragalus membranaceus and Ligustrum lucidum, decoct twice, combine and concentrate the filtrates obtained from the two filtrations, and dry under vacuum and reduced pressure to obtain dry extract powder. (3) Decoct and filter the weighed Oldenlandia diffusa and Scutellaria barbata respectively to obtain filtrates, adjust the pH values of the filtrates respectively to remove acid-insoluble components, concentrate separately, and mix after drying into dry extract powder. (4) Crush and mix the dry extract powders prepared in steps (2) and (3) to obtain the traditional Chinese medicine composition for treating solid tumors.

5. The preparation method according to claim 4, wherein In step (2), the soaking time is 30 min; decoct twice, wherein the weight ratio of water to the preparation raw materials (Astragalus membranaceus or Ligustrum lucidum) for each decoction is 5:1, and the decoction time for each time is 2 h.

6. The preparation method according to claim 4, characterized in that, In step (3), the weight ratio of water to the preparation raw materials (Oldenlandia diffusa or Scutellaria barbata) is 8:1, and the decoction time is 2 h.

7. The preparation method according to claim 4, characterized in that, Add pharmaceutically acceptable excipients to make capsules or granules.