Traditional Chinese medicine composition for alleviating gastrointestinal toxicity caused by chemotherapy

Abstract

A traditional Chinese medicine composition for alleviating gastrointestinal toxic side effects caused by chemotherapy, the traditional Chinese medicine composition for daily administration is prepared from the following weight ratio of traditional Chinese medicine formula: Taizishen 20-30g, Fuling 10-15g, Fried Baizhu 10-15g, Zhigancao 5-10g, Jiangbanxia 5-10g, Chenpi 5-15g. The formula can effectively alleviate the gastrointestinal toxic side effects caused by chemotherapy, such as nausea, vomiting, diarrhea, poor appetite, etc.

Description

[0001] The present application is a divisional application of the invention patent application with the application number 2019102372196, the application date of March 27, 2019, and the invention name of “Traditional Chinese medicine composition for relieving gastrointestinal toxic and side reactions caused by chemotherapy”. TECHNICAL FIELD

[0002] The present application belongs to the technical field of traditional Chinese medicine formula, and particularly relates to a traditional Chinese medicine composition for relieving gastrointestinal toxic and side reactions caused by chemotherapy. BACKGROUND

[0003] In the past two decades, the morbidity and mortality of colorectal cancer in China has been rising, and has jumped to the 4th place in the total morbidity and the 5th place in the total mortality. Oxaliplatin is the third generation of platinum derivatives, which can be flexibly used in combination with 5-fluorouracil / folic acid, and is widely used in colorectal cancer. However, as a moderate emetic drug, its incidence of vomiting is high, with a report of 30%-90% in the literature. After the patients use it, they have obvious digestive tract reactions, including nausea, vomiting, etc.

[0004] Although the current western antiemetic drugs have developed to the 6th generation, and can regulate vomiting from different pathways, the symptoms of nausea, the decrease of appetite and the constipation side reactions caused by antiemetic drugs seriously affect the quality of life. Some patients even stop chemotherapy or refuse to accept chemotherapy, which affects the curative effect of chemotherapy and may further affect the curative effect of chemotherapy in improving the cure rate. SUMMARY

[0005] Traditional Chinese medicine believes that chemotherapy drugs belong to “drug evil”, attack cancer, disturb the body's qi and blood, consume the healthy qi, and affect the normal operation of the functions of viscera, especially damage the postnatal spleen and stomach transportation function. The weak spleen and stomach, the disorder of ascending and descending, the failure of spleen qi to ascend, the failure of stomach qi to descend, and the vomiting of stomach qi, cause the symptoms of nausea and vomiting. The team of the inventor has engaged in the research of colorectal cancer for twenty years, and found in the previous work that the combination of traditional Chinese medicine treatment during chemotherapy can relieve the toxic and side reactions of chemotherapy. The formula of the traditional Chinese medicine composition involved in the present application is modified on the basis of Sijunzi Decoction, and has the effects of supporting healthy qi, strengthening the spleen and stomach, and descending and stopping vomiting.

[0006] The purpose of the present application is to provide a traditional Chinese medicine composition for relieving gastrointestinal toxic and side reactions caused by chemotherapy. The traditional Chinese medicine composition for daily use is prepared from the following weight ratio of traditional Chinese medicine formula: Taizishen 20-30g, Fuling 10-15g, Fried Baizhu 10-15g, Zhigancao 5-10g, Jiangbanxia 5-10g, and Chenpi 5-15g.

[0007] Preferably, the traditional Chinese medicine composition for daily administration is prepared from the following weight ratio of traditional Chinese medicine materials: 22-30 grams of Taizishen, 10-13 grams of Fuling, 10-13 grams of Fried Baizhu, 6-9 grams of Zhigancao, 6-10 grams of Jiangbanxia, and 6-12 grams of Chenpi.

[0008] Preferably, the traditional Chinese medicine composition for daily administration is prepared from the following weight ratio of traditional Chinese medicine materials: 22-30 grams of Taizishen, 10-13 grams of Fuling, 10-13 grams of Fried Baizhu, 6-9 grams of Zhigancao, 6-10 grams of Jiangbanxia, and 6-12 grams of Chenpi.

[0009] Preferably, the traditional Chinese medicine composition for daily administration is prepared from the following weight ratio of traditional Chinese medicine materials: 22-30 grams of Taizishen, 10-13 grams of Fuling, 10-13 grams of Fried Baizhu, 6-9 grams of Zhigancao, 6-10 grams of Jiangbanxia, and 6-12 grams of Chenpi.

[0010] Preferably, the traditional Chinese medicine composition is a decoction.

[0011] Preferably, the traditional Chinese medicine composition is a granule.

[0012] Preferably, the traditional Chinese medicine composition is a decoction, prepared by the following method: (I) weighing each kind of medicine material according to the weight ratio, and soaking all the medicine materials in clean cold water for 30-40 minutes, adding water to immerse the medicine materials by 1-2 centimeters, and making the medicine materials fully soaked; (II) boiling with strong fire and then changing to weak fire to keep a slight boil, and then filtering out the medicine juice after 20-30 minutes of decoction; (III) adding appropriate amount of water again, boiling, and then decocting with weak fire for 15-20 minutes, and filtering out the medicine juice; (IV) combining the medicine juice obtained in step (II) and the medicine juice obtained in step (III) to obtain the traditional Chinese medicine composition.

[0013] Preferably, the traditional Chinese medicine composition is a granule, prepared by the following method: (1) preparing granule preparations of each kind of traditional Chinese medicine material respectively; (2) mixing the corresponding granule preparations or formula granule preparations of each kind of medicine material according to the weight ratio to obtain the traditional Chinese medicine composition.

[0014] In the method, the granule preparations of each kind of traditional Chinese medicine material are prepared as follows.

[0015] Taizishen granule preparation: using Taizishen decoction pieces as raw materials, adding water in an amount of 5-10 times the weight of the medicine materials to the decoction pieces, and then carrying out two water extractions, combining the water extraction liquids, and then carrying out pressure reduction concentration and spray drying on the water extraction liquids to obtain spray dried powder, and then directly compressing the spray dried powder into blocks through a dry compression granulator and crushing the blocks into granules to obtain the Taizishen granule preparation, with each gram of the Taizishen granule preparation equivalent to 5 grams of Taizishen decoction pieces.

[0016] Poria cocos granule preparation: with Poria cocos decoction pieces as raw material, add 5-10 times of water to the decoction pieces, carry out two water extraction, then combine the water extract, reduce pressure concentration, spray drying to get spray drying powder, directly compress the spray drying powder into blocks by dry compression granulator, break into granules, to get Poria cocos granule preparation, 1 gram of Poria cocos granule preparation is equivalent to 5 grams of Poria cocos decoction pieces.

[0017] Fried atractylodes rhizome granule preparation: with fried atractylodes rhizome decoction pieces as raw material, add 5-10 times of water to the decoction pieces, carry out two water extraction, then combine the water extract, reduce pressure concentration, spray drying to get spray drying powder, directly compress the spray drying powder into blocks by dry compression granulator, break into granules, to get fried atractylodes rhizome granule preparation, 1 gram of fried atractylodes rhizome granule preparation is equivalent to 5 grams of fried atractylodes rhizome decoction pieces.

[0018] Baked licorice granule preparation: with baked licorice decoction pieces as raw material, add 5-10 times of water to the decoction pieces, carry out two water extraction, then combine the water extract, reduce pressure concentration, spray drying to get spray drying powder, directly compress the spray drying powder into blocks by dry compression granulator, break into granules, to get baked licorice granule preparation, 1 gram of baked licorice granule preparation is equivalent to 5 grams of baked licorice decoction pieces.

[0019] Ginger pinellia ternata formula granule preparation: with ginger pinellia ternata decoction pieces as raw material, use 5-10 times of water to carry out two continuous water extraction, combine the filtrate, water bath concentration to get extract, reduce pressure drying to get dry extract, crush the dry extract, sieve, add dextrin in a ratio of 1:1, use 90% ethanol to make soft material, sieve the soft material, reduce pressure drying and sieving, to get ginger pinellia ternata formula granule preparation, 1 gram of ginger pinellia ternata formula granule preparation is equivalent to 20 grams of ginger pinellia ternata decoction pieces.

[0020] Pericarpium citri reticulatae formula granule preparation: with pericarpium citri reticulatae decoction pieces as raw material, first extract volatile oil, add 5-10 times of water to the residue, carry out two water extraction, then combine the water extract, reduce pressure concentration, spray drying to get spray drying powder, directly compress the spray drying powder into blocks by dry compression granulator, break into granules, add the volatile oil to the formula granule after being wrapped with cyclodextrin and stabilized, mix evenly, to get pericarpium citri reticulatae formula granule preparation, 1 gram of pericarpium citri reticulatae formula granule preparation is equivalent to 10 grams of pericarpium citri reticulatae decoction pieces.

[0021] The traditional Chinese medicine composition provided by the application can effectively reduce the digestive tract side reactions such as nausea, vomiting, diarrhea and poor appetite during chemotherapy, improve the life quality of patients during chemotherapy, and improve the completion rate of chemotherapy of patients. DETAILED DESCRIPTION

[0022] In order to make the purposes, technical solutions and advantages of the present application clearer, the present application will be further described in detail. It should be understood that the specific embodiments described in the description are only used to explain and illustrate the present application, and are not used to limit the protection scope of the present application.

[0023] Example 1: Formulation for preparing the traditional Chinese medicine composition

[0024] The traditional Chinese medicine composition provided by the present application is preferably prepared from normatively processed traditional Chinese medicine decoction pieces. The formula for preparing a daily serving of the traditional Chinese medicine composition is as follows: 20-30 g of Taizishen, 10-15 g of Fuling, 10-15 g of fried Baizhu, 5-10 g of Zhigancao, 5-10 g of Jiangbanxia, and 5-15 g of Chenpi; preferably 22-30 g of Taizishen, 10-13 g of Fuling, 10-13 g of fried Baizhu, 6-9 g of Zhigancao, 6-10 g of Jiangbanxia, and 6-12 g of Chenpi; more preferably 25-30 g of Taizishen, 10-12 g of Fuling, 10-12 g of fried Baizhu, 6-8 g of Zhigancao, 8-10 g of Jiangbanxia, and 8-10 g of Chenpi; and most preferably 30 g of Taizishen, 10 g of Fuling, 10 g of fried Baizhu, 6 g of Zhigancao, 10 g of Jiangbanxia, and 10 g of Chenpi.

[0025]

Pharmacological properties

[0026] Taizishen: benefiting qi and invigorating the spleen, generating fluid and moistening the lung, used for treating spleen deficiency, loss of appetite, deficiency of qi and yin, spontaneous sweating and thirst, and dry cough.

[0027] Fuling: benefiting water and eliminating dampness, invigorating the spleen and calming the heart, used for treating edema, less urine, spleen deficiency, less food intake, loose stool, diarrhea, and mental unrest.

[0028] Fried Baizhu: drying dampness, benefiting water, stopping sweating, and stabilizing the fetus, used for treating spleen deficiency, abdominal distension, diarrhea, dizziness due to phlegm, edema, spontaneous sweating, and unstable fetus.

[0029] Zhigancao: tonifying the spleen and stomach, benefiting qi and restoring pulse, used for treating weakness of the spleen and stomach, fatigue, palpitation, and pulse blockage.

[0030] Jiangbanxia: drying dampness, reducing phlegm, and stopping vomiting, used for treating vomiting due to excessive phlegm and sputum or cold phlegm cough.

[0031] Chenpi: regulating qi, invigorating the spleen, drying dampness, and reducing phlegm, used for treating abdominal fullness, less food intake, vomiting and diarrhea, and cough with much phlegm.

[0032] Example 2: Decoction for preparing the traditional Chinese medicine composition

[0033] According to the following formula for preparing a traditional Chinese medicine composition for a daily serving, the required six medicinal materials are weighed, i.e. 30 grams of Taizi Shen, 10 grams of Fuling, 10 grams of Chao Baizhu, 6 grams of Zhi Gancao, 10 grams of Jiang Banxia, and 10 grams of Chenpi.

[0034] Example 3: Method for preparing granules of the traditional Chinese medicine composition

[0035] According to the following formula for preparing a traditional Chinese medicine composition for a daily serving, the required six medicinal materials are weighed, i.e. 30 grams of Taizi Shen, 10 grams of Fuling, 10 grams of Chao Baizhu, 6 grams of Zhi Gancao, 10 grams of Jiang Banxia, and 10 grams of Chenpi.

[0036] Any suitable process flow known to those skilled in the art is adopted to prepare the granular preparation of each medicinal material. As an exemplary illustration, the granular preparation of each medicinal material can be prepared as follows.

[0037] Taizi Shen granular preparation: with Taizi Shen decoction pieces as raw material, water is added to the decoction pieces in an amount of 5-10 times the weight of the medicinal material, and after two water extractions, the water extracts are combined. The water extracts are reduced pressure concentrated, spray dried to obtain spray dried powder, and the spray dried powder is directly compressed into blocks and broken into granules by a dry compression granulator to prepare Taizi Shen granular preparation, with each gram of Taizi Shen granular preparation equivalent to 5 grams of Taizi Shen decoction pieces.

[0038] Fuling granular preparation: with Fuling decoction pieces as raw material, water is added to the decoction pieces in an amount of 5-10 times the weight of the medicinal material, and after two water extractions, the water extracts are combined. The water extracts are reduced pressure concentrated, spray dried to obtain spray dried powder, and the spray dried powder is directly compressed into blocks and broken into granules by a dry compression granulator to prepare Fuling granular preparation, with each gram of Fuling granular preparation equivalent to 5 grams of Fuling decoction pieces.

[0039] Chao Baizhu granular preparation: with Chao Baizhu decoction pieces as raw material, water is added to the decoction pieces in an amount of 5-10 times the weight of the medicinal material, and after two water extractions, the water extracts are combined. The water extracts are reduced pressure concentrated, spray dried to obtain spray dried powder, and the spray dried powder is directly compressed into blocks and broken into granules by a dry compression granulator to prepare Chao Baizhu granular preparation, with each gram of Chao Baizhu granular preparation equivalent to 5 grams of Chao Baizhu decoction pieces.

[0040] The licorice granule preparation is prepared by using the licorice decoction pieces as raw materials, adding water with a weight of 5-10 times of the medicinal materials into the decoction pieces, carrying out two times of water extraction, combining the water extracts, carrying out vacuum concentration and spray drying on the water extracts to obtain spray dried powder, directly compressing the spray dried powder into blocks by a dry compression granulator, crushing the blocks into granules, and preparing the licorice granule preparation, wherein 1 gram of the licorice granule preparation is equivalent to 5 grams of the licorice decoction pieces.

[0041] The pinellia ternate granule preparation is prepared by using the pinellia ternate decoction pieces as raw materials, adding water with a weight of 5-10 times of the medicinal materials into the decoction pieces, carrying out two times of continuous water extraction, combining the filtrates, carrying out water bath concentration on the filtrates to obtain extract, drying the extract under vacuum to obtain dry extract, crushing and sieving the dry extract, adding dextrin at a ratio of 1:1, preparing soft material by using 90% ethanol, sieving the soft material, drying the sieved soft material under vacuum, and obtaining the pinellia ternate granule preparation, wherein 1 gram of the pinellia ternate granule preparation is equivalent to 20 grams of the pinellia ternate decoction pieces.

[0042] The dried tangerine peel granule preparation is prepared by using the dried tangerine peel decoction pieces as raw materials, extracting volatile oil, adding water with a weight of 5-10 times of the medicinal materials into the residue, carrying out two times of water extraction, combining the water extracts, carrying out vacuum concentration and spray drying on the water extracts to obtain spray dried powder, directly compressing the spray dried powder into blocks by a dry compression granulator, crushing the blocks into granules, and adding the volatile oil into the granules after being wrapped by cyclodextrin and being stabilized, and mixing the granules uniformly to obtain the dried tangerine peel granule preparation, wherein 1 gram of the dried tangerine peel granule preparation is equivalent to 10 grams of the dried tangerine peel decoction pieces.

[0043] The above granule preparations of various medicinal materials are mixed together to obtain the required traditional Chinese medicine composition.

[0044] Example 4: Therapeutic use and therapeutic effect of the traditional Chinese medicine composition

[0045] The inventors randomly selected 90 patients with early and middle stage colorectal cancer, and administered the traditional Chinese medicine composition of the present application to the patients for 1-6 days before chemotherapy to assist the chemotherapy. It was clinically observed that the digestive tract reactions, especially nausea, appetite and constipation, of most of the patients were improved, and the tolerance of the patients to the chemotherapy was improved, so that the chemotherapy was successfully completed.

[0046] Based on the above results, the inventors further carried out a retrospective analysis on the cases of treating digestive tract reactions by using the traditional Chinese medicine composition of the present application during the research process. The cases were all cases of treating gastric cancer and colorectal cancer by using XELOX and FOLFOX chemotherapy regimens, and their digestive tract reactions were all caused by the XELOX and FOLFOX chemotherapy regimens.

[0047] From 9802 cases of continuous cases, 1650 cases of gastric cancer and intestinal cancer patients receiving XELOX or FOLFOX chemotherapy were screened. The inclusion criteria are: pathologically diagnosed gastric cancer and colorectal cancer; received XELOX regimen or FOLFOX regimen chemotherapy; oral administration of traditional Chinese medicine composition for at least 5 days during chemotherapy; case history data contains detailed gastrointestinal reaction records (including nausea, vomiting, abdominal distension, constipation, diarrhea, anorexia); at least one visit record after oral administration of traditional Chinese medicine composition. Exclusion criteria: no gastrointestinal reaction record in case history data; no gastrointestinal symptoms after receiving Liujun'an Weifang treatment. Efficacy judgment criteria: gastrointestinal symptoms include any one of the following symptoms: nausea, vomiting, diarrhea, abdominal distension, constipation, anorexia, etc. The symptoms are improved, and other gastrointestinal symptoms are not aggravated. It is determined that the symptoms are relieved; after treatment, the gastrointestinal symptoms disappear, which is determined as complete remission. Among them, 1350 cases do not meet the inclusion criteria, 350 cases have no efficacy judgment or no record of gastrointestinal reactions caused by chemotherapy, and finally 104 cases enter the retrospective analysis. Among them, 20 cases of gastric cancer, 84 cases of colorectal cancer; 59 cases received XELOX regimen chemotherapy, 45 cases received FOLFOX regimen; 78 cases were adjuvant chemotherapy, and 26 cases were palliative chemotherapy. The results show that among the above cases with gastrointestinal reactions caused by chemotherapy regimens, the remission rate of gastrointestinal symptoms after treatment with the traditional Chinese medicine composition of the application is 87.5%.

[0048] In addition, the inventors used a large sample of 400 cases of randomized controlled trial (RCT) to verify the effect of the traditional Chinese medicine composition of the application in reducing gastrointestinal side effects during adjuvant chemotherapy of colorectal cancer.

[0049] The applicant has made a detailed description and description of the embodiments of the application, but those skilled in the art should understand that the above embodiments are only preferred embodiments of the application, and the detailed description is only to help the reader better understand the spirit of the application, and is not a limitation on the protection scope of the application. On the contrary, any improvement or modification based on the spirit of the application should fall within the scope of protection of the application.

Claims

1. A traditional Chinese medicine composition for alleviating gastrointestinal toxic side effects of nausea and / or poor appetite during chemotherapy of early and middle stage colorectal cancer, characterized in that, The traditional Chinese medicine composition for daily administration is prepared from the following weight ratio of traditional Chinese medicine: 20-30 grams of Taizishen, 10-15 grams of Fuling, 10-15 grams of fried Baizhu, 5-10 grams of Zhigancao, 5-10 grams of Jiangbanxia, and 5-15 grams of Chenpi; the traditional Chinese medicine composition is administered to the patient from the day before chemotherapy to the sixth day.

2. The traditional Chinese medicine composition for alleviating gastrointestinal toxic side effects of nausea and / or poor appetite during chemotherapy of early and middle stage colorectal cancer according to claim 1, characterized in that, The traditional Chinese medicine composition for daily administration is prepared from the following weight ratio of traditional Chinese medicine: 22-30 grams of Taizishen, 10-13 grams of Fuling, 10-13 grams of fried Baizhu, 6-9 grams of Zhigancao, 6-10 grams of Jiangbanxia, and 6-12 grams of Chenpi. 3.The traditional Chinese medicine composition for alleviating gastrointestinal toxic side effects of nausea and / or poor appetite during chemotherapy of early and middle stage colorectal cancer according to claim 1, characterized in that, The traditional Chinese medicine composition for daily administration is prepared from the following weight ratio of traditional Chinese medicine: 25-30 grams of Taizishen, 10-12 grams of Fuling, 10-12 grams of fried Baizhu, 6-8 grams of Zhigancao, 8-10 grams of Jiangbanxia, and 8-10 grams of Chenpi. 4.The traditional Chinese medicine composition for alleviating gastrointestinal toxic side effects of nausea and / or poor appetite during chemotherapy of early and middle stage colorectal cancer according to claim 1, characterized in that, The traditional Chinese medicine composition for daily administration is prepared from the following weight ratio of traditional Chinese medicine: 30 grams of Taizishen, 10 grams of Fuling, 10 grams of fried Baizhu, 6 grams of Zhigancao, 10 grams of Jiangbanxia, and 10 grams of Chenpi.

5. The traditional Chinese medicine composition for alleviating gastrointestinal toxic side reactions of nausea and / or poor appetite during chemotherapy of early and middle stage colorectal cancer according to claim 1, characterized in that: The traditional Chinese medicine composition is a decoction. 6.The traditional Chinese medicine composition for alleviating gastrointestinal toxic side effects of nausea and / or poor appetite during chemotherapy of early and middle stage colorectal cancer according to claim 1, characterized in that: The traditional Chinese medicine composition is a granule.