A traditional Chinese medicine composition for treating radiation-induced intestinal injury, and its preparation method and application

Abstract

The invention discloses a traditional Chinese medicine composition for treating radiation-induced intestinal injury and application thereof. The composition is prepared from the following raw materials in parts by weight: 10-20 parts of astragalus, 10-14 parts of atractylodes, 10-14 parts of sanguisorba officinalis, 10-14 parts of dendrobium, 10-14 parts of clary vine, 10-14 parts of coix seed, 4-8 parts of costus root, and 4-8 parts of liquorice. The whole composition has the functions of invigorating qi and nourishing yin, cooling blood and dispersing blood stasis, and clearing intestines and removing dampness, and has the efficacy of treating RIII. The composition has good therapeutic effect, is safe and reliable, and uses traditional Chinese medicine, so the raw materials are easily available.

Description

Technical Field

[0001] The present invention relates to a Chinese medicine composition and a preparation method thereof, and in particular to a Chinese medicine composition for treating radiation intestinal injury prepared from Chinese herbal medicine as raw materials, and a preparation method and application thereof. Background Art

[0002] At present, cancer has become a major problem in the medical field and has caused a certain degree of damage to human health. Therefore, there are more and more treatment methods for cancer, and surgery, chemotherapy, radiotherapy, etc. are still important components of cancer treatment. Due to the development of tumor radiotherapy, medical imaging and computer technology, radiotherapy technology has made great strides and has become one of the main means of comprehensive cancer treatment. It can be used alone or in combination with surgery, chemotherapy, targeted therapy, immunotherapy and other treatment methods. It can effectively reduce the mortality rate of the disease and prolong the survival of patients in clinical practice. However, ionizing radiation does not have the ability to discriminate and cannot distinguish between tumor lesions and normal tissues. Any organism exposed to radiation will produce a series of biological effects. Damage to normal tissues or organs cannot be completely avoided. Some of the clinical symptoms that appear are called radiation damage. Radiation-introduced intestinal injury (RIII) is common after radiotherapy for abdominal and pelvic tumors, such as rectal cancer, prostate cancer, bladder cancer, and gynecological malignancies. The small intestine, colon, and rectum are the primary sites of injury. Common early clinical symptoms include diarrhea, abdominal pain, abdominal distension, urinary urgency, flatulence, fecal incontinence, rectal bleeding, and weight loss (usually occurring within three months). Later, intestinal obstruction and even intestinal perforation, fistulas, and abscesses may develop (usually within six to three months after initial radiotherapy). Currently, modern medical treatment for RIII primarily relies on symptomatic treatment with antibiotics and glucocorticoids, which are highly susceptible to adverse reactions such as intestinal dysbiosis, resulting in suboptimal overall efficacy.

[0003] At a 2017 conference organized by the Chinese Association of Traditional Chinese Medicine, a consensus among TCM experts on the diagnosis and treatment of radiation-induced intestinal injury established a clear TCM name for the condition, dubbing it "intestinal diarrhea." The earliest record of "intestinal diarrhea" appears in the Suwen (Suwen) chapter on Taiyin and Yangming, which states: "If one eats and drinks excessively, and has irregular daily routines, the yin will be affected... When it enters the five internal organs, it causes fullness and obstruction, resulting in diarrhea, and over time, intestinal diarrhea." The text then describes its symptoms, including "blood in the stool," "bloody pus in the stool," and "white foam in the stool." Later physicians have also verified this. Li Dongyuan of the Jin and Yuan dynasties, in his Treatise on the Spleen and Stomach, states: "Intestinal diarrhea is when food and blood combine to form a separate fluid, like gushing out of a bucket." The clinical manifestations of radiation-induced intestinal injury reveal that the disease is located in the intestines, and the underlying pathogenesis is a combination of underlying deficiency and superficial excess, a mixture of deficiency and excess. Many renowned TCM practitioners have proposed that the prevention and treatment of radiation-induced intestinal injury should primarily focus on eliminating pathogenic factors while also nourishing yin and strengthening the spleen.

[0004] In recent years, traditional medicine has rapidly developed, and Traditional Chinese Medicine (TCM) has achieved promising results in treating RIII. Numerous clinical studies have demonstrated that TCM can improve the clinical symptoms of RIII. Therefore, developing a TCM composition for the treatment of RIII, guided by traditional TCM theory, is of great significance. Summary of the Invention

[0005] The present invention provides a traditional Chinese medicine composition for treating radiation-induced intestinal injury with significant efficacy and minimal side effects, and a preparation method thereof. The whole formula comprises a combination of medicines, has a mild medicinal property, and will not cause imbalance of yin and yang in the body. At the same time, it also complies with the treatment principle of "preventive treatment". The composition has significant efficacy and solves technical problems such as the difficulty of existing treatment and the poor effect of Western medicine.

[0006] In order to achieve the above-mentioned purpose, the present invention adopts the following technical scheme: a traditional Chinese medicine composition for treating radiation-induced intestinal injury, which is prepared from the following raw materials in parts by weight: 10-20 parts of astragalus, 10-14 parts of white atractylodes, 10-14 parts of sanguisorba officinalis, 10-14 parts of dendrobium, 10-14 parts of red vine, 10-14 parts of coix seed, 4-8 parts of costus root, and 4-8 parts of licorice.

[0007] The traditional Chinese medicine composition for treating radiation-induced intestinal injury is prepared from the following raw materials in parts by weight: 15 parts of astragalus, 12 parts of atractylodes, 12 parts of sanguisorba officinalis, 12 parts of dendrobium, 12 parts of clary vine, 12 parts of coix seed, 6 parts of costus root, and 6 parts of liquorice.

[0008] In the traditional Chinese medicine composition for treating radiation-induced intestinal injury, the astragalus is raw, the white atractylodes is stir-fried, the coix seed is raw, the costus root is simmered, and the licorice is raw.

[0009] The preparation method of the traditional Chinese medicine composition for treating radiation-induced intestinal injury comprises the following steps: weighing the above medicinal materials according to the dosage, adding 10-20 times the weight of water, soaking for 3 hours, heating to boiling, decocting twice, each time for 2-3 hours, combining the decoctions, filtering, evaporating and concentrating, cooling, adding 1.5 times the amount of ethanol, fully mixing, standing overnight, taking the supernatant, washing the precipitate with a small amount of 50% ethanol, combining the washing liquid and the filtrate, recovering the ethanol under reduced pressure, concentrating, cooling and standing, filtering, vacuum-concentrating at low temperature to a thick paste, spray drying, passing through a 300-mesh sieve, adding appropriate amounts of auxiliary materials and preparing the preparation.

[0010] The traditional Chinese medicine composition for treating radiation-induced intestinal injury is in the form of granules, tablets, capsules, powders, pills or pastes.

[0011] The preparation method of the traditional Chinese medicine composition for treating radiation-induced intestinal injury comprises the following steps: weighing the above medicinal materials according to the dosage, adding 10-20 times the weight of water, soaking for 3 hours, heating to boiling, decocting twice, each time for 2-3 hours, combining the decoctions, filtering, evaporating and concentrating, and cooling to obtain a decoction or oral solution.

[0012] Application of the traditional Chinese medicine composition for treating radiation-induced intestinal injury in the preparation of medicine for treating radiation-induced intestinal injury.

[0013] Beneficial effects:

[0014] 1. Based on the theory of "stasis and heat" by Professor Zhou Zhongying, a master of traditional Chinese medicine, the applicant proposed that the nature of radiation-induced intestinal injury is always a mixture of deficiency and excess, with the disease located in the intestines and involving the spleen and stomach. The main pathological factors are deficiency, dampness, stasis, heat, and toxicity. The basic pathogenesis is damage to both qi and yin, the mutual binding of stasis and heat, and the downward flow of dampness and heat. The syndrome is diagnosed as "dampness and heat accumulating in the intestines". The treatment is mainly based on invigorating qi and nourishing yin, cooling blood and dispersing stasis, clearing the intestines and eliminating dampness. The treatment principle should be to strengthen the body and eliminate evil, and to distinguish the primary and secondary aspects of clearing evil and the body.

[0015] Drawing on years of clinical experience, the applicant, following the etiology, pathogenesis, and treatment principles of radiation-induced intestinal injury, has developed a traditional Chinese medicine composition based on the underlying pathogenesis, evidence-based formulation, and method-driven treatment. This composition consists of roasted Astragalus membranaceus, stir-fried Atractylodes macrocephala, raw Sanguisorba officinalis, Dendrobium officinale, Caulis Scutellariae, raw Coix seed, simmered Aucklandia lappa, and raw Licorice root. Astragalus membranaceus and Atractylodes macrocephala serve as the main ingredients, tonifying Qi, strengthening the spleen, and supporting vital Qi. Sanguisorba officinalis clears heat, cools blood, and stops bleeding; Dendrobium officinale clears heat, nourishes Yin, and promotes fluid production; Caulis Scutellariae clears heat, detoxifies, and activates blood circulation. Coix seed, dissipating dampness, strengthens the spleen, and stops diarrhea, serves as the adjuvant. Aucklandia lappa unblocks the Qi system, while Licorice root harmonizes the other ingredients, serving as the guiding ingredient. Together, these ingredients tonify Qi and Yin, cool blood, disperse blood stasis, and clear the intestines, eliminating dampness, often achieving excellent results.

[0016] This recipe differs from other traditional Chinese medicine compositions for treating radiation-induced intestinal injury in that current traditional Chinese medicine compositions for treating RIII are primarily based on qi-tonifying and yin-nourishing herbs such as ginseng, astragalus, dendrobium, and ophiopogon, or primarily on heat-clearing and dampness-drying herbs such as phellodendron, sophora flavescens, and qinpi, with little attention paid to the element of "stasis." Radiotherapy patients, already suffering from cancer, are plagued by stasis in their bodies. Furthermore, external attacks of toxic heat and fire combine to create a complex system of invisible heat and visible stasis, easily leading to the secondary pathological product of "stasis-heat." Stagnant heat lingers in the body and persists for a long time, so treatment should always focus on cooling the blood and dispersing stasis. The present invention, while not only tonifying qi and nourishing yin, clearing the intestines and eliminating dampness, also has the effect of cooling the blood and dispersing stasis. This composition is condensed into a traditional Chinese medicine composition with good clinical efficacy, few toxic side effects, and suitability for long-term use, enhancing the prevention and treatment methods of traditional Chinese medicine and improving the efficacy of traditional Chinese medicine in preventing and treating RIII.

[0017] 2. The Chinese medicine composition provided by the present invention has the efficacy of treating RIII, has good therapeutic effect, is safe and reliable, and uses Chinese medicine, and the raw materials are easily available. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 is the incidence of radiation-induced intestinal injury in the control group and the experimental group in the clinical case of the present invention;

[0019] Figure 2 The distribution of intestinal reaction grades at the end of radiotherapy in the control group and the experimental group in the clinical case of the present invention;

[0020] Figure 3 This is a distribution diagram of the intestinal reaction graded efficacy evaluation of the control group and the experimental group in the clinical case of the present invention;

[0021] Figure 4 This is a distribution diagram of TCM symptom score efficacy evaluation of the control group and the experimental group in the clinical case of the present invention;

[0022] Figure 5 is a line graph of weight changes of mice in the experimental examples of the present invention;

[0023] Figure 6 These are the pathological characteristics of each group at different time points in the experimental examples of the present invention (Note: the magnification of each group is HE staining ×200);

[0024] In the above figures, NC is the control group, IR is the model group, IRL is the low-dose group, IRM is the medium-dose group, IRH is the high-dose group, and IRAC is the compound glutamine enteric-coated capsule group (i.e., the positive drug control group). DETAILED DESCRIPTION

[0025] The present invention will be further described below with reference to the embodiments, but the present invention is not limited to these specific examples.

[0026] Example 1

[0027] Take 150g of roasted Astragalus, 120g of stir-fried Atractylodes, 120g of raw Sanguisorba officinalis, 120g of Dendrobium, 120g of Red Caulis, 120g of raw Coix seed, 60g of stewed Aucklandia lappa, and 60g of raw Licorice, mix the herbs, weigh the above herbs according to the amount, add 15 times the weight of water, soak for 3 hours, heat to boiling, decoct twice, each time for 2 hours, combine the decoctions, filter, evaporate and concentrate, and cool to make 2000 ml of decoction.

[0028] Example 2

[0029] Take 150g of roasted astragalus, 120g of stir-fried white atractylodes, 120g of raw sanguisorba officinalis, 120g of dendrobium, 120g of red vine, 120g of raw coix seed, 60g of stewed costus root, and 60g of raw licorice, mix the medicinal materials, weigh the above medicinal materials according to the amount, add 20 times the weight of water, soak for 3 hours, heat to boiling, decoct twice, each time for 2 hours, combine the decoctions, filter, evaporate and concentrate, add 1.5 times the amount of ethanol after cooling, mix thoroughly, let it stand overnight, take the supernatant, wash the precipitate with a small amount of 50% ethanol, combine the washing liquid and the filtrate, recover the ethanol under reduced pressure, concentrate, cool and stand, filter, vacuum concentrate to a thick paste at low temperature, spray dry, pass through a 300-mesh sieve, and add an appropriate amount of starch to prepare granules.

[0030] Example 3

[0031] Take 100g of Astragalus, 140g of Atractylodes, 100g of Sanguisorba officinalis, 140g of Dendrobium, 100g of Sargentodoxae, 140g of Coix Seed, 40g of Costus Root, and 80g of Licorice, mix the medicinal materials, weigh the above medicinal materials according to the amount, add 15 times the weight of water, soak for 3 hours, heat to boiling, and decoct twice, each time for 2 hours. Combine the decoctions, filter, evaporate and concentrate, and cool to make 2000 ml of decoction.

[0032] Example 4

[0033] Take 100g of Astragalus, 140g of Atractylodes, 100g of Sanguisorba officinalis, 140g of Dendrobium, 100g of Sargentodoxae, 140g of Coix Seed, 40g of Aucklandia, and 80g of Licorice, and mix the medicinal materials. After weighing the above medicinal materials according to the amount, add 20 times the weight of water, soak for 3 hours, heat to boiling, and decoct twice, each time for 2 hours. Combine the decoctions, filter, evaporate and concentrate, add 1.5 times the amount of ethanol after cooling, mix thoroughly, let it stand overnight, take the supernatant, wash the precipitate with a small amount of 50% ethanol, combine the washing liquid and the filtrate, recover the ethanol under reduced pressure, concentrate, cool and stand, filter, vacuum concentrate to a thick paste at low temperature, spray dry, pass through a 300-mesh sieve, add an appropriate amount of dextrin and make tablets.

[0034] Example 5

[0035] Take 200g of roasted Astragalus, 100g of Atractylodes, 140g of Sanguisorba officinalis, 100g of Dendrobium, 140g of Sargentodoxae, 100g of Coix Seed, 80g of Costus Root, and 40g of Licorice, mix the herbs, weigh the above herbs according to the amount, add 15 times the weight of water, soak for 3 hours, heat to boiling, decoct twice, each time for 2 hours, combine the decoctions, filter, evaporate and concentrate, and cool to make 200 ml of decoction.

[0036] Example 5

[0037] Take 200g of roasted Astragalus, 100g of Atractylodes, 140g of Sanguisorba officinalis, 100g of Dendrobium, 140g of Sargentodoxae, 100g of Coix Seed, 80g of Aucklandia, and 40g of Licorice, and mix the medicinal materials. After weighing the above medicinal materials according to the amount, add 20 times the weight of water, soak for 3 hours, heat to boiling, and decoct twice, each time for 2 hours. Combine the decoctions, filter, evaporate and concentrate, add 1.5 times the amount of ethanol after cooling, mix thoroughly, let it stand overnight, take the supernatant, wash the precipitate with a small amount of 50% ethanol, combine the washing liquid and the filtrate, recover the ethanol under reduced pressure, concentrate, cool and stand, filter, vacuum concentrate to a thick paste at low temperature, spray dry, pass through a 300-mesh sieve, add an appropriate amount of starch and prepare capsules.

[0038] Example 6: Clinical study of the therapeutic effect of the present invention on RIII

[0039] 1. Research Methods

[0040] 1.1 Case Source

[0041] Patients with abdominal or pelvic malignancies (colorectal cancer, cervical cancer, endometrial cancer, prostate cancer, etc.) who underwent radiotherapy at the outpatient clinic or ward of Jiangsu Provincial Hospital of Traditional Chinese Medicine or the Zidong Campus of Jiangsu Provincial Hospital of Traditional Chinese Medicine between June 2022 and September 2023 and experienced intestinal reactions within a few days of radiotherapy were selected. This study protocol was approved by the Ethics Committee of Jiangsu Provincial Hospital of Traditional Chinese Medicine, an affiliated hospital of Nanjing University of Chinese Medicine, with the review approval number 2022NL-143-02.

[0042] 1.2 Usage: The experimental group received a full treatment cycle (25 doses) of oral Chinese medicine plus radiotherapy. The decoction prepared according to Example 1 was taken, mixed thoroughly, and then taken twice. The daily dosage was 15g of roasted Astragalus, 12g of stir-fried Atractylodes macrocephala, 12g of raw Sanguisorba officinalis, 12g of Dendrobium officinale, 12g of Red Caulis Sargentodoxae, 12g of raw Coix seed, 6g of stewed Aucklandia lappa, and 6g of raw Licorice root. The control group received radiotherapy alone.

[0043] 1.3 Statistical methods

[0044] An Excel database was established to record detailed basic information and data from the clinical observation records. All data were processed and analyzed using SPSS 23.0 software. Enumeration data were analyzed using the chi-square test. Measurement data were expressed as mean ± standard deviation (x ± s). Normal distributions were analyzed using the t-test; skewed distributions were analyzed using the rank-sum test. Rank-order data were analyzed using the Mann-Whitney rank-sum test. P < 0.05 indicated statistical significance, and P ≥ 0.05 indicated no statistical significance.

[0045] 2. Research Results

[0046] 2.1 Incidence of radiation-induced intestinal injury

[0047] Both the control and experimental groups completed radiotherapy as planned. Of the 29 patients in the control group, 21 experienced varying degrees of radiation-induced bowel injury, with an incidence of 72.41%. Of the 30 patients in the experimental group, 19 experienced varying degrees of radiation-induced bowel injury, with an incidence of 63.33%. There was no statistically significant difference between the two groups, as shown in Table 1. Figure 1 .

[0048] Table 1 Incidence of radiation-induced intestinal injury in the two groups

[0049]

[0050] 2.2 Rating criteria for radiation-induced intestinal injury

[0051] (1) The intestinal reactions of the control and experimental groups were evaluated at three time points: before the start of radiotherapy, during the middle of radiotherapy, and at the end of radiotherapy. The clinical symptoms were graded according to the RTOG acute radiation injury grading standard (Table 2). See Table 3, Table 4, Table 5 for details. Figure 2 .

[0052] Table 2 RTOG grading criteria for radioactive intestinal reactions

[0053]

[0054] Table 3 Distribution of intestinal reaction grades in the two groups before radiotherapy

[0055]

[0056] Note: According to the rank sum test, Z=0, P=1>0.05, there was no statistical difference between the two groups.

[0057] Table 4 Distribution of intestinal reaction grades in the two groups during the middle stage of radiotherapy

[0058]

[0059] Note: The rank sum test showed that Z = -0.643, P = 0.520 > 0.05, indicating that there was no statistical difference between the two groups.

[0060] Table 5 Distribution of intestinal reaction grades in the two groups at the end of radiotherapy

[0061]

[0062] Note: The rank sum test showed that Z=-2.299, P=0.022<0.05, indicating that there was a statistically significant difference between the two groups.

[0063] (2) The efficacy of intestinal reactions was evaluated at the middle and end of radiotherapy. The results showed that the control group had 0 cases of marked effect, 3 cases of effective, 14 cases of stable, and 4 cases of aggravation; the experimental group had 2 cases of marked effect, 6 cases of effective, 11 cases of stable, and 0 cases of aggravation. The rank sum test showed that Z = -2.528, P = 0.011 < 0.05, and there was a statistically significant difference between the two groups. See Table 6 for details. Figure 3 .

[0064] Table 6 Intestinal reaction grading efficacy evaluation table

[0065]

[0066] 2.3 Traditional Chinese Medicine Symptom Score

[0067] (1) The TCM symptom scores of the control group and the experimental group were recorded at three time points: before the start of radiotherapy, during the middle of radiotherapy, and at the end of radiotherapy. The symptom scores of the control group and the experimental group before the start of radiotherapy were compared (P>0.05), with no statistical difference; the symptom scores of the control group and the experimental group during the middle of radiotherapy were compared (P>0.05), with no statistical difference; the symptom scores of the control group and the experimental group at the end of radiotherapy were compared (P<0.05), with a statistical difference. See Table 7 for details.

[0068] Table 7 Comparison of TCM symptom scores between the two groups at different time points

[0069]

[0070] (2) The efficacy of TCM symptoms was evaluated at two time points: before the start of radiotherapy and at the end of radiotherapy. The results showed that in the control group, there were 0 cases cured, 5 cases with marked effect, 10 cases with effect, and 14 cases with ineffectiveness, with a total effective rate of 51.72%; in the experimental group, there were 2 cases cured, 16 cases with marked effect, 4 cases with effect, and 8 cases with ineffectiveness, with a total effective rate of 73.33%. The rank sum test showed that Z = -2.877, P = 0.004 < 0.05, indicating that there was a statistically significant difference between the two groups. See Table 8 for details. Figure 4 .

[0071] Table 8 TCM symptom score efficacy evaluation table

[0072]

[0073] 2.4 Safety evaluation

[0074] Blood routine, liver function, renal function, and coagulation function were recorded before, during, and at the end of radiotherapy for both the control and experimental groups. No significant abnormalities were observed, and no significant side effects or adverse events were observed during treatment. Some patients experienced low white blood cells and platelets due to radiotherapy-induced bone marrow suppression, which resolved after appropriate symptomatic treatment and allowed them to continue radiotherapy. This suggests that the Chinese herbal composition has no significant side effects and is safe for clinical use in the treatment of radiation-induced intestinal injury.

[0075] 3. Conclusion

[0076] This study administered oral Chinese herbal medicine to patients in the experimental group. The treatment period lasted from the beginning to the end of radiotherapy. The oral Chinese medicine was combined with radiotherapy to complete the entire treatment process. The clinical efficacy evaluation was mainly based on the degree of improvement in the patient's clinical symptoms and quality of life. The specific research results are as follows:

[0077] (1) The probability of radiation-induced intestinal injury in the experimental group was lower than that in the control group, which was 63.33% and 72.41% respectively, indicating that the Chinese medicine composition can reduce the incidence of radiation-induced intestinal injury.

[0078] (2) In the middle and late stages of radiotherapy, the number of patients in the experimental group who had grade 1-2 radiation intestinal reactions was less than that in the control group; and in the middle and end stages of radiotherapy, the number of patients in the experimental group who had significant and effective results was more than that in the control group, and no patient in the experimental group had worsening intestinal reactions, indicating that the Chinese medicine composition can effectively prevent and treat the occurrence and development of radiation intestinal reactions.

[0079] (3) The total effective rate of the TCM symptom integral efficacy evaluation test group was significantly higher than that of the control group, which were 73.33% and 51.72% respectively, indicating that the TCM composition can effectively improve the patients' TCM clinical symptoms such as abdominal pain, diarrhea, bloody stools with mucus, tenesmus, fatigue, and dry mouth.

[0080] In summary, the Chinese medicine composition of the present invention has good clinical efficacy in preventing and treating acute radiation-induced intestinal injury, can effectively improve the patients' clinical symptoms such as abdominal pain, diarrhea, bloody stools with mucus, tenesmus, fatigue, and dry mouth, can effectively prevent the further occurrence and development of radiation-induced intestinal injury, and can improve the patients' quality of life. In addition, no obvious abnormal changes in safety indicators were found during the treatment process.

[0081] Example 7: Study on the therapeutic mechanism of the present invention on RIII

[0082] 1. Experimental Animals

[0083] Ninety SPF male C57BL / 6J mice, 6–8 weeks old, weighing 18–22 g, were purchased from Hangzhou Medical College under license SCXK (Zhejiang) 2019-0002. Animals were housed at the Laboratory Animal Barrier Center of Nanjing University of Chinese Medicine under license SYXK (Suzhou) 2018-0049. This study was approved by the Animal Ethics Committee of Nanjing University of Chinese Medicine under approval number 202210A008.

[0084] 2. Experimental Methods

[0085] 2.1 Drug preparation

[0086] The Chinese medicine composition decoction prepared according to Example 1 was placed in a rotary evaporator and concentrated under reduced pressure, and the concentrate was placed in a -20°C refrigerator for later use. The dosage was calculated according to the "Equivalent Dose Ratio Table between Humans and Animals Converted by Body Surface Area", with the high-dose dosage being 2 times the clinical equivalent dose for adults, the medium-dose dosage being the clinical equivalent dose for adults, and the low-dose dosage being 0.5 times the clinical equivalent dose for adults, with concentrations of 2.262 g / mL, 1.131 g / mL, and 0.5655 g / mL, respectively. Each mouse was administered orally daily, with a dosage volume of 0.2 mL / 10 g.

[0087] Compound glutamine enteric-coated capsules were used as a positive control drug. The drug was provided by Chengdu Pharmaceutical Co., Ltd. of Diao Group, with the national medicine standard number H51023598. The preparation method of the positive drug was as follows: the powder in the compound glutamine capsules was dissolved in distilled water to prepare a suspension with a concentration of 12.48 mg / mL. Each mouse was given the drug by gavage every day, and the dosage volume was 0.2 mL / 10 g.

[0088] 2.2 Animal grouping and model preparation

[0089] 90 mice were randomly divided into 6 groups, 15 mice in each group, specifically divided into:

[0090] Blank group (NC): no irradiation;

[0091] Model group (IR): irradiation + 0.9% saline gavage;

[0092] IR+ positive group (IRAC): irradiation + oral administration of glutamine suspension;

[0093] IR+low-dose Chinese medicine composition of the present invention group (IRL): irradiation+oral administration of low-dose Chinese medicine composition;

[0094] IR+medium-dose Chinese medicine composition of the present invention group (IRM): irradiation+oral administration of medium-dose Chinese medicine composition;

[0095] IR+high-dose Chinese medicine composition of the present invention group (IRH): irradiation+gastric administration of high-dose Chinese medicine composition.

[0096] Except for the blank group, the other groups used a VitalBeam linear accelerator (Varian, USA, serial number SN5069), provided by the Radiotherapy Center of the Zidong Branch of Jiangsu Provincial Hospital of Traditional Chinese Medicine, with an energy of 6MV X-rays for irradiation, an irradiation field of 15*15cm, a source-target distance of 100cm, a dose rate of 400cGy / min, and a single full-dose irradiation, with a dose of 15Gy.

[0097] 2.3 Statistical methods

[0098] All data were processed and analyzed using SPSS 23.0 software. Measurement data were expressed as mean ± standard deviation (x-±s). Normal distributions were analyzed using the t-test. Skewed distributions were analyzed using the rank-sum test. Multiple group comparisons were performed using one-way analysis of variance. P < 0.05 indicated statistically significant differences, and P ≥ 0.05 indicated no statistical differences.

[0099] 3. Experimental Results

[0100] 3.1 Changes in mouse body weight

[0101] The body weight of the blank group increased normally before and after irradiation. Before irradiation, due to preventive drug administration, the body weight of the positive group, low-dose group, medium-dose group, and high-dose group increased slowly, showing a normal growth trend. After irradiation, the body weight of the model group decreased significantly, reaching the lowest level 7 days after irradiation, and then began to gradually recover. Compared with the model group, the body weight loss of the other drug-treated groups was relatively low. Although showing a downward trend, the body weight was still higher than that of the model group, reaching the lowest level 7 days after irradiation, and then began to gradually recover, and the recovery growth rate was faster than that of the model group. The specific changes in body weight of each group are shown in Figure 5 .

[0102] 3.2 Morphological changes in the mouse intestine

[0103] Samples were collected 3.5 days, 7 days, and 14 days after irradiation. Tissues used for pathological studies were immediately fixed in 4% neutral formalin solution. Changes in the pathological morphology of tumor cells were observed under a light microscope by professionals.

[0104] The results of small intestinal pathological staining of mice in the blank group showed that the intestinal villus epithelium was intact, the intestinal glands in the lamina propria were neatly arranged and evenly distributed, and there was no abnormality in the submucosa, with intact morphology and no defects or shedding.

[0105] 3.5 days after irradiation, compared with the blank group, the model group had shorter intestinal villi, granulocyte infiltration in the lamina propria, mild intestinal gland hyperplasia and increased volume. Except for the high-dose group, the other treatment groups did not show obvious pathological abnormalities.

[0106] 7 days after irradiation, compared with the blank group, the model group showed a large number of intestinal epithelial cells shedding, small focal necrosis of the mucosal lamina propria, disappearance of intestinal gland structure, reduction of goblet cells, connective tissue replacing the original intestinal glands, mild expansion of the intestinal glands, accompanied by a small amount of neutrophil infiltration. The pathology of the drug-treated group was aggravated compared with 3.5 days after irradiation, but was alleviated compared with the model group.

[0107] 14 days after irradiation, compared with the blank group, the length of intestinal villi in the model group was shorter, a small number of intestinal mucosal epithelial cells fell off, a small number of intestinal mucosal epithelial cells separated from the lamina propria, and no obvious inflammatory cell infiltration was observed, indicating that the pathological process of intestinal injury in mice gradually recovered. Compared with the model group, except for the high-dose group, which still had mild hydropic degeneration of epithelial cells, the pathological process of intestinal injury in mice in the other drug-treated groups gradually recovered. Figure 6 .

[0108] In summary, through experimental observations on the general condition, weight changes, intestinal tissue pathological morphology, etc. of mice with radiation-induced intestinal injury, it is shown that the Chinese medicine composition can play a protective role in mice with radiation-induced intestinal injury, can improve the severity of intestinal damage, and the medium dose effect of the Chinese medicine composition is better.

[0109] 4. Conclusion

[0110] The results of this study showed that positive drugs and Chinese herbal compositions of different concentrations had a certain degree of improvement effect on radiation-induced intestinal injury. Judging from the results obtained at various time points and different concentrations of Chinese herbal compounds, the low-dose group and the medium-dose group had better effects, followed by the positive group, and the high-dose group had an average improvement effect.

[0111] In summary, experimental observations on the general condition, weight changes, intestinal tissue pathological morphology, etc. of RIII mice indicate that the present invention can reduce the severity of intestinal damage and exert an anti-radiation injury effect.

[0112]

[0113]

[0114]

Claims

1. A Chinese medicine composition for treating radiation-induced intestinal injury, characterized in that: The invention is prepared from the following raw materials in parts by weight: 10-20 parts of astragalus, 10-14 parts of atractylodes, 10-14 parts of sanguisorba officinalis, 10-14 parts of dendrobium, 10-14 parts of clary vine, 10-14 parts of coix seed, 4-8 parts of costus root, and 4-8 parts of liquorice. The preparation method comprises the following steps: weighing the above medicinal materials according to the amount used, adding 10-20 times the weight of water, soaking for 3 hours, heating to boiling, decocting twice, each time for 2-3 hours, combining the decoctions, filtering, evaporating and concentrating, cooling, adding 1.5 times the amount of ethanol, fully mixing, standing overnight, taking the supernatant, washing the precipitate with a small amount of 50% ethanol, combining the washing liquid and the filtrate, recovering the ethanol under reduced pressure, concentrating, cooling and standing, filtering, vacuum-low-temperature concentrating to a thick paste, spray drying, passing through a 300-mesh sieve, adding appropriate amounts of auxiliary materials, and preparing the preparation.

2. The Chinese medicine composition for treating radiation-induced intestinal injury according to claim 1, wherein The medicine is prepared from the following raw materials in parts by weight: 15 parts of astragalus, 12 parts of atractylodes, 12 parts of sanguisorba officinalis, 12 parts of dendrobium, 12 parts of red vine, 12 parts of coix seed, 6 parts of costus root and 6 parts of liquorice.

3. The Chinese medicine composition for treating radiation-induced intestinal injury according to claim 1, wherein The astragalus is raw astragalus, the white atractylodes is fried atractylodes, the coix seed is raw coix seed, the costus root is simmered costus root, and the licorice is raw licorice.

4. The Chinese medicine composition for treating radiation-induced intestinal injury according to claim 1, wherein The dosage form of the preparation is one of granules, tablets, capsules, powders, pills or pastes.

5. A Chinese medicine composition for treating radiation-induced intestinal injury, characterized in that: The invention is prepared from the following raw materials in parts by weight: 10-20 parts of astragalus, 10-14 parts of atractylodes, 10-14 parts of sanguisorba officinalis, 10-14 parts of dendrobium, 10-14 parts of clary vine, 10-14 parts of coix seed, 4-8 parts of costus root, and 4-8 parts of liquorice. The preparation method comprises the following steps: weighing the above medicinal materials according to the usage amount, adding 10-20 times the weight of water, soaking for 3 hours, heating to boiling, decocting twice, each time for 2-3 hours, combining the decoctions, filtering, evaporating and concentrating, and cooling to obtain a decoction or an oral liquid.

6. Use of the traditional Chinese medicine composition for treating radiation-induced intestinal injury as claimed in claim 1 in the preparation of a medicine for treating radiation-induced intestinal injury.

Images