Traditional Chinese medicine composition for treating acute radiation proctitis and preparation method and application thereof

Abstract

The invention relates to a traditional Chinese medicine composition for treating acute radiation proctitis and a preparation method and application thereof, and particularly discloses a traditional Chinese medicine composition for treating acute radiation proctitis, which is characterized by being prepared from the following traditional Chinese medicines in parts by weight: 10-15 parts of dendrobe, 12-20 parts of white paeony root, 20-40 parts of astragalus membranaceus, 8-12 parts of frankincense and 5-8 parts of borneol. The traditional Chinese medicine composition for treating the acute radiation colitis is self-prepared under the guidance of the theory of traditional Chinese medicine, pharmacodynamic evaluation research is carried out through animal experiments, and pharmacological experiments prove that the traditional Chinese medicine composition provided by the invention has good potential for treating the radiation colitis and has good economic value and social significance.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedicine, and specifically relates to a Chinese medicine composition for treating acute radiation proctitis, a preparation method and use thereof. Background Art

[0002] Radiation proctitis (RP) mainly refers to a disease that causes rectal mucosal edema, congestion, bleeding, and even erosion and ulceration after receiving radiotherapy (RT) in the abdomen or pelvis. It is mainly manifested by abdominal pain, diarrhea, mucus and blood in the stool, etc. In severe cases, radiotherapy needs to be delayed or interrupted. The severity of radiation proctitis depends on radiation-related factors of radiotherapy and risk factors related to the patient himself. The pathogenesis of radiation proctitis is complex and has not yet been fully understood. In order to better understand the pathogenic process, it is divided into two subtypes. According to the time from the start of radiotherapy to the onset of symptoms and signs, it can be divided into acute radiation proctitis (ARP) and chronic radiation proctitis (CRP). ARP is characterized by only involving the surface mucosa of the rectum, which is a highly dose-dependent phenomenon. Currently, up to 75% of patients will have varying degrees of ARP symptoms within a short period of time after radiotherapy, and most of them recover within 3 months. CRP is a group of more complex clinical disease symptoms, characterized by full-thickness involvement of the rectal mucosa, accompanied by fibrosis and occlusive arteritis. Onset is usually late, with the first symptoms occurring more than three months after the start of radiation therapy; it may present 9-14 months after radiation exposure but may present any time up to 30 years after radiation.

[0003] The diagnosis of ARP requires a comprehensive analysis of clinical, endoscopic, imaging and histopathological manifestations. The clinical manifestations of ARP include but are not limited to blood in the stool, urgency, frequent stool, diarrhea, mucous stool, tenesmus and anal pain, and the symptoms are diverse and lack specificity. Its endoscopic manifestations include telangiectasia, mucosal congestion, ulcers, stenosis and necrosis, among which telangiectasia is the most common. Routine endoscopic biopsy is not recommended because the tissue healing ability is poor, and the damage caused by the biopsy may be prolonged and cause iatrogenic ulcers or even perforation. However, biopsy can be used to exclude the interference of intestinal malignant tumors when necessary. Radiation proctitis belongs to the category of "intestinal diarrhea", "diarrhea" and "blood in the stool" in traditional Chinese medicine, and the cause is mainly deficiency of the root and excess of the side. ARP is mainly manifested as intestinal damp-heat, qi stagnation and blood stasis syndrome, and the treatment is mainly to clear away heat and dampness, detoxify and cool the blood; CRP is mainly manifested as spleen and kidney yang deficiency, spleen and stomach weakness syndrome, and the treatment is mainly to warm the spleen and kidney, astringe the intestine and stop diarrhea. At present, the commonly used non-surgical treatments for ARP in the clinic include drug therapy (anti-inflammatory drugs, antibiotics, probiotics, antioxidants and antidiarrheal drugs, etc.), retention enema (sucralfate, steroid hormones and short-chain fatty acids, etc.), argon plasma coagulation and hyperbaric oxygen therapy, etc. However, whether it is Western medicine treatment, Chinese medicine treatment or integrated Chinese and Western medicine treatment, it is necessary to cooperate with radiotherapy at the same time to effectively reduce the incidence of ARP and alleviate clinical symptoms such as diarrhea, abdominal pain and blood in the stool. There is a lack of large-sample clinical efficacy observations in the existing technology, but most of them have not been studied in depth and lack unified standards. Therefore, exploring effective medication regimens for the prevention and treatment of ARP is still an urgent problem to be solved, which is of great significance to improving the quality of life and prognosis of patients with malignant tumors. Summary of the invention

[0004] Based on the deficiencies of the prior art, the present application provides a Chinese medicine composition for treating radiation proctitis, and a preparation method and use thereof, which specifically adopts the following technical scheme:

[0005] The first aspect of the present invention provides a Chinese medicine composition for treating acute radiation proctitis, which is prepared from the following Chinese medicines in parts by weight: 10 to 15 parts of dendrobium, 12 to 20 parts of white peony root, 20 to 40 parts of astragalus, 8 to 12 parts of frankincense, and 5 to 8 parts of borneol;

[0006] Furthermore, the Chinese medicine composition for treating acute radiation proctitis is prepared from the following Chinese medicines in parts by weight: 12 parts of dendrobium, 15 parts of white peony root, 30 parts of astragalus, 10 parts of frankincense, and 6 parts of borneol;

[0007] The second aspect of the present invention provides a method for preparing any one of the above-mentioned Chinese medicine compositions for treating acute radiation proctitis, comprising the following steps:

[0008] The above-mentioned Chinese medicine components are decocted with purified water for 1 to 3 times according to the weight ratio, the decoctions are combined, filtered, and concentrated to an appropriate volume to obtain the Chinese medicine composition;

[0009] The third aspect of the present invention provides a drug for treating acute radiation proctitis, comprising any one of the above-mentioned Chinese medicine compositions and a pharmaceutically acceptable carrier;

[0010] The third aspect of the present invention provides the use of any one of the above-mentioned Chinese medicine compositions in the preparation of a drug for treating acute radiation proctitis; BRIEF DESCRIPTION OF THE DRAWINGS

[0011] Figure 1 Colorectal photos and colorectal length and weight statistics after 7 days of medication

[0012] Figure 2 HE staining (magnification: 100×) to evaluate the efficacy of the Chinese medicine composition 7 days after medication

[0013] Figure 3 HE staining (magnification: 100×) to evaluate the efficacy of the Chinese medicine composition 14 days after medication

[0014] Figure 4 HE staining (magnification: 100×) to evaluate the efficacy of the Chinese medicine composition 21 days after medication

[0015] Figure 5 HE staining (magnification: 100×) to evaluate the toxicity of the Chinese medicine composition for 7 days, 14 days, and 21 days

[0016] Figure 6 Diagram for evaluating the toxicity of Chinese medicine combination for blood biochemistry experiment

[0017] Beneficial Effects

[0018] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0019] The present invention aims at the syndromes of deficiency in the root and excess in the side, damp-heat in the intestine, and qi stagnation and blood stasis of ARP, and develops a Chinese medicine composition with dendrobium as the main medicine and white peony as the assistant medicine. Dendrobium as the main medicine has the effects of benefiting the stomach and promoting fluid, nourishing yin and clearing heat, and replenishing both qi and yin; the assistant medicine white peony plays the role of nourishing blood and softening the liver, relieving pain, and restraining yin and sweating; astragalus nourishes qi and consolidates the exterior, promotes diuresis and removes toxins; frankincense reduces swelling, activates blood circulation and stops pain; and borneol clears heat and detoxifies. The five Chinese medicines are combined with each other to jointly play the effects of clearing heat and dampness, detoxifying and cooling blood, and replenishing qi and restraining yin. In addition, the present invention conducts pharmacodynamic evaluation research through animal experiments, and the Chinese medicine composition of the present invention can inhibit radiation enteritis, and the Chinese medicine composition has no obvious toxicity. DETAILED DESCRIPTION

[0020] The data basis of the present invention is further explained below in conjunction with specific embodiments. However, these embodiments are only used to illustrate the present invention and are not used to limit the scope of the present invention.

[0021] (I) Embodiment

[0022] Example 1

[0023] A Chinese medicine composition for treating acute radiation proctitis is prepared from the following Chinese medicines by weight: 10g of dendrobium, 12g of white peony root, 35g of astragalus, 12g of frankincense and 5g of borneol. The Chinese medicines of the above components are decocted twice with purified water according to the weight ratio, the decoctions are combined, filtered and concentrated to an appropriate volume to obtain the Chinese medicine composition.

[0024] Example 2

[0025] A Chinese medicine composition for treating acute radiation proctitis is prepared from the following Chinese medicines by weight: 15g of dendrobium, 20g of white peony root, 30g of astragalus, 8g of frankincense and 8g of borneol. The Chinese medicines of the above components are decocted twice with purified water according to the weight ratio, the decoctions are combined, filtered and concentrated to an appropriate volume to obtain the Chinese medicine composition.

[0026] Example 3

[0027] A Chinese medicine composition for treating acute radiation proctitis is prepared from the following Chinese medicines by weight: 12 grams of dendrobium, 15 grams of white peony root, 30 grams of astragalus, 10 grams of frankincense, and 6 grams of borneol. The Chinese medicines of the above components are decocted twice with purified water according to the weight ratio, the decoctions are combined, filtered, and concentrated to an appropriate volume to obtain the Chinese medicine composition.

[0028] (II) Experimental Examples

[0029] 2.1 Experimental plan

[0030] 2.1.1 Preparation of Chinese medicine

[0031] The Chinese medicine composition of Example 3 was concentrated to 190 ml by rotary evaporation for animal administration, wherein the concentration of the mother solution was 0.37 g / ml and the concentration of the final solution was 1.36 g / ml.

[0032] 2.1.2 Model construction, drug administration, and collection of test indicators

[0033] The mice were 7-week-old balb / c mice, which were randomly divided into 4 groups, namely, negative control group, Chinese medicine group, irradiation group, and irradiation + drug administration group, with 10 mice in each group. Mice were intraperitoneally injected with 75 mg / kg sodium pentobarbital according to their respective body weights to complete pre-irradiation anesthesia. A single full abdominal irradiation model was performed using the American Varian Clinac 23EX electronic medical linear accelerator. 6MV X-rays were used, the source skin distance (SSD) was 100 cm, the irradiation dose was 12 Gy, the dose rate was 400 cGy / min, the irradiation field size was 2 cm*2 cm, the upper edge of the irradiation field was parallel to the upper edge of the mouse's lower limbs, and the lower edge was to the genital opening. After irradiation, the mice were returned to the animal room for feeding after they were fully awake. The Chinese medicine composition was given on the day of irradiation, and the administration method was gavage administration, 200 μL was gavaged each time through a No. 10 gavage needle, and gavage was once a day, in which the negative control group and the irradiation group were given the same amount of normal saline. During the model construction and administration, the body weight, molding score and other data were recorded. Mice were killed 1 week, 2 weeks, and 3 weeks after the administration of the Chinese medicine composition, with 4, 3, and 3 mice killed respectively. Blood was collected from the eyeballs, and the heart, liver, spleen, lung, kidney, and colon were collected after dissection. The serum was quickly frozen in liquid nitrogen and stored in a -80°C refrigerator, and the heart, liver, spleen, lung, and kidney were fixed in paraformaldehyde.

[0034] 2.1.3 Toxicity assessment of traditional Chinese medicine compositions

[0035] 1. HE staining to evaluate the toxicity of Chinese medicine compositions

[0036] (1) Preparation and sectioning of tissue sample wax blocks

[0037] After the heart, liver, spleen, lung, and kidney were fixed in 4% paraformaldehyde solution for 48 hours, they were soaked in water for 2-3 hours, then soaked in 70% ethanol for 1 hour, and then placed in 80% v / v ethanol, 95% v / v ethanol, 100% v / v ethanol, ethanol: xylene volume ratio of 1:1 solution, and xylene for 30 minutes to fully dehydrate and permeabilize the tissue. Then the tissue was soaked in pre-melted paraffin overnight to allow the paraffin to fully penetrate the interior of the tissue. The tissue was embedded in paraffin using a tissue embedding machine and cooled. The next step was to slice the tissue. The wax block was cut into 5μm thick wax slices using a fully automatic paraffin slicer, and the slices were placed in 47°C water for rinsing. After the tissue was flattened, the slices were picked up with a slide, spread at 37°C, and finally the tissue slices were dried and stored in a 37°C oven.

[0038] (2) H&E staining

[0039] Paraffin sections were placed in a 60°C oven to fully melt the paraffin, and then placed in an automatic staining machine for H&E staining. First, they were immersed in xylene twice, each time for 5 minutes, and then placed in 100% v / v, 95% v / v, 85% v / v, 75% v / v ethanol and distilled water for gradient rehydration for 3 minutes. Then the tissue sections were stained with hematoxylin stain for 20 minutes, and the floating color on the sections was washed away with distilled water. The tissue sections were differentiated with differentiation solution for 3 minutes and then rinsed with distilled water twice, each time for 3 minutes. Then the tissue sections were immersed in eosin stain for 1 minute, and the floating color on the sections was washed away with distilled water. Then they were immersed in 75% v / v, 85% v / v, 95% v / v, and 100% v / v ethanol for 2-3 seconds for rapid dehydration, 100% v / v ethanol for 1 minute, and xylene for 2 times, each time for 1 minute for permeabilization. Finally, a fully automatic sealing machine was used to seal the slices, and a fully automatic pathology slice scanning system was used to scan the slices.

[0040] 2. Evaluation of toxicity of Chinese medicine compositions by serum biochemical indices

[0041] The serum of the control group and the Chinese medicine group was centrifuged at 4,000 rpm for 10 min, and the supernatant was collected and stored in a -80°C refrigerator. The serum biochemical indicators such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatine kinase (CK), urea (BUN), and creatinine (CR) were then detected using a fully automatic biochemical analyzer from the Hangzhou Institute of Medicine, Chinese Academy of Sciences. The toxicity of the Chinese medicine combination was evaluated by comparing the serum biochemical indicators of different groups.

[0042] 3. Evaluating the efficacy of traditional Chinese medicine composition by colorectal HE staining

[0043] The colorectal tissues were dehydrated, embedded, sliced, and stained with HE. The morphological changes of intestinal villi and intestinal crypts and the infiltration of inflammatory cells in each group after irradiation and Chinese medicine treatment were observed to evaluate whether the Chinese medicine composition could improve radiation colitis.

[0044] 2.2 Experimental Results

[0045] 2.2.1 Evaluation of the efficacy of Chinese medicine compositions:

[0046] 1. HE staining to evaluate the efficacy of the Chinese medicine composition 7 days after medication

[0047] like Figure 2As shown, the non-irradiated Chinese medicine control group and Chinese medicine group had normal intestinal mucosal structure; 7 days after irradiation, the villi and crypt structure of the intestinal tissue disappeared in the irradiated group, the lamina propria was digested and disintegrated, and a large number of inflammatory cells infiltrated in the submucosal layer, reaching a level of damage of 4, proving the occurrence of radiation enteritis; in the irradiation plus Chinese medicine group, the villi of the intestinal tissue maintained a basically intact structure, the crypt structure disappeared by about 1 / 3, and there was inflammatory cell infiltration between the mucosal epithelial layer and the lamina propria, reaching a level of damage of 1 to 2, proving that the Chinese medicine composition can inhibit radiation enteritis. Figure 1 This is a photo of the colon and rectum after 7 days of medication ( Figure 1 A) and colorectal length and weight statistics ( Figure 1 B) (**: P<0.01, ***: P<0.001).

[0048] 2. HE staining to evaluate the efficacy of the Chinese medicine composition after 14 days of medication

[0049] like Figure 3 As shown, the non-irradiated Chinese medicine control group and Chinese medicine group had normal intestinal mucosal structure; 14 days after irradiation, the intestinal mucosal villi of the irradiated group remained basically intact, the crypt structure disappeared by about 1 / 3, and a large number of inflammatory cells infiltrated the mucosal lamina propria, reaching the degree of damage of grade 2 to 3; in the irradiation plus Chinese medicine group, the intestinal mucosal villi maintained an intact structure without obvious damage, proving that the Chinese medicine composition can inhibit radiation enteritis.

[0050] 3. HE staining to evaluate the efficacy of the Chinese medicine composition after 21 days of medication

[0051] like Figure 4 As shown, the non-irradiated Chinese medicine control group and Chinese medicine group had normal intestinal mucosal structure; 21 days after irradiation, the intestinal mucosal villi of the irradiated group remained intact, the crypt structure disappeared by about 1 / 3, and a large number of inflammatory cells infiltrated the mucosal lamina propria, reaching the degree of grade 2 damage; in the irradiation plus Chinese medicine group, the intestinal mucosal villi maintained an intact structure without obvious damage, proving that the Chinese medicine composition can inhibit radiation enteritis.

[0052] 2.2.2 Toxicity assessment of Chinese medicine compositions:

[0053] 1. As Figure 5 As shown, HE staining was used to evaluate the toxicity of the Chinese medicine composition at 7 days, 14 days, and 21 days: the HE staining results of the heart, liver, spleen, lung, and kidney of the control group and the Chinese medicine group at 7 days, 14 days, and 21 days showed no obvious damage, proving that the Chinese medicine composition had no toxicity.

[0054] 2. Blood biochemistry to evaluate the toxicity of Chinese medicine composition:

[0055] like Figure 6 As shown, after 21 days of administration of the Chinese medicine composition, Figure 6As shown in AG, the serum biochemical indices of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatine kinase (CK), urea (BUN), and creatinine (CR) showed no significant differences compared with the control group, confirming that the Chinese medicine composition had no obvious toxicity.

[0056] The basic principles, main features and advantages of the present invention are shown and described above, but the present invention is not limited to the embodiments. Various changes and improvements may be made to the present invention without departing from the spirit and scope of the present invention, and these changes and improvements all fall within the scope of the present invention to be protected.

Claims

1. A Chinese medicine composition for treating acute radiation proctitis, characterized in that: The invention is prepared from the following traditional Chinese medicines in parts by weight: 10-15 parts of dendrobium, 12-20 parts of white peony root, 20-40 parts of astragalus, 8-12 parts of frankincense and 5-8 parts of borneol.

2. The Chinese medicine composition for treating acute radiation proctitis according to claim 1, characterized in that: The Chinese medicine composition for treating acute radiation proctitis is prepared from the following Chinese medicines in parts by weight: 12 parts of dendrobium, 15 parts of white peony root, 30 parts of astragalus, 10 parts of frankincense and 6 parts of borneol.

3. A method for preparing the Chinese medicine composition for treating acute radiation proctitis according to any one of claims 1 to 2, characterized in that: The following steps are involved: The above-mentioned Chinese medicine components are decocted with purified water for 1 to 3 times according to the weight ratio, the decoctions are combined, filtered, and concentrated to a suitable volume to obtain the Chinese medicine composition.

4. A drug for treating acute radiation proctitis, characterized in that: It comprises the Chinese medicine composition according to any one of claims 1 to 2 and a pharmaceutically acceptable carrier.

5. Use of the traditional Chinese medicine composition according to any one of claims 1 to 2 in the preparation of a drug for treating acute radiation proctitis.

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