CN114886935B - Traditional Chinese medicine composition for blocking conversion of colonitis cancer and preparation method thereof - Google Patents
Traditional Chinese medicine composition for blocking conversion of colonitis cancer and preparation method thereof Download PDFInfo
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Abstract
The invention relates to a traditional Chinese medicine composition for blocking colonitis cancer transformation and a preparation method thereof, and the technical characteristics are that: the traditional Chinese medicine composition comprises the following components in parts by weight: 9-30g of radix pseudostellariae, 3-9g of rhizoma atractylodis, 3-10g of ligusticum wallichii, 6-15g of honeysuckle, 9-15g of rosewood heart wood and 3-10g of nutmeg. According to the pathogenesis of colon cancer, the radix pseudostellariae, the rhizoma atractylodis, the rhizoma ligustici wallichii, the honeysuckle, the rosewood and the nutmeg are subjected to traditional Chinese medicine compatibility, and various traditional Chinese medicine raw material components can play a role in synergy according to a certain dosage proportion, can effectively relieve intestinal mucosa inflammatory reaction, radically reverse the process of chronic enteritis 'inflammatory cancer transformation', and can be widely used for treating colonitis related colon cancer such as acute and chronic enteritis, ulcerative colitis, colon crohn disease and the like.
Description
Technical Field
The invention belongs to the technical field of traditional Chinese medicine compositions, and in particular relates to a traditional Chinese medicine composition for blocking conversion of colonitis cancer and a preparation method thereof.
Background
Colon cancer (colorectal cancer, CRC) is one of the common digestive tract tumors. Global cancer burden data published by the world health organization international cancer research institute in 2020 shows that CRC incidence is second to breast and lung cancer, and mortality is second to lung cancer. 38.76 ten thousand cases of new cases of CRC in China in 2015 account for 9.87% of the cases of all malignant tumors according to the latest data published by the national cancer center; 18.71 ten thousand cases of death caused by CRC account for 8.01% of all malignant tumor deaths. How to reduce the incidence rate and the death rate of CRC is one of the major public health problems to be solved urgently in China.
Researchers find that CRC is a chronic uncontrolled intestinal inflammation abnormal hyperplasia, gradually developing into cancerous processes, and the progress from inflammation-atypical hyperplasia-cancer is called colitis-cancer transformation. Due to the complex interactions between external environmental factors and host systems during the transformation of colitis cancer, there is currently no targeted drug that effectively blocks this cascade.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a traditional Chinese medicine composition for blocking the conversion of colonitis cancer and a preparation method thereof, which can effectively reverse the conversion process of inflammatory cancer of chronic enteritis.
The invention solves the technical problems in the prior art by adopting the following technical scheme:
a traditional Chinese medicine composition suitable for blocking the conversion of colonitis cancer comprises the following components in parts by weight: 9-30g of radix pseudostellariae, 3-9g of rhizoma atractylodis, 3-10g of ligusticum wallichii, 6-15g of honeysuckle, 9-15g of rosewood heart wood and 3-10g of nutmeg.
12 parts of radix pseudostellariae, 8 parts of rhizoma atractylodis, 6 parts of ligusticum wallichii, 15 parts of honeysuckle, 8 parts of rosewood heart wood and 4 parts of nutmeg.
A preparation method of a Chinese medicinal composition suitable for blocking colitis cancer transformation comprises weighing raw materials according to the ratio of Chinese medicinal materials, decocting with 10 times of water for 2 times each for 1 hr, and mixing filtrates to obtain decoction of Chinese medicinal composition.
The invention has the advantages and positive effects that:
the traditional Chinese medicine composition is reasonable in design, and according to the pathogenesis of colon cancer, radix pseudostellariae, rhizoma atractylodis, rhizoma ligustici wallichii, honeysuckle, rosewood and nutmeg are subjected to traditional Chinese medicine compatibility, and various traditional Chinese medicine raw material components can obviously play a synergistic effect according to a certain dosage proportion, so that intestinal mucosa inflammatory reaction can be effectively relieved, and the process of chronic enteritis 'inflammatory cancer conversion' is fundamentally reversed. In addition, the traditional Chinese medicine composition can be prepared into decoction, pills, powder, granules, formula granules, capsules and the like, and can be widely used for treating colonic cancer related to colonitis such as acute and chronic enteritis, ulcerative colitis, colon crohn disease and the like.
Drawings
FIG. 1 is a graph showing colon tissue morphology of rats in each group obtained by the pharmacodynamic test of the present invention;
FIG. 2 is a histogram of colon tumor numbers of rats in each group obtained by the pharmacodynamic test of the present invention;
FIG. 3 is a graph showing colon pathology of rats in each group obtained by the pharmacodynamic test of the present invention.
Detailed Description
Embodiments of the present invention are described in further detail below with reference to the accompanying drawings.
According to the theory of traditional Chinese medicine, the colitis-cancer transformation process is considered to be a dynamic process of gradual evolution of pathogenesis, and the basic disease is located in the intestines and is closely related to the spleen and the stomach. The pathogenesis involved in the whole inflammatory-cancerous transition can be attributed to spleen deficiency and damp-heat accumulation in the intestinal tract. Aiming at the core pathogenesis, we put forward a core treatment method for preventing and treating the conversion of colonitis cancer, namely regulating qi, eliminating dampness, promoting blood circulation, removing toxicity, regulating the middle-jiao qi in clinical use, leading liver qi to be soothing and relieving pain, strengthening spleen qi, eliminating dampness, promoting blood circulation, removing stagnation and reducing toxicity.
Based on the design concept, the invention provides a traditional Chinese medicine composition suitable for blocking the conversion of colonitis cancer, which comprises the following components in parts by weight: 9-30g of radix pseudostellariae, 3-9g of rhizoma atractylodis, 3-10g of ligusticum wallichii, 6-15g of honeysuckle, 9-15g of rosewood heart wood and 3-10g of nutmeg.
The traditional Chinese medicine composition of the invention has the preferable scheme that: 12 parts of radix pseudostellariae, 8 parts of rhizoma atractylodis, 6 parts of ligusticum wallichii, 15 parts of honeysuckle, 8 parts of rosewood heart wood and 4 parts of nutmeg.
The radix pseudostellariae in the traditional Chinese medicine composition is sweet and flat in taste, and has the effects of tonifying middle-jiao and Qi, promoting the production of body fluid and strengthening spleen; the rhizoma atractylodis has bitter and warm nature and has the effects of eliminating dampness and turbid urine, promoting qi circulation and relieving pain; ligusticum wallichii is pungent and warm in nature, and has the effects of activating blood circulation to dissipate blood stasis, resolving masses and relieving pain; honeysuckle flower has cold nature and sweet taste, enters lung, heart and stomach channels, and has the effects of clearing heat and detoxicating and dispelling wind and heat; the rosewood heart-fire-reducing spleen-activating seasoning has the effects of promoting qi circulation, relieving pain, treating chest and abdominal distention and treating diarrhea; nutmeg Wen Xinxing has effects of warming spleen and stomach, astringing intestine, activating qi-flowing and resolving food stagnation. The whole formula is used for cold and heat and has the effects of tonifying qi and activating blood, promoting qi circulation and relieving pain, drying dampness and stopping diarrhea.
Based on the traditional Chinese medicine composition suitable for blocking the conversion of the colonitis cancer, the invention also provides a preparation method of the traditional Chinese medicine composition for blocking the conversion of the colonitis cancer, which comprises the following steps: weighing the raw materials according to the proportion of the medicinal materials of the traditional Chinese medicine composition, adding 10 times of water, decocting for 2 times, each time for 1 hour, and combining the filtrates to obtain the decoction of the traditional Chinese medicine composition.
The traditional Chinese medicine composition can also be prepared into pills, powder, granules, formula granules, capsules and the like according to the conventional preparation technology, and is used for treating colonic cancer related to colonitis such as acute and chronic enteritis, ulcerative colitis, crohn's disease and the like. The administration method comprises the following steps: one adult dose is taken a day, 1 time in the morning and at night, and 1 treatment course is 8 weeks.
In order to prove the efficacy of the invention, the applicant conducted the following efficacy experiment of the traditional Chinese medicine composition for blocking the conversion of colitis to CRC malignancy.
1 materials and methods
1.1 laboratory animals
SPF-grade male Wistar rats 75, 5-6 weeks, initial body mass 200-250g, purchased from Si Bei Fu (Beijing) Biotechnology Co., ltd. The selected animals are raised at room temperature of 18-25 ℃ and relative humidity of 50% -60% and alternate day and night for 12 hours. The experiments were approved by the ethical committee for experimental animals at the university of Beijing Chinese medicine (number: BUCM-4-2017120101-4038).
1.2 reagents and medicaments
(1) Molding inducer: 1, 2-Dimethylhydrazine (DMH), CAS number 540-73-8, stored at low temperature and purchased from Sigma company.
(2) A Chinese medicinal composition comprises: radix Pseudostellariae, rhizoma Atractylodis, rhizoma Ligustici Chuanxiong, flos Lonicerae, lignum Dalbergiae Odoriferae and semen Myristicae are all purchased from Beijing herbal prescription source limited company, the decoction pieces are weighed according to weight, 10 times of water is added for 2 times, each time for 1 hour, the filtrates are combined, dried at 60 ℃ and crushed for standby.
1.3 major instruments, materials and reagents
Sodium phenobarbital for injection, a magnetic stirrer, an OLYMPUS microscope, paraformaldehyde, adhesive glass slides and cover slips, xylene and the like.
1.4 establishment of animal models and group administration
Rats were fed adaptively for 7 days, and were randomly divided into 10 normal groups and 30 model groups according to body weight using a random digital table method. A DMH method is adopted to prepare a rat colon cancer inflammatory cancer transformation model, namely, after the model-making rat is adaptively fed for 1 week, 1mmol/L EDTA is used for preparing a DMH solution with the concentration of 0.35% from the 2 nd period, 1mol/L NaHCO3 is used for regulating the PH to 6.5-7.0, and filtering and sterilizing are carried out. Freshly prepared DMH was intraperitoneally injected 1 time at 30mg/kg body weight on day 1 of the week, and molding was continued for 15 weeks. While the control group did not participate in the modeling, the same dose of EDTA solution was injected intraperitoneally weekly.
After successful modeling, 30 rats were equally divided into model, high dose and low dose groups using a random digital meter method. Weighing appropriate amount of dry extract of Chinese medicinal composition, and adding distilled water to prepare stomach-lavage solution. The stomach was irrigated 2 times per day, 2ml each, with 8 weeks of continuous intervention. The body weight of the rats was weighed weekly to determine the dose, and the high and low dose groups were administered with 19.08g crude drug/kg and 4.77g crude drug/kg by gavage (corresponding to 4-fold and 1-fold of the clinically equivalent dose, respectively). The model group and the control group were filled with equal volumes of distilled water.
1.5 animal Material availability and Observation index
Disease Activity Index (DAI): the percentage weight loss, stool consistency and rectal bleeding were recorded weekly and the average calculated as DAI. The DAI specific scoring criteria are as follows: weight loss of <1%, normal fecal character, no hematochezia, score 0; the fecal character is dispersed, the blood-occult positive and the weight reduction rate is 1% -5%, 6% -10% and 11% -15% are respectively marked as 1,2 and 3 minutes; the feces were diarrhea-like, blood was visible to the naked eye, and weight loss was >15%, recorded as 4 minutes.
Inflammatory factors: after the experiment is finished, the materials are fasted for 24 hours without water inhibition before taking materials. The day of sampling was anesthetized rats (0.2 mL/100 g) with 2% sodium pentobarbital, the abdominal aorta was bled, and serum was collected for later use after centrifugation, and the content of TNF-alpha, IL-1 beta, IL-6 was determined by ELISA.
And (3) pathological observation: the large intestine above the anus was taken and the colorectal state was observed under natural light. Under the low temperature condition, the mesentery is dissected on filter paper to observe whether mucous membrane damage exists or not, strip-shaped tissues are cut at the damaged part, the strip-shaped tissues are placed on the filter paper to be wrapped and fixed, after the strip-shaped tissues are marked clearly by a sign pen, the strip-shaped tissues are placed in 10% formalin to be fixed for 24 hours, conventional paraffin embedding is carried out, HE pathological staining sections are manufactured and observed, and pathological diagnosis is carried out according to WHO digestive system tumor classification.
2 experimental results
2.1 DAI comparisons for groups
Before model replication, each group of rats had a DAI of 0; after model replication, the DAI values were significantly higher for each group than for the normal control group (P < 0.05), and after 8 weeks of dosing, the DAI values were significantly lower for each group (P < 0.05) compared to the model group.
Table 1 DAI comparison of rats in each group
Note that: p <0.05 compared to control group; compared to model group, #P <0.05
2.2 general morphological and pathological features of colon tissue
After 8 weeks of intervention, the rectum of the rats in the model group was seen to become shorter and stiffer, the mucosa was thickened, engorged red and swollen, nodular elevation was seen with naked eyes, the diameter was 2-4mm, the convexity was toward the intestinal lumen, bleeding, necrosis and/or ulceration of the surface of individual nodules, and an average of 8.7 nodules were observed on each rat. The colon length of the traditional Chinese medicine composition group is increased, and the diameter of the nodule is smaller than 2mm. The colon tumor numbers of the high-dose group and the low-dose group are respectively 1.2 and 4.3, which are obviously lower than that of the model group, as shown in fig. 1 and 2, in fig. 1, A is a control group; b is a model group; c is a high dose group; d is the low dose group.
The results of the colorectal tissue HE staining show that the mucosa of colorectal tissue of rats in the control group is complete, the crypts are orderly arranged, and the goblet cells are sufficient. The model group can see that adenocarcinoma invades to serosa layers, crypt arrangement is disordered, intrinsic gland structures are destroyed, and a large amount of inflammatory cells infiltrate. The traditional Chinese medicine composition groups are all stopped at the stage of intraepithelial neoplasia, no adenocarcinoma is found, the inherent glands are reduced, the arrangement is disordered, no mucosal myoproliferation is found, the lymphocytes are slightly infiltrated, and the effect of improving the malignancy degree of the tumor is better in the high-dose group, as shown in figure 3, wherein A is a control group; b is a model group; c is a low dose group; d is the high dose group.
2.3 inflammatory factor levels
The significant increase in IL-1β, IL-6 and TNF- α levels in the model group compared to the normal control group suggests that proinflammatory cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor- α (TNF- α) are involved in the malignant transformation of chronic enteritis inflammation. After 8 weeks of dosing, the levels of all three inflammatory factors were significantly reduced compared to the model group.
TABLE 2 expression levels of IL-1 beta, IL-6 and TNF-alpha in rat serum of each group
Note that: p <0.05 compared to control group; compared to the model group, #p <0.05.
The animal experiments show that the invention can obviously improve the mucosa pathological state of rats with precancerous lesions of colon cancer induced by 1, 2-Dimethylhydrazine (DMH), relieve intestinal mucosa inflammatory reaction and radically reverse the process of chronic enteritis 'inflammatory cancer transformation'.
It should be emphasized that the examples described herein are illustrative rather than limiting, and therefore the invention includes, but is not limited to, the examples described in the detailed description, as other embodiments derived from the technical solutions of the invention by a person skilled in the art are equally within the scope of the invention.
Claims (3)
1. A traditional Chinese medicine composition for blocking the transformation of colonitis cancer is characterized in that: the composite material consists of the following raw materials in parts by weight: 9-30g of radix pseudostellariae, 3-9g of rhizoma atractylodis, 3-10g of ligusticum wallichii, 6-15g of honeysuckle, 9-15g of rosewood heart wood and 3-10g of nutmeg.
2. The traditional Chinese medicine composition for blocking the transformation of colonitis cancer according to claim 1, wherein: the composition comprises 12 parts of radix pseudostellariae, 8 parts of rhizoma atractylodis, 6 parts of ligusticum wallichii, 15 parts of honeysuckle, 8 parts of rosewood heart wood and 4 parts of nutmeg.
3. A method for preparing a traditional Chinese medicine composition for blocking the transformation of colonitis cancer according to claim 1 or 2, characterized in that: weighing the raw materials according to the proportion of the medicinal materials of the traditional Chinese medicine composition, adding 10 times of water, decocting for 2 times each for 1 hour, and combining the filtrates to obtain the decoction of the traditional Chinese medicine composition.
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