CN105560267A - Application of polysaccharide of bighead atractylodes rhizome in preparation of drugs for treating intestinal catarrh and imbalance of intestinal flora caused by chemotherapeutic drugs - Google Patents
Application of polysaccharide of bighead atractylodes rhizome in preparation of drugs for treating intestinal catarrh and imbalance of intestinal flora caused by chemotherapeutic drugs Download PDFInfo
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Abstract
The invention relates to an application of polysaccharide of bighead atractylodes rhizome in the preparation of drugs for treating intestinal catarrh and imbalance of intestinal flora caused by chemotherapeutic drugs (especially irinotecan and 5-fluorouracil). The polysaccharide of bighead atractylodes rhizome and common auxiliary materials in pharmacy can be made into a plurality of oral dosage forms such as tablets, oral liquid, granules, and the like. The pharmacological research finds that polysaccharide of bighead atractylodes rhizome can prominently relieves the symptoms caused by chemotherapeutic drugs such as weight loss, intestinal mucosal injury, intestinal flora disturbance, and the like, and is an ideal drug for treating intestinal catarrh and imbalance of intestinal flora caused by chemotherapeutic drugs.
Description
Technical field
The invention belongs to the field of Chinese medicines, be specifically related to Rhizoma Atractylodis polysaccharide and preparing the application in the esoenteritis and alteration of intestinal flora that chemotherapeutics causes.
Background technology
Along with the rising year by year of tumor incidence, the toxic and side effects caused by chemotherapy is subject to the common concern of people, wherein caused by chemotherapy, intestinal mucosa inflammation is a kind of common adverse reactions that chemotherapy causes, be more common in and accept 5-fluorouracil (5-FU), irinotecan, methotrexate, in the chemotherapeutics such as cytosine arabinoside and cisplatin, the visible intestinal mucosa of patient accepting 5-FU treatment as about 80% is scorching.Esoenteritis often causes the symptom such as ulcer, hemorrhage, diarrhoea, pain, reduces patients ' life quality, increases Infection probability and mortality rate, also have impact on chemotherapy process.Generation, the development of esoenteritis can cause alteration of intestinal flora again, and increase the weight of symptom of diarrhea and improve Infection probability, chemotherapeutics causes esoenteritis and alteration of intestinal flora reciprocal causation, jointly causes the injury of gastrointestinal tract that chemotherapy is relevant.
The esoenteritis that chemotherapeutics causes mainly is divided into following double teacher: the 1. starting stage: chemotherapeutics brings out a series of inflammatory reaction, affects enterocyte and endotheliocyte; 2. bring out inflammation phase: enterocyte, the immunocyte in mucous layer secretes a large amount of pro-inflammatory cytokines, causes tissue injury and cell injury.3. the inflammatory signals cascade-multiplied stage: in vivo bioactivity material, the positive feedback loop of the signal that causes inflammation, further incite inflammation reaction; 4. in the ulcer stage: junction opened between inflammatory mediator inducing cell, crypts increases, fine hair shortens, apoptosis atrophy, gut barrier is impaired, and mucous membrane tissue is open, causes intestinal local flora to grow, cause inflammatory cell infiltration further, aggravation is infected and ulcer.5. healing phases: be mainly concerned with extracellular matrix, epithelial cell is migrated, differentiation, propagation, and reconstruct forms callus.
The esoenteritis at present chemotherapy caused and alteration of intestinal flora, current therapeutic strategy is symptomatic treatment and prevention administration effect mainly, as given Elental, glutamine etc.; Also by giving the esoenteritis always such as anti-inflammatory drug 5-aminosalicylic acid, minocycline.To symptoms such as the diarrhoea that chemotherapy causes, by giving probiotic bacteria, as bacillus bifidus improves symptom of diarrhea.
The Rhizoma Atractylodis Macrocephalae Rhizoma Atractylodis Macrocephalae is the dry rhizome of the feverfew Rhizoma Atractylodis Macrocephalae.It is warm in nature, sweet in the mouth, hardship, has invigorating the spleen and benefiting QI, dampness diuretic, hidroschesis, antiabortive effect, is usually used in insufficiency of the spleen lack of appetite, abdominal distention is had loose bowels, the disease such as phlegm retention vertigo and palpitation, edema, spontaneous perspiration, frequent fetal movement.The Rhizoma Atractylodis Macrocephalae is mainly containing the composition such as volatile oil, glycoside, polysaccharide, lactone, aminoacid, and wherein Rhizoma Atractylodis polysaccharide has immunoregulation, defying age, blood sugar lowering, adjustment gastrointestinal function, antitumor, heart tonifying and alleviates cerebral edema, improves the effects such as function of nervous system is impaired.
It is closely related that chemotherapeutics causes function of intestinal mucosa barrier in patient to be undermined alteration of intestinal flora.Intestinal microecology balance is that intestinal mucosa is brought into normal play the basis of function, and its Short-Chain Fatty Acids serves very important effect, it is mainly produced through anaerobe zymolysis at colonic by indigested fiber, polysaccharide etc., as acetic acid, propanoic acid, isopropylformic acid., butanoic acid, isovaleric acid, valeric acids etc., by the zymolysis to fibrous polysaccharaide, the growth of probiotic bacteria can be promoted, there is provided nutrition to intestinal epithelial cell, if butanoic acid is the very important energy source of these cells, play an important role in cell differentiation and growth.Although studies have found that at present Rhizoma Atractylodis polysaccharide in vitro model has good growth promoting function to probiotic bifidobacterium and lactobacillus as seen.Not yet study at present the impact of intestinal mucosa injury that Rhizoma Atractylodis polysaccharide causes chemotherapeutics and alteration of intestinal flora.
Summary of the invention
The object of the present invention is to provide a kind of effective medicine improving esoenteritis that chemotherapy causes and alteration of intestinal flora.
The Rhizoma Atractylodis polysaccharide that the present invention is used, is obtained by extracting method extraction once:
1) get Rhizoma Atractylodis Macrocephalae appropriate, dry, shatter, cross and shine (20 order);
2) in above-mentioned Rhizoma Atractylodis Macrocephalae powder, add the pure water of its quality 10 times amount volume, decoct 3 times, each 2h, filter, merging filtrate, obtains Rhizoma Atractylodis Macrocephalae aqueous extract.
3) concentrating under reduced pressure Rhizoma Atractylodis Macrocephalae extracting solution is 1.30 to its proportion.
4) at above-mentioned concentrated Rhizoma Atractylodis Macrocephalae extracting solution, add 95% ethanol while stirring, regulate determining alcohol to 75%, hold over night.
5) after precipitation to be precipitated, with the centrifugal above-mentioned solution 10min of 3000rpm, get precipitation and add extracting three times, the lyophilization repeatedly of proper amount of acetone, ethanol, obtain the Rhizoma Atractylodis Macrocephalae crude polysaccharides of brownish-yellow powder shape.
6) Rhizoma Atractylodis Macrocephalae crude polysaccharides is dissolved as the aqueous solution of 1mg/mL, adds the trichloroacetic acid of isopyknic 20%, stir 1 hour, centrifugal, get supernatant and adjust pH to neutral.
7) adding active carbon to quality of activated carbon mark in above-mentioned solution for continuous is 1%, 60 DEG C of stirrings 30 minutes, centrifugal rear concentrated, adds 95% ethanol and adjusts determining alcohol to 75%, precipitation hold over night.
8) by centrifugal for above-mentioned mixed liquor, get precipitation, add ethanol in proper amount extracting three times, lyophilization repeatedly.Obtain Rhizoma Atractylodis polysaccharide.
By the Rhizoma Atractylodis polysaccharide that above-mentioned steps is obtained, its polyoses content is between 50%-95%.
For enabling above-mentioned dosage form realize, the acceptable adjuvant of pharmacy need be added when preparing these dosage forms, such as: sweeting agent, correctives, antiseptic, filler, disintegrating agent, lubricant, suspending agent, binding agent, substrate etc.Sweeting agent comprises: saccharin sodium, Aspartane, sucrose, cyclamate, enoxolone etc.; Correctives comprises: sweeting agent and various essence; Antiseptic comprises: parabens, benzoic acid, sodium benzoate, sorbic acid and its esters, Ben Zha Australia is fixed by, acetic acid chloroethene, by leaf oil etc.; Filler comprises: starch, pregelatinized Starch, mannitol, chitin, microcrystalline Cellulose, sucrose etc.; Disintegrating agent comprises: starch, pregelatinized Starch, microcrystalline Cellulose, sodium carboxymethyl cellulose, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose etc.; Lubricant comprises: magnesium stearate, sodium lauryl sulphate, Pulvis Talci, silicon dioxide etc.; Suspending agent comprises: polyvinylpyrrolidone, microcrystalline Cellulose, sucrose, agar, hydroxypropyl emthylcellulose etc.; Binding agent comprises: starch slurry, polyvinylpyrrolidone, hydroxypropyl emthylcellulose etc.; Substrate comprises: PEG6000, PEG4000, sodium polyacrylate, polyvinylpyrrolidone, gelatin, sodium carboxymethyl cellulose, glycerol, kaolin, azone, propylene glycol, insect wax, water etc.
Below by following experimental example, curative effect of the present invention is further elaborated.
Experiment 1: Rhizoma Atractylodis polysaccharide is to the improvement result of the mice esoenteritis that 5-fluorouracil causes
1. material
1.1 laboratory animal
SPF level Balb/c mice 50, male, body weight 20 ± 2g, is provided (quality certification SCXK (Hangzhoupro) 2012-0004) by Zhejiang Medical academy of science Experimental Animal Center.
1.2 medicine
The preparation of modeling medicine 5-fluorouracil (5-FU): take a certain amount of 5-fluorouracil, be configured to 5mgmL with normal saline
-1solution.
2. experimental technique
2.1 modelings and grouping
All experiment mice regular supply water and Feeding material, adaptability raises 7 days before the experiments.At random 50 Balb/c mices are divided into 5 groups before administration.Mice group situation is as follows:
1. normal group: 10, every day gives normal saline gavage by body weight 0.1mL/10g;
2. model group: 10, presses the weight of animals lumbar injection 5-FU50mg/kg every day;
3. Rhizoma Atractylodis polysaccharide low dose group: 10, presses the weight of animals lumbar injection 5-FU50mg/kg every day, after 1 hour, give Rhizoma Atractylodis polysaccharide aqueous solution 50mg/kg by the weight of animals gavage;
4. dosage group in Rhizoma Atractylodis polysaccharide: 10, presses the weight of animals lumbar injection 5-FU50mg/kg every day, after 1 hour, give Rhizoma Atractylodis polysaccharide aqueous solution 100mg/kg by the weight of animals gavage;
5. Rhizoma Atractylodis polysaccharide high dose group: 10 every days press the weight of animals lumbar injection 5-FU50mg/kg, give Rhizoma Atractylodis polysaccharide aqueous solution 200mg/kg after 1 hour by the weight of animals gavage.
Rhizoma Atractylodis polysaccharide low dose group, middle dosage group, high dose group, prevention administration starts modeling two days later.Start modeling after 5 days, tested every one day.Animal gets blood in EP pipe (containing heparin), 4000rmin at 4 DEG C
-1centrifugal 10min, gets supernatant; Put to death, separately get small intestinal, to rinse in clean intestinal the contents such as feces, the jejunum getting about 1.5cm long is placed in 10% formalin, and all the other small intestinals are longitudinally cut open, use microscope slide scraping intestinal mucosa respectively.Above-mentioned biological sample is all kept at-80 DEG C of refrigerators, for subsequent use.
2.2 observed and recorded
1) each group of diarrhea of mouse situation and body weight change is recorded
Give sufficient standard feed and drinking water every day, (classification of diarrhoea is with reference to KuritaA etc. to record 1 body weight, diarrhoea situation every day
[4]diarrhoea methods of marking, 0 point: stool is normal or do not have; 1 point: laxativeness, stool is visible slight wet soft; 2 points: mild diarrhea, stool is comparatively wet and shapeless, and has slight crissum painted; 3 points: severe is suffered from diarrhoea, watery stool, hair color situation, drowsiness tired situation etc. painted with severe crissum.
2) each group mouse jejunum pathological section and enteric epithelium villus length statistics
Small intestine is placed in 10% formalin, routine is drawn materials, dehydration, paraffin embedding.Section is dyeed through H & E, carries out pathologic finding:
A. observation by light microscope: (1) mucosal epithelial cells is with or without degeneration, necrosis, and fine hair interstitial is with or without edema; (2) mucosa lamina propria is with or without hyperemia, edema, cell infiltration; (3) Submucosa, muscle layer, placenta percreta are with or without hyperemia, edema, cell infiltration.Scoring respectively according to pathological changes degree is from light to heavy 0.5 point (slightly), 1 point (slightly), 2 points (moderate), 3 points (severe), be designated as 0 point without obvious pathological changes, cumulative all marks, draw total score, calculate and often organize dividing equally (mean ± SD) of every animal, t inspection between organizing.
B. the olympus microscope that (eyepiece 10 ×, object lens 20 ×) adopts Japan to manufacture under 200 times of light microscopics and the Computer digital image analysis (DP2-BSW) carried thereof measure the long poison of every routine small intestinal at least 10 fine hair.And calculate every routine specimen average fluff length, compare between measurement result group, carry out t inspection.
The detection of TNF-α and IL-6 in 2.3 mice intestinal mucosas
By above-mentioned-80 DEG C of freezing intestinal mucosas, extracting solution (0.1mol/L phosphate buffer is added by 4mL/g tissue, pH value is 6.5) homogenate under ice-water bath, 9000g low-temperature centrifugation (4 DEG C) centrifugal 10min, gets supernatant and measures its protein content and TNF-α and IL-6 content.Determining the protein quantity: adopt BCA method to survey its protein content.
TNF-α and IL-6 assay, carry out in strict accordance with mice TNF-α and IL-6ELISA test kit operating procedure.
2.4 date processing and statistics
Experimental data SPSS16.0 statistical software packet rows independent samples t-test, P < 0.05 represents that difference has statistical significance, and data mean+SD (mean ± SD) represents.
3 experimental results
3.1 respectively organize mice general state, Scours index
3.1.1 general state
Mouse Weight is respectively organized in first three sky of modeling to be increased all to some extent, appetite is also normal, after modeling starts, normal group mice appetite and body weight grow with each passing day, model group, Rhizoma Atractylodis polysaccharide low dose group, middle dosage group and high dose group mice a few days ago occur that after lumbar injection 5-FU obvious appetite reduces, lose weight, there is loose stool, part anus is filthy, god is soft dispirited, the poly-heap of happiness is curled up, withered or the at random perpendicular hair of hair color, hogback, slowly movable, the animal syndrome of spleen-deficiency such as bradykinesia, within 7-8 days, above-mentioned Symptoms is more obvious, there is loose stool and anus filth, compare with normal group mice, become thin and obviously (lose weight obviously), wherein in Rhizoma Atractylodis polysaccharide dosage group and the Rhizoma Atractylodis polysaccharide high dose group mice mental status comparatively model group mice is slightly good, happiness is dynamic.
3.1.2 Scours index statistics
Normal group mice is without diarrhoea situation, in model group, Rhizoma Atractylodis polysaccharide low dose group, Rhizoma Atractylodis polysaccharide, dosage group and Rhizoma Atractylodis polysaccharide high dose group observe laxativeness in first 2 days after injection 5-FU, stool is visible slight wet soft, within 3rd day, start each group of mice and have mild diarrhea, stool is comparatively wet and shapeless, and have slight crissum painted, within 8 days, starting each group of mice has severe to suffer from diarrhoea, and watery stool is also painted with severe crissum.In Rhizoma Atractylodis polysaccharide dosage group and Rhizoma Atractylodis polysaccharide high dose group relative model group Scours index lower, this show Rhizoma Atractylodis polysaccharide can extenuate 5-FU induction diarrhea of mouse.Each treated animal Scours index is as shown in table 1
Table 1 is group diarrhea of mouse index statistical table (Mean ± SD, n=10) respectively
#, p < 0.01, compared with normal group;
*, p < 0.05, compared with model group;
*, p < 0.01, compared with model group;
3.2 pathological sections and the statistical result of enteric epithelium villus length
Normal group: small intestinal is made up of mucous layer, Submucosa, muscle layer and placenta percreta four-layer structure, and each hierarchical structure is clear.Mucous layer table, by simple columnar epithelium, forms elongated fine hair, marshalling to enteric cavity is raised.Enteraden is had in lamina propria.Submucosa is loose connective tissue, and muscle layer is thicker, and serous coat is mesothelium, simple squamous shape.
Model group: more blank group of intestinal villi is short, but morphosis is still complete, 10 example tables are by the degeneration of epithelial cell moderate, and nothing is obviously downright bad.Slight and the Mild edema of 6 top of villi interstitials, lamina propria has a small amount of cell infiltration, and inflammatory cell type is mainly mononuclear cell, lymphocyte, and Submucosa and muscle layer are without obvious pathological changes.Intestinal villi compared with normal group is short, broadening, compares with normal group, has statistical significant difference.
After giving the Rhizoma Atractylodis polysaccharide of various dose, visible mice intestinal mucosa pathological changes comparatively model group obviously alleviates, and show as top of villi edema degree and reduce, cell infiltration that lamina propria is slight reduces, and intestinal villi length increases.
By marking to its pathological section and adding up rear discovery to villus length result, Rhizoma Atractylodis polysaccharide significantly can reduce intestinal mucosa injury that chemotherapeutics causes and intestinal villi reduces.Concrete outcome is in table 2 and table 3.
Table 2 small intestinal lesion score and villus length (Mean ± SD, n=10)
#, p < 0.01, compared with normal group;
*, p < 0.05, compared with model group;
*, p < 0.01, compared with model group;
As can be seen here, model group mice intestinal intrinsic mucous membrane surface epithelial cell degeneration after modeling, fine hair cripetura, interstitial edema, mucosa lamina propria has the Pathologicals such as cell infiltration.Can alleviate the degeneration of small bowel villus epithelial cells after giving Rhizoma Atractylodis polysaccharide, interstitial edema degree alleviates, villus length increases, and wherein middle and high dosage group effect is best.
TNF-α and IL-6 measurement result in 3.3 mouse small intestine mucosas
Result shows, and the TNF-α in model group mice intestinal mucosa and IL-6 content compared with normal group significantly raise (P < 0.01); Giving in Rhizoma Atractylodis polysaccharide low dose group mice intestinal mucosa, having no the change (p > 0.05) of TNF-α and IL-6 content.In Rhizoma Atractylodis polysaccharide, dosage and high dose significantly can suppress the secretion of TNF-α and IL-6 in mice intestinal mucosa.Prompting Rhizoma Atractylodis polysaccharide can alleviate the esoenteritis of 5-FU induction.
The concentration (Mean ± SD, n=10) of TNF-α and IL-6 in table 3 mouse small intestine mucosa
#, p < 0.01, compared with normal group;
*, p < 0.05, compared with model group;
*, p < 0.01, compared with model group;
4. conclusion
Rhizoma Atractylodis polysaccharide can significantly improve the esoenteritis having 5-Fu to cause, and shows as the body weight increasing model mice, the symptom of diarrhea improving model mice, reduces the small intestinal lesion score of model mice and increases the villus length of model mice.This may can to reduce the secretion of pro-inflammatory cytokine TNF-α and IL-6 in small intestinal mucosa relevant with Rhizoma Atractylodis polysaccharide.
Experiment 2: the impact of the mouse intestinal flora imbalance that the many 5-Fu of Rhizoma Atractylodis polysaccharide cause
Treating excess syndrome tests the mice cecal content collected in 1, adopts gas chromatographic technique to measure the content of the short-chain fatty acid in mice cecal content.
Specific experiment step is as follows:
1) intestinal contents is weighed, and gets about 0.1g intestinal contents, accurately weighed, adds the phosphoric acid water buffer of 0.5% of 9 times amount, homogenate, and the centrifugal 10min of vortex 2min, 18000g, gets supernatant 0.4mL, adds mark (30.5 μm of olmL in 10 μ L
-1tetramethyl valeric acid) and 0.4mL ethyl acetate, the centrifugal 10min of vortex 2min, 18000g, gets ethyl acetate layer, to be measured.
2) GC conditions
Chromatographic column: FFAP fused-silica capillary column (30m × 0.25mm × 0.25 μm); Temperature programming: 0 ~ 4min, 90 ~ 150 DEG C (15 DEG C/min); 4 ~ 14.33min, 150 ~ 230 DEG C (15 DEG C/min); 14.33 ~ 16.33min, 230 DEG C (0 DEG C/min); 16.33 ~ 19.33min, 230 ~ 170 DEG C (15 DEG C/min); Fid detector, temperature 280 DEG C; Injector temperature 270 DEG C; Split sampling, sample size 1.0 μ L; Carrier gas: high pure nitrogen, flow velocity 2mL/min.
As shown in Table 4, the short-chain fat acid content in the esoenteritis mice cecal content of 5-FU induction significantly reduces, and if the content of acetic acid, butanoic acid, valeric acid is compared with normal group, significantly declines (p < 0.01).Prompting chemotherapeutics can cause mouse intestinal flora to lack of proper care, and after giving Rhizoma Atractylodis polysaccharide, acetic acid in mice cecal content, butanoic acid, valeric acid content have remarkable rising (p < 0.05 or p < 0.01), and prompting Rhizoma Atractylodis polysaccharide has the function improving the alteration of intestinal flora that chemotherapeutics causes.
Table 4 mice cecal content Short-Chain Fatty Acids content (Mean ± SD, n=10)
#, p < 0.01, compared with normal group;
*, p < 0.05, compared with model group;
*, p < 0.01, compared with model group;
Detailed description of the invention
Form by the following examples, foregoing of the present invention is described in further detail again, but this should be interpreted as that the scope of the above-mentioned theme of the present invention is only limitted to following example, all technology realized based on foregoing of the present invention all belong to scope of the present invention.
Embodiment 1: the oral liquid of medicine of the present invention or syrup preparation method, its step is as follows:
Take the Rhizoma Atractylodis Macrocephalae of 1000g, beat powder, add 10 times amount soak by water twice, collect extracting solution, filter, merging filtrate, be concentrated into 200mL, add 95% ethanol, adjust concentration of alcohol to 75%, after hold over night, centrifugal, get precipitation, acetone, ethanol is extracting three times, lyophilization repeatedly, obtains the Rhizoma Atractylodis Macrocephalae crude polysaccharides of brownish-yellow powder shape.Rhizoma Atractylodis Macrocephalae crude polysaccharides is dissolved as the aqueous solution of 1mg/mL, adds the trichloroacetic acid of isopyknic 20%, stirs 1 hour, centrifugal, getting supernatant adjusts pH to neutral, continues to add active carbon (1%), and 60 DEG C are stirred 30 minutes, centrifugal rear concentrated, add 95% ethanol and adjust determining alcohol to 75%, after precipitation leaves standstill a night, centrifugal, get precipitation, ethanol is extracting three times, lyophilization repeatedly.Configuration concentration is 5mg/mL Rhizoma Atractylodis polysaccharide aqueous solution, adds sodium benzoate a little, and correctives is appropriate, stirs evenly, and filter, embedding, sterilizing, subpackage (25mL/ props up), namely makes oral liquid or syrup.
Claims (3)
1. Rhizoma Atractylodis polysaccharide is improving the purposes in the esoenteritis and alteration of intestinal flora symptom that chemotherapeutics causes.
2. Rhizoma Atractylodis polysaccharide as claimed in claim 1, is characterized in that Rhizoma Atractylodis polysaccharide content is at 50%-95%.
3. Rhizoma Atractylodis polysaccharide as claimed in claim 2, is characterized in that, this polysaccharide is aided with pharmaceutically conventional adjuvant can be prepared into various peroral dosage form, comprises tablet, oral liquid, granule, capsule etc.
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| CN115957247A (en) * | 2022-03-07 | 2023-04-14 | 上海中医药大学 | Application of rhizoma atractylodis macrocephalae extract in preparation of medicine for treating gastrointestinal mucosa injury |
| CN117414404A (en) * | 2023-12-05 | 2024-01-19 | 宁夏医科大学 | Application of traditional Chinese medicine composition in preparation of medicines for treating intestinal flora imbalance diseases |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111494404A (en) * | 2019-01-31 | 2020-08-07 | 成都中医药大学 | Application of atractylodes macrocephala polysaccharide and volatile oil in preparing medicine for preventing or treating chronic atrophic gastritis |
| CN111494403A (en) * | 2019-01-31 | 2020-08-07 | 成都中医药大学 | Application of atractylodes macrocephala polysaccharide in preparing medicine for preventing and treating ulcerative colitis |
| CN115957247A (en) * | 2022-03-07 | 2023-04-14 | 上海中医药大学 | Application of rhizoma atractylodis macrocephalae extract in preparation of medicine for treating gastrointestinal mucosa injury |
| CN117414404A (en) * | 2023-12-05 | 2024-01-19 | 宁夏医科大学 | Application of traditional Chinese medicine composition in preparation of medicines for treating intestinal flora imbalance diseases |
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