CN103405482B - Chimonanthus salicifolius extract is in preparation treatment inflammatory bowel and the application alleviated in the medicine of the injury to alimentary tract that chemotherapeutics causes - Google Patents
Chimonanthus salicifolius extract is in preparation treatment inflammatory bowel and the application alleviated in the medicine of the injury to alimentary tract that chemotherapeutics causes Download PDFInfo
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Abstract
The present invention relates to medical art, particularly relate to Chimonanthus salicifolius extract in preparation treatment inflammatory bowel and the application alleviated in the medicine of the injury to alimentary tract that chemotherapeutics causes.This medicine is prepared from through water extraction by Chimonanthus salicifolius, can prepare Prevention and Curation diarrhoea, gastroenteritis with it; the medicine of the diseases such as inflammatory bowel; and can cancer chemotherapy be assisted, reduce the toxicity of antitumor drug, can be used as anti-mucositis and intestinal protection drug development.
Description
Technical field
The present invention relates to medical art, particularly relate to Chimonanthus salicifolius extract in preparation treatment inflammatory bowel and the application alleviated in the medicine of the injury to alimentary tract that chemotherapeutics causes.
Background technology
Chimonanthus salicifolius (
chimonathusSalicifoliusHu) be Calycanthaceae Chimonanthus praecox (L.) Link. platymiscium, be half evergreen shrubs, gain the name because its blade is Folium Salicis Babylonicae shape.The ground such as Zhejiang, Anhui, Jiangxi are mainly distributed at China's Chimonanthus salicifolius.The local She common people of Lishui of Zhejiang often pluck its stem and leaf and decoct soup, and are referred to as " Chi monanthus salicifolius ", and according to Conventional wisdom, Chimonanthus salicifolius is decocted soup and had treatment anemofrigid cold, abdominal pain diarrhea, dyspeptic effect.We also show animal experiment study in the past, and Chimonanthus salicifolius can treat the diarrhea of mouse symptom that Folium Sennae and Oleum Ricini cause, and therapeutic effect can match in excellence or beauty with conventional antidiarrheal imodium (imudium) clinically.Analysis display is carried out to Chimonanthus salicifolius leaf composition: its protein, crude fat content are higher, reach 27.86% and 31.25% respectively, account for more than 50% of dry weight; The content of Chimonanthus salicifolius Free Amino Acids and vitamin is also very abundant, and compared with green tea, vitamin B1 content exceeds 4 times, B2 exceeds 2.5 times, vitamin C exceeds 0.5 times; In addition, the volatile oil content of Chimonanthus salicifolius is also quite high, and oil productivity can reach about 2%, and utilizing gas chromatography-mass spectrum (GC-MS) to analyze its volatile oil main component is terpenoid alkene and terpenoid alkene alcohols material.
Inflammatory bowel (inflammatoryboweldisease, IBD) be that a class is chronic, the bowl inflammatory diseases of recurrent exerbation, clinically, different according to its pathological characters, IBD is divided into Crohn disease (Crohn`sDisease, and ulcerative colitis (UlcerativeColitis, UC) two kinds CD).IBD disease is fallen ill with its person between twenty and fifty, recurrence is frequent, stubbornness does not heal, complication is many and canceration risk high, people's quality of life and social productive forces are produced and has a strong impact on, by World Health Organization (WHO) (WorldHealthOrganization, WHO) one of modern refractory disease is defined as, be subject to showing great attention to of various circles of society, the research of its related pathologies mechanism, and the exploitation of clinical treatment and targeted drug also becomes area research focus.
Antineoplaston often with serious side effect, causes damage of intestines, limits the application of medicine.This mainly generally has lethal for the cell of fast breeding due to antitumor drug, and normal cell is as enterocyte, responsive equally to this type of medicine, therefore can cause apoptosis, intestinal mucosa structural damage, is clinically called mucositis.Its cardinal symptom for becoming thin, suffering from diarrhoea, have blood in stool, infection etc.Therefore, carrying out the exploitation of targeted drug for alleviating patient's misery, improving tumor cure rate significant.
Summary of the invention
In order to solve above-mentioned technical problem, an object of the present invention is to provide the application of Chimonanthus salicifolius extract in the medicine of preparation treatment inflammatory bowel.Another object of the present invention is to provide Chimonanthus salicifolius extract and is preparing in chemotherapy of tumors process as the application alleviated in the medicine of the injury to alimentary tract that chemotherapeutics causes.
Disclosure sets forth a kind of medicine with protection gastrointestinal function.This medicine is prepared from through water extraction by Chimonanthus salicifolius.Mouse experiment represents: medicine involved in the present invention all has obvious preventive and therapeutic action to the intestinal injury model that mice inflammatory bowel disease models and cancer therapy drug cause under multiple dose concentration.Therefore can prepare Prevention and Curation diarrhoea, gastroenteritis, the medicine of the diseases such as inflammatory bowel with it, and can cancer chemotherapy be assisted, reduce the toxicity of antitumor drug, can be used as anti-mucositis and intestinal protection drug development.
Accompanying drawing explanation
Fig. 1, Fig. 2 are Chimonanthus salicifolius extract to the effect diagram of normal Mouse Weight and clinical score.
Fig. 3, Fig. 4 are Chimonanthus salicifolius extract to the effect diagram of IBD Mouse Weight and clinical score.
Fig. 5 is the intestinal wall edema figure that Chimonanthus salicifolius extract alleviates IBD and causes.
Fig. 6 is the too drastic figure of Chimonanthus salicifolius extract Immunosuppression.
Fig. 7 is the increase figure that Chimonanthus salicifolius extract decreases spleen weight.
Fig. 8 is the effect diagram of Chimonanthus salicifolius extract to mouse Colon pathological score.
Fig. 9 is the effect diagram that Chimonanthus salicifolius extract declines to the Mouse Weight that 5-Fu causes.
Figure 10 is that Chimonanthus salicifolius extract and imodium administration can effectively reduce diarrhoea scoring figure.
Figure 11 is other each group does not have effect diagram to the symptom of having blood in stool of 5-Fu induction.
Figure 12 is blood parameters variation diagram.
Figure 13, Figure 14 are intestinal tissue length variations figure.
Figure 15, Figure 16 are Gut Mucosa Morphology Epidemiological Analysis figure.
Detailed description of the invention
embodiment 1: the preparation of Chimonanthus salicifolius water extract
Pulverize after fresh Chimonanthus salicifolius stem and leaf are dried, solids is mixed by certain mass volume ratio with water, soak and boil 5-30 minute after 0.5-2 hour, residue is abandoned in filtration, gained supernatant is that Chimonanthus salicifolius water gets extract, and this water extract can be prepared into extractum after low-temperature freeze drying or heating, vacuum concentrate.
embodiment 2: Chimonanthus salicifolius is to the therapeutical effect of poly glucose sodium (DSS) inducing mouse inflammatory bowel
Pulverize after fresh Chimonanthus salicifolius stem and leaf being dried, mixed by solids, soak after 1 hour, boil 10min under room temperature with water by mass volume ratio 4:25, after being filtered by medicinal residues, gained supernatant is that Chimonanthus salicifolius water gets extract.
20 C57 mices are divided into 4 groups at random: Normal group, normal Chimonanthus salicifolius group, model group and model Chimonanthus salicifolius group.IBD model substitutes normal water 5 days induction by 2%DSS aqueous solution, period mice freely drink water, and the DSS solution more renewed every day, gains as normal drinking water on the 5th day by DSS; Matched group does not replace drinking-water.Start the continuous gavage of mice 4 days after DSS drug withdrawal, each 0.4ml water or Chimonanthus salicifolius water extract.
In experimentation, every day records Mouse Weight, and gathers mice fresh excreta, carries out double-blind method clinical score to mice.Standards of grading are in table 1.Cervical dislocation is put to death after mice, is separated and measures the weight of spleen and mesenteric lymph node; After colon exenterates, record length and weight, the colon weight of unit of account length.Get about 2cm colon, be placed in neutral formalin and fix, routine paraffin wax embedding, 5 μm of sections, hematoxylin-eosins (HE) are dyeed, section result double-blind method pathological score.Pathological score standard is as shown in table 2.
Table 1 clinical score standard
| Fecal consistency | Have blood in stool | Weight loss |
| 0: normal | 0: without occulting blood | 0: have no weight loss |
| 1: moistening feces, slightly soft | 1：+ | 1: lose weight 0 ~ 5% |
| 2: feces is soft and show to be clamminess | 2: ++ | 2: lose weight 5 ~ 10% |
| 3: soft | 3: +++ | 3: lose weight 10 ~ 15% |
| 4: watery stools, shapeless | 4: ++++ | 4: weight loss is more than 15% |
Table 2 histopathological scores standard
| Mucous layer damages | Inflammatory cell infiltration |
| 0: not damaged | 0: without infiltrating |
| 1: a small amount of goblet cell reduces | 1: crypt base has inflammatory infiltration |
| 2: a large amount of goblet cell reduces | 2: mucosa lamina propria and crypt base occur that moderate inflammatory infiltrates |
| 3: a large amount of goblet cell minimizing disappears with a small amount of crypts | 3: infiltrate to Submucosa and Mild edema |
| 4: a large amount of goblet cell and crypts disappear | 4: massive inflammatory cells infiltrated to Submucosa, and with inflammation edema |
Experimental result shows: all there will be the process that body weight declines slightly after the feedwater of normal group mouse stomach or Chimonanthus salicifolius water extract, but, obviously increasing the weight of does not appear in fecal consistency and index of just occulting blood, and two groups of mices do not have the difference of body weight (as Fig. 1) and clinical score (as Fig. 2) aspect yet.Illustrate that " Chi monanthus salicifolius " does not have detrimental effect to intestinal, side effect is little, takes safety.
After DSS modeling, each group Mouse Weight slightly declines, but without statistical discrepancy (as Fig. 3).Model mice fecal consistency and index of having blood in stool all have and add reconstructed image, and diarrhoea and the symptom of having blood in stool of Chimonanthus salicifolius administration group all take a favorable turn, and clinical score result display Chimonanthus salicifolius accelerates the recovery (as Fig. 4) of IBD.
Mice compares the change of Ge Zujian tissue weight after dissecting, result shows: model mice colon unit weight increases, and shows that intestinal wall exists inflammatory edema; And Chimonanthus salicifolius administration group mouse Colon unit weight is less than matched group, both have significant difference, and the intestinal wall edema (as Fig. 5) that Chimonanthus salicifolius alleviates IBD and causes is described.Mesenteric lymph node is one of intestinal Main Immune Organs, and in model mice, mesenteric lymph node weight increases, and illustrates that lymph node endolymph cell can increase; And the mesenteric lymph node that Chimonanthus salicifolius administration obviously alleviates model mice expands, illustrate that Chimonanthus salicifolius can Immunosuppression too drastic (as Fig. 6).Chimonanthus salicifolius administration decreases the increase of spleen weight equally, but both do not have statistical significance (as Fig. 7).
Contrast four groups of mouse Colon pathology H & E sections to find: each Rotating fields of normal group colon is clear, and epithelium is neat, crypts structural integrity, and goblet cell enriches, and does not have difference between water or Chimonanthus salicifolius water extract administration group.And DSS model group section of colon all occurs that goblet cell and crypts reduce, part mucosa structure disappears, inflammatory cell infiltration and Submucosa edema etc., and pathological score Chimonanthus salicifolius administration mice symptom is obviously lighter than the negative group (as Fig. 8) of model.
Show based on the above results, Chimonanthus salicifolius can alleviate the inflammatory bowel disease models of DSS induction, points out it to have antiinflammatory action, can as the medicine for the treatment of inflammatory bowel.
embodiment 3: Chimonanthus salicifolius is to the therapeutical effect of anticancer chemotherapeutic agent 5-fluorouracil (5-FU) inducing mouse mucositis
Pulverize after fresh Chimonanthus salicifolius stem and leaf being dried, mixed by mass volume ratio 8:100 with water by solids, soak and boil 10 minutes after 2 hours, filter and abandon residue, gained supernatant is that Chimonanthus salicifolius water gets extract, after low-temperature freeze drying, be prepared into extractum.Extractum is dissolved in the Chimonanthus salicifolius water that water is prepared into variable concentrations and gets extract (CS), corresponding every milliliter of medicinal liquid is containing crude drug 0.25g, 0.5g, 0.75g and 1g respectively.
56 C57 mices are divided into 7 groups at random: Normal group, model group, model+positive drug group and model+Chimonanthus salicifolius group (4 gradient concentrations).The continuous gastric infusion of all mices 13 days, twice daily, each 0.1ml/10g, positive drug adopts imodium (Xian-Janssen Pharmaceutical Ltd.) suspension (0.1mg/ml), Chimonanthus salicifolius group gives the Chimonanthus salicifolius water extract of four kinds of concentration respectively, and Normal group and model group give distilled water.Mucositis model is by forming in the 5-Fu injection induction of the 5 to 7 day lumbar injection 50mg/kg.
The body weight change of observation period record mice every day, scoring of suffering from diarrhoea and have blood in stool.13rd day, mouse orbit was taken a blood sample, and prepares serum and detects for blood biochemical, and cervical dislocation puts to death mice, was separated the length that full intestinal also records large and small intestinal respectively.After intestinal tissue exenterates, be placed in neutral formalin to fix, routine paraffin wax embedding, 5 μm of sections, hematoxylin-eosins (HE) are dyeed, and section result utilizes optical microscope and software kit thereof to calculate the Crypt depth of intestinal villi length and large and small intestinal.
Experimental result shows: serious weight loss has all appearred in each group model mice after 5-Fu administration; and Chimonanthus salicifolius administration can weaken the weight loss that 5-Fu causes; but imodium alleviates not impact to Mouse Weight, show the absorption function (as Fig. 9) of Chimonanthus salicifolius protection intestinal.
Observe diarrhea of mouse and situation discovery of having blood in stool: 5-Fu injection causes mice produce severe diarrhea and have blood in stool, wherein Chimonanthus salicifolius and imodium administration can effectively reduce diarrhoea and mark (as Figure 10); Only have the Chimonanthus salicifolius administration of 3g/kg just can alleviate the degree of having blood in stool, and other each group does not affect (as Figure 11) on the symptom of having blood in stool of 5-Fu induction.Result shows that Chimonanthus salicifolius can alleviate the clinical symptoms of mucositis.
Blood biochemical analysis shows: 5-Fu administration causes hepatic injury associated blood biochemical indicator to raise, but on the no impact of injury of kidney indicator.Chimonanthus salicifolius administration alleviates the liver toxicity of 5-Fu, decreases the level of blood parameters AST and ALT.And for CRE and BUN, equal zero difference between each group, illustrates that 5-Fu itself is without nephrotoxicity, and Chimonanthus salicifolius administration also can not cause injury of kidney, and drug safety is high, side effect little (as Figure 12).
The intestinal change of more large and small intestinal shows that 5-Fu administration causes intestinal tissue to shorten, and Chimonanthus salicifolius is under 1g/ml dosage, all has mitigation (as Figure 13 and Figure 14) to the shortening of large and small intestinal.This illustrates that Chimonanthus salicifolius has inhibitory action to the intestinal tissue shortening that 5-Fu causes, and contributes to protecting intestinal injury, maintains intestinal normal function.
Pathological analysis shows that 5-Fu administration causes intestinal villi to shorten, but crypts of small intestine is not affected, and Chimonanthus salicifolius 0.75g/ml and 1g/ml administration can alleviate the minimizing of intestinal villi length, imodium administration simultaneously also shows the protective effect to intestinal villi; In large intestine, 5-Fu administration mice shows Crypt depth and reduces, and imodium and the administration of 1g/ml Chimonanthus salicifolius all can alleviate crypts shortening (as Figure 15 and Figure 16) that 5-Fu causes.This illustrates that Chimonanthus salicifolius all has protective effect to large and small intestinal, alleviates the intestinal mucosa injury that 5-Fu causes.
Show based on the above results; Chimonanthus salicifolius can alleviate the mucositis model that chemotherapeutics 5-Fu induces; prompting Chimonanthus salicifolius can be applied to anticancer adjuvant treatment; alleviate the liver toxicity of cancer treatment drugs and the damage to intestinal thereof; alleviate lose weight, suffer from diarrhoea, the symptom such as to have blood in stool; protection intestinal, maintains the integrity of intestinal mucosa 26S Proteasome Structure and Function.Painful for ameliorate tumor patient, improve tumor cure rate significant.
Claims (2)
1. the application of Chimonanthus salicifolius water extract in the medicine of preparation treatment inflammatory bowel; The preparation method that Chimonanthus salicifolius water gets extract is pulverize after fresh Chimonanthus salicifolius stem and leaf being dried, solids is mixed by certain mass volume ratio with water, soak and boil 5-30 minute after 0.5-2 hour, filter and abandon residue, gained supernatant is Chimonanthus salicifolius water extract.
2. Chimonanthus salicifolius water extract is being prepared in chemotherapy of tumors process as the application alleviated in the medicine of the injury to alimentary tract that chemotherapeutics causes; The preparation method that Chimonanthus salicifolius water gets extract is pulverize after fresh Chimonanthus salicifolius stem and leaf being dried, solids is mixed by certain mass volume ratio with water, soak and boil 5-30 minute after 0.5-2 hour, filter and abandon residue, gained supernatant is Chimonanthus salicifolius water extract.
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| CN105395580A (en) * | 2015-12-24 | 2016-03-16 | 济南新时代医药科技有限公司 | Application of folium chimonanthi nitentis tablet to preparation of drug for inhibiting human colonadenocarcinoma cell line (HCT-8) cell proliferation |
| CN105663677A (en) * | 2016-02-03 | 2016-06-15 | 刘松军 | Traditional Chinese medicine composition for treating radiation gastritis |
| CN107260774A (en) * | 2017-05-27 | 2017-10-20 | 浙江华润三九众益制药有限公司 | The purposes of wax-cakes bait Genes For Plant Tolerance pathogenic infection |
| CN111481578A (en) * | 2019-01-26 | 2020-08-04 | 丽水学院 | Application of chimonanthus salicifolius ethyl acetate part in preparation of auxiliary anti-tumor medicine |
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