CN104815028A - Application of gold-edge rose extract to preparation of drug for preventing chemotherapy side effects, protecting intestinal mucosal barrier and/or improving body immunity - Google Patents
Application of gold-edge rose extract to preparation of drug for preventing chemotherapy side effects, protecting intestinal mucosal barrier and/or improving body immunity Download PDFInfo
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Abstract
The invention discloses application of a gold-edge rose extract to preparation of a drug for preventing chemotherapy side effects, protecting the intestinal mucosal barrier and/or improving the body immunity. Through establishing an irinotecan hydrochloride rat chemotherapy model and respectively injecting water and alcohol extracts of a gold-edge rose as well as imodium, glutamine and interleukin-2, the water or alcohol extract of the gold-edge rose has the effects of preventing chemotherapy side effects, protecting the intestinal mucosal barrier and improving the body immunity. Therefore, the water or alcohol extract of the gold-edge rose can be used for preparing the drug for preventing chemotherapy side effects, protecting the intestinal mucosal barrier and/or improving the body immunity. The invention finds the novel application of the gold-edge rose and provides a novel drug for treating chemotherapy side effects.
Description
Technical field
The present invention relates to the application of golden-rimmed Flos Rosae Rugosae, be specifically related to the application of golden-rimmed rose extract in the anti-chemotherapy side effect of preparation, protection intestinal mucosal barrier and/or raising immunity of organisms medicine.
Background technology
Cancer, also claims malignant tumor, is not normal by control growth and proliferation of cell mechanism and disease that is that cause.According to " world's cancer report in 2014 " display that WHO issues, whole world cancer burden constantly increases the weight of, and following 20 years annual new cancer cases will reach 2,200 ten thousand, and cancer mortality number will rise to 1,300 ten thousand examples the same period, as can be seen here, cancer has become the first killer affecting human health.Chemotherapy, as one of the essential therapeutic arsenals of malignant tumor, has been widely used in clinical.But chemotherapeutics is killing and wounding or while anticancer, normal tissue organ also has infringement or toxic action, therefore there is many side effect, such as gastrointestinal toxicity, Viscus toxicity, immunosuppressant etc., can cause accompanying infection and function of human body to die of exhaustion and die time serious.
Chemotherapeutics is while killing and wounding cancerous cell, the gastrointestinal mucosal that on cell proliferation is enlivened causes major injury, cause intestinal motive force obstacle and intestinal microecology dysequilibrium, and make intestinal mucosal barrier present imperfect connection, permeability increases, cell and tissue fluid moisture run off in a large number to enteric cavity, and cause diarrhoea, Chemotherapy-induced Diarrhea is up to 55.2%.Chemotherapeutics mostly generally is immunosuppressant, inhibitory action is in various degree had to body's immunity, also often Viscus toxicity is caused, such as Liver and kidney toxicity and splenatrophy etc., spleen is the important immune organ of body, the nutrient molecule caused after intestinal mucosal injury runs off, and splenatrophy and immunosuppressant in addition, exacerbates the immunologic function degression of body.Develop a kind of medicine of chemotherapy side effect, protection intestinal mucosa, raising immunity of organisms that can resist to be significant.
For chemotherapy side effect, mainly contain following several medicine at present: (1) anticholinergic agent.By the smooth muscle activity of cholinergic innervation after suppression receptor section, alleviate gastrointestinal convulsion, for Prophylactic chemotherapy acute diarrhea, representing medicine is atropine.But it easily causes paralytic ileus and is only limitted to the antidiarrheal agent for treating at chemotherapy initial stage.(2) opioid receptor agonist.By the μ-opiate receptor of exciting intestinal wall and the release of prevention acetylcholine and prostaglandin, antagonism smooth muscle contraction, and reduce enterokinesia and secretion, the holdup time extending intestinal contents reaches anti-diarrhea effect, and representing medicine is imodium.But because it suppresses enterokinesia, easily cause intestinal obstruction, cause tormina, and therapeutic effect is not had to the osmotic diarrhea caused because of intestinal mucosal injury.(3) adsorptivity diarrhea.As montmorillonite powder, there is fixing, inhibitory action to the toxin of the virus in digestive tract, pathogenic bacteria and generation thereof, have covering power to gastrointestinal mucosal, and by be combineding with each other with mucous glycoprotein, improve mucosal barrier to the defense function of attack factor.But it easily causes constipation, and maintenance effect be there is no to intestinal mucosa.(4) nutrient substance.Supplement immunostimulation and the nutrient to the nutritious maintenance effect of intestinal mucosa, as glutamine, arginine, phospholipid, unsaturated fatty acid, contribute to rebuilding intestinal mucosal barrier, protect its integrity, reduce the invasion and attack of pathogenic bacterium in enteric cavity.Glutamine is conditionally essential amino acid, can increase the absorption of intestinal to sodium and chlorine, and then increases intestinal to the absorption of moisture, be of value to diarrhoea patient, and the body nitrogen balance can improved under morbid state, maintain the normal permeability of intestinal, protection intestinal mucosal barrier; Arginine has nutrition and immunomodulating dual function, is the sercretogogue stimulating Some Hormones, can increases collage synthesis and wound healing, thus protection intestinal mucosal barrier.(5) probiotic bacteria.Intestinal microbial population has field planting and reproductive ability, the field planting of outer flora in intestinal and breeding can be stoped, wherein the colonization resistance of anaerobe to body has important function, thus is of value to the reparation of intestinal mucosal barrier, and conventional probiotic bacteria is lactobacillus and bacillus bifidus clinically; (6) Chinese medicine.Research report, Radix Et Rhizoma Rhei can promote a large amount of hypertrophy of goblet cell in intestinal mucosa, increases the secretion of mucus in enteric cavity, compact siro spinning technology between protection intestinal mucosa cells; Ligustrazine can protect gut barrier function after hemorrhagic shock-reperfusion.(7) immunostimulant.Recombinant human interleukin--2 is a kind of lymphokine, lymphopoiesis can be stimulated to break up, the secretion of inducing interferon and cytokine profiles, thus strengthens immunocompetence; Mannatide sheet, for the auxiliary treatment of immunologic hypofunction, recurrent respiratory tract infection, leukopenia and aplastic anemia and tumor, alleviates the side effect of Radiotherapy chemotherapy to hemopoietic system.But be used for the treatment of chemotherapy side effect, protection intestinal mucosa about golden-rimmed rose extract, improve in immunity of organisms, there is not been reported.
Summary of the invention
For the deficiencies in the prior art; the object of the present invention is to provide the application of golden-rimmed rose extract in the anti-chemotherapy side effect of preparation, protection intestinal mucosa and/or raising immunity of organisms medicine, make it have good curative effect with medicine prepared by golden-rimmed rose extract.
Object of the present invention is achieved through the following technical solutions:
Present invention finds golden-rimmed rose water extract or ethanol extract has anti-chemotherapy side effect, protects intestinal mucosal barrier and improve the effect of immunity of organisms, specific as follows:
(1) golden-rimmed rose water extract has the effect of anti-chemotherapy side effect
Per os of the present invention gives golden-rimmed rose water extract 5g/kg (with crude drug gauge, identical below), imodium (clinical chemotherapy antidiarrheal) 1.6mg/kg, continuous 8 days, lumbar injection irinotecan hydrochloride is adopted to set up mouse chemotherapy model therebetween, after administration in the 8th day, excrement particles number and character in record 30min, calculate the Scours index=loose stool rate ratio of total just number (every animal institute passage of loose stools number with) × loose stool level (to pollute with loose stool the size that filter paper forms stain area to define the level, be divided into 4 grades: 1 grade to be that pollution diameter is less than 1cm; 2 grades are polluted diameter 1-1.9cm; 3 grades are polluted diameter is 2-3cm; 4 grades are polluted diameter and are greater than 3cm), carry out charcoal end gavage after completing, put to death mice after 20min, dissect, measure small intestinal length and charcoal end advance distance, calculate charcoal end propelling rate (%)=(charcoal end advance distance cm/ small intestinal length cm) × 100.
Result display (Fig. 1), normal group mice, feces is moderate cylindric of hardness, moisture, and Scours index is 0.05 ± 0.16; Model group feces is shapeless, water sample loose stool state, and Scours index is 1.87 ± 0.77; Imodium group feces is shapeless, water sample loose stool state, and Scours index is 1.67 ± 0.85; Golden-rimmed rose water extract group feces is in normally having shape state, and slight rare soft, Scours index is 0.97 ± 0.54.Show the diarrhoea that golden-rimmed rose water extract effectively can be alleviated chemotherapy and causes, effect is better than clinical application imodium.
Result display (Fig. 2), normal group mice, charcoal end propelling rate is 65.30 ± 5.70; Model group charcoal end propelling rate is 14.21 ± 5.29; Imodium group, charcoal end propelling rate is 25.88 ± 7.81; Golden-rimmed rose water extract group, charcoal end propelling rate is 43.66 ± 4.82.Show that the intestinal motive force that golden-rimmed rose water extract can have efficient recovery chemotherapy to cause is not enough.
(2) golden-rimmed rose water extract has the effect of protection intestinal mucosal barrier
Per os of the present invention gives golden-rimmed rose water extract 5g/kg, glutamine 3g/kg, continuous 8 days, lumbar injection irinotecan hydrochloride is adopted to set up mouse chemotherapy model therebetween, mice is put to death in the 8th day, measure small intestinal weight and length, calculate small intestinal coefficient=small intestinal weight g/ small intestinal length cm, measure colon weight and length, calculate colon coefficient=colon weight g/ colon lengths cm.
Result display (Fig. 3), normal group mice, small intestinal coefficient is 0.0359 ± 0.0066g/cm, model group small intestinal coefficient is 0.0275 ± 0.0043g/cm, L-glutamine group small intestinal coefficient is 0.0301 ± 0.0061g/cm, and the small intestinal coefficient of golden-rimmed rose water extract group is 0.0315 ± 0.0024g/cm.Show that golden-rimmed rose water extract has the effect that protection mucous membrane of small intestine organizational structure is complete.
Result display (Fig. 3), normal group mice, colon coefficient is 0.0523 ± 0.0048g/cm, model group colon coefficient is 0.0360 ± 0.0042g/cm, L-glutamine group colon coefficient is 0.0450 ± 0.0078g/cm, and the colon coefficient of golden-rimmed rose water extract group is 0.0384 ± 0.0056g/cm.Show that golden-rimmed rose water extract has the trend of protection colon mucosa tissues structural integrity.
(3) golden-rimmed rose water extract has the effect improving immunity of organisms
The present invention gives golden-rimmed rose water extract 2g/kg through lumbar injection, and subcutaneous injection gives interleukin II, and amount is 5 × 10
4iU/kg, continuous 8 days, lumbar injection irinotecan hydrochloride is adopted to set up mouse chemotherapy model therebetween, took Mouse Weight in the 8th day, cervical dislocation is put to death, and dissects, take liver,kidney,spleen weight respectively, calculate the heavy g/ body weight g of liver index=liver, the heavy g/ body weight g of renal index=kidney, the heavy g/ body weight g*100 of index and spleen index=kidney.
Result display (Fig. 4), the liver index of normal group mice is 0.0441 ± 0.0054, model group liver index is 0.0572 ± 0.0049, and the liver index of interleukin II group is 0.0510 ± 0.0058, and the liver index of golden-rimmed rose water extract group is 0.0492 ± 0.0042.Show that golden-rimmed rose water extract is effective in alleviation hepatotoxicity.
Result display (Fig. 4), the renal index of normal group mice is 0.0121 ± 0.0018, model group renal index is 0.0160 ± 0.0013, and the renal index of interleukin II group is 0.0147 ± 0.0025, and the renal index of golden-rimmed rose water extract group is 0.0140 ± 0.0017.Show that golden-rimmed rose water extract is effective in alleviation Toxicity of Kidney.
Result display (Fig. 5), the index and spleen index of the every 100g body weight of normal group mice is 0.355 ± 0.057, model group index and spleen index is 0.207 ± 0.031, and the index and spleen index of interleukin II group is 0.256 ± 0.043, and the index and spleen index of golden-rimmed rose water extract group is 0.221 ± 0.023.Show that golden-rimmed rose water extract can alleviate splenatrophy, enlighten golden-rimmed rose water extract has effect in raising immunity of organisms.
(4) golden-rimmed rhodinol extract has the effect of anti-chemotherapy side effect
Per os of the present invention gives golden-rimmed rhodinol extract 5g/kg, imodium (clinical chemotherapy antidiarrheal) 1.6mg/kg, continuous 8 days, lumbar injection irinotecan hydrochloride is adopted to set up mouse chemotherapy model therebetween, after administration in the 8th day, excrement particles number and character in record 30min, calculate the Scours index=loose stool rate ratio of total just number (every animal institute passage of loose stools number with) × loose stool level (to pollute with loose stool the size that filter paper forms stain area to define the level, be divided into 4 grades: 1 grade to be that pollution diameter is less than 1cm; 2 grades are polluted diameter 1-1.9cm; 3 grades are polluted diameter is 2-3cm; 4 grades are polluted diameter and are greater than 3cm), carry out charcoal end gavage after completing, put to death mice after 20min, dissect, measure small intestinal length and charcoal end advance distance, calculate charcoal end propelling rate (%)=(charcoal end advance distance cm/ small intestinal length cm) × 100.
Result display (Fig. 1), normal group mice, feces is moderate cylindric of hardness, moisture, and Scours index is 0.05 ± 0.16; Model group feces is shapeless, water sample loose stool state, and Scours index is 1.87 ± 0.77; Imodium group feces is shapeless, water sample loose stool state, and Scours index is 1.67 ± 0.85; Golden-rimmed rhodinol extract group feces is in normally having shape state, and slight rare soft, Scours index is 1.23 ± 0.52.Show the diarrhoea that golden-rimmed rhodinol extract effectively can be alleviated chemotherapy and causes, effect is better than clinical application imodium.
Result display (Fig. 2), normal group mice, charcoal end propelling rate is 65.30 ± 5.70; Model group charcoal end propelling rate is 14.21 ± 5.29; Imodium group, charcoal end propelling rate is 25.88 ± 7.81; Golden-rimmed rhodinol extract group, charcoal end propelling rate is 36.48 ± 7.79.Show that the intestinal motive force that golden-rimmed rhodinol extract can have efficient recovery chemotherapy to cause is not enough.
(5) golden-rimmed rhodinol extract has the effect of protection intestinal mucosal barrier
Per os of the present invention gives golden-rimmed rhodinol extract 5g/kg, glutamine 3g/kg, continuous 8 days, lumbar injection irinotecan hydrochloride is adopted to set up mouse chemotherapy model therebetween, mice is put to death in the 8th day, measure small intestinal weight and length, calculate small intestinal coefficient=small intestinal weight g/ small intestinal length cm, measure colon weight and length, calculate colon coefficient=colon weight g/ colon lengths cm.
Result display (Fig. 3), normal group mice, small intestinal coefficient is 0.0359 ± 0.0066g/cm, model group small intestinal coefficient is 0.0275 ± 0.0043g/cm, L-glutamine group small intestinal coefficient is 0.0301 ± 0.0061g/cm, and the small intestinal coefficient of golden-rimmed rhodinol extract group is 0.0285 ± 0.0036g/cm.Show that golden-rimmed rhodinol extract has the effect that protection mucous membrane of small intestine organizational structure is complete.
Result display (Fig. 3), normal group mice, colon coefficient is 0.0523 ± 0.0048g/cm, model group colon coefficient is 0.0360 ± 0.0042g/cm, L-glutamine group colon coefficient is 0.0450 ± 0.0078g/cm, and the colon coefficient of golden-rimmed rhodinol extract group is 0.0413 ± 0.0022g/cm.Show that golden-rimmed rhodinol extract has the effect of protection colon mucosa tissues structural integrity.
(6) golden-rimmed rhodinol extract has the effect improving immunity of organisms
The present invention gives golden-rimmed rhodinol extract 2g/kg through lumbar injection, and subcutaneous injection gives interleukin II, and amount is 5 × 10
4iU/kg, continuous 8 days, lumbar injection irinotecan hydrochloride is adopted to set up mouse chemotherapy model therebetween, took Mouse Weight in the 8th day, cervical dislocation is put to death, and dissects, take liver,kidney,spleen weight respectively, calculate the heavy g/ body weight g of liver index=liver, the heavy g/ body weight g of renal index=kidney, the heavy g/ body weight g*100 of index and spleen index=spleen.
Result display (Fig. 4), the liver index of normal group mice is 0.0441 ± 0.0054, model group liver index is 0.0572 ± 0.0049, and the liver index of interleukin II group is 0.0510 ± 0.0058, and the liver index of golden-rimmed rhodinol extract group is 0.0485 ± 0.0055.Show that golden-rimmed rhodinol extract is effective in alleviation hepatotoxicity.
Result display (Fig. 4), the renal index of normal group mice is 0.0121 ± 0.0018, model group renal index is 0.0160 ± 0.0013, and the renal index of interleukin II group is 0.0147 ± 0.0025, and the renal index of golden-rimmed rhodinol extract group is 0.0152 ± 0.0030.Show that golden-rimmed rhodinol extract is effective in alleviation Toxicity of Kidney.
Result display (Fig. 5), the index and spleen index of the every 100g body weight of normal group mice is 0.355 ± 0.057, model group index and spleen index is 0.207 ± 0.031, and the index and spleen index of interleukin II group is 0.256 ± 0.043, and the index and spleen index of golden-rimmed rhodinol extract group is 0.129 ± 0.028.Show that golden-rimmed rhodinol extract cannot alleviate splenatrophy, splenatrophy symptom can be increased the weight of on the contrary.
Based on the above results, the invention provides the application of golden-rimmed Flos Rosae Rugosae in the anti-chemotherapy side effect of preparation, protection intestinal mucosa and/or raising immunity of organisms medicine.
Present invention also offers the application of golden-rimmed rose extract in the anti-chemotherapy side effect of preparation, protection intestinal mucosa and/or raising immunity of organisms medicine.Described golden-rimmed rose extract is: golden-rimmed rose water extract or golden-rimmed rhodinol extract.
The preparation of described golden-rimmed rose water extract comprises following steps: decoct with water after being pulverized by golden-rimmed Flos Rosae Rugosae, filter, concentrated.The preparation of described golden-rimmed rhodinol extract comprises following steps: add the ethanol extraction that concentration range is 70%-95% after being pulverized by golden-rimmed Flos Rosae Rugosae, filter, concentrated.
A kind of anti-chemotherapy side effect, protection intestinal mucosa and/or raising immunity of organisms medicine, comprise golden-rimmed rose extract, also comprise the adjuvant pharmaceutically allowed.The dosage form of described medicine is preferably oral formulations or ejection preparation.
Present invention finds the purposes that golden-rimmed Flos Rosae Rugosae is new, the treatment for chemotherapy side effect provides new medicine.
Accompanying drawing explanation
Fig. 1 is that golden-rimmed rose water extract, ethanol extract are on the impact of chemotherapeutic diarrhoea and and the comparative result figure of imodium.In figure,
##p<0.01, has pole significant difference compared with normal group; * p<0.05, has significant difference compared with model group.
Fig. 2 is that golden-rimmed rose water extract, ethanol extract are on the impact of intestinal motive force after chemotherapy and and the comparative result figure of imodium.In figure,
##p<0.01, has pole significant difference compared with normal group; * p<0.01, has pole significant difference compared with model group.
Fig. 3 is that golden-rimmed rose water extract, ethanol extract are on the impact of small intestinal, colon coefficient and and the comparative result figure of glutamine.In figure, small intestinal coefficient:
##p<0.01, has pole significant difference compared with normal group; * p<0.05, has significant difference compared with model group.Colon coefficient:
aap<0.01, has pole significant difference compared with normal group;
bp<0.05,
bbp<0.01 has significance, pole significant difference compared with model group.
Fig. 4 is that golden-rimmed rose water extract, ethanol extract are on the impact of liver, kidney and and the comparative result figure of interleukin II.In figure, liver index:
##p<0.01, has pole significant difference compared with normal group; * p<0.05, * * p<0.01 has significance, pole significant difference compared with model group.Renal index:
aap<0.01, has pole significant difference compared with normal group;
bp<0.05, has significant difference compared with model group.
Fig. 5 is that golden-rimmed rose water extract, ethanol extract are on the impact of spleen and and the comparative result figure of interleukin II.In figure,
##p<0.01, has pole significant difference compared with normal group; * p<0.05, * * p<0.01 has significance, pole significant difference compared with model group.
Detailed description of the invention
Following examples are used for further illustrating content of the present invention, but should not be construed as limitation of the present invention, and without departing from the spirit and substance of the case in the present invention, the amendment do the inventive method, step or condition or replacement all belong to scope of the present invention.
Embodiment 1
Golden-rimmed rose water extract compositions injects water to 1000mL, subpackage 500 by the golden-rimmed Flos Rosae Rugosae of 100g.Preparation method is: take golden-rimmed Flos Rosae Rugosae 100g, and pulverize, adding distil water 1000mL decocts 2h, repeats 3 times, merges decoction liquor, filters, is concentrated into 100mL.4 DEG C of cold preservations make contamination precipitation, filter, add the water for injection of sterilizing to 1000mL, 4 DEG C of refrigerated overnight, take out, are placed to room temperature, sucking filtration, filtrate phosphoric acid and phosphate regulate pH to 5.8 ~ 6.2, then add activated carbon decolorizing, stirring at room temperature 10min, filters, adds sterilized water for injection to full dose, with 0.22 μm of microporous filter membrane fine straining, embedding, sterilizing subpackage, often props up containing golden-rimmed rose water extract 200mg.
Embodiment 2
Golden-rimmed rose water extract compositions makes 1000 by the golden-rimmed Flos Rosae Rugosae of 100g, starch 35g, dextrin 75g, magnesium stearate 2g, Pulvis Talci 6g, 70% appropriate amount of ethanol.Preparation method: take golden-rimmed Flos Rosae Rugosae 100g, pulverize, adding distil water 1000mL decocts 2h, repeats 3 times, merges decoction liquor, filters, is condensed into extractum, adds supplementary product starch, dextrin mixing, crosses 40 mesh sieve and make mix homogeneously three times.That is disperseed by appropriate 70% ethanol pours mixed-powder into, mix homogeneously as far as possible, and make soft material, make wet grain by 18-20 mesh sieve, 40-60 DEG C of drying, dry granular moisture Control is below 1.5%.With 18-20 mesh sieve granulate, mix, calculated weight with magnesium stearate, Pulvis Talci, measure content, then tabletting or fill capsule, every (sheet) is containing golden-rimmed rose water extract 100mg.
Embodiment 3
Golden-rimmed rhodinol extract compositions injects water to 1000mL, subpackage 500 by the golden-rimmed Flos Rosae Rugosae of 100g.Preparation method is: take golden-rimmed Flos Rosae Rugosae 100g, pulverizes, and adds 95% ethanol 1000mL and extracts 3h, repeat 3 times, merge extractive liquid, filter, be concentrated into ethanol and all volatilize.4 DEG C of cold preservations make contamination precipitation, filter, add the water for injection of sterilizing to 1000mL, 4 DEG C of refrigerated overnight, take out, are placed to room temperature, sucking filtration, filtrate phosphoric acid and phosphate regulate pH to 5.8 ~ 6.2, then add activated carbon decolorizing, stirring at room temperature 10min, filters, adds sterilized water for injection to full dose, with 0,22 μm of microporous filter membrane fine straining, embedding, sterilizing subpackage, often props up containing golden-rimmed rhodinol extract 200mg.
Embodiment 4
Golden-rimmed rhodinol extract compositions makes 1000 by the golden-rimmed Flos Rosae Rugosae of 100g, starch 35g, dextrin 75g, magnesium stearate 2g, Pulvis Talci 6g, 70% appropriate amount of ethanol.Preparation method: take golden-rimmed Flos Rosae Rugosae 100g, pulverizes, and adds 95% ethanol 1000mL and extracts 3h, repeat 3 times, merge extractive liquid, filter, be condensed into extractum, adds supplementary product starch, dextrin mixing, crosses 40 mesh sieve and make mix homogeneously three times.That is disperseed by appropriate 70% ethanol pours mixed-powder into, mix homogeneously as far as possible, and make soft material, make wet grain by 18-20 mesh sieve, 40-60 DEG C of drying, dry granular moisture Control is below 1.5%.With 18-20 mesh sieve granulate, mix, calculated weight with magnesium stearate, Pulvis Talci, measure content, then tabletting or fill capsule, every (sheet) is containing golden-rimmed rhodinol extract 100mg.
Embodiment 5
The present embodiment selects golden-rimmed rose water extract, ethanol extract as anti-chemotherapy side effect medicine, by setting up irinotecan hydrochloride mouse chemotherapy model, inquire into golden-rimmed rose water extract and ethanol extract to chemotherapeutic diarrhoea and the hypodynamic therapeutical effect of enterocinesia, be intended to the anti-chemotherapy side effect novel drugs selecting a kind of determined curative effect, few side effects.
1, materials and methods
(1) medicine and reagent
Golden-rimmed Flos Rosae Rugosae: Kunming branch company of Xin Gou commerce and trade company limited first; Irinotecan hydrochloride: Jiangsu Yutian Bio-Pharmaceutical Technology Co., Ltd., lot number 140801; Imodium: Xian-Janssen Pharmaceutical Ltd., lot number 140709510; Dehydrated alcohol, Chemical Reagent Co., Ltd., Sinopharm Group, lot number 20140414.
(2) animal and feedstuff
SPF level KM mice, body weight 20-22g, Wuhan University's animal experimental center provides, and the animal quality certification number is NO.42000500001804, production licence number: SCXK (Hubei Province) 2008-2004.Mus feedstuff, is purchased from Wuhan University's Experimental Animal Center.
2, experimental technique
(1) experimental drug preparation
Golden-rimmed rose water extract (5g/kg): take golden-rimmed Flos Rosae Rugosae 12.5g, pulverize, adding distil water 125mL decocts 2h, repeats 3 times, merges decoction liquor, filters, is concentrated into 12.5mL.4 DEG C of cold preservations make magazine precipitate, and filter, add distilled water to 50mL, 4 DEG C of refrigerated overnight, take out, are placed to room temperature, sucking filtration, and filtrate is the golden-rimmed rose water extract 5g/kg group of experiment.
Golden-rimmed rhodinol extract (5g/kg): take golden-rimmed Flos Rosae Rugosae 12.5g, pulverizes, and adds 95% ethanol 125mL and extracts 3h, repeat 3 times, merge extractive liquid, filter, be concentrated into ethanol and all volatilize.4 DEG C of cold preservations make contamination precipitation, filter, add distilled water to 50mL, 4 DEG C of refrigerated overnight, take out, are placed to room temperature, sucking filtration, and filtrate is the golden-rimmed rhodinol extract 5g/kg group of experiment.
Imodium (1.6mg/kg): take 4mg imodium, grind into powder, adds 50mL distilled water, is prepared into imodium suspension stand-by.
Irinotecan hydrochloride (3.75mg/mL): take 0.375g irinotecan hydrochloride powder, adds 60mL 5% glucose solution, stirs, add 20g propylene glycol, stir, then add 0.5g tween 80, finally be settled to 100mL with 5% glucose solution, the system that stirs is to clarification.
(2) animal grouping and modeling
Mice random packet: normal group, model group, model+imodium group (imodium dosage 1.6mg/kg), model+golden-rimmed rose water extract group (golden-rimmed rose water extract dosage 5g/kg), model+golden-rimmed rhodinol extract group (golden-rimmed rhodinol extract dosage 5g/kg).Each group all adopts gastric infusion, and dosage is 0.2mL/10g b.w., every day 1 time, continuous 8 days, normal group and the isodose distilled water of model group gavage.2nd day starts, and the solution except normal group lumbar injection is except 5% glucose solution, all the other respectively group all before administration 30min give lumbar injection 75mg/kg irinotecan hydrochloride, dosage is 0.2mL/10g b.w., continuous 4 days, prepares mouse chemotherapy model.
(3) Testing index
1) Scours index: after administration in the 8th day, excrement particles number and character in record 30min, calculate the Scours index=loose stool rate ratio of total just number (every animal institute passage of loose stools number with) × loose stool level (to pollute with loose stool the size that filter paper forms stain area to define the level, be divided into 4 grades: 1 grade to be that pollution diameter is less than 1cm; 2 grades are polluted diameter 1-1.9cm; 3 grades are polluted diameter is 2-3cm; 4 grades are polluted diameter and are greater than 3cm; ), without loose stool, loose stool rate is 0, and loose stool level is blank, and Scours index is 0.
2) charcoal end propelling rate: after the 8th day administration 30min, carry out 5% charcoal end aqueous solution gavage, dosage is 0.1mL/10g b.w., after 20min, cervical dislocation puts to death mice, dissect, measure small intestinal length and charcoal end advance distance, calculate charcoal end propelling rate (%)=(charcoal end advance distance cm/ small intestinal length cm) × 100.
3, experimental result
(1) golden-rimmed rose water extract, ethanol extract to the mitigation of chemotherapeutic diarrhoea and with the comparing of imodium effect
Result is as shown in Figure 1: normal group mice, and feces is moderate cylindric of hardness, moisture, and Scours index is 0.05 ± 0.16; Model group feces is shapeless, water sample loose stool state, and Scours index is 1.87 ± 0.77; Imodium group feces is shapeless, water sample loose stool state, and Scours index is 1.67 ± 0.85; Golden-rimmed rose water extract group feces is in normally having shape state, and slight rare soft, Scours index is 0.97 ± 0.54; Golden-rimmed rhodinol extract group feces is in normally having shape state, and slight rare soft, Scours index is 1.23 ± 0.52.Show the diarrhoea that golden-rimmed rose water extract, ethanol extract all effectively can be alleviated chemotherapy and cause, effect is better than clinical application imodium, and water extract is better than ethanol extract.
(2) golden-rimmed rose water extract, ethanol extract to chemotherapy cause the hypodynamic therapeutical effect of enterocinesia and with the comparing of imodium
Result is as shown in Figure 2: normal group mice, and charcoal end propelling rate is 65.30 ± 5.70; Model group charcoal end propelling rate is 14.21 ± 5.29; Imodium group, charcoal end propelling rate is 25.88 ± 7.81; Golden-rimmed rose water extract group, charcoal end propelling rate is 43.66 ± 4.82; Golden-rimmed rhodinol extract group, charcoal end propelling rate is 36.48 ± 7.79.Show that the intestinal motive force that golden-rimmed rose water extract, ethanol extract all can have efficient recovery chemotherapy to cause is not enough.
4, experiment conclusion
The diarrhoea that golden-rimmed rose water extract, ethanol extract produce after all can effectively alleviating chemotherapy; effect is better than clinical application imodium; the intestinal motive force that golden-rimmed rose water extract, ethanol extract can also have efficient recovery chemotherapy to cause is not enough; and water extract is better than ethanol extract; disclose life-time service chemotherapy diarrhea imodium can aggravate to suppress enterokinesia simultaneously; cause intestinal obstruction, so the medicine researching and developing a kind of intestinal mucosa protection type is significant to chemotherapy metenteron side effect such as diarrhoea and intestinal motive force deficiencies.
Embodiment 6
The present embodiment selects golden-rimmed rose water extract, ethanol extract as the medicine inquiring into the effect of protection intestinal mucosal barrier; by setting up intestinal mucosal injury model after irinotecan hydrochloride mouse chemotherapy, inquire into golden-rimmed rose water extract and ethanol extract to the maintenance effect of intestinal mucosal injury.
1, materials and methods
(1) medicine and reagent
Golden-rimmed Flos Rosae Rugosae: Kunming branch company of Xin Gou commerce and trade company limited first; Irinotecan hydrochloride: Jiangsu Yutian Bio-Pharmaceutical Technology Co., Ltd., lot number 140801; Glutamine: Zhengzhou Ta Bai commerce and trade company limited; Dehydrated alcohol, Chemical Reagent Co., Ltd., Sinopharm Group, lot number 20140414.
(2) animal and feedstuff
SPF level KM mice, body weight 20-22g, Wuhan University's animal experimental center provides, and the animal quality certification number is NO.42000500001804, production licence number: SCXK (Hubei Province) 2008-2004.Mus feedstuff, is purchased from Wuhan University's Experimental Animal Center.
2, experimental technique
(1) experimental drug preparation:
Golden-rimmed rose water extract (5g/kg): take golden-rimmed Flos Rosae Rugosae 12.5g, pulverize, adding distil water 125mL decocts 2h, repeats 3 times, merges decoction liquor, filters, is concentrated into 12.5mL.4 DEG C of cold preservations make magazine precipitate, and filter, add distilled water to 50mL, 4 DEG C of refrigerated overnight, take out, are placed to room temperature, sucking filtration, and filtrate is the golden-rimmed rose water extract 5g/kg group of experiment.
Golden-rimmed rhodinol extract (5g/kg): take golden-rimmed Flos Rosae Rugosae 12.5g, pulverizes, and adds 95% ethanol 125mL and extracts 3h, repeat 3 times, merge extractive liquid, filter, be concentrated into ethanol and all volatilize.4 DEG C of cold preservations make contamination precipitation, filter, add distilled water to 50mL, 4 DEG C of refrigerated overnight, take out, are placed to room temperature, sucking filtration, and filtrate is the golden-rimmed rhodinol extract 5g/kg group of experiment.
Glutamine (3g/kg): take 7.5g glutamine, adds 50mL distilled water, and mixing, is prepared into glutamine suspension stand-by.
Irinotecan hydrochloride (3.75mg/mL): take 0.375g irinotecan hydrochloride powder, adds 60mL 5% glucose solution, stirs, add 20g propylene glycol, stir, then add 0.5g tween 80, finally be settled to 100mL with 5% glucose solution, the system that stirs is to clarification.
(2) animal grouping and modeling
Mice random packet: normal group, model group, model+L-glutamine group (glutamine dosage 3g/kg), model+golden-rimmed rose water extract group (golden-rimmed rose water extract dosage 5g/kg), model+golden-rimmed rhodinol extract group (golden-rimmed rhodinol extract dosage 5g/kg).Each group all adopts gastric infusion, and dosage is 0.2mL/10g b.w., every day 1 time, continuous 8 days, normal group and the isodose distilled water of model group gavage.2nd day starts, solution except normal group lumbar injection is except 5% glucose solution, all the other respectively group all before administration 30min give lumbar injection 75mg/kg irinotecan hydrochloride, dosage is 0.2mL/10g b.w., continuous 4 days, prepare intestinal mucosal injury model after mouse chemotherapy.
(3) Testing index
Small intestinal, colon coefficient: after the 8th day administration 1h, cervical dislocation puts to death mice, dissects, measure small intestinal weight and length, calculate small intestinal coefficient=small intestinal weight g/ small intestinal length cm, measure colon weight and length, calculate colon coefficient=colon weight g/ colon lengths cm.
3, experimental result
Golden-rimmed rose water extract, ethanol extract to the protective effect of intestinal mucosal barrier structure and with the comparing of glutamine effect
Result is as shown in Figure 3: normal group mice, and small intestinal coefficient is 0.0359 ± 0.0066g/cm, and colon coefficient is 0.0523 ± 0.0048g/cm; Model group small intestinal coefficient is 0.0275 ± 0.0043g/cm, and colon coefficient is 0.0360 ± 0.0042g/cm; L-glutamine group small intestinal coefficient is 0.0301 ± 0.0061g/cm, and colon coefficient is 0.0450 ± 0.0078g/cm; The small intestinal coefficient of golden-rimmed rose water extract group is 0.0315 ± 0.0024g/cm, and colon coefficient is 0.0384 ± 0.0056g/cm; The small intestinal coefficient of golden-rimmed rhodinol extract group is 0.0285 ± 0.0036g/cm, and colon coefficient is 0.0413 ± 0.0022g/cm.Show golden-rimmed rose water extract, ethanol extract have protection small intestinal, colon mucosa tissues structural integrity effect.
4, experiment conclusion
The intestinal mucosal permeability that golden-rimmed rose water extract, ethanol extract can effectively improve caused by chemotherapy increases; the structural intergrity of protection intestinal mucosal barrier; wherein water extract effect in mucous membrane of small intestine protection is better; ethanol extract is better to mucous membrane of colon protection, is the mucosa protective agent with important research and development significance.
Embodiment 7
The present embodiment selects golden-rimmed rose water extract, ethanol extract as inquiring into the medicine strengthening immunization, by setting up irinotecan hydrochloride mouse chemotherapy model, study the influence of Liver and kidney toxicity that golden-rimmed rose water extract and ethanol extract cause chemotherapy and splenatrophy.
1, materials and methods
(1) medicine and reagent
Golden-rimmed Flos Rosae Rugosae: Kunming branch company of Xin Gou commerce and trade company limited first; Irinotecan hydrochloride: Jiangsu Yutian Bio-Pharmaceutical Technology Co., Ltd., lot number 140801; Injection RhIL-2, specification 500,000 IU/0.4mL/ bottle, Beijing Sihuan Biopharmaceutical Co., Ltd.; Dehydrated alcohol, Chemical Reagent Co., Ltd., Sinopharm Group, lot number 20140414.
(2) animal and feedstuff
SPF level KM mice, body weight 20-22g, Wuhan University's animal experimental center provides, and the animal quality certification number is NO.42000500001804, production licence number: SCXK (Hubei Province) 2008-2004.Mus feedstuff, is purchased from Wuhan University's Experimental Animal Center.
2, experimental technique
(1) experimental drug preparation:
Golden-rimmed rose water extract (2g/kg): take golden-rimmed Flos Rosae Rugosae 5g, add sterilized water for injection to 50mL, method is shown in embodiment 1.
Golden-rimmed rhodinol extract (2g/kg): take golden-rimmed Flos Rosae Rugosae 5g, add sterilized water for injection to 50mL, method is shown in embodiment 3.
Interleukin-2 (50000IU/kg): the interleukin-2 drawing 0.12mL, is diluted to 30mL with sterile saline stand-by.
Irinotecan hydrochloride (3.75mg/mL): take 0.375g irinotecan hydrochloride powder, adds 60mL 5% glucose solution, stirs, add 20g propylene glycol, stir, then add 0.5g tween 80, finally be settled to 100mL with 5% glucose solution, the system that stirs is to clarification.
(2) animal grouping and modeling
Mice random packet: normal group, model group, model+injection RhIL-2 group (RhIL-2 dosage 50000IU/kg), model+golden-rimmed rose water extract group (golden-rimmed rose water extract dosage 2g/kg), model+golden-rimmed rhodinol extract group (golden-rimmed rhodinol extract dosage 2g/kg).Normal group, model group intraperitoneal injection of saline, golden-rimmed rose extract group intraperitoneal injection, dosage is 0.2mL/10g b.w., and positive controls gives subcutaneous injection RhIL-2, and dosage is 0.1mL/10g b.w., every day 1 time, continuous 8 days.2nd day starts, and the solution except normal group lumbar injection is except 5% glucose solution, all the other respectively group all before administration 30min give lumbar injection 75mg/kg irinotecan hydrochloride, dosage is 0.2mL/10gb.w., continuous 4 days, prepares mouse chemotherapy model.
(3) Testing index
1) liver, renal index: 1h takes Mouse Weight after administration in the 8th day, cervical dislocation is put to death, and dissects, takes liver, kidney weight, calculates liver index=liver weight g/ body weight g, renal index=kidney weight g/ body weight g.
2) index and spleen index: take spleen weight, calculates index and spleen index=spleen weight g/ body weight g*100.
3, experimental result
(1) golden-rimmed rose water extract, ethanol extract to the mitigation of Liver and kidney toxicity and with the comparing of interleukin II effect
Result is as shown in Figure 4: the liver index of normal group mice is 0.0441 ± 0.0054, and renal index is 0.0121 ± 0.0018; Model group liver index is 0.0572 ± 0.0049, and renal index is 0.0160 ± 0.0013; The liver index of interleukin II group is 0.0510 ± 0.0058, and renal index is 0.0147 ± 0.0025; The liver index of golden-rimmed rose water extract group is 0.0492 ± 0.0042, and renal index is 0.0140 ± 0.0017; The liver index of golden-rimmed rhodinol extract group is 0.0485 ± 0.0055, and renal index is 0.0152 ± 0.0030.Show that golden-rimmed rose water extract, ethanol extract are effective in alleviation hepatotoxicity, Toxicity of Kidney.
(2) golden-rimmed rose water extract, ethanol extract to the mitigation of splenatrophy and with the comparing of interleukin II effect
Result is as shown in Figure 5: the index and spleen index of the every 100g body weight of normal group mice is 0.355 ± 0.057, model group index and spleen index is 0.207 ± 0.031, the index and spleen index of interleukin II group is 0.256 ± 0.043, the index and spleen index of golden-rimmed rose water extract group is 0.221 ± 0.023, and the index and spleen index of golden-rimmed rhodinol extract group is 0.129 ± 0.028.Show that golden-rimmed rose water extract can alleviate splenatrophy, and ethanol extract can increase the weight of splenatrophy symptom, enlighten golden-rimmed rose water extract has effect in raising immunity of organisms.
4, experiment conclusion
Golden-rimmed rose water extract, ethanol extract all have good result in alleviation hepatotoxicity, Toxicity of Kidney, in addition, golden-rimmed rose water extract also can alleviate splenatrophy, but golden-rimmed rhodinol extract can increase the weight of splenatrophy symptom, enlighten golden-rimmed rose water extract more effective in raising immunity of organisms, and ethanol extract because of effectively and harmful components fail to understand, need more deep research.
Claims (8)
1. the application of golden-rimmed Flos Rosae Rugosae in the anti-chemotherapy side effect of preparation, protection intestinal mucosa and/or raising immunity of organisms medicine.
2. the application of golden-rimmed rose extract in the anti-chemotherapy side effect of preparation, protection intestinal mucosa and/or raising immunity of organisms medicine.
3. application according to claim 2, is characterized in that: described golden-rimmed rose extract is: golden-rimmed rose water extract or golden-rimmed rhodinol extract.
4. application according to claim 3, is characterized in that: the preparation of described golden-rimmed rose water extract comprises following steps: decoct with water after being pulverized by golden-rimmed Flos Rosae Rugosae, filter, concentrated.
5. application according to claim 3, is characterized in that: the preparation of described golden-rimmed rhodinol extract comprises following steps: add 70-95% ethanol extraction after being pulverized by golden-rimmed Flos Rosae Rugosae, filter, concentrated.
6. anti-chemotherapy side effect, protection intestinal mucosa and/or a raising immunity of organisms medicine, is characterized in that: comprise golden-rimmed rose extract.
7. anti-chemotherapy side effect according to claim 6, protection intestinal mucosa and/or raising immunity of organisms medicine, is characterized in that: containing comprising the adjuvant pharmaceutically allowed.
8. the medicine according to claim 6 or 7, is characterized in that: dosage form is oral formulations or ejection preparation.
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Application publication date: 20150805 |