CN109620828A - Method for establishing model, model and the application of chemotherapy metenteron adverse reaction - Google Patents
Method for establishing model, model and the application of chemotherapy metenteron adverse reaction Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/0004—Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
- A61K49/0008—Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure
Abstract
The present invention provides method for establishing model, model and the applications of a kind of chemotherapy metenteron adverse reaction, are related to pharmaceutical technology field.Then the method for establishing model of the chemotherapy metenteron adverse reaction carries out chemotherapy processing to animal tumor model according to the dosage filtered out, obtains the model of chemotherapy metenteron adverse reaction by the dosage of screening chemotherapeutics；The dosage for wherein screening chemotherapeutics includes carrying out intestines toxicity assessment to the animal tumor model by chemotherapeutics processing, obtains animal tumor model and dosage of the alimentary canal with adverse reaction when occurs.The gastral ill symptoms that the model that this method obtains occurs are as caused by chemotherapeutics, when being therefore used to research and develop the drug for alleviating the adverse reaction of chemotherapy metenteron for this kind of model, the symptom of model is conducive to the mechanism for accurately filtering out the alleviation chemotherapy metenteron adverse reaction for the drug that drug is filtered out with research closer to actual pathological phenomenon.
Description
Technical field
The present invention relates to pharmaceutical technology fields, more particularly, to a kind of model foundation side of chemotherapy metenteron adverse reaction
Method, model and application.
Background technique
Colon cancer is the most common malignant tumour of alimentary system, and main happening part is that rectum and sigmoid colon join
Place.In recent years, colon cancer accounts for the 4th of cancer morbidity in European and American developed countries' disease incidence, and the death rate is second.With
Living-pattern preservation, China's colorectal cancer patients quantity constantly increase, and acute epidemiology statistics are rapid with annual 4.2% speed
Increase, average annual new hair colon cancer cases are more than 170,000, and even more than global average incremental is horizontal, come malignant tumour and lethal disease
The 4th of cause, it has also become threaten one of the malignant tumour of our people's health.The pathogenic factor of colon cancer is not yet complete
It illustrates, leading to the pathogenic factors of colon cancer mainly includes the factors such as environment, heredity, disease, and the occurrence and development of colon cancer are often
The interactive result of multifactor, multi-step, internal and external reasons.
Currently, the matter of utmost importance that treatment of cancer is faced is exactly effective treatment of local recurrence cancer and controlling for metastatic carcinoma
It treats.The primary goal for the treatment of is the removal lesion tissue by surgery, depending on the severity of disease, further auxiliaryization
Treatment or radiotherapy.According to NCCI clinical treatment in 2017, for treatment of colon cancer scheme there are several types of: 5- fluorine urine is phonetic
Pyridine/LV, capecitabine, capecitabine+oxaliplatin, FOLFIRI scheme (5 FU 5 fluorouracil+Irinotecan+LV), the side FOLFOX
Case (LV+5FU+ oxaliplatin), FOLFOXIRI scheme (LV+5FU+ oxaliplatin), Irinotecan etc..In numerous treatment sides
In case, with 5 FU 5 fluorouracil, Irinotecan, three kinds of chemotherapeutics of oxaliplatin frequency of use highest, these chemotherapeutics are treating
It, can be along with serious gastrointestinal tract toxic side effect: DNA alkylating agents chemotherapy medicine, such as cis-platinum, cyclophosphamide and Austria when colon cancer
Husky benefit platinum includes that can cause nausea,vomiting,diarrhea or constipation to gastrointestinal tract toxic side effect；Antimetabolite based chemotherapy medicine such as 5- fluorine
Uracil, capecitabine, gemcitabine and methotrexate (MTX) to gastrointestinal tract toxic side effect include can cause nausea,vomiting,diarrhea or
Abdominal pain；Topoisomerase enzyme inhibitor Irinotecan includes that can cause Nausea and vomiting and violent delay to gastrointestinal tract toxic side effect
Property diarrhea.Toxic side effect not only influences life in patients, but will limit the therapeutic effect of chemotherapeutic.Therefore a kind of make is established
The model of side effect of digestive tract after carrying out chemotherapy with chemotherapeutic is to the medicine for developing the side effect of digestive tract after alleviating chemotherapy
Object is highly important.
In view of this, the present invention is specifically proposed.
Summary of the invention
The first object of the present invention is to provide a kind of method for establishing model of chemotherapy metenteron adverse reaction；The present invention
Second be designed to provide a kind of model that the method for establishing model using above-mentioned chemotherapy metenteron adverse reaction is established；This
The third of invention is designed to provide the method for establishing model of above-mentioned chemotherapy metenteron adverse reaction or is obtained by the above method
Model preparing the application for mitigating the drug of side effect after chemotherapy, alleviate and existing in the prior art lack a kind ofization
The technical issues for the treatment of the method for establishing model of metenteron adverse reaction.
In order to solve the above technical problems, spy of the present invention adopts the following technical scheme that
A kind of method for establishing model of chemotherapy metenteron adverse reaction, the method for establishing model include: screening chemotherapy
Then the dosage of drug carries out chemotherapy processing to animal tumor model according to the dosage filtered out, after obtaining chemotherapy
The model of side effect of digestive tract；
The dosage of the screening chemotherapeutics includes carrying out intestines to the animal tumor model by chemotherapeutics processing
Toxicity assessment obtains animal tumor model and dosage of the alimentary canal with adverse reaction when occurs.
Preferably, the chemotherapeutics includes cis-platinum, cyclophosphamide, oxaliplatin, 5 FU 5 fluorouracil, capecitabine, Ji
One or more of western his shore, methotrexate (MTX) and Irinotecan；Preferably Irinotecan, oxaliplatin, 5 FU 5 fluorouracil,
One of cyclophosphamide and methotrexate (MTX) are a variety of.
Preferably, the intestines toxicity assessment includes the survival rate for measuring animal, enteron aisle propulsion rate and animal tumor model
Defecation situation.
Preferably, the animal tumor model includes the mouse for being vaccinated with cancer cell；
Preferably, the source of the cancer cell include in lung cancer, breast cancer, gastric cancer, colon and rectum carcinoma and liver cancer extremely
Few one kind；
Preferably, the cancer cell includes mouse colonic cell.
It is established the present invention also provides a kind of method for establishing model using above-mentioned chemotherapy metenteron adverse reaction of name
Model.
Preferably, the model is the tumor-bearing mice using chemotherapeutics successive administration；The chemotherapeutics includes Yi Li
For health or oxaliplatin.
Preferably, the tumor-bearing mice is CT lotus knurl BALB/c mouse.
Preferably, the dosage of the Irinotecan is 60-80mg/kg；Preferably 70-80mg/kg；More preferably
75mg/kg。
Preferably, the dosage of the oxaliplatin is 4-6mg/kg；Preferably 4.5-5.5mg/kg；More preferably
5mg/kg。
The present invention also provides above-mentioned method for establishing model or above-mentioned animal tumor model after preparation is for mitigating chemotherapy
The application of the drug of side effect.
Compared with prior art, the invention has the following beneficial effects:
The method for establishing model of chemotherapy metenteron adverse reaction provided by the invention, by the administration for screening chemotherapeutics
Then dosage carries out chemotherapy processing to animal tumor model according to the dosage filtered out, it is bad to obtain chemotherapy metenteron
The model of reaction；The dosage for wherein screening chemotherapeutics includes carrying out to the animal tumor model by chemotherapeutics processing
Intestines toxicity assessment obtains animal tumor model and dosage of the alimentary canal with adverse reaction when occurs.
The gastral ill symptoms that model that this method obtains occurs are as caused by chemotherapeutics, therefore by this kind of mould
When type is used to research and develop the drug of alleviation chemotherapy metenteron adverse reaction, the symptom of model closer to actual pathological phenomenon,
Be conducive to the mechanism for accurately filtering out the alleviation chemotherapy metenteron adverse reaction for the drug that drug is filtered out with research.It is based on
Foregoing invention design, the present invention also provides a kind of method for establishing model using above-mentioned chemotherapy metenteron adverse reaction to establish
Model and above-mentioned chemotherapy metenteron adverse reaction method for establishing model or by model obtained by the above method preparation use
The application of the drug of side effect after mitigating chemotherapy.
Specific embodiment
Technical solution of the present invention is clearly and completely described below in conjunction with embodiment, it is clear that described reality
Applying example is a part of the embodiment of the present invention, instead of all the embodiments.Based on the embodiments of the present invention, the common skill in this field
Art personnel every other embodiment obtained without making creative work belongs to the model that the present invention protects
It encloses.The person that is not specified actual conditions in embodiment, carries out according to conventional conditions or manufacturer's recommended conditions.Agents useful for same or instrument
Production firm person is not specified, is the conventional products that can be obtained by commercially available purchase.
The present invention provides a kind of method for establishing model of chemotherapy metenteron adverse reaction, the method for establishing model packets
It includes: screening the dosage and administration time of chemotherapeutics, then according to the dosage and administration time filtered out to animal
Tumor model carries out chemotherapy processing, obtains the model of chemotherapy metenteron adverse reaction；
The dosage and administration time of the screening chemotherapeutics include to the animal tumor by chemotherapeutics processing
Model carries out intestines toxicity assessment, when obtaining dosage and the administration when animal tumor model alimentary canal occurs with adverse reaction
Between.
Chemotherapeutics in treating cancer, often can along with gastral adverse reaction, such as nausea,vomiting,diarrhea or
Abdominal pain etc., therefore be highly desirable to the drug that can alleviate chemotherapy metenteron adverse reaction, but can delay developing
When solving the drug of chemotherapy metenteron adverse reaction, due to lacking the model of chemotherapy metenteron adverse reaction, cause to develop
The drug that can be relieved general dyspeptic illness it is not applicable or be not properly suited for dyspeptic disease caused by chemotherapy
Shape.The method for establishing model of chemotherapy metenteron adverse reaction provided by the invention has alimentary canal not after available chemotherapy
The animal tumor model of good reaction, to be further used for the drug that the adverse reaction of chemotherapy metenteron is alleviated in preparation, this method behaviour
Make simple, suitable Treated with Chemotherapeutic Drugs object and kinds of experiments animal.And the model that this method obtains occurs gastral bad
Symptom be as caused by chemotherapeutics, therefore by this kind of model be used to research and develop alleviate the adverse reaction of chemotherapy metenteron drug
When, the symptom of model is conducive to the drug for accurately filtering out drug and research filters out closer to actual pathological phenomenon
Alleviation chemotherapy metenteron adverse reaction mechanism.
In some alternative embodiments, the chemotherapeutics includes cis-platinum, cyclophosphamide, oxaliplatin, 5- fluorine urine
One or more of pyrimidine, capecitabine, gemcitabine, methotrexate (MTX) and Irinotecan.Said medicine is that NCCN suffers from
The combination of the drug for including in person's clinical chemotherapy scheme, said medicine or drug is usually used in the chemotherapy of cancer, can chemotherapy cancer
Type includes lung cancer, breast cancer, gastric cancer, colorectal cancer and liver cancer etc., and can be generated in above-mentioned chemotherapeutics Nausea and vomiting,
The side effect of digestive tract such as diarrhea or constipation.Therefore suitable using said medicine as the model for establishing chemotherapy metenteron adverse reaction
Model for side effect of digestive tract caused by after kinds cancer chemotherapy.
Wherein, Irinotecan, oxaliplatin, 5 FU 5 fluorouracil, cyclophosphamide and methotrexate (MTX) are Common Chemotherapy drug, extensively
It is general to be used in treatment of cancer, therefore in some preferred embodiments, the chemotherapeutics includes Irinotecan, Ao Shali
One of platinum, 5 FU 5 fluorouracil, cyclophosphamide and methotrexate (MTX) are a variety of.
Irinotecan (CPT-11) belongs to the camptothecin in cell toxicant kind anti-cancer drugs object, is a kind of DNA topoisomerase
(I) inhibitor can make to inhibit DNA reconnection step, DNA chain fracture, DNA replication dna and RNA biosynthesis block, and then cell occurs and wither
It dies, inhibits cell division.Irinotecan be the malignant tumours such as Small Cell Lung Cancer, gastric cancer, oophoroma commonly use effective chemotherapeutics it
One.Irinotecan is mainly shown as that delayed diarrhea, the incidence of diarrhea are up to 82% to the attached effect of the poison of intestinal mucosa.
The entitled chemical name of oxaliplatin chemistry is that (1R, 2R) -1,2- diamino hexamethylene oxalate closes platinum, is that one kind has wide spectrum
The third generation platinum medicine of anti-tumor activity, clinic are chiefly used in the treatment of metastatic knot, the carcinoma of the rectum.The action target spot of oxaliplatin
It is DNA molecular, can inhibit the synthesis and duplication of DNA.Oxaliplatin is that can cause Nausea and vomiting and abdomen to the toxic side effect of enteron aisle
It rushes down.
5 FU 5 fluorouracil is uracil derivative, is thymidylate synthetase (TS) inhibitor, is converted into 5- fluorine urine in vivo
Fudr acid (5F-dUMP) can make the tumour cell quickly divided because of thyminesless death.5 FU 5 fluorouracil
Antitumor action is extensive, significant in efficacy to chorioepithelioma chorioadenoma, to digestive system tumor, such as cancer of the esophagus, stomach
Cancer, intestinal cancer, cancer of pancreas and liver cancer and breast cancer treatment effect are good.5 FU 5 fluorouracil can cause bone marrow suppression, mucositis, diarrhea,
Cardiac toxic, Central neurotoxicity, alopecia, cutaneous pigmentation, hepatic injury etc..
Cyclophosphamide is a kind of nitrogen mustards compound, is non-specific cell cycle nitrogen mustards cell toxicity medicament, ring phosphinylidyne
Amine aoxidizes after entering body through liver microsomes Cytochrome P450, activates as 4- hydroxyl cyclophosphamide, can in tumour cell
The Glyciphosphoramide and methacrylaldehyde for having strong toxicity to oncocyte are resolved into, to play antineoplastic action.Cyclophosphamide is to intestines
The toxic side effect in road is that can cause Nausea and vomiting, abdominal pain and diarrhea.
Entitled L- (+)-N- [4- [[(2,4- diamino -6- pteridyl) methyl] methylamino] benzoyl of methotrexate (MTX) chemistry
Base] glutamic acid, mechanism of action is to cause dihydrofoilic acid that cannot be reduced into physiology by the inhibition to dihyrofolate reductase
Active tetrahydrofolic acid, and make purine and thymidylic acid biosynthesis block, achieve the purpose that hinder DNA of tumor cell and RNA synthesis, from
And inhibit the growth and breeding of tumour cell.Methotrexate (MTX) is that can cause Nausea and vomiting, abdominal pain and abdomen to the toxic side effect of enteron aisle
It rushes down.
In some alternative embodiments, the intestines toxicity assessment includes the survival rate for measuring animal, enteron aisle propulsion rate
With the defecation situation of animal tumor model.
Chemotherapeutics dosage is excessive to will lead to experimental animal death, therefore measures the survival rate of animal, suitable to determine
The dosage of chemotherapeutics avoids experimental animal when carrying out chemotherapy processing since chemotherapeutics is excessive to experimental animal toxicity or dosage
It is excessive to cause death.
The experiment of enteron aisle propulsion rate refers to through movement of the certain time internal labeling object in animal gastrointestinal tract after measurement administration
Distance observes influence of the drug to gastrointestinal peristalsis, and the evaluation chemotherapeutics that measurement alvine pushing rate can quantify is to gastral pair
Effect, and is aided with and observes the defecation situation of animal tumor model, to determine disappearing after whether experimental animal chemotherapy occurs
Change road adverse reaction.In some alternative embodiments, the measuring method of alvine pushing rate for example can be but be not limited to carbon
Last propelling method, phenol red method, glucan blue laws, BASO method or baton round administration by gavage etc..
Since mouse is small in size, feeding management is convenient, easily controllable, and Reproduction is fast, possesses a large amount of with not
With the inbred strais of feature, mutantion line and closed colony, and a variety of internationally recognized standard strains are formed, has been widely used in various
In nutrition experimental study, therefore preferably to be vaccinated with the mouse of cancer cell as animal tumor model；Preferably, the cancer is thin
The source of born of the same parents includes at least one of lung cancer, breast cancer, gastric cancer, colon and rectum carcinoma and liver cancer；The cancer cell preferably wraps
Include mouse colonic cell.
The present invention also provides a kind of moulds that the method for establishing model using above-mentioned chemotherapy metenteron adverse reaction is established
Type, the model established by the above method, the adverse reaction of chemotherapy metenteron can occur in experimental animal, to be further used for
Mitigate the experiment and research of the drug of adverse reaction.
In some preferred embodiments, the model is the tumor-bearing mice using chemotherapeutics successive administration；Wherein
The chemotherapeutics includes Irinotecan or oxaliplatin, after Irinotecan or oxaliplatin can cause tumor-bearing mice chemotherapy
Enteron aisle adverse reaction, and not will lead to mouse mortality, therefore preferably Irinotecan or oxaliplatin is as chemotherapeutics.More
Preferably, the model is the lotus knurl BALB/c under the model with chemotherapeutics successive administration one week CT lotus knurl BALB/c mouse
Mouse can keep survival under conditions of chemotherapy occur after side effect of digestive tract, can be applied to further to mitigationization
Treat the research and experiment of the drug of metenteron adverse reaction.CT lotus knurl BALB/c mouse is Mice Inoculated colon cancer cell
BALB/c mouse.Wherein preferably, the dosage of Irinotecan is 60-80mg/kg；Such as it can be but be not limited to
60mg/kg, 62mg/kg, 65mg/kg, 67.5mg/kg, 70mg/kg, 72.5mg/kg, 75mg/kg, 77.5mg/kg or 80mg/
kg；Preferably 70-80mg/kg；More preferably 75mg/kg；Preferably, the dosage of oxaliplatin is 4-6mg/kg, such as
Can be but be not limited to 4mg/kg, 4.2mg/kg, 4.5mg/kg, 4.7mg/kg, 4.8mg/kg, 5mg/kg, 5.1mg/kg,
5.2mg/kg, 5.5mg/kg, 5.6mg/kg, 5.8mg/kg or 6mg/kg；Preferably 4.5-5.5mg/kg；More preferably 5mg/
kg.CT lotus knurl BALB/c mouse can be further adjusted by adjusting the dosage with optimization Irinotecan and oxaliplatin
The severity of the symptom of chemotherapy metenteron adverse reaction.
It is obtained the present invention also provides the method for establishing model of above-mentioned chemotherapy metenteron adverse reaction or by the above method
Model preparing the application for mitigating the drug of side effect after chemotherapy, such as can be but be not limited to be used to prepare mitigation
The preparation of the drug of lung cancer, breast cancer, gastric cancer, colon and rectum carcinoma and chemotherapy of hepatocellular carcinoma metenteron undesirable side effect.
Beneficial effects of the present invention are further illustrated below with reference to preferred embodiment.
Embodiment
Experimental drug:
Oxaliplatin (50mg/ bottles) (Hengrui Medicine Co., Ltd., Jiangsu Prov.), (river 5 FU 5 fluorouracil (100mg/10ml)
Hengrui Medicine limited liability company, Soviet Union), hydrochloride for injection Irinotecan (40mg/ bottles) (the limited public affairs of Jiangsu Hengrui Medicine share
Department), cyclophosphamide (20mg/ bottles), methotrexate (50mg/ bottles).
Dosage regimen:
CT lotus knurl BALB/c mouse is divided into nine groups, selects Irinotecan, oxaliplatin, 5 FU 5 fluorouracil, cyclophosphamide
And methotrexate (MTX) multiclass chemotherapeutic, chemotherapeutic is injected intraperitoneally in addition to blank group, by daily single, observes mouse in administration process
In survival state and defecation situation, all kinds of chemotherapeutics are finally evaluated with each group mouse survival rate, alvine pushing rate after ten days and are caused
The intestines toxicity assessment of tumor-bearing mice, dosage are as shown in table 1:
The dosage of all kinds of chemotherapeutics of table 1
Alvine pushing rate measurement:
Animal is marked using picric acid.Successive administration, for 24 hours, 30min, removes blank after the last administration for fasting before last dose
Remaining outer each group of group is injected intraperitoneally chemotherapeutic respectively, after 15min, the phenol red solution (0.3mL/ of each group gastric infusion 0.05%
Only), after 20min, cervical vertebra takes off cervical approach and puts to death, and cardia to rectum end is taken to take intestines, takes out small intestine and separates mesenterium, clip pylorus is extremely
The intestinal tube in ileocecum portion, is placed on pallet, and small intestine is gently pulled into straight line, measures the distance of phenol red advance.
Distance/small intestine overall length × 100% of the phenol red advance of Intestinal propulsive rate (Intestinal transit) %=
Experimental result:
Irinotecan high dose group, dead after 48h is administered, low dosage is dead after administration 7 days, and large dosage of Yi Li is replaced
It in Diarrhea Model caused by health, causes survival time of mice short, can not there is preferable assessment to its tumor killing effect.
After oxaliplatin is administered continuously, high dose group is all dead at the 4th day, and lower survival rate influences commenting for drug effect
It is fixed, and low dose group survival rate 100%, its defecation and alvine pushing rate are observed after the 7th day, sand difficult to understand is being given in discovery
The stool in mice of sharp platinum group is in brief summary shape, and color is deep, and prompting mouse, there are abnormal defecation situations, thus select low dose group as
Modeling condition.
5 FU 5 fluorouracil group high dose is dead after administration four days, and low dose group is dead after seven days, can be observed obvious
Diarrhea phenomenon.
Group is dead entirely after administration 7 days for methotrexate (MTX), and does not observe diarrhea phenomenon.
Cyclophosphamide does not have the change of apparent state after administration ten days, is prompted according to document, methotrexate (MTX) and ring phosphorus
Amide should not be as the therapeutic agent of colon cancer.
In Intestinal pushing experiment, the alvine pushing rate of blank mouse is 52.3%, after Irinotecan low dose group is administered seven days
Measuring alvine pushing rate is 88.6%, and oxaliplatin low dose group alvine pushing rate is 72.9%.According to NCCN clinical treatment and
The assessment of caused intestines toxic model, it is final to determine that with Irinotecan, oxaliplatin be treatment CT26 bearing mouse model, and
Irinotecan determine maximum dosage be 75mg/kg, successive administration one week；Oxaliplatin maximum dosage is 5mg/
Kg, successive administration one week.
By causing the assessment of the intestines toxic model of tumor-bearing mice to Treated with Chemotherapeutic Drugs, the preliminary item of modeling is finally determined
Part, condition are as follows: Irinotecan dosage be 75mg/kg, successive administration one week；Oxaliplatin dosage is determined as 5mg/
Kg, successive administration one week.
Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention., rather than its limitations；To the greatest extent
Pipe present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that: its according to
So be possible to modify the technical solutions described in the foregoing embodiments, or to some or all of the technical features into
Row equivalent replacement；And these are modified or replaceed, various embodiments of the present invention technology that it does not separate the essence of the corresponding technical solution
The range of scheme.
Claims (10)
1. a kind of method for establishing model of chemotherapy metenteron adverse reaction, which is characterized in that the method for establishing model includes:
The dosage of chemotherapeutics is screened, chemotherapy processing then is carried out to animal tumor model according to the dosage filtered out, is obtained
Obtain the model of chemotherapy metenteron adverse reaction；
The dosage of the screening chemotherapeutics includes carrying out intestines toxicity to the animal tumor model by chemotherapeutics processing
Evaluation obtains animal tumor model and dosage of the alimentary canal with adverse reaction when occurs.
2. method for establishing model according to claim 1, which is characterized in that the chemotherapeutics includes cis-platinum, ring phosphinylidyne
One or more of amine, oxaliplatin, 5 FU 5 fluorouracil, capecitabine, gemcitabine, methotrexate (MTX) and Irinotecan；
Preferably one of Irinotecan, oxaliplatin, 5 FU 5 fluorouracil, cyclophosphamide and methotrexate (MTX) or a variety of.
3. method for establishing model according to claim 1, which is characterized in that the intestines toxicity assessment includes measurement animal
The defecation situation of survival rate, enteron aisle propulsion rate and animal tumor model.
4. method for establishing model according to claim 1, which is characterized in that the animal tumor model includes being vaccinated with cancer
The mouse of cell；
Preferably, the source of the cancer cell includes at least one in lung cancer, breast cancer, gastric cancer, colon and rectum carcinoma and liver cancer
Kind；
Preferably, the cancer cell includes mouse colonic cell.
5. a kind of method for establishing model using the chemotherapy metenteron adverse reaction of any of claims 1-4 is established
Model.
6. model according to claim 5, which is characterized in that the model is the lotus knurl using chemotherapeutics successive administration
Mouse；
The chemotherapeutics includes Irinotecan or oxaliplatin.
7. model according to claim 6, which is characterized in that the tumor-bearing mice is CT lotus knurl BALB/c mouse.
8. animal tumor model according to claim 7, which is characterized in that the dosage of the Irinotecan is 60-
80mg/kg；Preferably 70-80mg/kg；More preferably 75mg/kg.
9. animal tumor model according to claim 7, which is characterized in that the dosage of the oxaliplatin is 4-
6mg/kg；Preferably 4.5-5.5mg/kg；More preferably 5mg/kg.
10. animal described in any one of method for establishing model of any of claims 1-4 or claim 5-9 is swollen
Tumor model is preparing the application for mitigating the drug of side effect after chemotherapy.
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| CN113244280A (en) * | 2021-06-08 | 2021-08-13 | 天津现代创新中药科技有限公司 | Chenopodium quinoa willd extract composition and preparation method and application thereof |
| CN114885900A (en) * | 2022-03-03 | 2022-08-12 | 甘肃中医药大学 | Construction and evaluation method of in vivo chemotherapy drug side effect research model |
| CN114885900B (en) * | 2022-03-03 | 2023-08-22 | 甘肃中医药大学 | Method for constructing and evaluating in-vivo chemotherapeutic drug side effect research model |
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