CN108096528A - It is a kind of to be used to enhance Chinese medicine composition and its application of the cancer of the esophagus to chemotherapy drug susceptibility - Google Patents

It is a kind of to be used to enhance Chinese medicine composition and its application of the cancer of the esophagus to chemotherapy drug susceptibility Download PDF

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CN108096528A
CN108096528A CN201810045674.1A CN201810045674A CN108096528A CN 108096528 A CN108096528 A CN 108096528A CN 201810045674 A CN201810045674 A CN 201810045674A CN 108096528 A CN108096528 A CN 108096528A
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chinese medicine
esophagus
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cancer
medicine composition
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CN108096528B (en
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吴耀松
郭现辉
陈玉龙
彭贵军
任闪闪
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Henan University of Traditional Chinese Medicine HUTCM
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    • A61K36/888Araceae (Arum family), e.g. caladium, calla lily or skunk cabbage
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    • A61K36/896Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
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    • A61K2236/30Extraction of the material
    • A61K2236/33Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/331Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction

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Abstract

The present invention relates to a kind of for enhancing Chinese medicine composition and its application of the cancer of the esophagus to chemotherapy drug susceptibility, belongs to technical field of traditional Chinese medicines.The present invention for enhancing Chinese medicine composition of the cancer of the esophagus to chemotherapy drug susceptibility, be mainly made of the component of following parts by weight:18~22 parts of Radix Salviae Miltiorrhizae, 13~17 parts of Radix Curcumae, 8~12 parts of fritillaria thunbergii, 8~12 parts of dried orange peel, 8~12 parts of the tuber of pinellia, 3~7 parts of Radix Glycyrrhizae.The Chinese medicine composition of the present invention has antitumaous effect, can particularly enhance sensibility of the cancer of the esophagus to chemotherapeutics, improve the inhibiting rate and lethality to esophageal cancer cell, change drug resistance of the esophageal cancer cell to chemotherapeutics, improve clinical therapeutic efficacy, reduce the death rate of patient with esophageal carcinoma.

Description

It is a kind of for enhance the cancer of the esophagus to the Chinese medicine composition of chemotherapy drug susceptibility and its Using
Technical field
The present invention relates to a kind of for enhancing Chinese medicine composition and its application of the cancer of the esophagus to chemotherapy drug susceptibility, belongs to Technical field of traditional Chinese medicines.
Background technology
The cancer of the esophagus is one of common malignant tumour, and China there are about the cancer of the esophagus case that 250,000 newly diagnose, accounts for full generation every year The half of boundary's cancer of esophagi number of cases, five year survival rate is less than 15%.Operation and chemotherapy are common therapies, but clinically right Chemotherapy effective reaction rate only has 19%-40%, and tumor drug resistance becomes the major obstacle of the treatment cancer of the esophagus.
The cancer of the esophagus belongs to the scope of " dysphagic " disease of the traditional Chinese medical science, from oesophagus " excreting foodstuff instead of storing essence ", the function of " being reduced to use with logical " For feature, cancer of the esophagus lesion Radix Angelicae Sinensis and the traditional Chinese medical science " internal organs " disease, but said again without " oesophagus " one in six internal organs, because of itself and stomach function phase Sihe Contact in dissection, therefore should be attributed to " stomach " internal organs lesion in theory.Cancer of esophagi owner will lose with qi and blood, body fluid and negative and positive Adjust several aspects related.
Traditional Chinese medicine thinks that the generation of tumour is to cause body qi and blood not normal due to various reasons, caused by stopping up stagnant part, although Without it is manifestly intended that stop up stagnant local qi and blood how metaplasia tumour, but it follows that local qi and blood disorder is to cause tumour The essential condition of generation.Local qi and blood is disorderly and the micro- raw environment of local cells changes closely similar, local qi and blood disorder institute The state and tumor microenvironment that phlegm, the stasis of blood, poison of generation etc. are built are close.Traditional Chinese medicine directly acts on tumour cell may be very It is weak, and even more than improve the relation of tumour cell and microenvironment, also mostly on tcm clinical is cooperation chemotherapy application.
Therefore, using the sensibility of traditional Chinese medicine enhancing chemotherapeutics, the drug resistance of chemotherapeutics is reduced, it is clinical for improving Prevention is horizontal and ability, the quality of life of raising cancer of esophagi patient, the reduction patient with esophageal carcinoma death rate are of great significance.
The content of the invention
The object of the present invention is to provide a kind of for enhancing Chinese medicine composition of the cancer of the esophagus to chemotherapy drug susceptibility, can Enhance sensibility of the cancer of the esophagus to chemotherapeutics, reduce the drug resistance of chemotherapeutics.
The present invention also provides a kind of above-mentioned Chinese medicine composition in the enhancing cancer of the esophagus to answering in terms of chemotherapy drug susceptibility With.
In order to achieve the goal above, the present invention for enhancing Chinese medicine composition institute of the cancer of the esophagus to chemotherapy drug susceptibility The technical solution adopted is that:
It is a kind of to be used to enhance Chinese medicine composition of the cancer of the esophagus to chemotherapy drug susceptibility, mainly by the group of following parts by weight It is grouped into:18~22 parts of Radix Salviae Miltiorrhizae, 13~17 parts of Radix Curcumae, 8~12 parts of fritillaria thunbergii, 8~12 parts of dried orange peel, 8~12 parts of the tuber of pinellia, Radix Glycyrrhizae 3 ~7 parts.
The present invention for enhancing the cancer of the esophagus in the Chinese medicine composition of chemotherapy drug susceptibility, Radix Salviae Miltiorrhizae is bitter and be slightly cold, and has There is promoting blood circulation, it is inducing meastruation to relieve menalgia, it is monarch drug in a prescription the effect of cool blood to disappear carbuncle,《Sheng Nong's herbal classic》Claim it:" trusted subordinate's perverse trend, borborygmus are faint Such as leak water, fever and chills accumulation breaks disease except lump in the abdomen, stops dysphoria, QI invigorating ".Radix Curcumae works hard and trembles with fear,《Book on Chinese herbal medicine is looked for the truth》Say it:" its gas first on Capable and micro- to assign, all objects for having place blood clotting product and have extravesated blood can't bear go its gas prior to upper place;If make its evil its phlegm of its gas its Blood is on diaphragm and the difficulty person of disappearing that the careful preferably temperature of palpus is preferably cool, is same as his taste, and simultaneous is medical treatment ".Energy principal drug assistance is promoting blood circulation and removing blood stasis logical in side Meridian and relieving pain, and can promoting qi circulation and removing obstruction in the collateral.The benefits of fritillaria thunbergii, bitter cold has clearing heat and eliminating phlegm, opens strongly fragrant dissipating bind,《Book on Chinese herbal medicine is just》Say that it " most drops phlegm Gas is apt to relieving stagnation, and relieve the pain pain, and dissipate-swelling is full ", in side and Radix Curcumae is ministerial drug together.The tuber of pinellia, it is acrid in flavour and warm in nature, there is eliminating dampness and eliminating phlegm, drop The effect of check is vomitted, dissolving lump and resolving mass,《It does not record》Think that it can:" the full knot of trusted subordinate's chest diaphragm phlegm heat that disappears, cough with dyspnea, acute pain in the epigastrium Hard ruffian, when gas vomit inverse, subduing inflammation ".Dried orange peel, it is bitter, pungent, it is warm-natured, there is regulating qi-flowing for strengthening spleen, eliminating dampness and eliminating phlegm energy.《Compendium of Materia Medica》 Say that it can:" treatment vomit the sound of vomiting gastric disorder causing nausea it is noisy, when hydroptysis ";Dried orange peel, the tuber of pinellia can both help ministerial drug reducing phlegm and resolving masses in side, have tool to go Gas clearing damp prevents the source of producing phlegm, is altogether adjutant.Radix Glycyrrhizae, it is sweet in flavor, it is mild-natured, it can invigorate the spleen and benefit qi, clearing heat and detoxicating, coordinating the drug actions of a prescription, in side In to make medicine.Six kinds of drugs cooperate, gather altogether promoting blood circulation and removing blood stasis, reducing phlegm and resolving masses the effect of, agree with the cancer of the esophagus interpretation of the cause, onset and process of an illness.
Based on the Incidence of Esophageal Cancer initial stage interpretation of the cause, onset and process of an illness is contained so that this void is evil, then based on deficiency of vial QI, deficiency of vial QI runs through middle and advanced stage The whole process of entire Incidence of Esophageal Cancer.Traditional Chinese medicine mainly has anxiety and rage, diet wine wound, healthy tendency to the teiology understanding of the cancer of the esophagus Weak, his disease conversion etc..Based on the Incidence of Esophageal Cancer initial stage interpretation of the cause, onset and process of an illness is contained so that this void is evil, middle and advanced stage is then based on deficiency of vial QI, healthy tendency Weakness runs through the whole process of entire Incidence of Esophageal Cancer.The present invention for enhancing Chinese medicine group of the cancer of the esophagus to chemotherapy drug susceptibility Object is closed, there is certain antitumaous effect, can particularly enhance sensibility of the cancer of the esophagus to chemotherapeutics, improve thin to the cancer of the esophagus The inhibiting rate and lethality of born of the same parents changes drug resistance of the esophageal cancer cell to chemotherapeutics, improves the effect of clinical treatment, reduces food The death rate of pipe cancer patient.
The present invention for enhancing Chinese medicine composition of the cancer of the esophagus to chemotherapy drug susceptibility, prescription is small, and expense is low;Curative effect Definitely;It can be made into pure Chinese medicinal preparation;Safe and convenient;Meet traditional Chinese medicine prescription theory.
Preferably, the mass ratio of fritillaria thunbergii, dried orange peel and the tuber of pinellia is 1:1:1.
The Chinese medicine composition of the present invention is in the enhancing cancer of the esophagus to the used technology of application in terms of chemotherapy drug susceptibility Scheme is:
A kind of above-mentioned Chinese medicine composition enhancing the cancer of the esophagus to the application in terms of chemotherapy drug susceptibility, including following step Suddenly:The each component of formula ratio is taken to be decocted with water, removes the dregs of a decoction, fried liquid is made.
The Chinese medicine composition of the present invention is carried out in terms of the enhancing cancer of the esophagus is to chemotherapy drug susceptibility in application, technique is simple It is single, it can be made any conventional oral preparations, such as Chinese medicine preparation of the present invention can be pulvis, granule or oral liquid, Have the characteristics that expense is low, safe and convenient, be convenient for promoting and applying.
The each component of formula ratio is taken to be decocted after can mixing, can also separate and be decocted.
Preferably, before each component is decocted, first impregnated with water.During immersion, the body per the water that 1g Chinese medicines use Product is 15~25mL.In order to make the efficient dissolution of the active ingredient in Chinese medicine material, Chinese medicine material can also be carried out before immersion It crushes.The time of the immersion is 30~150min.
Preferably, described decoct is first to boil by intense fire, then turns to be cooked by slow fire 20~40min.During decoction, per 1g Chinese medicine materials The volume of the water used is 15~25mL.
Above-mentioned Chinese medicine composition, to the application in terms of chemotherapy drug susceptibility, is additionally included in fried liquid in the enhancing cancer of the esophagus Ethyl alcohol mixing is added in, then separation of solid and liquid, then liquid obtained by separation of solid and liquid is concentrated or dried.
Ethyl alcohol is added in fried liquid can generate precipitation.The method that centrifugation or filtering may be employed in separation of solid and liquid.Preferably, The volume fraction that ethyl alcohol to ethyl alcohol are added in fried liquid is 70~80%, then carries out separation of solid and liquid again.
Preferably, in fried liquid add in ethyl alcohol mixing after, do not stop to shake up not shorter than for 24 hours after, centrifuge out supernatant.
Preferably, the ethyl alcohol in liquid obtained by separation of solid and liquid is removed, is then concentrated or dried again.Such as it may be employed The method of distillation removes ethyl alcohol.
The drying is freeze-drying or low-temperature negative-pressure drying.
Above-mentioned Chinese medicine composition further includes the application in terms of chemotherapy medicament sensitive in the enhancing cancer of the esophagus by separation of solid and liquid institute After liquid is dried, the obtained solid of drying is crushed.
Above-mentioned Chinese medicine composition is additionally included in obtained by drying the application in terms of chemotherapy drug susceptibility in the enhancing cancer of the esophagus Customary adjuvant is added in the liquid of solid or concentration gained, required dosage form is made.
Description of the drawings
Fig. 1 is that the size of tumour growth changes over time tendency chart;
Fig. 2 is the average weight block diagram of different groups of transplantation tumors, wherein:M is model group;S is cis-platinum group;Z is Chinese medicine Group;S+Z is cisplatin combined Chinese medicine group.
Specific embodiment
Technical scheme is further described below in conjunction with specific embodiment.
Chinese medicine employed in specific embodiment is purchased from the 3rd affiliated hospital of Henan College Of Traditional Chinese Medicine, and through the Henan traditional Chinese medical science The 3rd affiliated hospital connoisseur of medicine university is accredited as genuine piece.
Embodiment 1
The present embodiment for enhancing Chinese medicine composition of the cancer of the esophagus to chemotherapy drug susceptibility, by following parts by weight Component forms:22 parts of Radix Salviae Miltiorrhizae, 17 parts of Radix Curcumae, 12 parts of fritillaria thunbergii, 12 parts of dried orange peel, 12 parts of the tuber of pinellia, 7 parts of Radix Glycyrrhizae.
The Chinese medicine composition of the present embodiment enhancing the cancer of the esophagus to the application in terms of chemotherapy drug susceptibility, including following step Suddenly:
1) take formula ratio each component mix after crush, then according in every 1g Chinese medicines plus water 20mL ratio, 1h is soaked in Chinese medicine after crushing, boils by intense fire and turns to be cooked by slow fire 30min, filter out the dregs of a decoction, obtain fried liquid;
2) volume fraction that ethyl alcohol to ethyl alcohol are added in fried liquid is 75%, shakes up for 24 hours, is then centrifuged for, takes supernatant Rotary distillation removal ethyl alcohol is carried out, is then concentrated to dryness, obtains solid, crush, obtain Chinese medical extract powder.
Embodiment 2
The present embodiment for enhancing Chinese medicine composition of the cancer of the esophagus to chemotherapy drug susceptibility, by following parts by weight Component forms:18 parts of Radix Salviae Miltiorrhizae, 13 parts of Radix Curcumae, 8 parts of fritillaria thunbergii, 8 parts of dried orange peel, 8 parts of the tuber of pinellia, 3 parts of Radix Glycyrrhizae.
The Chinese medicine composition of the present embodiment enhancing the cancer of the esophagus to the application in terms of chemotherapy drug susceptibility, including following step Suddenly:
1) take formula ratio each component mix after crush, then according in every 1g Chinese medicines plus water 20mL ratio, 1h is soaked in Chinese medicine after crushing, boils by intense fire and turns to be cooked by slow fire 30min, filter out the dregs of a decoction, obtain fried liquid;
2) volume fraction that ethyl alcohol to ethyl alcohol are added in fried liquid is 75%, shakes up for 24 hours, is then centrifuged for, takes supernatant Rotary distillation removal ethyl alcohol is carried out, is then freeze-dried, obtains solid, crush, obtain Chinese medical extract powder.
It is obtained using the Chinese medicine composition of the present embodiment in the enhancing cancer of the esophagus to the application in terms of chemotherapy drug susceptibility Chinese medical extract powder can account for the 4.5~6% of medicinal raw material total weight.
Embodiment 3
The present embodiment for enhancing Chinese medicine composition of the cancer of the esophagus to chemotherapy drug susceptibility, by following parts by weight Component forms:20 parts of Radix Salviae Miltiorrhizae, 15 parts of Radix Curcumae, 10 parts of fritillaria thunbergii, 10 parts of dried orange peel, 10 parts of the tuber of pinellia, 5 parts of Radix Glycyrrhizae.
The Chinese medicine composition of the present embodiment enhancing the cancer of the esophagus to the application in terms of chemotherapy drug susceptibility, including following step Suddenly:
1) take formula ratio each component mix after crush, then according in every 1g Chinese medicines plus water 30mL ratio, 1h is soaked in Chinese medicine after crushing, boils by intense fire and turns to be cooked by slow fire 30min, filter out the dregs of a decoction, obtain fried liquid;
2) volume fraction that ethyl alcohol to ethyl alcohol are added in fried liquid is 75%, shakes up for 24 hours, is then centrifuged for, takes supernatant Rotary distillation removal ethyl alcohol is carried out, is then freeze-dried, obtains solid, crush, obtain Chinese medical extract powder.
Embodiment 4
The present embodiment for enhancing Chinese medicine composition of the cancer of the esophagus to chemotherapy drug susceptibility, by following parts by weight Component forms:21 parts of Radix Salviae Miltiorrhizae, 16 parts of Radix Curcumae, 9 parts of fritillaria thunbergii, 9 parts of dried orange peel, 9 parts of the tuber of pinellia, 6 parts of Radix Glycyrrhizae.
The Chinese medicine composition of the present embodiment enhancing the cancer of the esophagus to the application in terms of chemotherapy drug susceptibility, including following step Suddenly:
1) take formula ratio each component mix after crush, then according in every 1g Chinese medicines plus water 30mL ratio, 1h is soaked in Chinese medicine after crushing, boils by intense fire and turns to be cooked by slow fire 30min, filter out the dregs of a decoction, obtain fried liquid;
2) volume fraction that ethyl alcohol to ethyl alcohol are added in fried liquid is 75%, shakes up for 24 hours, is then centrifuged for, takes supernatant Rotary distillation removal ethyl alcohol is carried out, is then freeze-dried, obtains solid, crush, obtain Chinese medical extract powder.
Embodiment 5
The present embodiment for embodiment 1 Chinese medicine composition in the enhancing cancer of the esophagus to the application in terms of chemotherapy drug susceptibility, Comprise the following steps:
1) take formula ratio each component mix after crush, then according in every 1g Chinese medicines plus water 30mL ratio, 1h is soaked in Chinese medicine after crushing, boils by intense fire and turns to be cooked by slow fire 30min, filter out the dregs of a decoction, obtain fried liquid;
2) volume fraction that ethyl alcohol to ethyl alcohol are added in fried liquid is 75%, shakes up for 24 hours, is then centrifuged for, takes supernatant Rotary distillation removal ethyl alcohol is carried out, is then freeze-dried, obtains solid, crush, obtain Chinese medical extract powder.
Experimental example 6
The present embodiment for embodiment 1 Chinese medicine composition in the enhancing cancer of the esophagus to the application in terms of chemotherapy drug susceptibility, Comprise the following steps:The each component of formula ratio is taken to crush respectively, then according to the ratio for adding water 30mL in every 1g Chinese medicines, is divided 1h is soaked in traditional Chinese medicinal components not after each crushing, turns to be cooked by slow fire 30min after boiling by intense fire, filters out the dregs of a decoction, is obtained each Filtrate after traditional Chinese medicinal components decoction, mixing obtain fried liquid.
Embodiment 7
The present embodiment for enhancing Chinese medicine composition of the cancer of the esophagus to chemotherapy drug susceptibility, by following parts by weight Component forms:19 parts of Radix Salviae Miltiorrhizae, 14 parts of Radix Curcumae, 11 parts of fritillaria thunbergii, 11 parts of dried orange peel, 9 parts of the tuber of pinellia, 4 parts of Radix Glycyrrhizae.
The Chinese medicine composition of the present embodiment enhancing the cancer of the esophagus to the application in terms of chemotherapy drug susceptibility, including following step Suddenly:
1) take formula ratio each component mix after crush, then according in every 1g Chinese medicines plus water 25mL ratio, 30min is soaked in Chinese medicine after crushing, boils by intense fire and turns to be cooked by slow fire 40min, filter out the dregs of a decoction, obtain fried liquid;
2) volume fraction that ethyl alcohol to ethyl alcohol are added in fried liquid is 80%, shakes up for 24 hours, is then centrifuged for, takes supernatant Rotary distillation removal ethyl alcohol is carried out, is then freeze-dried, obtains solid, crush, obtain Chinese medical extract powder.
Embodiment 8
The present embodiment for enhancing Chinese medicine composition of the cancer of the esophagus to chemotherapy drug susceptibility, by following parts by weight Component forms:20 parts of Radix Salviae Miltiorrhizae, 15 parts of Radix Curcumae, 10 parts of fritillaria thunbergii, 9 parts of dried orange peel, 11 parts of the tuber of pinellia, 6 parts of Radix Glycyrrhizae.
The Chinese medicine composition of the present embodiment enhancing the cancer of the esophagus to the application in terms of chemotherapy drug susceptibility, including following step Suddenly:
1) take formula ratio each component mix after crush, then according in every 1g Chinese medicines plus water 15mL ratio, 150min is soaked in Chinese medicine after crushing, boils by intense fire and turns to be cooked by slow fire 20min, filter out the dregs of a decoction, obtain fried liquid;
2) volume fraction that ethyl alcohol to ethyl alcohol are added in fried liquid is 70%, shakes up 30h, it is then centrifuged for, takes supernatant Rotary distillation removal ethyl alcohol is carried out, is then freeze-dried, obtains solid, crush, obtain Chinese medical extract powder.
Experimental example
This experimental example enhances Chinese traditional medicine composition the cancer of the esophagus to cis-platinum by taking the Common Chemotherapy drugs Cisplatin for treating the cancer of the esophagus as an example Sensibility is tested.
(1) material
1st, cell line:Human esophagus cancer cell strain Eca9706 is purchased from Chinese Academy of Medical Sciences's cell centre.
2nd, animal:It is dynamic to be purchased from Shanghai Si Laike experiments by BALB/C (nu/nu) female nude mice, 5 week old, 15~18g of weight Object Co., Ltd.
3rd, main agents:1640 culture mediums of RPMI Medium (Solarbio companies), trypsase-EDTA digestive juices (Solarbio companies), hyclone (Gemini companies), tetramethyl azo azoles salt (MTT) (Solarbio companies), cell withers Die/cycle detection kit (BD biotech firms).
4th, laboratory apparatus:CO2Incubator (German Eppendorf companies), (the safe and sound air technique in Suzhou has superclean bench Limit company), fluorescence inverted phase contrast microscope (German Laica companies), ELx-800 types microplate reader (BIO-TEK companies), centrifuge (Hunan Xiang Yi centrifuges Instrument Ltd.), vernier caliper (Shanghai Measuring and Cutting Tools Plant).
(2) experiment in vitro
1st, the inhibitory action of Chinese medicine and cisplatin on human cancer of the esophagus strain EC9706 cells.In test process, Chinese medicine group medication is Chinese medical extract powder obtained is dissolved in culture medium system in embodiment 2, during Chinese medicine+cis-platinum group medication is obtained in embodiment 2 Medicament extract powder and cis-platinum are dissolved in culture medium.As+1 μ g/mL cis-platinum groups of 100 μ g/mL Chinese medicines refer to Chinese medical extract powder and Cis-platinum adds in the admixing medical solutions formed after culture medium, and the concentration of Chinese medical extract is 100 μ g/mL, and the concentration of cis-platinum is 1 μ g/mL, Then EC9706 cells (similarly hereinafter) are added in.
MTT is detected:It takes the logarithm growth period esophageal carcinoma 9706 cells kind plate.Four experiment packets are set:Normal group, + 1 μ g/mL cis-platinum groups of normal control, Chinese medicine group ,+1 μ g/mL cis-platinum groups of Chinese medicine.Wherein+1 μ g/mL cis-platinum groups of Chinese medicine group and Chinese medicine 200 μ g/mL, 100 μ g/mL, 50 μ g/mL, 25 μ g/mL, tetra- Chinese medicine concentration gradients are set respectively.It takes out afterwards for 24 hours, takes original training Base is supported, empirically grouping carries out dosing, and every group of three multiple holes are incubated 48h, and mtt assay is with microplate reader microplate reader at 570/630nm Survey each hole light absorption value (OD values).
Calculate the average inhibition of each medication group, cell inhibitory rate=(control group OD values-experimental group OD values)/control group OD Value × 100%.Experiment is repeated 3 times, and testing result is shown in Table 1.
1 different experiments group of table to the inhibitory action of EC9706 cells (N=3)
Evaluate drug combination drug effect:Using the equal method of Nintaus, drug combination index q values are calculated according to the following formula:Q=EA+B/ (EA+EB-EA×EB), wherein EARepresent effect when A medicines are administered alone, EBRepresent effect when B medicines are administered alone, EA+BIt represents A, two medicines of B merge the effect after administration.If actually measured merging effect is equal to desired value, i.e. q=1 is is added, q>1 is association Together, q<1 is antagonism.
By the data in table 1, each group drug combination index q values, wherein E are calculated according to Jin's formulaARepresent cis-platinum list Solely inhibiting rate during administration, EBRepresent inhibiting rate when Chinese medicine is administered alone, EA+BIt represents cis-platinum and Chinese medicine merges the suppression after administration Rate processed.When 200 μ g/ml, 100 μ g/ml, 50 μ g/ml, 25 μ g/ml Chinese medicines and the cisplatin combined effects of 1 μ g/ml, q values are respectively 1.19、1.27、1.26、1.06.It is known that 200 μ g/ml, 100 μ g/ml, 50 μ g/ml, 25 μ g/ml Chinese medical extracts with it is suitable There is synergistic function during platinum use in conjunction, that is to say, that Chinese medicine improves sensibility of the esophageal cancer cell to cis-platinum, wherein 100 μ g/ml and cis-platinum synergistic function are the most notable, we select 100 μ g/ml drug extracts as subsequent experimental.
2nd, Chinese medicine and the various concentration Cisplatin with concentration are to the apoptosis and cycle influences of EC9706 cells.
Experimental method:It takes the logarithm growth period cell, sets 6 dosing groups to be respectively:Blank control group, 0.5 μ g/ml are suitable Platinum, 1 μ g/ml cis-platinums group, 100 μ g/ml Chinese medicines groups ,+0.5 μ g/ml cis-platinums group of 100 μ g/ml Chinese medicines ,+1 μ g/ of 100 μ g/ml Chinese medicines Ml cis-platinum groups.After dosing is incubated 48h, cell is collected, strictly illustrates to handle cell by apoptosis, cycle kit, up flow type in 1h Cell instrument is detected, and records result.It is shown in Table 2.
Table 2 with concentration Contained Serum joint various concentration cis-platinum to the Apoptosis of EC9706 cells (N=5)
Note::Compared with blank control group;:Compared with 100 μ g/ml Chinese medicine groups;:Compared with the cis-platinum group of same concentration
From data in table 2:After acting on 48h, compared with to blank photo group, (the P > in addition to 50 μ g/mL Chinese medicine groups 0.05), other each group apoptosis rates raise, statistically significant (P<0.05);Compared with the cis-platinum group of same concentration, add in The cis-platinum group apoptosis rate of Chinese medicine all apparent increase (P<0.05), there is statistical significance.Cycle result is shown:With blank control group Compare, cis-platinum group and Chinese medicine prevent cell in the S phases with Cisplatin group;Compared with same concentration cis-platinum, 1 μ g/mL cis-platinums add After entering Chinese medicine, the cells ratio for being stopped in the S phases significantly improves (P<0.05).
Act on 48h after, compared with the control group compared with, in addition to 100 μ g/ml Chinese medicine groups (P > 0.05), other each group Apoptosis Rate raises, statistically significant (P<0.05);Compared with the cis-platinum group of same concentration, it is all bright to add in Chinese medicine+cis-platinum group apoptosis rate Aobvious rise (P<0.05), there is statistical significance.Cycle result is shown:Compared with the control group, cis-platinum group and Chinese medicine+cis-platinum group are equal Cell was prevented in the S phases;Compared with same concentration cis-platinum ,+1 μ g/ml cis-platinum groups of Chinese medicine, the cells ratio for being stopped in the S phases is apparent Improve (P<0.05).It can thus be appreciated that:Chinese medicine enhances mechanism of the esophageal cancer cell to chemotherapy common drug cisplatin sensitivity It is related with division with the apoptosis for influencing tumour cell.
(3) experiment in vivo
The influence that Chinese medicine combination with cisplatin grows esophageal cancer cell EC9706 transplanted tumor in nude mice
1 experimental method:It takes the logarithm the esophageal carcinoma 9706 cells in growth period, 0.1mL cells is subcutaneously injected in nude mice right flank (about 2 × 106A cell) suspension, after 7 days, the hard naked eyes of quality are visible as tumour.
Chinese medicine composition in the embodiment 1 of 7 consumption per days is taken, after mixing, the ratio of water 20mL is added according to every 1g Chinese medicines, uses water 1h is impregnated, intense fire changes after boiling is cooked by slow fire 30min, filters off the dregs of a decoction, and the fried liquid of Chinese medicine composition is made;Every mouse (body Estimated again by 20g) dosage is calculated by daily dosage 0.2mL, the fried liquid chamber temperature of Chinese medicine composition obtained is cooled down, is stored in 4 DEG C refrigerator is spare.
The successful nude mice of modeling is randomly divided into model group, Chinese medicine group, cis-platinum group, Chinese medicine+cis-platinum group, every group each 5, and Label remeasures the size of each transplanted tumor in nude mice, counts group difference.Model group gavages physiological saline (0.2mL/ is only secondary), Intraperitoneal injection of saline (0.2mL/ is only secondary), Chinese medicine group gavage the fried liquid of Chinese medicine composition (0.2mL/ is only secondary) intraperitoneal injection life Reason brine (0.2mL/ is only secondary), cis-platinum group gavage physiological saline (0.2mL/ is only secondary), and cis-platinum (0.2mL/ is only secondary) is injected intraperitoneally, in Medicine+cis-platinum group gavages the fried liquid of Chinese medicine composition (0.2mL/ is only secondary), and intraperitoneal injection cis-platinum (0.2mL/ is only secondary) gavages daily 1 It is secondary, intraperitoneal injection, the next day once, be administered 4 weeks.
With the major diameter (a) of each experimental mouse transplantable tumor of vernier caliper measurement and minor axis (b), by formula V=ab2/ 2 calculate shifting Knurl volume is planted, is measured 2 times weekly.The each measurement data of each group is counted, the results are shown in Table 3, it is bent to draw tumour growth according to average Line is shown in Fig. 1.Experimental mouse is put to death in dislocation, is removed tumor tissues, is weighed, the results are shown in Table 4, different groups of transplantation tumors are drawn according to table 4 Average weight block diagram, see Fig. 2.
Each experimental group experimental data carries out homogeneity test of variance and the normality of sample using SPSS19.0 softwares after collecting It examines, group difference compares with one-way analysis of variance, is as a result represented with x ± s, otherness describes to take α before and after notable level =0.05, draw statistical graph.
2 experimental results:
The influence of 2.1 Chinese medicines and Cisplatin to growth of transplanted human
3 different time of table measurement each group gross tumor volume average value (cm3)
Note:M is model group;S is cis-platinum group;Z is Chinese medicine group;S+Z is Chinese medicine and Cisplatin group (similarly hereinafter)
Influence of the 2.2 Chinese medicine combination with cisplatin to transplanting tumor weight
The different group transplantable tumors of table 4 weight (g) (N=5)
Group M S Z S+Z
Weight (g) 1.631±0.187 0.741±0.081* 1.257±0.301* 0.381±0.051*★▲
Note:*Compare with model group,S+Z compared with S groups,S+Z is compared with S groups
From data in table 4, each medication group transplantation tumor weight is significantly less than model group compared with model group, poor Different statistically significant (P<0.05), Chinese medicine and Cisplatin group more have notable difference with independent cis-platinum group or Chinese medicine group, Statistically significant (P<0.05);It can be seen that drug combination is substantially better than exclusive use cis-platinum to the influence for transplanting tumor weight Group illustrates that Chinese medicine enhances sensibility of the transplantable tumor to cis-platinum.
(4) Chinese medicine acute toxicity testing
It gives one group of animal median lethal dose (LD50) and observes seven days, as a result none animal dead;Give maximum medicine simultaneously It measures, as a result none animal dead.After second is administered, animal activity reduction is obvious, but recovers within second day normal.Observation Period, in addition to administration same day animal stops feed and has activity to change, from second day, animal recovers normal feed, and activity is normal, Weight gradually increases, and appearance is normal.It after seven days, puts to death and dissects animal, visually observe each important organ and be showed no abnormal change Become.
The experimental result tested from experiment in vivo, experiment in vitro and Chinese medicine acute poisoning:
1) Chinese medical extract of various concentration and Cisplatin effectively enhance cis-platinum and the inhibition of esophageal cancer cell are made With, it is seen then that Chinese medicine composition improves sensibility of the esophageal cancer cell to chemotherapeutics.
2) from apoptosis and cycle result as it can be seen that after cis-platinum addition Chinese medical extract, apoptosis and prevention to tumour cell divide The enhancing with obvious effects split, Chinese medicine composition improve esophageal cancer cell to the sensibility of chemotherapeutics, may with influence apoptosis and Cell division is closely related.
3) growth inhibitory effect of esophageal transplanted tumors is acted on than cisplatin alone when chemotherapeutics adds in Chinese medical extract Substantially, it is seen then that Chinese medicine composition enhances inhibitory action of the chemotherapeutics to transplantable tumor, effectively increases the cancer of the esophagus to chemotherapeutic The sensibility of object.
4) Chinese medicine composition of the invention is safe and effective, can effectively enhance sensibility of the cancer of the esophagus to chemotherapeutics.

Claims (7)

1. a kind of be used to enhance Chinese medicine composition of the cancer of the esophagus to chemotherapy drug susceptibility, it is characterised in that:Mainly by following heavy Measure the component composition of number:18~22 parts of Radix Salviae Miltiorrhizae, 13~17 parts of Radix Curcumae, 8~12 parts of fritillaria thunbergii, 8~12 parts of dried orange peel, the tuber of pinellia 8~ 12 parts, 3~7 parts of Radix Glycyrrhizae.
2. according to claim 1 for enhancing Chinese medicine composition of the cancer of the esophagus to chemotherapy drug susceptibility, feature exists In:The mass ratio of the fritillaria thunbergii, dried orange peel and the tuber of pinellia is 1:1:1.
3. a kind of Chinese medicine composition as described in claim 1 in the enhancing cancer of the esophagus to the application in terms of chemotherapy drug susceptibility, It is characterized in that:Comprise the following steps:The each component of formula ratio is taken to be decocted with water, removes the dregs of a decoction, fried liquid is made.
4. Chinese medicine composition according to claim 3 in the enhancing cancer of the esophagus to the application in terms of chemotherapy drug susceptibility, It is characterized in that:Before each component is decocted, first impregnated with water.
5. Chinese medicine composition according to claim 3 in the enhancing cancer of the esophagus to the application in terms of chemotherapy drug susceptibility, It is characterized in that:Addition ethyl alcohol mixing in fried liquid is additionally included in, then separation of solid and liquid, then liquid progress obtained by separation of solid and liquid is dense Contracting is dry.
6. Chinese medicine composition according to claim 5 in the enhancing cancer of the esophagus to the application in terms of chemotherapy drug susceptibility, It is characterized in that:The volume fraction that ethyl alcohol to ethyl alcohol are added in fried liquid is 70~80%, then carries out separation of solid and liquid again.
7. Chinese medicine composition according to claim 5 in the enhancing cancer of the esophagus to the application in terms of chemotherapy drug susceptibility, It is characterized in that:Ethyl alcohol in liquid obtained by separation of solid and liquid is removed, is then concentrated or is dried again.
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CN115607619B (en) * 2022-07-14 2024-03-15 湖南中医药大学 Traditional Chinese medicine composition for reversing drug resistance of platinum chemotherapeutic drugs and preparation method thereof

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