CN109512995A - A kind of antitumor Chinese and its extractive of volatile oil - Google Patents
A kind of antitumor Chinese and its extractive of volatile oil Download PDFInfo
- Publication number
- CN109512995A CN109512995A CN201910045120.6A CN201910045120A CN109512995A CN 109512995 A CN109512995 A CN 109512995A CN 201910045120 A CN201910045120 A CN 201910045120A CN 109512995 A CN109512995 A CN 109512995A
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- volatile oil
- oil extract
- parts
- ras
- traditional medicine
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Classifications
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- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
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- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction 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 or decoction
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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Abstract
The present invention relates to a kind of Chinese medicine compositions and its extractive of volatile oil to be overexpressed application in the drug of tumour after inhibiting ras Oncogene Mutation, which is made of cloves, fructus amomi, Chinese anise, cortex cinnamomi, white pepper, radix aucklandiae, rhizoma zingiberis.The Chinese medicine composition and its extractive of volatile oil can significantly inhibit the more vaginal orifice phenotypes of tumour sample for the Caenorhabditis elegans that ras proto-oncogene caused by let-60 is mutated is overexpressed, and making its torsion is the wild type phenotype with Kidney-Yin door.The above results show that Chinese medicine composition and its extractive of volatile oil provided by the present invention have the effect of the tumour for the treatment of ras gene overexpression, can inhibit to apply in the anti-tumor drug being overexpressed after ras Oncogene Mutation in preparation.
Description
Technical field
The present invention relates to a kind of Chinese medicine compositions and its extractive of volatile oil to be overexpressed after inhibiting ras Oncogene Mutation
Anti-tumor drug in application, belong to field of antineoplastic medicaments.
Background technique
Currently, malignant tumour has become the number one killer of the mankind, the serious health for endangering the mankind, world health group
The data knitted shows that the morbidity of annual whole world tumour is 10,000,000 people, dead about 7,000,000 people, the annual new hair of China's cancer
Case is 2,000,000, because of about the 1400000 of cancer mortality, in 5 people of China's death, that is, have 1 people die of cancer (Wang Mingzheng,
2017)。
About 30% human tumor be as leading to RAS albumen excessive activation after ras Oncogene Mutation caused by.?
There are the mutation of ras gene and the excessive activations of RAS albumen in 30% human tumor, wherein about 90% cancer of pancreas, 50%
There are ras gene mutation (Hara and Han, 1995) for the colon cancer of left and right and 20% or so acute leukemia.40%
KRAS mutation is detected in hereditary nonpolyposis colorectal cancer, 49% conventional follicular thyroid carcinoma has RAS mutation,
48% Hurthle cell thyroid tumor has RAS mutation.KRAS codon occurs in 83% cancer of pancreas and 85% cholangiocarcinoma
12 mutation.In addition to this, the cancers such as lung cancer, gastric cancer, breast cancer, bladder cancer and melanoma are all close with the mutation of ras gene
(Yang Qiwei etc., 2018) is closed in cut phase.Ras-MAPK signal transduction pathway takes part in the process of liver cancer extremely.With Ras signal path
Also become the research hotspot of tumor therapeutics for the antineoplaston of target, therefore, it is pernicious that ras has become generally acknowledged screening correlation
Cancer drug target spot (Liu Xuemei etc., 2008).Ras signal path is highly conserved from nematode to people, the let- in Caenorhabditis elegans
The conservative RAS albumen of 60 genes coding, it has 83% homology compared with the RAS albumen of the mankind.If ras gene is prominent
Become, nematode can be caused to generate more vaginal orifices in Caenorhabditis elegans, be then the malignant proliferation for causing cell in the mankind, cause to swell
The generation (Li Rui etc., 2016) of tumor.Therefore, model organism Caenorhabditis elegans (Caenorhabditis elegans) Ras/
MAPK signal path excessive activation type mutant is widely used in screening as tumor model and inhibits Ras access excessive activation
Anti-tumor drug (Hara and Han, 1995；Wang Fang, 2005；Liu Xuemei etc., 2008).The present invention uses Caenorhabditis elegans
For screening implement, the screening for lowering Ras/MAPK signal path excessive activation anti-tumor drug candidate is carried out.
Traditional chemotherapy and operation, radiotherapy etc. combine, though the treatment rate of Several Kinds of Malignancy is successfully improved,
But due to stronger side effect and drug resistance, so that the research for finding new treatment tumour is very urgent (Xiuyun Zhang, 2012).
The Chinese medicine in China has multi-faceted, multiple target point in treating cancer, is not likely to produce the advantages such as drug resistance, and it is multifactor, more to meet tumour
The pathogenic mechanism of link, antitumor active component, effective component and Study on mechanism have become at present research both at home and abroad
Hot spot, and achieve certain curative effect in terms of clinical cancer therapy, and toxicity is lower, open one for tumor prevention and treatment
The road Tiao Xin, Chinese medicine and its antitumor research work of effective component achieve a series of achievement in recent years, and some achievements have turned
Turn to clinically widely used anti-tumor drug (Yin Long etc., 2006；Xiuyun Zhang, 2012；Zhu Yuanzhang etc., 2017).
Dragon and tiger jintan is derived from the Cheng Fang " Zhuge's March Powder " that Chinese Gu has earliest, several improved, obtains existing prescription.
Dragon and tiger jintan is mainly by menthol, borneol, cloves, fructus amomi, Chinese anise, cortex cinnamomi, pepper, radix aucklandiae, rhizoma zingiberis, catechu, Radix Glycyrrhizae group
At.It can be mainly used for heatstroke dizziness, nausea and vomiting, diarrhea and carsickness with inducing resuscitation of having one's ideas straightened out, the turbid and middle preventing or arresting vomiting of driving away summer heatization, it is seasick.
So far, no document report crosses dragon and tiger jintan with anti-tumor activity.
And the present invention is improved on the basis of dragon and tiger jintan, it was found that one kind, which has, inhibits ras gene excessively to swash
Chinese medicine composition and its extractive of volatile oil living, the Chinese medicine composition and its extractive of volatile oil can be in treatment ras original cancers
It is applied in the tumour of gene excessive activation.Compared to dragon and tiger jintan, the Chinese medicine composition and its extractive of volatile oil can controlled
It treats and is applied in the tumour of ras proto-oncogene excessive activation.
Chinese medicine composition and its extractive of volatile oil provided by the invention can be with any pharmaceutically acceptables
Auxiliary material is mixed and made into various dosage forms, applies in the tumour for the treatment of ras proto-oncogene excessive activation.
Bibliography
Wang Mingzheng, the prevention of China's malignant tumour explore [J] traditional Chinese medicine Journal of Management with control strategy, 2017,25 (06):
8-9
Liu Xuemei, Deng's equality, drug targets progress [J] the pharmacy progress based on Ras signal transduction pathway, 2008,
32(11):481-485
To be able to suppress oncogene ras active drug Fudan University big using nematode as model organism screening by Wang Fang (2005)
Learn the outbound report of post-doctor
Hara M, Han M et al.Ras farnesyltransferase inhibitors suppress the
phenotype resulting from an activated ras mutation in Caenorhabditis elegans.
[J] .Developmental Biology, 1995,92 (4): 3333-3337
Xiuyun Zhang etc., anti-tumor Chinese medicine active component and Recent Advances of Chemical Constituents [J] science and technology visual field, 2012,7 (3):
177-178
Effect study status [J] the animal medicine of Yin Long, Xu Liang etc., anti-tumor Chinese medicine and its effective component is in progress,
2006,27(1):39-43
Zhu Yuanzhang, Zhang Guibiao etc., traditional medicine volatile oil antitumor mechanism progress [J] Chinese experimental pharmacology of traditional Chinese medical formulae magazine, 16
(8):227-234
Progress [J] of Yang Qiwei, Sui Yujie, Du Zhenwu, Zhang Guizhen .RAS gene family mutation rate in solid tumor
Chinese stereoscopy and image analysis, 2018 (03): 303-310.
Effect [J] of Li Rui, Song Weijiang, Zhang Shaopeng, Yao Shukun .Ras-MAPK access in onset of liver cancer mechanism is Sino-Japan
Friendly hospital's journal, 2016,30 (01): 47-49+54.
Summary of the invention
The object of the present invention is to provide a kind of Chinese medicine compositions by cloves, fructus amomi, Chinese anise, cortex cinnamomi, white pepper, wood
Fragrant, rhizoma zingiberis composition obtains the extractive of volatile oil crude product of the Chinese medicine composition using extraction by steam distillation, then with organic
Solvent extraction extracts resulting organic phase and volatilizes solvent, and dehydration and drying obtains the traditional medicine volatile oil extract.The present invention is to mention
Inhibiting the application in ras proto-oncogene overexpression for the Chinese medicine composition and its extractive of volatile oil, specific tumour is to control
Treat liver cancer, cancer of pancreas, lung cancer and colon cancer.
The present invention is practiced by following technical proposals.
The object of the present invention is to provide a kind of Chinese medicine composition, the Chinese medicine composition by following parts by weight raw material system
At: 5 parts of cloves, 5 parts of fructus amomi, 3 parts of Chinese anise, 8 parts of cortex cinnamomi, 3 parts of white pepper, 3 parts of radix aucklandiae, 5 parts of rhizoma zingiberis.
It is a further object to provide a kind of traditional medicine volatile oil extracts, and the traditional medicine volatile oil extract is by cloves
5 parts, 5 parts of fructus amomi, 3 parts of Chinese anise, 8 parts of cortex cinnamomi, 3 parts of white pepper, 3 parts of radix aucklandiae, 5 parts of rhizoma zingiberis be made, the preparation method is as follows: taking
Distilled water is added, using steam distillation in cloves, fructus amomi, Chinese anise, cortex cinnamomi, white pepper, radix aucklandiae, the rhizoma zingiberis of aforementioned proportion
Method is extracted, and extractive of volatile oil crude product is obtained, and the volatile oil extract crude product is extracted with organic solvent again, is extracted resulting organic
Solvent is mutually volatilized, dehydrates, obtains traditional medicine volatile oil extract.
The significant chemical constituent of the traditional medicine volatile oil extract contains eugenol 42.43-59.19%, acetic acid eugenol
Ester 13.05-15.28%, anethole 10.02-13.11%, carypohyllene 2.07-2.88%, Bronyl acetate 1.3-1.71%.
The density of the traditional medicine volatile oil extract is 1.0~1.1g/mL.
It is anti-swollen in preparation that it is a further object to provide the Chinese medicine compositions and its traditional medicine volatile oil extract
Application in tumor medicine.
The tumour is as caused by being overexpressed after ras Oncogene Mutation.
The tumour being specifically related to is liver cancer, cancer of pancreas, lung cancer and colon cancer.
Since Ras signal path is highly conserved from nematode to people, in Caenorhabditis elegans, let-60 gene coding is conservative
RAS albumen, it compared with the RAS albumen of the mankind with 83% homology.If ras is mutated, in Caenorhabditis elegans
The more vaginal orifice phenotypes that can cause nematode, are then the malignant proliferation for causing cell in the mankind, lead oncogenic generation.Therefore, mould
Formula biology Caenorhabditis elegans (Caenorhabditis elegans) Ras/MAPK signal path excessive activation type mutant quilt
It is widely used in the anti-tumor drug that screening inhibits Ras access excessive activation as tumor model.
Therefore, present invention employs Caenorhabditis elegans mutant excessively swashs as assessment inhibition ras proto-oncogene access
The model of drug living, and it is obvious to have shown that the Chinese medicine composition and traditional medicine volatile oil extract have ras proto-oncogene overexpression
Downward effect, with the conclusion for inhibiting ras proto-oncogene access excessive activation, and the Chinese medicine composition and traditional medicine volatile oil
Tumour cell caused by ras excessive activation caused by extract is only mutated let-60 works, and lacks to lin-15 prominent
Tumour cell caused by wild type ras excessive activation caused by becoming does not work, and application is safe, i.e., it acts only on cancer cell,
Without acting on normal cell, ras proto-oncogene overexpression can be significantly lowered, does not lead to gene mutation, not teratogenesis.Cause
This, the Chinese medicine composition and traditional medicine volatile oil extract can be overexpressed in the drug of tumour in preparation treatment ras proto-oncogene
Using.
The utility model has the advantages that
Chinese medicine composition and traditional medicine volatile oil extract of the invention can be with institute after specific downregulation ras Oncogene Mutation
The overexpression of cause can be overexpressed in caused malignant tumor medicine after preparation treatment is by ras Oncogene Mutation and apply, specifically
The tumour being related to is liver cancer, cancer of pancreas, lung cancer and colon cancer.The Chinese medicine composition and traditional medicine volatile oil extract are to ras gene
The therapeutic effect for being overexpressed tumour is not to rely on extensive cytotoxicity, but the mistake of specific downregulation ras proto-oncogene
Expression；The Chinese medicine composition and traditional medicine volatile oil extract swell to caused by ras excessive activation caused by being only mutated to let-60
Oncocyte works, and does not work to tumour cell caused by wild type ras excessive activation caused by lin-15 deletion mutation,
I.e. the Chinese medicine composition and traditional medicine volatile oil extract do not act on normal cell, not teratogenesis to cancer cell is acted only on, application
Safety.
Specific embodiment
Specific embodiment presented below illustrates the present invention, but the protection scope of claims of the present invention and specification is simultaneously
It is not limited to these embodiments.
The preparation of one traditional medicine volatile oil extract of embodiment
Bulk pharmaceutical chemicals: cloves, fructus amomi, Chinese anise, cortex cinnamomi, white pepper, radix aucklandiae, rhizoma zingiberis
Cloves 7.5g, fructus amomi 7.5g, Chinese anise 4.5g, cortex cinnamomi 12g, white pepper 4,5g, radix aucklandiae 4.5g, rhizoma zingiberis 7.5g.
Above-mentioned raw materials medicinal powder is broken, add 10 times of amount water, steam distillation extracts 3 hours, obtains traditional medicine volatile oil extraction
Object crude product.
Traditional medicine volatile oil extract crude product is extracted twice with ether, and the organic phase being obtained by extraction merges, and then volatilizes ether,
Traditional medicine volatile oil extract is obtained, resulting traditional medicine volatile oil extract is light yellow oil matter.
Analysis of Essential Oil Components: with the chemical component of GC-MS analysis extractive of volatile oil, the cloves of 42.43-59.19%
Phenol, the Acetyl eugenol of 11.85-15.28%, the anethole of 10.02-13.11%, the carypohyllene of 2.07-2.88%, 1.3-
1.71% Bronyl acetate.
1 traditional medicine volatile oil extract GC-MS result of table
Effect of the two traditional medicine volatile oil extract of embodiment to Caenorhabditis elegans MT2124 (let-60 mutation)
Ras excessive activation can cause nematode to generate more vaginal orifices in nematode, be then the pernicious increasing for causing cell in the mankind
It grows, if test medicine is able to suppress the generation of the more vaginal orifice phenotypes of tested nematode, promotes them to bud into wild type, then illustrate
Drug effect has lowered the excessive activation of the access in Ras access, has anti-tumor activity.MT2124 is let-60/ras mistake
The Caenorhabditis elegans of activation is spent, which is more vaginal orifice phenotypes, is equivalent to and has suffered from mankind's ras Oncogene Mutation
Refractory neoplasm.Caenorhabditis elegans MT2124 is handled using test medicine, if to be able to suppress tested nematode more for test medicine
The generation of vaginal orifice phenotype, promotes them to bud into wild type, then illustrates that drug effect in Ras access, has lowered the access
Excessive activation has anti-tumor activity.Wild type nematode ratio shared in tested nematode population is higher, shows test medicine
Function and effect are better.
Experimental material: Caenorhabditis elegans MT2124, genotype: let-60 (n1046sd, gf) IV is purchased from CGC；Large intestine
Bacillus OP50, uracil leaky mutant are purchased from CGC as the food of Caenorhabditis elegans.
S basal liquid: sodium chloride 2.925g, dipotassium hydrogen phosphate 0.5g, potassium dihydrogen phosphate 3g, distilled water 500mL, shake make it is molten
Solution, in 121 DEG C of sterilizing 20min；
1M citrate buffer solution: citric acid 2g, potassium citrate 29.35g, distilled water 100mL, shaking makes to dissolve, in 121 DEG C
Sterilize 20min；
Trace liquid: EDTA0.186g, FeSO4·7H2O 0.06g, MnCl2·4H2O 0.02g, CuSO4·
5H2O0.0025g, ZnSO4·7H2O 0.029g, distilled water 100mL, shaking makes to dissolve, in 121 DEG C of sterilizing 20min；
1M Adlerika: MgSO4·7H2O 24.647g, distilled water 100mL, shaking makes to dissolve, and sterilizes in 121 DEG C
20min；
1M calcium chloride solution: CaCl2·2H2O 14.702g, distilled water 100mL, shaking makes to dissolve, and sterilizes in 121 DEG C
20min；
5mg/mL cholesterol solution: cholesterol 0.05g, dehydrated alcohol 10mL, shaking makes to dissolve, and sets 4 DEG C and saves backup；
S liquid culture medium: S basal liquid 100mL, 1M citrate buffer solution 1mL, Trace liquid 1mL, 1M Adlerika
0.3mL, 1M calcium chloride solution 0.3mL, 5mg/mL cholesterol solution 0.1mL are uniformly mixed.
M9 buffer: sodium chloride 2.486g, disodium hydrogen phosphate 2.982g, potassium dihydrogen phosphate 1.496g, magnesium sulfate 0.06g,
Distilled water 500mL, shaking makes to dissolve, in 121 DEG C of sterilizing 20min；
Specific experiment step:
The culture of nematode: nematode is connect on the solid NGM plate for being coated with Escherichia coli OP50, then will be placed on 20 DEG C of training
It supports and is cultivated in case, nematode synchronization is carried out when nematode, which grows on adult and plank, ovum and young nematode.
Nematode synchronizes: being swept away the nematode on plate flushing liquor is sucked centrifuge tube with M9 buffer；4000rpm
It is centrifuged 3min, removes supernatant, M9 buffer then is being added, centrifugation is repeated several times, it is therefore an objective to by Escherichia coli wash clean；Add
Enter lysate (final concentration: 3.2%NaClO and 1M NaOH)；7min is shaken in vortex instrument, ruptures nematode, obtains ovum；
4000rpm is centrifuged 3min, removes supernatant, collects precipitating and obtains a large amount of line eggs；M9 buffer rinses twice, and 1mL M9 is added
Buffer is placed in 20 DEG C of incubators and hatches 48 hours.
Drug solution preparing: traditional medicine volatile oil extract is diluted to following concentration:
L:12.5 μ g/mL；M:25 μ g/mL；H:50 μ g/mL；HH:100 μ g/mL
Drug effect: the nematode synchronized is diluted to 80/20 μ L or so, in 96 orifice plates, is added in each hole
The cholesterol 20 μ L, 20 μ of medical fluid of Escherichia coli OP50 20 the μ L, 5mg/mL of above-mentioned 20 μ L, S liquid of nematode liquid 120 μ L, 10mg/mL
L, each concentration are arranged five in parallel.Medical fluid is not added in blank control group, and medical fluid is changed into isometric S liquid.20 DEG C of constant temperature incubations
To nematode maturation, the WT ratios (i.e. the nematode ratio of only one Kidney-Yin door) of nematode are detected under the microscope.With blank
Control group is compared, and the ratio of wild type is higher, illustrates that the effect of Drug inhibition ras activation is stronger.As a result as shown in the table:
Influence of the 2 traditional medicine volatile oil extract of table to Caenorhabditis elegans MT2124 (let-60 mutation) WT ratios
It * is the P < 0.05 compared with blank group
From table 2 it can be seen that traditional medicine volatile oil extract increases the WT ratios of Caenorhabditis elegans MT2124 significantly
Add, and be in concentration-dependent relation, illustrates that traditional medicine volatile oil extract acts on Ras access, to Ras/MAPK access excessive activation
There is obvious downward to act on, mutant is made to become wild type.Therefore, Chinese medicine extractive of volatile oil can act on Ras access, under
The excessive activation of the access has been adjusted, there is anti-tumor activity, it can be in the drug of preparation treatment ras proto-oncogene overexpression tumour
Middle application.
Effect of the three traditional medicine volatile oil extract of embodiment to Caenorhabditis elegans MT8189 (lin-15 mutation)
Lin-15 is located at the upstream of ras, is the suppressor of ras, after lin-15 deletion mutation, to the inhibiting effect of ras
It disappears, nematode shows more vaginal orifice phenotypes.Include in MT8189 (lin-15) nematode is wild type let60/ras copy, when
Traditional medicine volatile oil extract of the present invention can be such that the WT ratios of Caenorhabditis elegans MT2124 (let-60) obviously increase, and
When cannot inhibit more vaginal orifice phenotypes of MT8189 (lin-15) nematode, illustrate traditional medicine volatile oil extract of the present invention only to let-60
Tumour cell caused by ras excessive activation caused by being mutated works, and to wild type ras mistake caused by lin-15 deletion mutation
Tumour cell caused by degree activates does not work.Therefore, it was demonstrated that traditional medicine volatile oil extract of the present invention only acts on let-60
Tumour cell caused by ras excessive activation caused by being mutated, without acting on normal cell.
Experimental material: Caenorhabditis elegans MT8189, more vaginal orifice phenotypes, genotype: lin-15 (n765ts) X is purchased from
CGC；Escherichia coli OP50, uracil leaky mutant are purchased from CGC as the food of Caenorhabditis elegans.
Specific experiment step: with embodiment two.
Effect of the 3 traditional medicine volatile oil extract of table to Caenorhabditis elegans MT8189 (lin-15 deletion mutation)
As shown in table 3, traditional medicine volatile oil extract of the present invention cannot inhibit more vaginal orifice phenotypes of lin-15 (n765), according to
The upper principle of heredity, two experimental result of embodiment show the reversible let60/ downstream of traditional medicine volatile oil extract of the present invention
More vaginal orifice phenotypes caused by ras proto-oncogene excessive activation, i.e., traditional medicine volatile oil extract of the present invention cannot inhibit let60/ras
More vaginal orifice phenotypes of upstream gene lin-15 (n765).This is because include in lin-15 (n765) nematode is wild type
Let60/ras copy, let60/ras excessive activation caused by traditional medicine volatile oil extract of the present invention is only mutated let-60
Tumour works, insensitive to the tumour of let60/ras excessive activation caused by lin-15 deletion mutation, i.e., Chinese medicine of the present invention is waved
Hair oil extract only acts on tumour cell caused by ras excessive activation caused by let-60 is mutated, normal without acting on
Cell.
Effect of the example IV traditional medicine volatile oil extract to Caenorhabditis elegans CB1275 (lin-1 deletion mutation)
Lin-1 is a gene in the downstream ras, and being can be the negative of vaginal orifice development by the nuclear factor of MAPK phosphorylation
Regulatory factor, the signal path of the vaginal orifice development in the adjustable downstream let-60.Lin-1 and lin-31 forms complex, lin-1
Encode ETS family member, and when lin-31 encodes helix transcription winged because of, ras signal un-activation, lin-1 is mutual with lin-31
Effect composition complex, this complex prevent their expression in conjunction with the actuating section of oopod functional gene.lin-1
After deletion mutation, complex can not just be formed, and complex cannot be formed, can not be with the actuating section knot of oopod functional gene
It closes, oopod gene expression, and then generates false vaginal orifice and develop to form more vaginal orifice phenotypes (Ferguson, 1989).
That is lin-1 is a gene in the downstream ras, is the negative growth factor of vaginal orifice development, after lin-1 deletion mutation, is produced
Egg apparatus gene expression, nematode show more vaginal orifice phenotypes, and traditional medicine volatile oil extract cannot inhibit more vaginal orifice phenotypes of lin-1,
Illustrate drug effect site in the upstream lin-1, rather than lin-1, i.e. drug lowered ras excessive activation rather than directly suppression
The development for having made vaginal orifice cell is worked.
Experimental material: Caenorhabditis elegans genotype: lin-1 (e1275) IV derives from CGC (Caenorhabditis
Genetics Center), it is purchased from CGC；Escherichia coli OP50, uracil leaky mutant, the food as Caenorhabditis elegans
Object is purchased from CGC.
Specific experiment step: with embodiment two
Embodiment two the result shows that Drug inhibition more vaginal orifice phenotypes of nematode, but this result only prompts drug significant
The site for lowering let-60/ras excessive activation is let-60 or downstream, is able to suppress the more of MT2124 (let-60 mutation)
The drug of vaginal orifice phenotype, it is same to handle Caenorhabditis elegans CB1275, if its more vaginal orifice phenotype cannot be inhibited, illustrate that drug is made
With site in the upstream lin-1.Further, since lin-1 is nuclear factor, interacts with lin-31 and form complex, adjusts
The process of vaginal orifice cell development.If drug has significant inhibiting effect to more vaginal orifice phenotypes of the gene Inactivating mutations, illustrate
Drug can directly inhibit the development of vaginal orifice precursor, it is prevented to form more vaginal orifice phenotypes, it can inhibit ras proto-oncogene mistake
That expresses is antitumor.
Effect of the 4 traditional medicine volatile oil extract of table to Caenorhabditis elegans CB1275 (lin-1 deletion mutation)
As shown in table 4, more vaginal orifice phenotypes of CB1275 strain nematode are not affected by the influence of traditional medicine volatile oil extract, this table
Bright drug effect can inhibit more vaginal orifice phenotypes that ras excessive activation caused by let-60 is mutated is formed in Ras signal path, cannot
The more vaginal orifice phenotypes for inhibiting lin-1 deletion mutation to be formed illustrate that traditional medicine volatile oil extract of the present invention acts on ras without acting on
In lin-1, it was demonstrated that drug has lowered the excessive activation of ras rather than the Proliferation, Differentiation of cell is directly inhibited to work, i.e.,
It is Ras pathways dependence ground that traditional medicine volatile oil extract of the present invention, which works, rather than extensive cytotoxicity.
The work of five traditional medicine volatile oil extract of embodiment and simple to Caenorhabditis elegans MT2124 (let-60 mutation)
With
Experimental material: with embodiment two.
Each single pharmaceutical quantities keep crude drug amount consistent with traditional medicine volatile oil extract.
Each simple of table 5 and traditional medicine volatile oil compound extract crude drug amount
Specific experiment step: with embodiment two.
The effect of 6 traditional medicine volatile oil extract of table and volatile clove oil to Caenorhabditis elegans MT2124 (let-60 mutation)
Compare
The effect of 7 traditional medicine volatile oil extract of table and amomum fruit volatile oil to Caenorhabditis elegans MT2124 (let-60 mutation)
Compare
8 traditional medicine volatile oil extract of table and Chinese anise volatile oil are to Caenorhabditis elegans MT2124's (let-60 mutation)
Effect is compared
The effect of 9 traditional medicine volatile oil extract of table and Cortex Cinnamomi volatile oil to Caenorhabditis elegans MT2124 (let-60 mutation)
Compare
10 traditional medicine volatile oil extract of table and white pepper volatile oil are to Caenorhabditis elegans MT2124's (let-60 mutation)
Effect is compared
The work of 11 traditional medicine volatile oil extract of table and volatile oil of Radix Aucklandiae to Caenorhabditis elegans MT2124 (let-60 mutation)
With comparing
The work of 12 traditional medicine volatile oil extract of table and Rhizoma Zingiberis volatile oil to Caenorhabditis elegans MT2124 (let-60 mutation)
With comparing
As shown in table 6-12, the anti-tumor activity for the Chinese medical extract volatile oil that preparation method of the present invention is prepared
Obviously higher than the anti-tumor activity of simple volatile oil.
The work of five traditional medicine volatile oil extract of embodiment and eugenol to Caenorhabditis elegans MT2124 (let-60 mutation)
With
Prior art discovery is retrieved, eugenol has antitumor activity, and therefore, the present embodiment is extracted with regard to traditional medicine volatile oil
The effect of object and eugenol in the tumour for inhibiting ras proto-oncogene excessive activation compares, and experimental result is as follows:
The effect ratio of 13 traditional medicine volatile oil extract of table and eugenol to Caenorhabditis elegans MT2124 (let-60 mutation)
Compared with
As shown in table 13, although eugenol also shows the effect for inhibiting ras proto-oncogene to be overexpressed, the present invention is public
The anti-tumor activity for the traditional medicine volatile oil extract opened is significantly higher than the anti-tumor activity of eugenol, it can be seen that, present invention warp
The traditional medicine volatile oil extract for crossing rational proportion and extraction process acquisition realizes synergistic technical effect.
Therefore, the present invention relates to Chinese medicine compositions and its extractive of volatile oil is overexpressed tumour in treatment ras proto-oncogene
Application, and in particular to tumour be liver cancer, cancer of pancreas, lung cancer and colon cancer.The Chinese medicine composition and traditional medicine volatile oil extract
Object is not to rely on extensive cytotoxicity to the therapeutic effect of ras gene overexpression tumour, but specific downregulation ras is former
The overexpression of oncogene；Ras excessive activation caused by the Chinese medicine composition and traditional medicine volatile oil extract are only mutated let-60
Caused tumour cell works, and to tumour cell caused by wild type ras excessive activation caused by lin-15 deletion mutation
It not working, i.e. the traditional chinese medicine composition of the invention and traditional medicine volatile oil extract acts only on cancer cell, normal cell is not acted on,
Not teratogenesis, application are safe.
Claims (10)
1. a kind of Chinese medicine composition, which is characterized in that the Chinese medicine composition is made of raw material from the following weight: 5 parts of cloves,
5 parts of fructus amomi, 3 parts of Chinese anise, 8 parts of cortex cinnamomi, 3 parts of white pepper, 3 parts of radix aucklandiae, 5 parts of rhizoma zingiberis.
2. a kind of traditional medicine volatile oil extract, which is characterized in that the traditional medicine volatile oil extract by 5 parts of cloves, 5 parts of fructus amomi,
3 parts of Chinese anise, 8 parts of cortex cinnamomi, 3 parts of white pepper, 3 parts of radix aucklandiae, 5 parts of rhizoma zingiberis be made, the preparation method is as follows: taking the fourth of aforementioned proportion
Perfume, fructus amomi, Chinese anise, cortex cinnamomi, white pepper, radix aucklandiae, rhizoma zingiberis are added distilled water and are waved using extraction by steam distillation
Hair oil extract crude product, the volatile oil extract crude product are extracted with organic solvent again, are extracted resulting organic phase and are volatilized solvent, are taken off
Water is dry, obtains traditional medicine volatile oil extract.
3. traditional medicine volatile oil extract according to claim 2, which is characterized in that the mark of the traditional medicine volatile oil extract
Will chemical constituent contains eugenol 42.43-59.19%, Acetyl eugenol 13.05-15.28%, anethole 10.02-
13.11%, carypohyllene 2.07-2.88%, Bronyl acetate 1.3-1.71%.
4. a kind of traditional medicine volatile oil extract according to claim 3, which is characterized in that the traditional medicine volatile oil extract
Density be 1.0~1.1g/mL.
5. Chinese medicine composition application in preparation of anti-tumor drugs according to claim 1.
6. Chinese medicine composition application in preparation of anti-tumor drugs according to claim 5, which is characterized in that described
Tumour is as caused by being overexpressed after ras Oncogene Mutation.
7. Chinese medicine composition application in preparation of anti-tumor drugs according to claim 6, which is characterized in that described
Tumour is liver cancer, cancer of pancreas, lung cancer and colon cancer.
8. traditional medicine volatile oil extract application in preparation of anti-tumor drugs according to claim 2.
9. traditional medicine volatile oil extract application in preparation of anti-tumor drugs according to claim 8, which is characterized in that
The tumour is as caused by being overexpressed after ras Oncogene Mutation.
10. traditional medicine volatile oil extract application in preparation of anti-tumor drugs according to claim 9, feature exist
In the tumour is liver cancer, cancer of pancreas, lung cancer and colon cancer.
Priority Applications (3)
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| WO2020147275A1 (en) | 2020-07-23 |
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