CN101830945A - Arteannuin derivative and use thereof - Google Patents
Arteannuin derivative and use thereof Download PDFInfo
- Publication number
- CN101830945A CN101830945A CN201010179468A CN201010179468A CN101830945A CN 101830945 A CN101830945 A CN 101830945A CN 201010179468 A CN201010179468 A CN 201010179468A CN 201010179468 A CN201010179468 A CN 201010179468A CN 101830945 A CN101830945 A CN 101830945A
- Authority
- CN
- China
- Prior art keywords
- derivative
- tumor
- tumour
- radiation
- radiotherapy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the field of medicinal compounds and relates to an arteannuin derivative, a preparation method thereof and use thereof. The molecular formula of the arteannuin derivative is C24H41O9N; and the arteannuin derivative is in strict accordance with the two major basic characteristics of radiosensitizers, so when used alone (in normal dose of a tumor radiosensitizer), the arteannuin derivative does not kill cells, but only sensitizes the tumor cells. The arteannuin derivative has the tumor radiosensitization effect of a broad spectrum.
Description
Technical field
The invention belongs to the medical compounds field, relate to a kind of artemisinin derivative and application thereof, be specifically related to the application of artemisinin derivative as the tumour radiotherapy hypersitization medicine.
Background technology
Malignant tumour in the world, cardiovascular disorder and acquired immune deficiency syndrome (AIDS) are three big diseases of serious threat human health.Along with China resident's the mode of life and the change of home environment, the newly-increased case load of the cancer of China is rising year by year, and the incidence of some malignant tumours and mortality ratio are obvious ascendant trend.Most of in the world malignant tumours also do not have the method for radical cure at present, and the main means that are used for oncotherapy have operation, radiotherapy, chemotherapy, biotherapy and other (endocrine therapy, traditional Chinese medical herbal treatment, thermotherapy and radiofrequency ablation therapy) treatment etc.
Tumour radiotherapy (abbreviation radiotherapy) is exactly to use the radiation cure cancer.The development in century more than one has been experienced in radiotherapy.After the roentgen finds that X line, Madame Curie find radium, be respectively applied for the clinical treatment malignant tumour soon, radiotherapy up to this point is still the important methods of treatment of malignant tumour.About 70% cancer patient needs to use radiotherapy in the process of treatment cancer, have 40% cancer to effect a radical cure with radiotherapy approximately.The tumour that has is through radiotherapy even can cure or replace operative treatment, as nasopharyngeal carcinoma, the esophageal carcinoma, lymphoma etc.All need radiotherapy to be consolidated and improve curative effect after the more cancer patient chemotherapy, promptly complementary radiotherapy.Therefore, effect and the status of radiotherapy in oncotherapy becomes increasingly conspicuous.Radiotherapy has become one of main means of treatment malignant tumour.Radiotherapy mechanism comprises (1) coup injury effect, promptly mainly directly acts on organic molecule by ray and produces free radical and cause that dna molecular fracture occurs, intersects; (2) indirect injury effect, promptly mainly by ray to water generation ionization in the tissue, produce free radical, these free radicals are had an effect with biomacromolecule again, cause irreversible damage.Two kinds of effects have equal importance.
Though the effect of radiotherapy in the treatment malignant tumour is very remarkable undoubted, also will see the existence of radiation reaction and damage.The high dosage ray kill cancer cells simultaneously also can major injury healthy tissues and organ around the tumour, untoward reaction in various degree will appear in patient, as hemocytopenia, vomiting, different tissues or organ inflammation.Therefore, how to make radiotherapy can suppress and kill tumour cell to greatest extent, reducing as far as possible again or not producing healthy tissues and cells injury is that the order of formulating the tumor radiotherapy plan also is one of important problem of radiotherapy research circle.
Radiation sensitization medicine (a kind of tumour cell or tissue medicine responsive more to radiotherapy of making) is a new focus of tumor radiotherapy research field in recent years.Developing new antitumor drug has become the tumor research field of the hot topic that receives much concern both at home and abroad, also meets the current research direction of China, has certain meaning to improving China basis and using the medical research level.Fundamental research at present and clinical application are used another kind of (or multiple) medicine to some confusion in the use of radiation sensitization notion in the time of every radiotherapy, curative effect has increased, and has just said so enhanced sensitivity.This is the academic concept of having obscured radiation sensitization in fact.The biological effect that medicine and ray are superimposed roughly has three kinds of situations, that is: addition, reinforcement or enhanced sensitivity.Addition is the simple addition of two kinds of biological effects, 1+1=2.Strengthen or enhancing, the biological effect that refers to ray is 1, and the biological effect of medicine is less than 1, and the last biological effect of both additions is 2,1+＜1=2.The biological effect that the enhanced sensitivity of real academic significance refers to ray is 1, and the biological effect of medicine is 0 (or very little), and the biological effect after both additions is 2,1+0=2.So radiation sensitization medicine truly, must possess two characteristics: (1) itself does not have (or almost not having) to the tumor treatment effect; (2) only tumour cell there is sensitization.Hypersitization medicine will must provide the data of these two features by the evaluating of expert and pharmaceutical control and administration department.
The research of radiation sensitization pharmaceutical field mainly concentrates on (1) research at the radiosensitizer of tumor hypoxia cell in the world at present, as nitro glyoxaline radiosensitizer and sodium glycididazole etc.Because tumour cell usually is under weary oxygen environment; (2) research of the radiosensitizer of the dna damage reparation of inhibition radiation generation is as gemcitabine and sodium glycididazole; (3) research of the radiosensitizer of Cycle Regulation is as UCN-01 and caffeine; (4) regulate the medicine of cytogene and the research that protein antibodies is used, as the Cos-2 inhibitor; (5) at the research of aspects such as the relevant tumor suppressor gene regulation and control of radiotherapy, as with p53, tumor suppressor genes such as pTEN directly import to tumour and the research that produces radiation sensitization; (6) research of existing clinical tumor chemotherapeutics and radiotherapy radiation sensitization that combined utilization produces.As endoxan, Fluracil, VP-16, bleomycin, ametycin, (hydroxyl) camptothecine, taxol, Zorubicin etc.; (7) other research comprises research of photosensitizers Photofrin and multiple other porphyrin radiosensitizing effects or the like.Nitro glyoxaline radiosensitizer at the radiosensitizer of anoxic cell is the antitumor radiation sensitization medicine of a class that research both at home and abroad at present is comparatively ripe and have development prospect.The antitumor radiation sensitization medicine UCN-01 of Cycle Regulation has entered I or II phase clinical experiment.Also found extraordinary tumor radiotherapy effect of enhanced sensitivity by one class PTS, one sodium glycididazole of the country with independent intellectual property right that the researchist of China The 2nd Army Medical College develops.Though some radiosensitizer has entered in I phase or the II clinical trial phase, but clinical randomized controlled trial result shows in the III phase, the great majority test is failed, major cause is that toxicity (comprising neurotoxicity) has limited using dosage, causes tumour Chinese traditional medicine concentration not reach the enough concentration of enhanced sensitivity.In addition, most of radiation sensitization drug research substantially all fails to provide the experimental evidence of sensitization two big essential characteristics, that is: use the effect that does not have killer cell separately and only tumour cell is had sensitization.Whether therefore, even if proof chemotherapeutics and radiotherapy have the effect of mutual increase killer cell, maximum also can only be the effect of a kind of addition or reinforcement, be that the sensitization of academic significance waits to provide experimental evidence.In addition, the tumor-selective of existing most of radiation sensitization medicines, tumour-specific are not high or body had certain toxic action, and these have all limited the widespread use clinically of existing radiation sensitization medicine.Therefore, seek tumor-selective height, high specificity and cytotoxicity is little or the radiation sensitization medicine of no cytotoxicity is the important topic of domestic and international tumour radiotherapy circle.
Summary of the invention
The object of the invention provides a kind of artemisinin derivative.
For achieving the above object, the technical solution used in the present invention is: a kind of artemisinin derivative, and its chemical structural formula is:
In the technique scheme, the molecular formula of described artemisinin derivative is C
24H
41O
9N, this crystal easily is dissolved in acetone, vinyl acetic monomer, chloroform, benzene, Glacial acetic acid, ethanol, methyl alcohol, ether, sherwood oil and water; Fusing point is 143-144 ℃.
To further discovering of artemisinin derivative described in the technique scheme:
(1) pharmacological toxicology, only demonstrate different types of tumors cell (breast cancer, colorectal carcinoma leukemia, lymphoma, carcinoma of endometrium, cranial nerve knurl, carcinoma of the pancreas, liver cancer, cancer of the stomach and esophagus cancer) growth generation restraining effect according to the described artemisinin derivative of cell culture experiments in vitro data presentation at high dosage (＞250 μ M), be toxicity dose, these dosage are 240-250 times that described artemisinin derivative shows tumour cell radiation sensitization dosage; Simultaneously, for normal cell, the dosage of the described artemisinin derivative of dosage just demonstrates cell growth inhibition during greater than 560 μ M;
(2) described artemisinin derivative has the wide spectrum radiosensitizing effect: its SD
50(increasing the concentration of the required sensitizer of 50% radiotherapy susceptibility) is at different tumor cell lines (46 kinds of dissimilar human tumor cell lines, referring to table 1) be approximately between the 0.9-2.5 μ M, these dosage also only are the 0.1-0.5% of described artemisinin derivative cytotoxicity dosage; Simultaneously, reach same radiation sensitization effect in most of tumour cells, the used dosage of artemisinin derivative of the present invention only is 1/5 of artemisinine and other artemisinine derivative (comprising blue or green punt-pole amber ester, punt-pole methyl ether, arteether, two hydrogen artemisinine) dosage;
(3) artemisinin derivative of the present invention can increase the apoptosis that χ-beta radiation brings out, and is revealed as dose dependent;
(4) adopt three kinds of different tumor models (spontaneous tumor models, bringing out property tumor model and human tumor cell's Model in Nude Mice) finished radio therapy sensitization test in the animal body of artemisinin derivative of the present invention, the result shows that artemisinin derivative of the present invention all demonstrates very effective radio therapy sensitization effect at these three kinds of animal models.
Therefore, the present invention's application of claimed above-mentioned artemisinin derivative in preparation tumour radiotherapy hypersitization medicine simultaneously; The present invention is claimed a kind of tumour radiotherapy hypersitization medicine simultaneously, and the activeconstituents of described tumour radiotherapy hypersitization medicine is an artemisinin derivative of the present invention.
In the optimized technical scheme, artemisinin derivative concentration is smaller or equal to 5 μ mol/L in the tumor radio sensitization agent, and further in the optimized technical scheme, artemisinin derivative concentration is 2 μ mol/L～5 μ mol/L in the tumor radio sensitization agent.
Because the technique scheme utilization, the present invention compared with prior art has following advantage:
When 1, artemisinin derivative of the present invention is as the activeconstituents of tumour radiotherapy sensitizer, exceed 5-8 again doubly than the radio therapy sensitization effect of Artemisinin at identical dosage; Use this artemisinin derivative individual curing cell growth of low dosage not produce any influence, promptly do not have any cytotoxicity; And, more the good news is, compare with tumour cell, this artemisinin derivative need exceed the doubly above dosage of 10-15 could see its radiation sensitization effect at normal cell, therefore, this artemisinin derivative meets two big essential characteristics of radiation sensitization medicine fully, i.e. use separately (normal dosage as tumor radiotherapy sensitive-increasing agent) does not have the effect of killer cell and only tumour cell had sensitization.
2, artemisinin derivative of the present invention has the tumor radiotherapy effect of enhanced sensitivity of wide spectrum.
3, the parent substance Artemisinin of artemisinin derivative of the present invention has been used decades clinically, confirms that its side effect is few, is a medicine as safe as a house.Therefore, compare with existing radiation sensitization medicine, artemisinin derivative of the present invention has its very strong clinical application advantage.
Description of drawings
The apoptotic DNA agarose gel electrophoresis figure that Fig. 1 brings out for human breast cancer MDA-MB-231 cell radiation sensitization among the embodiment four;
Fig. 2 is difference in size figure after the radiotherapy of spontaneous tumor among the embodiment five;
Fig. 3 is difference in size figure after the breast cancer radiotherapy that chemical carcinogen DMBA brings out among the embodiment five;
Fig. 4 is difference in size figure after the radiotherapy of mouse papilloma among the embodiment five;
Fig. 5 is the molecular structure of embodiment one gained artemisinin derivative.
Embodiment
Below in conjunction with drawings and Examples the present invention is further described:
Embodiment one:
0.284g (1mmol) dihydroarteannuin is dissolved in the 20mL anhydrous methylene chloride, adds 2.00g (10mmol) polyoxyethylene glycol 500, bathe under the cooling at cryosel then, add the anhydrous AlCl of 0.01g (0.07mmol)
3(aluminum chloride) moments later removes ice bath, stirring at room.With thin plate chromatogram detection reaction process (GF2 silica-gel plate, 4-hydroxyl-3-methoxylbenxaldehyde, sulphuric acid soln colour developing).Question response is finished substantially, reaction solution is used saturated sodium bicarbonate solution (20mL * 3) successively, water (20mL * 2), saturated nacl aqueous solution (20mL * 3) washing is to being neutral, use anhydrous magnesium sulfate drying, filter, the pressure reducing and steaming solvent, remaining oily matter separates (petroleum ether-ethyl acetate mixed solvent gradient elution) through silica gel column chromatography, get 0.5g colorless oil compound behind the concentrating under reduced pressure, further purify, crystallization gets clear crystal (reference: Zhang Jianxin, Wang Junxia, Zhang Yu, etc. have the artemisinin derivative that contains polyethylene glycol groups synthetic of immunosuppressive action. Acta Pharmaceutica Sinica, 2006,41 (1): 65-7).
Identify above-mentioned clear crystal, getting its molecular formula is C
24H
41O
9N, this crystal easily is dissolved in acetone, vinyl acetic monomer, chloroform, benzene, Glacial acetic acid, ethanol, methyl alcohol, ether, sherwood oil and water; Fusing point is 143-144 ℃.
This crystalline molecular structural formula is referring to Fig. 5.
Annotate: green grass or young crops increases plain No. 1 and represents embodiment one gained artemisinine derivative in following examples.
Embodiment two, the pharmacological toxicology test:
Selected 46 kinds of dissimilar human tumor cell lines and 5 kinds of dissimilar human normal cell strains for use, cell culture method carries out the index cultivation routinely.The embodiment one gained artemisinin derivative of different concns (0-600 μ M) is added in the nutrient solution of cell of exponential growth.Use tetrazolium [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide, MTT] reduction method to measure the existence of cell after 24 hours.
Only just demonstrate according to above-mentioned cell culture experiments in vitro data presentation embodiment one gained artemisinin derivative that growth produces restraining effect, i.e. toxicity dose to the different types of tumors cell when high dosage (＞250 μ M).But for normal cell, when embodiment one gained artemisinin derivative dosage just demonstrates cell growth inhibition during greater than 560 μ M.
Embodiment three:
Selected 46 kinds of dissimilar human tumor cell lines and 5 kinds of dissimilar human normal cell strains for use, cell culture method carries out the index cultivation routinely.
Before χ-radiation exposure 24 or 48 hours, adopt in the nutrient solution of the artemisinine or derivatives thereof (comprising blue or green punt-pole amber ester, punt-pole methyl ether, arteether, two hydrogen artemisinine and embodiment one gained artemisinin derivative) of different concns (0-150 μ M) or the cell that other radiation sensitization medicine of having reported is added to exponential growth.
The ethanol of relative quantity (be used for dissolving artemisinine and its derivative) or other solvent also directly are added in the cell culture fluid as negative control, and these solvents not radiosensitivity of pair cell produce any influence.
Cell is accepted the χ-radiation exposure (0-10Gy) of various dose then.Use tetrazolium [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide, MTT] reduction method to measure the existence of cell after 24 hours.Adopt the concentration SD that the LOGIT method is calculated increases by 50% radiotherapy susceptibility
50Value is tested triplicate at least, the average SD of experiment
50As the final evaluation index of estimating external radiation sensitivity.
The result is as shown in table 1, and at different tumour cells and normal cell, different radiation sensitization medicines demonstrate different radiation sensitization effects.At the tumour cell of all detections, artemisinine and all artemisinine derivatives that detect here all demonstrate extraordinary radiation sensitization effect, SD
50Obviously the dosage than other radiation sensitization medicine of checking here is little.The radiation sensitization dosage pair cell of artemisinine and all artemisinine derivatives of detecting does not here produce any toxic effect.In all artemisinines and artemisinine derivative, the SD of embodiment one gained artemisinine derivative
50The dosage minimum, in other words, the radiation sensitization effect of embodiment one gained artemisinine derivative is best.And embodiment one gained artemisinine derivative shows the radiation sensitization effect of wide spectrum, its SD
50Also relatively more consistent at different tumor cell lines, approximately between the 0.9-2.5 μ M.These dosage also only are the 0.1-0.5% of embodiment one gained artemisinine derivative cytotoxicity dosage.Simultaneously, reach same radiation sensitization effect in most of tumour cells, the used dosage of embodiment one gained artemisinine derivative only is 1/5 of artemisinine and other artemisinine derivative doses.
The comparison of the different radiotherapy hypersitization medicine effect of enhanced sensitivity of table 1. is with SD
50(increase the dosage of 50% χ-ray radiotherapeutic effect, mean value (μ M) ± mean deviation, all test triplicate at least) for comparing index.
Annotate: CAF, caffeine; GEM, gemcitabine.HUVEC is the cell of positive human umbilical vein's endothelium; NHME is normal people's bronchial epithelial cell; HMEC is the normal human mammary epithelial cell; NHEK is normal people's keratinization of epidermis cell.
Embodiment four: embodiment one gained artemisinine derivative increases the apoptosis that radiation is brought out
In order whether to measure embodiment one gained artemisinine derivative radiation sensitization effect owing to increase the apoptosis that radiation is brought out.Adopt DNA agarose gel electrophoresis analytical procedure, under the embodiment one gained artemisinine derivative existence condition of having analyzed in various dose, the apoptotic result that radiation sensitization brings out.As shown in Figure 1, before human breast cancer MDA-MB-231 cell is accepted 5Gy χ-x radiation x, 24 hours pre-treatment of embodiment one gained artemisinine derivative can obviously increase the apoptosis that χ-x radiation x subsequently brings out, and can see that the dna fragmentation electrophoretic band degree that is uneven in length obviously increases.And the apoptosis that embodiment one gained artemisinine derivative increase χ-x radiation x brings out also is revealed as dose dependent.
Embodiment five: green grass or young crops increases plain No. 1 the interior radio therapy sensitization test of body
In-vivo tumour radio therapy sensitization test-results is to estimate the most important index of candidate radiotherapy hypersitization medicine validity.The animal transplanting tumor test is a most frequently used model in the screening anti-cancer agent.Therefore, the interior radio therapy sensitization test of animal body that we have adopted three kinds of different tumor models (spontaneous tumor model, bringing out property tumor model and human tumor cell's Model in Nude Mice) to finish embodiment one gained artemisinine derivative respectively is that clinical experiment is got ready to accumulate clinical preceding experimental data.
Test-results shows that embodiment one gained artemisinine derivative all demonstrates very effective radio therapy sensitization effect at these three kinds of animal models.The result of details is described below.In all experiments, all keep identical with the sex of animal in a collection of experiment, and the mouse of same strain is all adopted in the experiment of different batches.All experiments repeat twice at least, but most experiment has repeated three times at least.
(1) spontaneous tumor model
An abiogenous class tumour is referred to as spontaneous tumor without conscious artificial experiment disposal in the laboratory animal population.Selecting the spontaneous tumor type for use is that the advantage that object is studied is that spontaneous tumor is more more similar to the human tumour of being suffered from than the tumour of bringing out with experimental technique usually, help the experimentation on animals result pushed away and use the people, but can not obtain massive tumor at short notice and learn material, may use the people observing time than long and experiment, but can not obtain massive tumor at short notice and learn material, may expend bigger observing time than long and experiment.
We have adopted spontaneous knurl model to use maximum spontaneous breast cancers of C3H mouse.High incidence of breast cancer (spontaneous knurl can up to 70%) is arranged after the C3H mouse birth.We are divided into mouse four groups randomly: the control group of non-processor or irradiation, and χ-beta radiation irradiation group, green grass or young crops increases plain No. 1 group and green grass or young crops and increases element and add χ-beta radiation group No. 1.Every group of 10 mouse.All animal ears will be labeled so that follow the tracks of the growth history of mouse individual tumors.The C3H mouse of feeding at us takes place about nine months visible mammary gland position tumours greatly.It is significantly variant that the development of breast tumor and being grown in is not seen in each group.When tumor growth arrives the about 200mm of size
2After, green grass or young crops increases plain No. 1 group and green grass or young crops and increases and plainly add χ-beta radiation winding for No. 1 and be subjected to a Wednesday time 50mg/kg green grass or young crops to increase No. 1 intravenous injection of element totally two weeks, and then intravenous injection physiological saline is organized in the control group of non-processor or irradiation and χ-beta radiation irradiation.χ-beta radiation irradiation group and blue or green increasing plainly add χ-beta radiation group No. 1 and accept the χ of 7Gy-ray localization irradiation biweekly then.Between the light period, green grass or young crops increases plain No. 1 group and blue or green increasing plainly adds 50mg/kg green grass or young crops that χ-beta radiation group continues to accept Wednesday time for No. 1 and increase plain No. 1 intravenous injection and finish (irradiation two weeks of back) until experiment.When experiment finishes, carefully measure tumour size and the record of each mouse.Being measured as 2-3 time weekly of tumour size claims mouse heavy at every turn when measuring.
The calculation formula of gross tumor volume is: V=π/6 * a * b * c, wherein a, b and c represent length and width and height respectively.And adopt distribution free graceful Whitney U-check way to check the difference of tumour size between the experimental group.P＜0.05 is decided to be notable difference.Claim mouse heavy during each the measurement, body weight during body weight when calculating relative body weight (RWT)=test/on-test.As shown in Figure 2, tumour increases the control group mice growing tumors size no significant difference (p＞0.05) of plain No. 1 group mouse growing tumors size and non-processor or irradiation green grass or young crops.Compare with these control groups, χ-beta radiation irradiation group (p＜0.01) and green grass or young crops increase and plain add χ-beta radiation group mouse tumor (p＜0.005) No. 1 and then obviously reduce, and plain to add χ-beta radiation group mouse tumor No. 1 littler than χ-beta radiation irradiation group mouse tumor but green grass or young crops increases.Green grass or young crops increases and plain adds χ-beta radiation group mouse tumor No. 1 and χ-beta radiation irradiation group mouse body weight there is no significant difference.These data show that green grass or young crops increases the radiation sensitivity that element can obviously increase spontaneous tumor for No. 1.
(2) bringing out property tumor model
All can in all kinds of animals, bring out different types of tumors with chemical carcinogen, ray or virus.From the nosetiology angle analysis, it and human tumor are comparatively approximate, so model is usually used in specific further investigation.Now existing very sophisticated bringing out property tumor model can bring out breast cancer as extensive chemical carcinogens DMBA (DMBA) and methyl-cholanthrene.Therefore we adopt DMBA to bring out the female rats breast cancer to test and detect green grass or young crops and increase plain No. 1 radio therapy sensitization effect.The male mouse of the Sprague-Dawley of 2 moonrat sizes in age, single filling hello DMBA20 microgram/3 times was altogether finished in the week.The bimester rear udder attachment position visible tumor growth, success ratio is about 75%.Approximately April, tumour was long to 170mm
2Divide into groups by the experimental program of describing in the above spontaneous tumor model and handle in the size back.Every group of 10 rats.When experiment finishes, carefully measure tumour size and the record of each rat.And adopt distribution free graceful Whitney U-check way to check the difference of tumour size.Erect image is shown in Figure 3, and green grass or young crops increases plain No. 1 and adds χ-beta radiation group rat tumor than being untreated or the blue or green tumour obviously little (p＜0.005) that increases the control group of plain No. 1 individual curing, also comes for a short time than the tumour (p＜0.01) of χ-beta radiation irradiation group.These data show that green grass or young crops increases plain No. 1 and can obviously increase the breast cancer radiation sensitivity that chemical carcinogen DMBA brings out.
We also adopt DMBA to bring out the papilloma model.Both respectively be coated with a place with acetone solution DMBA 150 micrograms at male rat two side skin of back, and be coated with 21 days altogether, the 3rd week back is coated with totally 3～April weekly 2 times with Oleum Tiglii 0.5mg at same position.As knurl＞5mm
2Begin after the size to carry out grouping of cancer piece size animal and processing by the experimental program of describing in the above spontaneous tumor model.Every group of 10 mouse.When experiment finishes, carefully measure tumour size and the record of each mouse.And adopt distribution free graceful Whitney U-check way to check the difference of tumour size.It is minimum that the size of the tumor growth that erect image is shown in Figure 4, green grass or young crops increase the plain tumour that adds χ-beta radiation group mouse for No. 1, some tumour all measured less than.These experimental datas show has injected that blue or green to increase plain No. 1 mouse papilloma responsive more to χ-line radiotherapy, and tumor growth has been subjected to inhibition significantly.
Claims (3)
1. an artemisinin derivative is characterized in that, described artemisinin derivative chemical structural formula is:
2. the application of the described artemisinin derivative of claim 1 in preparation tumour radiotherapy hypersitization medicine.
3. a tumour radiotherapy hypersitization medicine is characterized in that it is artemisinin derivative that the activeconstituents of described tumour radiotherapy hypersitization medicine is arranged.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010179468A CN101830945A (en) | 2010-05-24 | 2010-05-24 | Arteannuin derivative and use thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010179468A CN101830945A (en) | 2010-05-24 | 2010-05-24 | Arteannuin derivative and use thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101830945A true CN101830945A (en) | 2010-09-15 |
Family
ID=42715181
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201010179468A Pending CN101830945A (en) | 2010-05-24 | 2010-05-24 | Arteannuin derivative and use thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101830945A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105198898A (en) * | 2015-09-23 | 2015-12-30 | 山东大学（威海） | Compound for preventing and/or treating cancer |
-
2010
- 2010-05-24 CN CN201010179468A patent/CN101830945A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105198898A (en) * | 2015-09-23 | 2015-12-30 | 山东大学（威海） | Compound for preventing and/or treating cancer |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103570695A (en) | Preparation of icaritin and derivatives thereof and application of icaritin and derivatives of icaritin in radiotherapy | |
| CN102614536B (en) | Cell apoptosis imaging medicament 68Ga-NOTA-Duramycin and preparation method thereof | |
| Qian et al. | Minimizing adverse effects of Cerenkov radiation induced photodynamic therapy with transformable photosensitizer-loaded nanovesicles | |
| CN103396419A (en) | Tumour photodynamic therapy medicine dihydroporphin e6-15-ethyl ester and preparation method thereof | |
| Wang et al. | Aggregation-Induced Emission Photosensitizer Synergizes Photodynamic Therapy and the Inhibition of the NF-κB Signaling Pathway to Overcome Hypoxia in Breast Cancer | |
| CN104398526A (en) | Application of triptolide and tripterine in preparation of antitumor drugs | |
| CN103143013B (en) | Photosensitive medicinal preparation containing amino poly-carboxylic acid modification tetraphenylporphyrin compound and purpose thereof | |
| Tan et al. | Erchen plus huiyanzhuyu decoction inhibits the growth of laryngeal carcinoma in a mouse model of phlegm-coagulation-blood-stasis syndrome via the STAT3/Cyclin D1 pathway | |
| CN106267238A (en) | A kind of metal fullerene complex and preparation method and application | |
| CN103191095B (en) | A kind of STAT3 signal path micromolecular inhibitor and the application in preparing antitumor drug thereof | |
| CN101830945A (en) | Arteannuin derivative and use thereof | |
| CN1995020B (en) | Radioactive iodine-17- allylamino-17-demethoxygeldanamycin and its preparation method | |
| CN105198934B (en) | The platinum-like compounds of Photodynamic activity near infrared absorption, preparation method and applications | |
| CN102772406B (en) | Novel application method of treating psoriasis by oxymatrine | |
| US20130267757A1 (en) | Anthraquinones for use as radiosensitizers in cancer treatment | |
| CN102363044B (en) | Application of three anthraquinone substances of targeted mitochondria as nasopharyngeal darcinoma radiosensitizers | |
| CN105566147B (en) | A kind of compound and its production and use and corresponding targeting drug delivery system and chemotherapeutics | |
| CN102772405A (en) | Novel application method of treating psoriasis by matrine | |
| CN101862339A (en) | Use of cryptotanshinone as radiation sensitizing medicament in oncotherapy | |
| CN107903258B (en) | Fat-soluble photosensitizer and preparation method and application thereof | |
| Zhang et al. | Absorption characteristics of combination medication of realgar and Indigo Naturalis: in vitro transport across MDCK-MDR1 cells and in vivo pharmacokinetics in mice after oral administration | |
| CN102114047B (en) | Woodlouse lyophilized powders 1 and 2 prepared by combined enzymolysis of pepsin and trypsinase and application thereof | |
| CN1321127C (en) | Iodine (I)-23-hydroxyl betulinic acid, rpeparation method and application thereof | |
| Li et al. | Cancer photodynamic therapy with chlorin e6-loaded, goat milk-derived extracellular vesicles:[18F] FDG lights up the way | |
| US10058611B2 (en) | Use of α-(8-quinolinyloxy) mono-substituted phthalocyanine zinc for treatment of psoriasis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Open date: 20100915 |