CN101485666B - Application of Gamabufotalin and salt thereof in preparing medicament for treating gynaecologic tumor - Google Patents
Application of Gamabufotalin and salt thereof in preparing medicament for treating gynaecologic tumor Download PDFInfo
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Abstract
The invention provides application of gamabufotalin and a salt compound thereof in preparation of a medicine for treating gynecological tumor. By comparing in vitro anti-cancer experiments of a bufadienolide extract and monomeric compounds, namely the gamabufotalin, cinobufagin, bufalin and bufotalin as well as hydrochlorides or sulfates of the four compounds to four gynecological tumors, namely human ovarian cancer cells A2780, human ovarian cancer cells SK-OV-3, human cervical carcinoma cells and human endometrial cancer cells, an experimental result shows that the gamabufotalin has stronger activity against gynecological tumor cells than the bufadienolide extract and the monomeric compounds, namely the cinobufagin, the bufalin and the bufotalin, and the hydrochloride or the sulfate of the gamabufotalin has stronger activity against gynecological tumor cells than the hydrochlorides or the sulfates of three compounds, namely the cinobufagin, the bufalin and the bufotalin. The gamabufotalin and the salt compound thereof provided by the invention have the advantages of clear components, controllable quality, strong anti-cancer activity, and small adverse reaction, and are expect tobe developed into a novel anti-cancer drug.
Description
Technical field
The present invention relates to the new purposes of Gamabufotalin and salt thereof, specifically relate to the application in preparation treatment gynecological tumor medicine of Gamabufotalin and salt thereof.
Background technology
Gynecological tumor is the major disease of harm WomanHealth, and common malignancy comprises carcinoma of endometrium, cervical cancer, breast carcinoma, ovarian cancer etc., and the cervical cancer prevalence is only suffered from by China and case fatality rate all accounts for the world 1/3rd.The conventional therapeutic scheme that adopts of the domestic and international medical circle of treatment gynecological tumor is chemotherapy, radiotherapy and excision etc.This scheme is when obtaining certain clinical efficacy, also because of the toxic and side effects of chemicals, the radiation injury that radiotherapy causes, and the cutting entirely or iatrogenic problem and corresponding disease that part excision etc. causes of operation plan sexual organ, bring huge misery to the patient, had a strong impact on women's life and health and quality of life.
The Chinese medicine Venenum Bufonis is Bufonidae animal Bufo siccus (Bufo bufo gargarizans Cantor) or the ear rear gland of Bufo melanostictus and the white serosity of skin gland secretion, makes through dry processing.Have heat-clearing and toxic substances removing, reducing swelling and alleviating pain, the refreshment effect of having one's ideas straightened out.Tcm clinical practice is used it for anesthesia, furuncle carbuncle, heatstroke vomiting and diarrhoea, laryngopharynx swelling and pain, toothache, heart failure, cancer etc.
Contain a large amount of bufotoxin class materials in the Venenum Bufonis, this type of material belongs to steroid, be bufadienolide biotransformation class (bufadienolide, bufadienolide), it is a class connects hexa-atomic unsaturated lactone ring (α-pyrone ring) in C-17 β position 24C cardenolide compounds, comprise that bufogenin, cinobufagin, Toadpoison Medicine (Bufalin), bufotalien (Bufatalin), Gamabufotalin (claim a day bufotoxin again, Gamabufotalin) etc.In application and research in the past, the bufadienolide biotransformation compounds is mainly used in the disease of treatment cardiovascular system aspect, as be used to strengthen myocardial contraction, be usually used in treating the heart failure disease clinically, though part Venenum Bufonis preparation is used for the treatment of leukemia clinically, the gastric cancer tumor disease, but do not see that handlebar bufadienolide biotransformation compounds is used for the gynecological tumor disease, and present Bufo siccus preparation, be used as medicine in the majority with the runic thing, complicated component removes and contains bufotalin, bufotoxin, outside the indoles alkaloid, also contain aminoacid, reducing sugar, the steroid class, polytype chemical constituents such as peptide class.Therefore, in clinical use, the Bufo siccus preparation has multiple shortcoming, anaphylaxis occurs, and the vascular stimulation symptom is used for the gynecological tumor treatment of diseases thereby adverse reaction rates such as digestive tract and cardiac toxicity height has limited it.
Summary of the invention
Technical problem to be solved by this invention is to overcome present Bufo siccus preparation complicated component, and the adverse reaction rate height is provided as and distinguishes one from the other, and is quality controllable, is the application of active component preparation treatment gynecological tumor disease medicament with Gamabufotalin and salt thereof.
The Gamabufotalin structural formula is:
Gamabufotalin salt compound provided by the invention specifically is a Gamabufotalin and hydrochloric acid, sulphuric acid, the acid of amber glass or hydrochlorate, sulfate, amber glass hydrochlorate or nitrate that nitric acid became.
Gamabufotalin provided by the invention and salt thereof and pharmaceutically acceptable carrier such as diluent, excipient, filler, binding agent, wetting agent, disintegrating agent, absorption enhancer, surfactant, absorption carrier, lubricant etc. can also add flavouring agent, sweeting agent etc. in case of necessity and be prepared into treatment gynecological tumor medicine.
Medicine of the present invention can be prepared into multiple dosage forms such as injection, tablet, injectable powder, granule, capsule, oral liquid, unguentum, cream by the pharmaceutical field conventional method.
When making tablet, Gamabufotalin provided by the invention and Gamabufotalin salt, add magnesium stearate lubricant when needing Gamabufotalin or Gamabufotalin salt and carrier lactose or corn starch, mix homogeneously, and tabletting is made tablet then.When Gamabufotalin provided by the invention and Gamabufotalin salt are made capsule Gamabufotalin or Gamabufotalin salt and carrier lactose or corn starch mix homogeneously, granulate, the encapsulated then capsule of making.When Gamabufotalin provided by the invention and Gamabufotalin salt are made granule, Gamabufotalin or Gamabufotalin salt and diluent lactose or corn starch mix homogeneously, granulate, drying is made granule.When Gamabufotalin provided by the invention or Gamabufotalin salt are made injection, get Gamabufotalin or Gamabufotalin salt adding physiological saline solution and add activated carbon then, stir, 80 ℃ were heated 30 minutes, filter, regulate pH value, be filtered to clear and bright with sintered glass funnel or other filter, fill was made injection in 30 minutes 100 to 115 ℃ of sterilizations.
The gynecological tumor of Gamabufotalin provided by the invention and Gamabufotalin salt comprises ovarian cancer, cervical cancer, carcinoma of endometrium or breast carcinoma etc.
Further investigate through the applicant, bufadienolide biotransformation extract and monomeric compound Gamabufotalin, cinobufacin, the hydrochlorate of Toadpoison Medicine and bufotalien and above four monomeric compounds or sulfate show that by anticancer experiment in vitro human breast carcinoma, ovarian cancer, cervical cancer, the different gynecological tumor cells of carcinoma of endometrium are all had stronger inhibition activity, and have dose-effect relationship preferably, experimental result shows that the anticancer effect of bufadienolide biotransformation compounds is better than the taxol that is widely used in the gynecological tumor treatment clinically.Find that by contrast IC50 value Gamabufotalin has the cinobufacin of ratio, the better gynecological tumor activity of Toadpoison Medicine or bufotalien, and the hydrochlorate of Gamabufotalin or sulfate also have than cinobufacin, the hydrochlorate of Toadpoison Medicine or three chemical compounds of bufotalien or the better gynecological tumor cell activity of sulfate.
The preparation of bufadienolide biotransformation chemical compound: get Venenum Bufonis 50g, with twice of ethyl acetate extraction, extract gets the 12.6g extract through 40 ℃ of concentrating under reduced pressure, and extract is mixed equivalent silica gel, carries out silica gel (200 orders are to 300 orders) column chromatography, with petroleum ether-acetone (1: 1) eluting, thin layer chromatography is followed the tracks of, and obtains effective site bufadienolide biotransformation extract, and the bufadienolide biotransformation extract is prepared the liquid phase purification, obtain monomeric compound Gamabufotalin, cinobufacin, Toadpoison Medicine and bufotalien.
The preparation of bufadienolide biotransformation salt: get cinobufacin, Toadpoison Medicine, bufotalien or Gamabufotalin 20mg add 10ml hydrochloric acid, sulphuric acid, the acid of amber glass or nitric acid 50 ℃ of following reflux 30 minutes, get reactant and mix equivalent silica gel, carry out silica gel (200 orders are to 300 orders) column chromatography, with petroleum ether-acetone (1: 1) eluting, thin layer chromatography is followed the tracks of, and obtains cinobufacin, Toadpoison Medicine, the salt of bufotalien or Gamabufotalin.
The present invention, compared with prior art has the following advantages as object of study with gynecological tumor:
1, Gamabufotalin and salt active component thereof are clear, quality controllable, and gynecological tumor is active strong;
2, the effective dose of Gamabufotalin and salt thereof inhibition gynecological tumor cell proliferation is less, and potential side effect is also little, uses safer;
3, Gamabufotalin and salt gynecological tumor effect thereof are better than the taxol that is widely used in the gynecological tumor treatment clinically, be expected to become the new drug of gynecological tumor, and resource are extensive, is easy to get, and cost is lower;
4, Gamabufotalin and salt energy thereof are prepared into different pharmaceutical dosage forms with different excipient, can make things convenient for clinical practice.
The specific embodiment:
Below in conjunction with specific embodiment, further illustrate the present invention, should understand these embodiment only is used to the present invention is described and is not used in and limit the scope of the invention, after having read the present invention, those skilled in the art all fall within the application's claims institute restricted portion to the modification of the various equivalent form of values of the present invention.
The employed experiment material of following examples is as follows:
Cell strain: Proliferation of Human Ovarian Cell (A2780), Proliferation of Human Ovarian Cell (SK-OV-3), human cervical carcinoma cell (SiHa) and people's endometrial carcinoma cell (shikawa) are provided by Nanjing University of Traditional Chinese Medicine pharmacological evaluation chamber; 96 orifice plates are available from Costar company; The RMPI1640 culture medium is available from Gibco company; The DMEM culture medium is available from Gibco company; McCoys 5A culture medium is available from SIGMA company; New-born calf serum is available from Hangzhou Ilex purpurea Hassk.[I.chinensis Sims company; Tetrazolium bromide (MTT) and DMSO are available from Amresco company; Paclitaxel injection is available from Haikou Pharmaceutical Factory Co., Ltd.'s (lot number: 080502).MCS-1: bufadienolide biotransformation extract, MCS-1-2: cinobufacin (cinobufagin), MCS-1-3: Toadpoison Medicine (bufalin), MCS-1-4: bufotalien (bufotalin) and MCS-1-5: Gamabufotalin (gamabufotalin), the cinobufacin hydrochlorate, the Toadpoison Medicine hydrochlorate, the bufotalien hydrochlorate, the Gamabufotalin hydrochlorate, cinobufacin sulfate, Toadpoison Medicine sulfate, bufotalien sulfate and Gamabufotalin sulfate are that Nanjing University of Traditional Chinese Medicine's prescription prepared in laboratory obtains.
The employed experimental apparatus of following examples is as follows:
Experimental apparatus: superclean bench (Suzhou purifies model SW-CJ-IFD), CO
2Incubator (the SANYO model: XD-101), microplate reader BIO-RAD (Model NO.550 Serial NO.16971).
The employed experimental technique of following examples is as follows:
Experimental technique: use mtt assay that the bufadienolide biotransformation compounds is carried out external gynecological tumor cell experiment: it is 5 * 10 that corresponding cell is digested, counts, makes concentration with pancreatin
4The cell suspension of individual/ml.Every hole in 96 orifice plates is added 100 μ l cell suspension (every holes 5 * 10
3Individual cell), place 37 ℃ then, 5%CO
2Cultivated 24 hours in the incubator; To required different tonsure concentration, every hole adds the corresponding pastille culture medium of 100 μ L, sets up negative control group simultaneously with complete medium dilution medicine, and solvent matched group and positive controls place 37 ℃ with 96 orifice plates, 5%CO again
2Cultivated 72 hours in the incubator.Every then hole adds 20 μ L MTT (5mg/ml), continue to cultivate 4 hours, stops cultivating, and discards culture medium, and every hole adds 150 μ LDMSO dissolving, and shaking table 10 minutes is mixing gently.Is the OD value at λ=490nm place with the absorbance that microplate reader detects every hole, calculates the suppression ratio of each medicine.
Embodiment 1: the bufadienolide biotransformation extract, and cinobufacin, Toadpoison Medicine, bufotalien or Gamabufotalin are to the inhibitory action of Proliferation of Human Ovarian Cell A2780.
Investigate bufadienolide biotransformation extract and four monomeric compound cinobufacin, Toadpoison Medicine, bufotalien or Gamabufotalins inhibitory action according to the MTT experimental technique to Proliferation of Human Ovarian Cell (A2780).
Experimental result shows bufadienolide biotransformation extract and four monomeric compound cinobufacin, Toadpoison Medicine, bufotalien or Gamabufotalin all have a stronger inhibitory action to Proliferation of Human Ovarian Cell (A2780), each dosage group has presented dose-effect relationship preferably, Gamabufotalin has shown the activity of better anti-human ovarian carcinoma cell (A2780), and its IC50 value is that 59.948nM is less than the other medicines group.Concrete experimental result as shown in Table 1 and Table 2.
Table 1 bufadienolide biotransformation extract is to the exercising result of Proliferation of Human Ovarian Cell (A2780)
Table 2 cinobufacin, Toadpoison Medicine, bufotalien and Gamabufotalin are to the exercising result of Proliferation of Human Ovarian Cell (A2780)
Embodiment 2: bufadienolide biotransformation extract, cinobufacin, Toadpoison Medicine, bufotalien or Gamabufotalin are to the inhibitory action of Proliferation of Human Ovarian Cell (SK-OV-3).
Press the MTT experimental technique and investigate bufadienolide biotransformation extract and four monomeric compound cinobufacin, Toadpoison Medicine, bufotalien or Gamabufotalins inhibitory action Proliferation of Human Ovarian Cell (SK-OV-3).
Experimental result shows that bufadienolide biotransformation extract and four monomeric compound cinobufacin, Toadpoison Medicine, bufotalien or Gamabufotalins all have stronger inhibitory action to Proliferation of Human Ovarian Cell (SK-OV-3), each dosage group has presented dose-effect relationship preferably, wherein Gamabufotalin has shown the activity of better anti-human ovarian carcinoma cell (SK-OV-3), and its IC50 value is that 76.83nM is less than the other medicines group.Concrete experimental result is shown in table 3 and table 4.
Table 3 bufadienolide biotransformation extract is to the exercising result of Proliferation of Human Ovarian Cell (SK-OV-3)
Table 4 cinobufacin, Toadpoison Medicine, bufotalien and Gamabufotalin are to the exercising result of Proliferation of Human Ovarian Cell (SK-OV-3)
Embodiment 3: the bufadienolide biotransformation extract, and cinobufacin, Toadpoison Medicine, bufotalien or Gamabufotalin are to the inhibitory action of human cervical carcinoma cell (SiHa).
Press the MTT experimental technique and investigate bufadienolide biotransformation extract and four monomeric compound cinobufacin, Toadpoison Medicine, bufotalien or Gamabufotalins inhibitory action Proliferation of Human Ovarian Cell (SK-OV-3).
Experimental result shows that bufadienolide biotransformation extract and four monomeric compound cinobufacin, Toadpoison Medicine, bufotalien or Gamabufotalins all have stronger inhibitory action to human cervical carcinoma cell (SiHa), each dosage group has presented dose-effect relationship preferably, wherein Gamabufotalin has shown the activity of better anti-human cervical carcinoma cell (SiHa), and its IC50 value is that 85.001nM is less than the other medicines group.Concrete experimental result is shown in table 5 and table 6.
Table 5 bufadienolide biotransformation extract is to the exercising result of human cervical carcinoma cell (SiHa)
Table 6 cinobufacin, Toadpoison Medicine, bufotalien and Gamabufotalin are to the exercising result of human cervical carcinoma cell (SiHa)
Embodiment 4: the bufadienolide biotransformation extract, and cinobufacin, Toadpoison Medicine, bufotalien or Gamabufotalin are to the effect of people's endometrial carcinoma cell (shikawa).：
Press the MTT experimental technique and investigate bufadienolide biotransformation extract and four monomeric compound cinobufacin, Toadpoison Medicine, bufotalien or Gamabufotalins inhibitory action Proliferation of Human Ovarian Cell (SK-OV-3).
Experimental result shows that bufadienolide biotransformation extract and four monomeric compound cinobufacin, Toadpoison Medicine, bufotalien or Gamabufotalins all have stronger inhibitory action to people's endometrial carcinoma cell (shikawa), each dosage group has presented dose-effect relationship preferably, wherein Gamabufotalin has shown the activity of better anti-people's endometrial carcinoma cell (shikawa), and its IC50 value is that 134.034nM is less than the other medicines group.Concrete experimental result is shown in table 7 and table 8.
Table 7 bufadienolide biotransformation extract is to the exercising result of people's endometrial carcinoma cell (shikawa)
Table 8 cinobufacin, Toadpoison Medicine, bufotalien and Gamabufotalin are to the exercising result of human cervical carcinoma cell (SiHa)
Embodiment 5: cinobufacin hydrochlorate, Toadpoison Medicine hydrochlorate, bufotalien hydrochlorate or Gamabufotalin hydrochlorate are to the effect of Proliferation of Human Ovarian Cell (A2780).
Pressing MTT experimental technique investigation cinobufacin hydrochlorate, Toadpoison Medicine hydrochlorate, bufotalien hydrochlorate or Gamabufotalin hydrochlorate acts on Proliferation of Human Ovarian Cell (A2780).
Experimental result shows that cinobufacin hydrochlorate, Toadpoison Medicine hydrochlorate, bufotalien hydrochlorate or Gamabufotalin hydrochlorate all have stronger inhibitory action to Proliferation of Human Ovarian Cell (A2780), each dosage group has presented dose-effect relationship preferably, and finds that by contrast IC50 value the Gamabufotalin hydrochlorate has the effect than cinobufacin hydrochlorate, Toadpoison Medicine hydrochlorate, the better anti-human ovarian carcinoma cell of bufotalien hydrochlorate (A2780).Concrete experimental result is as shown in table 9.
Table 9 cinobufacin hydrochlorate, Toadpoison Medicine hydrochlorate, bufotalien hydrochlorate or Gamabufotalin hydrochlorate are to the exercising result of Proliferation of Human Ovarian Cell (A2780)
Embodiment 6: cinobufacin hydrochlorate, Toadpoison Medicine hydrochlorate, bufotalien hydrochlorate or Gamabufotalin hydrochlorate are to the effect of Proliferation of Human Ovarian Cell (SK-OV-3).：
Press the MTT experimental technique and investigate the effect of cinobufacin hydrochlorate, Toadpoison Medicine hydrochlorate, bufotalien hydrochlorate or Gamabufotalin hydrochlorate Proliferation of Human Ovarian Cell (SK-OV-3).
Experimental result shows that cinobufacin hydrochlorate, Toadpoison Medicine hydrochlorate, bufotalien hydrochlorate or Gamabufotalin hydrochlorate all have stronger inhibitory action to Proliferation of Human Ovarian Cell (SK-OV-3), each dosage group has presented dose-effect relationship preferably, and finds that by contrast IC50 value the Gamabufotalin hydrochlorate has the effect than cinobufacin hydrochlorate, Toadpoison Medicine hydrochlorate, the better anti-human ovarian carcinoma cell of bufotalien hydrochlorate (SK-OV-3).Concrete experimental result is as shown in table 10.
Table 10 cinobufacin hydrochlorate, Toadpoison Medicine hydrochlorate, bufotalien hydrochlorate or Gamabufotalin hydrochlorate are to the exercising result of Proliferation of Human Ovarian Cell (SK-OV-3)
Embodiment 7: cinobufacin hydrochlorate, Toadpoison Medicine hydrochlorate, bufotalien hydrochlorate or Gamabufotalin hydrochlorate are to the effect of human cervical carcinoma cell (SiHa).
Press the MTT experimental technique and investigate the effect of cinobufacin hydrochlorate, Toadpoison Medicine hydrochlorate, bufotalien hydrochlorate or Gamabufotalin hydrochlorate human cervical carcinoma cell (SiHa).
Experimental result shows that cinobufacin hydrochlorate, Toadpoison Medicine hydrochlorate, bufotalien hydrochlorate or Gamabufotalin hydrochlorate all have stronger inhibitory action to human cervical carcinoma cell (SiHa), each dosage group has presented dose-effect relationship preferably, and finds that by contrast IC50 value the Gamabufotalin hydrochlorate has the effect than cinobufacin hydrochlorate, Toadpoison Medicine hydrochlorate, the better anti-human cervical carcinoma cell of bufotalien hydrochlorate (SiHa).Concrete experimental result is as shown in table 11.
Table 11 cinobufacin hydrochlorate, Toadpoison Medicine hydrochlorate, bufotalien hydrochlorate or Gamabufotalin hydrochlorate are to the exercising result of human cervical carcinoma cell (SiHa)
Embodiment 8: cinobufacin hydrochlorate, Toadpoison Medicine hydrochlorate, bufotalien hydrochlorate or Gamabufotalin hydrochlorate are to the effect of people's endometrial carcinoma cell (shikawa).：
Press the MTT experimental technique and investigate the effect of cinobufacin hydrochlorate, Toadpoison Medicine hydrochlorate, bufotalien hydrochlorate or Gamabufotalin hydrochlorate people's endometrial carcinoma cell (shikawa).
Experimental result shows that cinobufacin hydrochlorate, Toadpoison Medicine hydrochlorate, bufotalien hydrochlorate or Gamabufotalin hydrochlorate all have stronger inhibitory action to people's endometrial carcinoma cell (shikawa), each dosage group has presented dose-effect relationship preferably, and finds that by contrast IC50 value the Gamabufotalin hydrochlorate has the effect than cinobufacin hydrochlorate, Toadpoison Medicine hydrochlorate, the better anti-people's endometrial carcinoma cell of bufotalien hydrochlorate.Concrete experimental result is as shown in table 12.
Table 12 cinobufacin hydrochlorate, Toadpoison Medicine hydrochlorate, bufotalien hydrochlorate or Gamabufotalin hydrochlorate are to the exercising result of people's endometrial carcinoma cell (shikawa)
Embodiment 9: cinobufacin sulfate, Toadpoison Medicine sulfate, bufotalien sulfate or Gamabufotalin sulfate are to the effect of Proliferation of Human Ovarian Cell (A2780):
Press the MTT experimental technique and investigate the effect of cinobufacin sulfate, Toadpoison Medicine sulfate, bufotalien sulfate or Gamabufotalin sulfate Proliferation of Human Ovarian Cell (A2780).
Experimental result shows that cinobufacin sulfate, Toadpoison Medicine sulfate, bufotalien sulfate or Gamabufotalin sulfate all have stronger inhibitory action to Proliferation of Human Ovarian Cell (A2780), each dosage group has presented dose-effect relationship preferably, and finds that by contrast IC50 value Gamabufotalin sulfate has the effect than the better anti-human ovarian carcinoma cell of cinobufacin sulfate, Toadpoison Medicine sulfate or bufotalien sulfate (A2780).Concrete experimental result is as shown in table 13.
Table 13 cinobufacin sulfate, Toadpoison Medicine sulfate, bufotalien sulfate or Gamabufotalin sulfate are to Proliferation of Human Ovarian Cell (A2780)) exercising result
Embodiment 10: cinobufacin sulfate, Toadpoison Medicine sulfate, bufotalien sulfate or Gamabufotalin sulfate are to the effect of Proliferation of Human Ovarian Cell (SK-OV-3).
Press the MTT experimental technique and investigate the effect of cinobufacin sulfate, Toadpoison Medicine sulfate, bufotalien sulfate or Gamabufotalin sulfate Proliferation of Human Ovarian Cell (SK-OV-3).
Experimental result shows that cinobufacin sulfate, Toadpoison Medicine sulfate, bufotalien sulfate or Gamabufotalin sulfate all have stronger inhibitory action to Proliferation of Human Ovarian Cell (SK-OV-3), each dosage group has presented dose-effect relationship preferably, and has than the better anti-human ovarian carcinoma cell of cinobufacin sulfate, Toadpoison Medicine sulfate or bufotalien sulfate (SK-OV-3) by contrast IC50 value discovery Gamabufotalin sulfate and to act on.Concrete experimental result is as shown in table 14.
Table 14 cinobufacin sulfate, Toadpoison Medicine sulfate, bufotalien sulfate or Gamabufotalin sulfate are to the exercising result of Proliferation of Human Ovarian Cell (SK-OV-3)
Embodiment 11: cinobufacin sulfate, Toadpoison Medicine sulfate, bufotalien sulfate or Gamabufotalin sulfate are to the effect of human cervical carcinoma cell (SiHa).
Press the MTT experimental technique and investigate the effect of cinobufacin sulfate, Toadpoison Medicine sulfate, bufotalien sulfate or Gamabufotalin sulfate human cervical carcinoma cell (SiHa).
Experimental result shows that cinobufacin sulfate, Toadpoison Medicine sulfate, bufotalien sulfate or Gamabufotalin sulfate all have stronger inhibitory action to human cervical carcinoma cell (SiHa), each dosage group has presented dose-effect relationship preferably, and has than the better anti-human cervical carcinoma cell of cinobufacin sulfate, Toadpoison Medicine sulfate or bufotalien sulfate (SiHa) by contrast IC50 value discovery Gamabufotalin sulfate and to act on.Concrete experimental result is as shown in Table 15.
Table 15 cinobufacin sulfate, Toadpoison Medicine sulfate, bufotalien sulfate or Gamabufotalin sulfate are to the exercising result of human cervical carcinoma cell (SiHa)
Embodiment 12: cinobufacin sulfate, Toadpoison Medicine sulfate, bufotalien sulfate or Gamabufotalin sulfate are to the effect of people's endometrial carcinoma cell (shikawa).
Press the MTT experimental technique and investigate the effect of cinobufacin sulfate, Toadpoison Medicine sulfate, bufotalien sulfate or Gamabufotalin sulfate people's endometrial carcinoma cell (shikawa).
Experimental result shows that cinobufacin sulfate, Toadpoison Medicine sulfate, bufotalien sulfate or Gamabufotalin sulfate all have stronger inhibitory action to people's endometrial carcinoma cell (shikawa), each dosage group has presented dose-effect relationship preferably, and has than the better anti-people's endometrial carcinoma cell of cinobufacin sulfate, Toadpoison Medicine sulfate or bufotalien sulfate (shikawa) by contrast IC50 value discovery Gamabufotalin sulfate and to act on.Concrete experimental result is shown in table 16.
Table 16 cinobufacin sulfate, Toadpoison Medicine sulfate, bufotalien sulfate or Gamabufotalin sulfate are to the exercising result of people's endometrial carcinoma cell (shikawa)
The hydrochlorate or the sulfate that draw bufadienolide biotransformation extract and monomeric compound cinobufacin, Toadpoison Medicine, bufotalien, Gamabufotalin (MCS-1-5) and above four monomeric compounds according to above experimental result are shown in table 17 to the IC50 value of Proliferation of Human Ovarian Cell (A2780), Proliferation of Human Ovarian Cell (SK-OV-3), human cervical carcinoma cell (SiHa) and people's endometrial carcinoma cell (shikawa).
Each chemical compound of table 17 is to the IC50 value of gynecological tumor cell
Draw Gamabufotalin by last table, cinobufacin, Toadpoison Medicine and four compound exhibits of bufotalien good gynecological tumor activity, the IC50 value has all reached the concentration range of nM, find that by contrast Gamabufotalin has demonstrated than bufadienolide biotransformation extract and monomeric compound cinobufacin, the better cell of Toadpoison Medicine or bufotalien is selected active, promptly has better gynecological tumor activity, especially the IC50 value of Proliferation of Human Ovarian Cell (A2780) had only 59.948nM, experimental result shows that also the hydrochlorate of Gamabufotalin or sulfate compare cinobufacin simultaneously, Toadpoison Medicine, the hydrochlorate of three chemical compounds of bufotalien or sulfate have better anti-human ovarian carcinoma cell (A2780), Proliferation of Human Ovarian Cell (SK-OV-3), the activity of human cervical carcinoma cell (SiHa) and people's endometrial carcinoma cell (shikawa)
The amber glass hydrochlorate of Gamabufotalin or nitrate all are to have active Gamabufotalin of gynecological tumor and the acid of amber glass or nitric acid formed amber glass hydrochlorate or nitrate, not change pharmacologically active after the formation salt, equally also to have the gynecological tumor effect.It can also be seen that from experimental result Gamabufotalin and salt thereof have shown the activity than the better gynecological tumor of taxol, and active component is clear, effective dose is low, the effective dose of Gamabufotalin is 1/2 to 1/9 of a bufadienolide biotransformation extract effective dose, therefore potential side effect is littler, and getting a good chance of exploitation becomes gynecological tumor medicine of new generation.
Claims (3)
1. Gamabufotalin and salt thereof the application in preparation treatment ovarian cancer medicine.
2. the application in preparation treatment ovarian cancer medicine of Gamabufotalin according to claim 1 and salt thereof, it is characterized in that: the Gamabufotalin salt is hydrochlorate, sulfate, amber glass hydrochlorate or the nitrate of Gamabufotalin.
3. the application in preparation treatment ovarian cancer medicine of Gamabufotalin according to claim 1 and 2 and salt thereof is characterized in that: the medicine that Gamabufotalin or Gamabufotalin salt is become injection, tablet, injectable powder, granule, capsule, unguentum, cream or oral liquid formulation with pharmaceutically acceptable preparing carriers.
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| CN102000091B (en) * | 2010-10-29 | 2011-12-21 | 中国人民解放军第二军医大学 | Application of bufarenogin,its derivatives and pharmaceutically acceptable salts thereof |
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| CN108836982A (en) * | 2018-07-06 | 2018-11-20 | 合肥华方医药科技有限公司 | A kind of toad skin active component and preparation method thereof |
| CN117695293A (en) * | 2021-09-08 | 2024-03-15 | 长沙欧邦生物科技有限公司 | Preparation method and application of degradation product of bufogenin component |
| CN115645419A (en) * | 2022-11-17 | 2023-01-31 | 中南大学湘雅医院 | Application of gamabufotalin in preparation of medicines for treating choriocarcinoma |
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| CN101041004A (en) * | 2006-03-24 | 2007-09-26 | 黄振华 | Novel antineoplastic compound medicine |
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