CN101491531A - Use of bufadienolides compound and bufadienolides salinization compound in preparing medicine for treating gynecological tumor - Google Patents
Use of bufadienolides compound and bufadienolides salinization compound in preparing medicine for treating gynecological tumor Download PDFInfo
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Abstract
The invention provides application of a bufadienolide compound and a bufadienolide salt compound in preparing a medicine for treating gynecological tumor. Anti-cancer experiments of four gynecological tumor, namely human ovarian cancer cells (A2780), human ovarian cancer cells (SK-OV-3), human cervical carcinoma cells (SiHa) and human endometrial cancer cells (shikawa) are carried out in vitro through a bufadienolide extract and monomeric compounds, namely cinobufagin, bufalin, bufotalin and gamabufotalin as well as hydrochlorides or sulfates of the four monomeric compounds, and an experimental result shows that the bufadienolide extract, the monomeric compounds, namely the cinobufagin, the bufalin, the bufotalin and the gamabufotalin, and the hydrochlorides or the sulfates of the four monomeric compounds have strong inhibition effect on four gynecological tumor cells. The anti-cancer activity of the bufadienolide compound and the bufadienolide salt compound is stronger than that of a positive drug paclitaxel, and the bufadienolide compound and a bufadienolide salt compound have small adverse reaction and expect to be developed into a novel anti-cancer drug.
Description
Technical field
The present invention relates to the new purposes of bufadienolide biotransformation compounds and bufadienolide biotransformation salt, specifically relate to the application that bufadienolide biotransformation compounds and bufadienolide biotransformation salt are used to prepare treatment gynecological tumor disease medicament.
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 is used to strengthen myocardial contraction, is 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 and bufadienolide biotransformation salt are used for the treatment of the gynecological tumor disease, and present Bufo siccus preparation, it is in the majority to be used as medicine with the runic thing, complicated component, and active component is unclear, except that containing bufotalin, bufotoxin, indoles alkaloid, also contain polytype chemical constituents such as aminoacid, reducing sugar, steroid class, peptide class.Therefore, in clinical use, the Bufo siccus preparation has multiple shortcoming, anaphylaxis appears, the vascular stimulation symptom, adverse reaction rate height such as digestive tract and cardiac toxicity, this all is because active component is unclear, the many reasons of invalid impurity that contain cause, and therefore having limited it is used for the gynecological tumor treatment of diseases.
Summary of the invention
Technical problem to be solved by this invention is to overcome Bufo siccus preparation complicated component, the defective that adverse reaction rate is high, provide a kind of one-tenth to distinguish one from the other, quality controllable, be the application of active component preparation treatment gynecological tumor disease medicament with bufadienolide biotransformation compounds and bufadienolide biotransformation salt.Bufadienolide biotransformation compounds structural formula is as follows:
R1 is CHO or CH3 in the formula; R2 is OH or H; R3 is OH; R4 is H; Or R3 and R4 formation epoxy bridge; R5 is H or OAc.
Bufadienolide biotransformation salt provided by the invention is bufadienolide biotransformation compounds and hydrochloric acid, sulphuric acid, the acid of amber glass or the formed hydrochlorate of nitric acid, sulfate, amber glass hydrochlorate or nitrate.
Bufadienolide biotransformation compounds provided by the invention is to surpass 50% extract with bufadienolide biotransformation content.
Bufadienolide biotransformation compounds provided by the invention and bufadienolide biotransformation salt 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 bufadienolide biotransformation compounds provided by the invention and bufadienolide biotransformation salt are made tablet bufadienolide biotransformation compounds or bufadienolide biotransformation salt and carrier lactose or corn starch, add magnesium stearate lubricant when needing, mix homogeneously, tabletting is made tablet then.When bufadienolide biotransformation compounds provided by the invention or bufadienolide biotransformation salt are made capsule bufadienolide biotransformation compounds or bufadienolide biotransformation salt and carrier lactose or corn starch mix homogeneously, granulate, the encapsulated then capsule of making.When bufadienolide biotransformation compounds provided by the invention or bufadienolide biotransformation salt are made granule, bufadienolide biotransformation compounds or bufadienolide biotransformation salt and diluent lactose or corn starch mix homogeneously, granulate, drying is made granule.When bufadienolide biotransformation compounds provided by the invention or bufadienolide biotransformation salt are made injection, get bufadienolide biotransformation compounds or bufadienolide biotransformation 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.
Being 0.03 to 30mg/ people/sky with bufadienolide biotransformation compounds or bufadienolide biotransformation salt cubage effective dose when bufadienolide biotransformation compounds provided by the invention or bufadienolide biotransformation salt are made various drug form administration, is 0.3 to 7.0mg/ people/sky as its dosage of preferred version.
The gynecological tumor of bufadienolide biotransformation compounds provided by the invention and bufadienolide biotransformation salt comprises ovarian cancer, cervical cancer, carcinoma of endometrium or breast carcinoma.
Further investigate through the applicant, the bufadienolide biotransformation extract, cinobufacin, Toadpoison Medicine, bufotalien, Gamabufotalin and cinobufacin, Toadpoison Medicine, the hydrochlorate or the sulfate anticancer experiment in vitro of bufotalien and four chemical compounds of Gamabufotalin show human breast carcinoma, ovarian cancer, cervical cancer, different gynecological tumor cells such as carcinoma of endometrium all have stronger inhibition activity, and have dose-effect relationship preferably, experimental result shows that the anticancer effect of bufadienolide biotransformation compounds and bufadienolide biotransformation salt is better than the taxol that is widely used in the gynecological tumor treatment clinically.
The preparation of bufadienolide biotransformation compounds: get Venenum Bufonis 150g, with twice of ethyl acetate extraction, extract gets the 36.8g extract at 40 ℃ of concentrating under reduced pressure, extract is mixed 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, after the acquisition effective site, column chromatography once more, thin layer chromatography is followed the tracks of, and merges identical fraction, obtains the bufadienolide biotransformation extract, the bufadienolide biotransformation extract is prepared the liquid phase purification, obtain the monomeric compound cinobufacin, Toadpoison Medicine, bufotalien and Gamabufotalin.
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 is with the object of gynecological tumor as research, and the medicine for preparing gynecological tumor with bufadienolide biotransformation compounds or bufadienolide biotransformation salt has the following advantages: 1, have specificity at the gynecological tumor cell that has cancerated.2, the effective dose of bufadienolide biotransformation and bufadienolide biotransformation salt inhibition gynecological tumor cell proliferation is less, and potential side effect is also little, uses safer.3, to have the active main component of gynecological tumor clear, quality controllable for bufadienolide biotransformation compounds and bufadienolide biotransformation salt.4, bufadienolide biotransformation compounds and bufadienolide biotransformation salt anticancer effect are better than the taxol that is widely used in the gynecological tumor treatment clinically, be expected to become the new drug of new gynecological tumor, and resource are extensive, is easy to get, and cost is lower.5, bufadienolide biotransformation compounds and bufadienolide biotransformation salt energy 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:
Experiment material: 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 (the total steroid alkene of Bufo siccus content is 55%), 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: 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 bufadienolide biotransformation compounds and bufadienolide biotransformation salt are 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 L DMSO 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: bufadienolide biotransformation extract, cinobufacin, Toadpoison Medicine, bufotalien or Gamabufotalin are to the inhibitory action of Proliferation of Human Ovarian Cell:
Investigate bufadienolide biotransformation extract, cinobufacin, Toadpoison Medicine, bufotalien or Gamabufotalin inhibitory action according to the MTT experimental technique to Proliferation of Human Ovarian Cell (A2780).
Experimental result: experimental result show bufadienolide biotransformation extract, cinobufacin, Toadpoison Medicine, bufotalien or Gamabufotalin to Proliferation of Human Ovarian Cell A2780 all have a stronger inhibitory action, each dosage group has presented dose-effect relationship preferably.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, cinobufacin, Toadpoison Medicine, bufotalien or Gamabufotalin inhibitory action Proliferation of Human Ovarian Cell (SK-OV-3).
Experimental result shows that bufadienolide biotransformation extract, cinobufacin, Toadpoison Medicine, bufotalien or Gamabufotalin all have stronger inhibitory action to Proliferation of Human Ovarian Cell (SK-OV-3), and each dosage group has presented dose-effect relationship preferably.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: bufadienolide biotransformation extract, 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, cinobufacin, Toadpoison Medicine, bufotalien or Gamabufotalin inhibitory action human cervical carcinoma cell (SiHa).
Experimental result shows that bufadienolide biotransformation extract, cinobufacin, Toadpoison Medicine, bufotalien or Gamabufotalin all have stronger inhibitory action to human cervical carcinoma cell (SiHa), and each dosage group has presented dose-effect relationship preferably.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: bufadienolide biotransformation extract, 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, cinobufacin, Toadpoison Medicine, bufotalien or Gamabufotalin inhibitory action people's endometrial carcinoma cell (shikawa).
Experimental result shows that bufadienolide biotransformation extract, cinobufacin, Toadpoison Medicine, bufotalien or Gamabufotalin all have stronger inhibitory action to people's endometrial carcinoma cell (shikawa), and each dosage group has presented dose-effect relationship preferably.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), and each dosage group has presented dose-effect relationship preferably.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), and each dosage group has presented dose-effect relationship preferably.Concrete experimental result is as shown in table 10.
Table 10 cinobufacin hydrochlorate, Toadpoison Medicine hydrochlorate, bufotalien hydrochlorate and 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), and each dosage group has presented dose-effect relationship preferably.Concrete experimental result is as shown in table 11.
Table 11 cinobufacin hydrochlorate, Toadpoison Medicine hydrochlorate, bufotalien hydrochlorate and 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), and each dosage group has presented dose-effect relationship preferably.Concrete experimental result is as shown in table 12.
Table 12 cinobufacin hydrochlorate, Toadpoison Medicine hydrochlorate, bufotalien hydrochlorate and 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), and each dosage group has presented dose-effect relationship preferably.Concrete experimental result is as shown in table 13.
Table 13 cinobufacin sulfate, Toadpoison Medicine sulfate, bufotalien sulfate and 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), and each dosage group has presented dose-effect relationship preferably.Concrete experimental result is as shown in table 14.
Table 14 cinobufacin sulfate, Toadpoison Medicine sulfate, bufotalien sulfate and 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), and each dosage group has presented dose-effect relationship preferably.Concrete experimental result is as shown in Table 15.
Table 15 cinobufacin sulfate, Toadpoison Medicine sulfate, bufotalien sulfate and 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), and each dosage group has presented dose-effect relationship preferably.Concrete experimental result is shown in table 16.
Table 16 cinobufacin sulfate, Toadpoison Medicine sulfate, bufotalien sulfate and 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 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).
Table 17 bufadienolide biotransformation compounds and bufadienolide biotransformation salt are to tumor cell IC50 value
Draw the bufadienolide biotransformation extract by last table, Gamabufotalin, cinobufacin, the hydrochlorate of Toadpoison Medicine and bufotalien and above four chemical compounds or sulfate all have the good restraining effect to 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).The bufadienolide biotransformation extract, cinobufacin, Toadpoison Medicine, the hydrochlorate of bufotalien and Gamabufotalin and above four chemical compounds or sulfate have shown good active anticancer, the IC50 value has all reached the concentration range of nM, find that by contrast Gamabufotalin has demonstrated than bufadienolide biotransformation extract and three monomeric compound cinobufacin, Toadpoison Medicine, the better cell of bufotalien is selected active, promptly has better gynecological tumor activity, especially the IC50 value of Proliferation of Human Ovarian Cell (A2780) is had only 59.948nM, experimental result shows that the hydrochlorate or the sulfate of Gamabufotalin have the cinobufacin of ratio simultaneously, Toadpoison Medicine, the better gynecological tumor effect of the hydrochlorate of three monomeric compounds of bufotalien or sulfate.
The amber glass hydrochlorate of bufadienolide biotransformation compounds or nitrate all are to have active bufadienolide biotransformation compounds of gynecological tumor and the acid of amber glass or nitric acid formed amber glass hydrochlorate or nitrate, do not change pharmacologically active after forming salt, equally have the gynecological tumor effect yet.
It can also be seen that from experimental result bufadienolide biotransformation compounds and salt thereof have demonstrated the activity than the better gynecological tumor of taxol, and active component is clear, effective dose is low, and potential side effect is little, and getting a good chance of exploitation becomes gynecological tumor medicine of new generation.
Claims (5)
1, bufadienolide biotransformation compounds and the bufadienolide biotransformation salt application in preparation treatment gynecological tumor medicine.
2, bufadienolide biotransformation compounds according to claim 1 and the bufadienolide biotransformation salt application in preparation treatment gynecological tumor medicine, it is characterized in that: the bufadienolide biotransformation compounds is to surpass 50% extract in bufadienolide biotransformation content weight ratio.
3, bufadienolide biotransformation compounds according to claim 1 and the bufadienolide biotransformation salt application in preparation treatment gynecological tumor medicine, it is characterized in that: the bufadienolide biotransformation salt is hydrochlorate, sulfate, amber glass hydrochlorate or the nitrate of bufadienolide biotransformation.
4, according to the application in preparation treatment gynecological tumor medicine of claim 1,2 or 3 described bufadienolide biotransformation compounds and bufadienolide biotransformation salt, it is characterized in that: bufadienolide biotransformation compounds or bufadienolide biotransformation salt are become injection, tablet, injectable powder, granule, capsule, oral liquid, unguentum with pharmaceutically acceptable preparing carriers, or the medicine of cream.
5, according to the application in preparation treatment gynecological tumor medicine of claim 1,2 or 3 described bufadienolide biotransformation compounds and bufadienolide biotransformation salt, it is characterized in that: gynecological tumor is ovarian cancer, cervical cancer, carcinoma of endometrium or breast carcinoma.
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| CN101822832A (en) * | 2010-04-16 | 2010-09-08 | 马宏跃 | Composition with anti-tumor effect and application thereof in preparing medicament for treating tumor |
| CN102247337A (en) * | 2011-06-02 | 2011-11-23 | 陈彦 | Bufotalin dry powder inhalers and preparation method as well as application thereof |
| CN112920253A (en) * | 2019-12-05 | 2021-06-08 | 中国科学院上海药物研究所 | Bufonis venenum diene derivative, and preparation method, application and pharmaceutical composition thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101785777A (en) * | 2010-03-30 | 2010-07-28 | 上海现代药物制剂工程研究中心有限公司 | Application of bufotalin std. in preparing medicament for treating lung tumors |
| CN101785777B (en) * | 2010-03-30 | 2011-11-16 | 上海现代药物制剂工程研究中心有限公司 | Application of bufotalin std. in preparing medicament for treating lung tumors |
| CN101822832A (en) * | 2010-04-16 | 2010-09-08 | 马宏跃 | Composition with anti-tumor effect and application thereof in preparing medicament for treating tumor |
| CN101822832B (en) * | 2010-04-16 | 2012-09-05 | 马宏跃 | Composition with anti-tumor effect and application thereof in preparing medicament for treating tumor |
| CN102247337A (en) * | 2011-06-02 | 2011-11-23 | 陈彦 | Bufotalin dry powder inhalers and preparation method as well as application thereof |
| CN102247337B (en) * | 2011-06-02 | 2013-03-13 | 陈彦 | Bufotalin dry powder inhalers and preparation method as well as application thereof |
| CN112920253A (en) * | 2019-12-05 | 2021-06-08 | 中国科学院上海药物研究所 | Bufonis venenum diene derivative, and preparation method, application and pharmaceutical composition thereof |
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