CN1478479A - New use of verbascum glycoside - Google Patents
New use of verbascum glycoside Download PDFInfo
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- CN1478479A CN1478479A CNA031144543A CN03114454A CN1478479A CN 1478479 A CN1478479 A CN 1478479A CN A031144543 A CNA031144543 A CN A031144543A CN 03114454 A CN03114454 A CN 03114454A CN 1478479 A CN1478479 A CN 1478479A
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Abstract
An application of verbascum glycoside in preparing the medicines for treating cancers by oral application or injection is disclosed.
Description
Technical field
The present invention relates to a kind of purposes of polyphenol compound Verbascoside.
Background technology
Verbascoside is a kind of polyphenol compound that extracts from goatweed (Scrophulariaceae).Its molecular formula is C
29O
15H
36, molecular weight is 624, the physical constant of structure is:
Specific rotation: [α]
D 20,-68 (C=0.4, MeOH)
Ultraviolet: UV λ
Max MeOH(nm): 208 (lg ε 4.30), 217 (lg ε 4.45)
292(lgε4.10)，329(lgε4.25)
Infrared: IR v
Max KBr(cm
-1): 3400 (OH), 2932 (C-H), 1700 (conjugation ester groups), 1631 (C=C), 1604,1521 (aromatic rings).
The hydrogen spectrum:
1HNMR (400MHz, DMSO-d
6, TMS) δ ppm:0.97 (d, J=6.0Hz, 3H, the methyl of rhamnose), 2.70 (t, J=7.0Hz, 2H, Ar-CH
2-CH
2), 4.36 (d, J=7.2Hz, 1H, the H-1 of glucose), (4.72 t, J=9.6Hz, 1H, the H-4 of glucose), 5.03 (d, J=1.1Hz, 1H, the H-1 of rhamnose), 6.21 (d, J=15.8Hz, 1H, Ar-CH=CH), 6.49-7.01 (6H, aromatic ring H), 7.47 (d, J=15.8Hz, 1H, Ar-CH=CH), 8.69,8.75,9.19,9.62 (4 * OH).
The carbon spectrum:
13CNMR (100MHz, DMSO-d
6, TMS) δ ppm:129.1 (C-1), 116.3 (C-2), 145.0 (C-3), 143.5 (C-4), 115.8 (C-5), 119.5 (C-6), 70.2 (C-α), 35.0 (C-β), 125.5 (C-1 '), 114.7 (C-2 '), 145.5 (C-3 '), 148.4 (C-4 '), 113.6 (C-5 '), 121.4 (C-6 '), (115.5 C-α '), 145.5 (C-β '), 165.7 (C=O).Glucose: 102.3 (C-1), 74.5 (C-2), 79.1 (C-3), 69.1 (C-4), 74.5 (C-5), 60.7 (C-6).Rhamnose: 101.2 (C-1), 70.5 (C-2), 70.4 (C-3), 71.7 (C-4), 68.7 (C-5), 18.1 (C-6).
Mass spectrum: FABMS (m/s): 631[M+Li]
+, 64.7[M+Na]
+
Its molecular structure is as follows:
Chinese invention patent application 99123015.9 discloses the extracting method of Verbascoside.The application of Verbascoside in the medicine of treatment muscle fatigue once disclosed in Chinese invention patent application 99123009.4.But Verbascoside other application in medicine does not have disclosure as yet.
Summary of the invention
The invention relates to the new purposes of Verbascoside.It specifically is the medicine that Verbascoside is used for treatment of cancer.
In the present invention, Verbascoside is oral, perhaps intravenous, and perhaps in intramuscular injection, the perhaps application in the cancer treatment drugs of lumbar injection.
The medicine of existing used all kinds of treatment cancers generally can all have destruction to organizing normally, even there is the medicine of part treatment cancer that bigger toxicity is arranged, just because of these reasons, it is very restricted in clinical practice, simultaneously its therapeutic effect is affected.But studies show that, adopt Verbascoside can not produce basically and destroy or negative influence also do not have toxic and side effects basically through the inventor to normal structure in the treatment treatment of cancer.The present invention also is surprised to find Verbascoside also to have the tissue that makes canceration and induces to reverse and be the phenomenon of normal structure, and this phenomenon yet there are no report in the research that has disclosed.The present invention will describe in detail in conjunction with specific embodiments.
Specific embodiment
Embodiment 1
Nude mice is raised in other laboratory of SPF (special isolation source of disease) level, and laboratory adopts the air filtration isolation cover to isolate.Feeding and management of nude mice and use are according to " management of laboratory animal and guide for use " operation of health ministry promulgation.
It is subcutaneous earlier human liver cancer cell (MHCC97-H) to be inoculated into a healthy nude mice, wait to grow up to the tumor piece after, the tumor piece is stripped down, be cut into a plurality of 3mm
3Fritter.Get 12 of healthy nude mices, at fritter of the back, left side of every nude mice inoculation.Mus is normal to be raised 10 days to being tried then.It is big to be tried Mus tumor block length on one's body after 10 days, will be tried nude mice again and be divided into administration group and matched group at random, every group of 6 Mus.With the Verbascoside physiological saline solution, administration group Mus is pressed 200mg/kg dosage, with the administration of lumbar injection mode, once a day, successive administration 17 days; The normal saline of matched group lumbar injection and administration group equivalent.Treated the 18th day, and put to death and tried Mus, peel off the tumor piece, and survey its volume and weight that survey the alpha-fetoprotein content of serum simultaneously, the data of surveying see Table 1
| Table 1 medicine is to transplanting the inhibition of people's hepatocarcinoma tumor piece in the nude mouse | ||||
| Dosage (mg/kg) | The tumor block amasss (cm3) | Tumor piece weight (mg) | Alpha-fetoprotein (μ g/L) | |
| Matched group (n=6) | ????0×17d | ??0.62±0.20 | ??613±115 | ????16.0±8.6 |
| Administration group (n=6) | ????200×17d | ??0.16±0.15 ** | ??198±184 ** | ????4.9±4.8 ** |
*P＜0.05,
*P＜0.01, n is the number of elements of experimental mouse
The result shows that medicine of the present invention can obviously suppress the growth of tumor piece, to tumor piece volume and weight, divides and has suppressed 74.2% and 67.7%.And the present invention also can make the serum alpha-fetoprotein as the pernicious sign of hepatocarcinoma that tangible minimizing is arranged, and makes alpha-fetoprotein reduce by 69.4%.This shows that the present invention can make the pernicious of hepatocarcinoma reduce greatly.
Embodiment 2
(it is 37 ℃ promptly with people's adenocarcinoma of stomach cell (MGc80-3) incubation earlier in temperature, cultivate in the cell culture incubator of 5% carbon dioxide) be in the RPMI-1640 culture fluid of 20 μ mol/L Verbascosides in concentration, simultaneously with people's adenocarcinoma of stomach cell incubation of equivalent in not containing medicine, but contain in the RPMI-1640 culture fluid of DMSO group in contrast.Incubation is collecting cell after 7 days, and routine makes 5 * 10 after cleaning 3 times
7The cell solution of/mL.Get 8 of healthy nude mices, every Mus buttocks one side with syringe inject through medicine handled 5 * 10
6Individual cell, again every Mus buttocks opposite side inject with syringe equivalent matched group cell in contrast.The control sides position of back 8 nude mices all grows heavier tumor piece around normal the raising, the about 1g of its average weight, and have only a Mus to grow the heavy tumor piece of about 0.5g through the drug treating side.It is pernicious that this experiment shows that the present invention can make gastric carcinoma cells lose, and reverses to normal cell.
Embodiment 3
Personnel selection adenocarcinoma of stomach cell (MGc80-3) and gastric carcinoma cells (MKN45) are as the experiment material of present embodiment.
With 5 * 10
4People's adenocarcinoma of stomach cell of/mL is put into the RPMI-1640 culture fluid, at 37 ℃, cultivates 24 hours under 5% the carbon dioxide conditions.After discarding culture fluid, these adenocarcinoma of stomach cells are divided into two parts, portion is put into the RPMI-1640 culture fluid of the Verbascoside that contains 20 μ mol/L and is cultivated, and portion is put into and do not contained Verbascoside in addition, cultivates in contrast but contain in the RPMI-1640 culture fluid of 200mmol/LDMSO.Incubation is harvesting after 7 days, and it is inferior to use D-Hank ' s solution to give a baby a bath on the third day after its birth, and is made into 1 * 10
6The Cell sap of individual cell/mL.Survey cell surface electric charge and cell number doubling time.Other gets the part cell and puts on the coverslip and cultivate, with containing 2.5% valeryl aldehyde, pH value be the phosphate buffer of 7.4 0.1mol/L at 4 ℃ of fixed samples, use ethanol dehydration then, place critical exsiccator inner drying to handle, give cell gold-plated again.Producing S-520 scanning electric mirror observing cell configuration of surface with Hitachi changes.
Gastric carcinoma cells (MKN45) is divided into some groups of equivalent, place the RPMI-1640 culture fluid that contains 10% hyclone respectively, the administration group add respectively variable concentrations the Verbascoside aqueous solution, matched group does not add any medicine, only adds the distilled water of equivalent.In aforementioned solution, 37 ℃, incubation is 48 hours under 5% the carbon dioxide conditions with each group.Harvesting makes cytolysis with the SDS lytic agent, places on ice after 30 minutes, and under 4 ℃ of 1600rpm rotating speeds centrifugal 20 minutes, reuse PCR ELISA telomerase test kit was surveyed telomerase activation.Verbascoside (17.7 μ g/ml) incubation gastric carcinoma cells with the telomerase 503nhibiting concentration carries out centrifugal treating after 8 weeks, again isolated cell genomic DNA, program survey telomere length routinely; And survey cancer cell-apoptosis with flow cytometer.
The present invention that the analysis showed that after above-mentioned experiment has following effect:
1, can make people's adenocarcinoma of stomach cell decreased growth.The cell doubling time of matched group is 48.2 hours, and extends to 68.5 hours through the cell doubling time of drug treating group.
2, the cancerous cell surface charge is reduced.Reduce more than 28.4% through the surface charge of drug treating group cell than the surface charge of cellular control unit.
3, the observation of pair cell configuration of surface shows, the present invention can make cancerous cell surface microcilium come off, and becomes smooth like that near normal cell.
4, can make the telomerase activation of gastric carcinoma cells reduce more than 50%.
5, telomere length is obviously shortened.The cancerous cell telomere length of matched group is 7.31kb, and the telomere length of the cancerous cell of crossing through drug treating of the present invention then shortens to 6.20kb.
6, Shi Du drug level can make cancer cell-apoptosis.In above-mentioned experiment, find, cancer cell-apoptosis 18.3% when drug level is 17.8 μ g/ml, and the apoptosis phenomenon of cancerous cell does not take place in matched group.
Above result shows that Verbascoside can make cancerous cell trend towards reversing, and becomes normal cell, also can make cancer cell-apoptosis simultaneously.1 and 4 of above-mentioned effect shows that also the present invention can make the permanent splitting ability of cancerous cell obviously reduce, and this has also shown a little less than the malignant change of cancerous cell after the Verbascoside processing.
Embodiment 4
Get 40 of healthy Kunming white mice, male and female half and half are divided into matched group (10 Mus), test three groups of one group (15 Mus) and experiments two groups (15 Mus) etc., every 3-5 Mus one cage, and male and female are divided foster.Inject by default drug dose after 24 hours in fasting, each group experiment is as follows:
Matched group: normal saline injection, 0.4ml/ only, every day lumbar injection once, totally 14 days.
Test one group: 0.8g (Verbascoside)/kg (Mus body weight), 0.4ml/ only, every day lumbar injection once, totally 14 days, accumulative total Verbascoside accumulated dose was 11.2g/kg.
Test two groups: 2.0g (Verbascoside)/kg (Mus body weight), 0.4ml/ only, every day lumbar injection once, totally 14 days, accumulative total Verbascoside accumulated dose was 28.0g/kg.
Behind each lumbar injection, observe in 30～40 minutes in the experiment and tried Mus and have or not the visible abnormal response of naked eyes, situations such as the diet of observation Mus, feces, behavior, fur in 14 days of experiment.In the 15th day Mus is put to death, perform an autopsy on sb, organs such as the heart of naked eyes detection Mus, liver,spleen,kidney, lung, and do pathological section and carry out microscopy and chromosome examination.Experimental result is as follows:
(1) in 30～40 minutes after the per injection:
Matched group: female Mus is had a liking for and licks the dermal needle mouth, begins normal feed and drinking-water after a while, the Mus freedom of movement;
Experimental group (comprising two groups of one group of experiment and experiments): injection back Mus contract one jiao motionless, go into action after about 5 minutes, like slightly uncomfortable; Appetite is strong not as matched group, after about 10 minutes the action of each Mus normal substantially, the fur drying, female Mus is had a liking for and licks the dermal needle mouth simultaneously.
(2) injected continuously 14 days during:
Two experimental group Mus body weight are suitable with matched group, referring to table 2.The fur drying of Mus, smooth, the nothing perspiration and the hair phenomenon of falling, diet, feces and action are all normal, and details sees Table 3.In none Mus death of experimental session.
(3) postmortem result:
Perusal: the organs such as the heart, liver,spleen,kidney, lung that respectively tried Mus all do not have visible unusual, and each organ color and luster is normal, and stiff reactions such as immaculate see Table 3
(4) histopathologic slide's microscopy:
Heart: cardiac muscular tissue is normal, and the myocardial cell nuclear staining is clear, and the cardiac muscle fiber form is normal, does not have loose
Deng abnormal phenomena.
Liver: the hepatic tissue structure is normal, and liver cell nuclear dyeing is clear, and form is identical with the normal control group, and liver is thin
Born of the same parents' structural integrity, no swelling phenomenon.
Stomach: the gastric epithelial tissue is normal, and gastric gland is normal.
Kidney: the nephridial tissue structure is normal, renal corpuscle and each section of renal tubules and normal control group indistinction.
Conclusion: according in " new drug (Western medicine) the preclinical study guideline compilation " of China Ministry of Public Health bureau of drug administration promulgation about relevant limit experimental requirements in the rat long term toxicity guideline: " as the toxic orally give pharmaceutical quantities of chmice acute greater than the 5g/kg body weight; injected dose can be considered only to do one and be higher than the dosage group that plan is used for 50 times of clinical dosages during greater than the heavy reaction of toxigenicity not yet of 20g/kg and dead or only indivedual toxic reaction " Verbascoside as can be seen belongs to nontoxic substantially.Can be used as oral medication fully, perhaps local muscle injecting drug use, or intravenous injection medication, or lumbar injection medication.
| Table 2 matched group and experimental group are injected mice body weight (g) variation in 7 days | ||||||||
| Matched group | Experimental group | |||||||
| Female | Female | Male | Male | Female | Female | Male | Male | |
| The 1st day | ????16.0 | ????15.5 | ????16.0 | ????16.5 | ????15.8 | ????16.3 | ????16.0 | ????16.5 |
| The 2nd day | ????20.3 | ????21.0 | ????21.7 | ????20.0 | ????21.1 | ????20.0 | ????21.5 | ????21.7 |
| The 5th day | ????24.5 | ????25.3 | ????26.5 | ????23.5 | ????24.5 | ????24.5 | ????24.5 | ????25.3 |
| The 7th day | ????27.0 | ????25.5 | ????28.0 | ????24.5 | ????26.0 | ????24.5 | ????26.0 | ????27.0 |
| Table 3 abdominal cavity is injected Verbascoside continuously and was tried Mus behavior and postmortem result in 14 days | |||
| Matched group | Test one group | Test two groups | |
| Profile | Each Corium Mus hair shaft is dry smooth; Behavior, spirit, D﹠E are all normal | All are identical with matched group, and only injection the 6th day, the testis color of Mus was dark slightly | All are identical with matched group, and only injection the 6th day, the testis of Mus was dark slightly, and the activity of Mus hind leg shows slightly slow |
| Postmortem | The organ such as the heart, liver,spleen,kidney, lung that is respectively tried Mus is all normal | All are identical with matched group | Organ colors such as the heart of Mus, liver,spleen,kidney, lung are dark slightly, but immaculate and hemorrhage situation |
Claims (5)
1, the new purposes of Verbascoside is characterized in that the application in cancer treatment drugs.
2, the new purposes of Verbascoside according to claim 1 is characterized in that the application in oral cancer treatment drugs.
3, the new purposes of Verbascoside according to claim 1 is characterized in that the application in intravenous cancer treatment drugs.
4, the new purposes of Verbascoside according to claim 1 is characterized in that the application in the cancer treatment drugs of intramuscular injection.
5, the new purposes of Verbascoside according to claim 1 is characterized in that the application in the cancer treatment drugs of lumbar injection.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03114454 CN1231220C (en) | 2003-01-16 | 2003-01-16 | New use of verbascum glycoside |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03114454 CN1231220C (en) | 2003-01-16 | 2003-01-16 | New use of verbascum glycoside |
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| Publication Number | Publication Date |
|---|---|
| CN1478479A true CN1478479A (en) | 2004-03-03 |
| CN1231220C CN1231220C (en) | 2005-12-14 |
Family
ID=34152556
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 03114454 Expired - Fee Related CN1231220C (en) | 2003-01-16 | 2003-01-16 | New use of verbascum glycoside |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106619664A (en) * | 2016-12-01 | 2017-05-10 | 南京医科大学附属口腔医院 | Application of verbascoside in preparation of medicine for treating oral squamous cell carcinoma |
| KR20190066779A (en) * | 2017-12-06 | 2019-06-14 | 김좌진 | Pharmaceutical Composition for Treatment and Inhibiting Metastasis of Brain Tumor Comprising Acteoside |
| KR20190104118A (en) * | 2019-08-28 | 2019-09-06 | 김좌진 | Pharmaceutical Composition for Treatment and Inhibiting Metastasis of Brain Tumor Comprising Acteoside |
| CN113440534A (en) * | 2020-03-26 | 2021-09-28 | 上海医药工业研究院 | Application of verbascoside in preparation of medicines |
-
2003
- 2003-01-16 CN CN 03114454 patent/CN1231220C/en not_active Expired - Fee Related
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106619664A (en) * | 2016-12-01 | 2017-05-10 | 南京医科大学附属口腔医院 | Application of verbascoside in preparation of medicine for treating oral squamous cell carcinoma |
| KR20190066779A (en) * | 2017-12-06 | 2019-06-14 | 김좌진 | Pharmaceutical Composition for Treatment and Inhibiting Metastasis of Brain Tumor Comprising Acteoside |
| KR102018085B1 (en) * | 2017-12-06 | 2019-09-04 | 김좌진 | Pharmaceutical Composition for Treatment and Inhibiting Metastasis of Brain Tumor Comprising Acteoside |
| KR20190104118A (en) * | 2019-08-28 | 2019-09-06 | 김좌진 | Pharmaceutical Composition for Treatment and Inhibiting Metastasis of Brain Tumor Comprising Acteoside |
| KR102135148B1 (en) * | 2019-08-28 | 2020-07-20 | 김좌진 | Pharmaceutical Composition for Treatment and Inhibiting Metastasis of Brain Tumor Comprising Acteoside |
| CN113440534A (en) * | 2020-03-26 | 2021-09-28 | 上海医药工业研究院 | Application of verbascoside in preparation of medicines |
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| Publication number | Publication date |
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| CN1231220C (en) | 2005-12-14 |
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