CN104644663B - A kind of cynanchum otophyllum saponin composition and its application - Google Patents
A kind of cynanchum otophyllum saponin composition and its application Download PDFInfo
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- CN104644663B CN104644663B CN201410787370.4A CN201410787370A CN104644663B CN 104644663 B CN104644663 B CN 104644663B CN 201410787370 A CN201410787370 A CN 201410787370A CN 104644663 B CN104644663 B CN 104644663B
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- cynanchum otophyllum
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- 241000299680 Cynanchum otophyllum Species 0.000 title claims abstract description 61
- 239000001397 quillaja saponaria molina bark Substances 0.000 title claims abstract description 36
- 229930182490 saponin Natural products 0.000 title claims abstract description 36
- 150000007949 saponins Chemical class 0.000 title claims abstract description 36
- 239000000203 mixture Substances 0.000 title claims abstract description 34
- 230000003556 anti-epileptic effect Effects 0.000 claims abstract description 25
- 239000001961 anticonvulsive agent Substances 0.000 claims abstract description 19
- 241000208340 Araliaceae Species 0.000 claims 1
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 claims 1
- 235000003140 Panax quinquefolius Nutrition 0.000 claims 1
- 235000008434 ginseng Nutrition 0.000 claims 1
- WRLGYAWRGXKSKG-UHFFFAOYSA-M phenobarbital sodium Chemical compound [Na+].C=1C=CC=CC=1C1(CC)C(=O)NC([O-])=NC1=O WRLGYAWRGXKSKG-UHFFFAOYSA-M 0.000 abstract description 18
- 230000000694 effects Effects 0.000 abstract description 16
- 238000010521 absorption reaction Methods 0.000 abstract description 6
- 235000017709 saponins Nutrition 0.000 description 26
- 239000003814 drug Substances 0.000 description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
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- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 2
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- FJPYVLNWWICYDW-UHFFFAOYSA-M sodium;5,5-diphenylimidazolidin-1-ide-2,4-dione Chemical compound [Na+].O=C1[N-]C(=O)NC1(C=1C=CC=CC=1)C1=CC=CC=C1 FJPYVLNWWICYDW-UHFFFAOYSA-M 0.000 description 2
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- VWLXIXALPNYWFH-UHFFFAOYSA-N Aglycon-B Natural products CC12CCC(O)CC1=CCC1(O)C2CC(OC(=O)C=C(C)C(C)C)C2(C)C(O)(C(C)=O)CCC21O VWLXIXALPNYWFH-UHFFFAOYSA-N 0.000 description 1
- 208000018152 Cerebral disease Diseases 0.000 description 1
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- 235000007516 Chrysanthemum Nutrition 0.000 description 1
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- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 206010068676 Pneumoretroperitoneum Diseases 0.000 description 1
- IMRGSWAJVVVYOW-ZCARJHNXSA-N Qingyangshengenin Chemical compound O([C@H]1[C@@]2(C)[C@]([C@@]3(CC=C4C[C@@H](O)CC[C@]4(C)[C@H]3C1)O)(O)CC[C@@]2(O)C(=O)C)C(=O)C1=CC=C(O)C=C1 IMRGSWAJVVVYOW-ZCARJHNXSA-N 0.000 description 1
- IMRGSWAJVVVYOW-UHFFFAOYSA-N Qingyangshengenin Natural products CC(=O)C1(O)CCC(C2(CC=C3CC(O)CCC3(C)C2C2)O)(O)C1(C)C2OC(=O)C1=CC=C(O)C=C1 IMRGSWAJVVVYOW-UHFFFAOYSA-N 0.000 description 1
- 208000005727 Retropneumoperitoneum Diseases 0.000 description 1
- BMWPBKOFJSHJAW-UHFFFAOYSA-N Saponin B Natural products CC1(C)CCC2(CCC3(C)C(=CCC4C5(C)CCC(OC6OC(CO)C(O)C(OC7OC(CO)C(O)C(O)C7O)C6=O)C(C)(C)C5CCC34C)C2C1)C(=O)O BMWPBKOFJSHJAW-UHFFFAOYSA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
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- 229960003965 antiepileptics Drugs 0.000 description 1
- 230000002567 autonomic effect Effects 0.000 description 1
- 229960000796 barbital sodium Drugs 0.000 description 1
- FTOAOBMCPZCFFF-UHFFFAOYSA-N barbitone sodium Natural products CCC1(CC)C(=O)NC(=O)NC1=O FTOAOBMCPZCFFF-UHFFFAOYSA-N 0.000 description 1
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- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
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- PPRSVUXPYPBULA-UHFFFAOYSA-N saponin A Natural products CC1(C)CCC2(CCC3(C)C(=CCC4C5(C)CCC(OC6OC(CO)C(O)C(O)C6=O)C(C)(C)C5CCC34C)C2C1)C(=O)O PPRSVUXPYPBULA-UHFFFAOYSA-N 0.000 description 1
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- RGHFKWPGWBFQLN-UHFFFAOYSA-M sodium;5,5-diethylpyrimidin-3-ide-2,4,6-trione Chemical compound [Na+].CCC1(CC)C([O-])=NC(=O)NC1=O RGHFKWPGWBFQLN-UHFFFAOYSA-M 0.000 description 1
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- Medicines Containing Plant Substances (AREA)
Abstract
The invention discloses a kind of cynanchum otophyllum saponin composition, said composition includes cynanchum otophyllum saponin M1 and cynanchum otophyllum saponin M2, in mass ratio 1:1 is combined, and is experimentally verified that, said composition can be used in combination by oral absorption with sodium phenobarbital, can strengthen the antiepileptic action of sodium phenobarbital, effect be better than it is single use, said composition can turn into antiepileptic.
Description
Technical field
The invention belongs to national the effective elements of the medicine field and antiepileptic compound field, more particularly to a kind of Cynanchum otophyllum Schneid
Saponin(e is combined and its application in antiepileptic is prepared.
Background technology
Epilepsy（epilepsy）" epilepsy " or " epilepsy " being commonly called as, is the electric discharge of cerebral neuron paroxysmal abnormality,
Cause a kind of chronic disease of of short duration cerebral disorder.China there are about 9,000,000 or so epileptic, wherein 500~600
Ten thousand be movable Patients with Epilepsy, while newly increasing epileptic about 400,000 every year, it is only secondary to have become neurology department in Chinese epilepsy
In the second largest common disease of headache.
Cynanchum otophyllum Schneid（Cynanchumotophyllum）It is a kind of conventional ethnic drug in Cynanchum plant, divides extensively
It is distributed in Southwestern China area, primary treatment epilepsy, dizziness, tinnitus, the disease such as soreness and weakness of waist and knees.Its chloroform extract is opened at present
Piece agent listing is sent out, combines the Antiepileptic drugs such as phenobarbital, dilantin sodium, the big breaking-out of intractable epilepsy is treated【Kuang Pei
Root etc., Cynanchum otophyllum Schneid treatment grand mal, Journal of Traditional Chinese Medicine, 1980 (8)】.In addition, there is document to report for work Cynanchum otophyllum Schneid for Chronic Liver
It is scorching【Jeanne Levy and Estera Miahel-Ber.Therapin 22(3)671-88(1967)(Fr); C.A.67
52609h；He Shuxun etc.：Cynanchum otophyllum Schneid treatment metastatic hepatitis, chronic hepatitis observation of curative effect, the research of autonomic drug-Cynanchum otophyllum Schneid is produced in Yunnan
Data 1981；65-62】, Meniere's disease【Wooden full chapter etc.：Cynanchum otophyllum Schneid glycosides third is to glycosides five compounds in heptan and preparation method thereof
And application；CN9611280 3.8】, the illness such as depression have preventive and therapeutic action【Yang Qingxiong, artificial cultivation Cynanchum otophyllum Schneid chemistry into
Divide and antidepressant activity research, Guizhou science, 2007（25）421-426】.
Only has the document report antiepileptic action of the total glycosides of Cynanchum otophyllum Schneid at present【Li Xianchun, the total glycosides antiepileptic action of Cynanchum otophyllum Schneid
Molecular mechanism research, East China Normal University Ph.D. Dissertation, 2005】.It is only wooden for the specific active ingredient of anti-epileptic
Cynanchum otophyllum saponin A and B that full chapter etc. was once carried, but reliable data is not seen, whether other compositions have anti-epileptic
Effect is not reported so far.
The characteristics of Chinese medicine/natural drug multicomponent multiple target effect, has become the common recognition of researcher, but how quick
Its effective substance is efficiently screened, the group of effective components particularly constituted comprising multiple compositions, is that domestic and foreign scholars are continuous
The problem of exploration.The material base research of traditional Chinese medicine/natural drug is to carry out extracting and developing, structure to its chemical composition
Identification, then carries out bioactivity screening, determines active ingredient.As New methods in working is suggested over nearly 10 years, Chinese medicine day
Right drug substance basic research has fast development.For example with activity for the material foundation of tcm research of guiding, based on modularization
The bioactive components research of or chemisorptive fibres concept, the middle medicinal substances base based on spectrum effect relationship or group effect relation
Plinth research etc.【Tu Pengfei, Shi Shepo, Jiang Yong material foundation of tcm Research Thinking and method [J] Chinese herbal medicines, 2012,43 (2):
209-215.】.But conventional method take it is long, it is inefficient；In-vitro screening and meter are too paid attention to or be confined to new method
Calculation machine virtual screening, but some external effective compositions can not be inactivated after absorption or metabolism, some compositions are invalid in vitro
And metabolic conversion is active component in vivo, or drug effect is played by neurohumoral systems, thus in-vitro screening can not be accurate
Really, it is efficiently obtained effective substance【Research of Xiao Qiuyuan, Ma Chaoying the serum drugs chemistry in terms of material foundation of tcm
Precious traditional Chinese medical science traditional Chinese medicines, 2009,20 (5) during progress [J]: 1061-1062】.Importantly, the screening of the above and separation Chinese medicine are lived
Property composition research method, destroy Chinese medicine with multiple compound groups into active component group systemic feature, result in often
The situation of " more separate and more do not imitate " for seeing.
In face of case above, it would be desirable to screen the active ingredient and group of effective components of Cynanchum otophyllum Schneid with new method.It is based on
The traditional Chinese medicine ingredients screening of serum drug chemistry is a kind of efficient screening technique【Yellow wealth is suitable, Xiang Cheng, Li Baocai, Kong Jing, king
Cherish the present situation and problem Chinese herbal medicines of active ingredient screenings of the base based on serum pharmaceutical chemistry, 2014,45 (20):
3009-3014】, its core views is " Chinese medicine can be probably effective component by the composition of intestines and stomach absorbed into serum ".Cynanchum otophyllum Schneid
Conventional use is oral, so it is probably its active ingredient to enter blood component；If it is substantially fewer than active compound composition to enter blood component, or even only
There is a few, then blood component can be segregated into specific aim and activity is tested, the workload of research will be greatly reduced, improve effect
Rate；It can more importantly attempt that blood component will be entered and be reconfigured, build the group of effective components of Cynanchum otophyllum Schneid, more definitely
Characterize the Active regenerator of Cynanchum otophyllum Schneid.
The content of the invention
It is an object of the invention to provide a kind of cynanchum otophyllum saponin composition, said composition includes cynanchum otophyllum saponin M1 and Qingyang
Join saponin(e M2；It is experimentally verified that, said composition can be used in combination by oral absorption with sodium phenobarbital, benzene bar ratio can be strengthened
The antiepileptic action of appropriate sodium, effect be better than it is single use, therefore said composition can be developed into antiepileptic.
Cynanchum otophyllum saponin M1 structure adds for Qingyanshengenin 3-O--D- oleanders pyranose-(1 → 4)-- D- takes
Big pyranose-(1 → 4)-- D- digoxigenin pyranosides；Cynanchum otophyllum saponin M2 structure be Qingyanshengenin 3-O--
Canadian pyranose-(1 → 4)-- D- digoxigenins pyranoses of D- oleanders pyranose-(1 → 4)-- D--(1 →
4) the Canadian pyranosides of-- D-；
Cynanchum otophyllum saponin M1 structural formula is as follows：
；
Cynanchum otophyllum saponin M2 structural formula is as follows：
；
Their design feature is all the C21 steroid saponins containing Qingyanshengenin, and the sugar chain length of 3 is 3-4 sugar, its
In first three sugar structure and on-link mode (OLM) be the Canadian pyranose of 3-O--D- oleanders pyranose-(1 → 4)-- D-
Base-(1 → 4)-- D- digoxigenin pyranoses.
The present invention is another object is that said composition is applied to prepare in antiepileptic.
Composition of the present invention, employs the effective component of chinese medicine screening side based on serum drug chemistry of novelty
Method, its substantially step is as follows：
1st, blood component is participated in using serum drug chemical method screening Qingyang, i.e., by the gavage absorption test of rat, used
HPLC-UV technology for detection Qingyang conopsea extraction enters blood component, and discovery mainly has two prototype compounds to be absorbed into blood,
For screening target component；
2nd, the fixed point separation of blood component is participated in Qingyang and is identified, i.e., the guidance of target component is filtered out in previous step
Under, using Phytochemistry means, from the conopsea extraction of Qingyang targetedly isolated two enter blood component：Cynanchum otophyllum saponin
M1 and cynanchum otophyllum saponin M2, and identify its accurate chemical constitution by means such as nuclear-magnetism, mass spectrums；
3rd, the anti-epileptic combination of active principles of Cynanchum otophyllum Schneid is built, the HPLC results of blood component screening are participated in as mould using Qingyang
Plate, main blood component is entered by two --- and cynanchum otophyllum saponin M1 and cynanchum otophyllum saponin M2--- are according near in the conopsea extraction of Qingyang
Like ratio（Mass ratio 1:1）It is combined, builds the anti-epileptic combination of active principles of Cynanchum otophyllum Schneid, and use mouse maximal electroshock
Breaking-out experiment（MES）Epilepsy model tests its antiepileptic action.As a result show：The anti-epileptic combination of active principles and benzene of Cynanchum otophyllum Schneid
Barbital sodium use in conjunction, can significantly increase sodium phenobarbital antiepileptic efficacy, with synergy；Its action effect also compared with
To be considerably stronger than monomeric compound cynanchum otophyllum saponin M1 or cynanchum otophyllum saponin M2 and effect associated with sodium phenobarbital individually.
One or more acceptable auxiliary materials can be added in composition of the present invention, capsule, tablet, particle is made
The diversified forms such as agent, pill, oral liquid and parenteral solution, combine the antiepileptics such as sodium phenobarbital, dilantin sodium, are used as epilepsy
Ancillary drug, treat intractable epilepsy.The auxiliary material includes the conventional sorbefacient of pharmaceutical field, surfactant, dilute
Agent, adhesive, excipient, filler and stabilizer etc. are released, pigment, flavouring agent and sweetener etc. can be also added if necessary.
The anti-epileptic composition of Cynanchum otophyllum Schneid provided by the present invention, because its screening, uniqueness of construction method, have
Following advantage：1st, chemical composition composition is clear and definite, and the structure of composition is clearly, complicated better than traditional extract component and be difficult to what is talked clearly
Situation；2nd, the combination of active principles of an entirety is made up of two compositions, the system sheet with " multicomponent " of Chinese medicine/natural drug
Matter feature is consistent, better than single compound；3rd, as a result of the method for selection of serum drug chemistry, so the combination filtered out
Compound can have a preferable oral absorption characteristic, it is to avoid in-vitro screening and the inconsistent situation screened in vivo；4th, build
The process of combination of active principles is that, using Cynanchum otophyllum Schneid into blood situation is divided into as template, there is an objective basis, process better than separated prescriptions and
Being optionally combined by rule of thumb.The invention of the combination, can be developed into antiepileptic, or the quality of Cynanchum otophyllum Schneid medicinal material
Control, pharmacological research establish important basis.
Brief description of the drawings
Fig. 1 is to carry out the HPLC schematic diagrames that Qingyang participates in blood component screening using serum drug chemistry；
Fig. 2 is the process flow diagram of fixed point separation and identification that blood component is participated in Qingyang.
Embodiment
The present invention is described in further detail below in conjunction with drawings and examples, but protection scope of the present invention is not limited to
In following embodiment, embodiment, the implementation of unreceipted actual conditions, according to normal condition, or according to institute of manufacturer
It is recommended that condition tested.
Embodiment 1：Qingyang is carried out using serum drug chemistry and participates in blood component screening
（1）After Cynanchum otophyllum Schneid pulverizing medicinal materials, mass percent concentration is used to be extracted for 70% alcohol reflux, extract solution concentration is
Medicinal extract, is made Qingyang conopsea extraction；
（2）Qingyang conopsea extraction is analyzed using HPLC or LC-MS, the finger-print of Cynanchum otophyllum Schneid medicinal material is set up；
（3）Using step（1）Extract carries out animal oral absorption experiment, and rat is divided into high, medium and low dosage three by experiment
Group, then carries out gavage with Qingyang conopsea extraction, and high dose group dosage is 450mg/kg, middle dose group dosage
200mg/kg, low dose group dosage is 110mg/kg；Every group of rat 18, each time point is parallel 3, respectively at 0
Min, 15min, 30min, 60min, 120min, 180 min extract femoral artery blood, and 4000rpm centrifugations prepare blood plasma, and put to death dynamic
Thing, collects gastrointestinal content；
（4）Merge the plasma sample of all time points collections of each group, be extracted with ethyl acetate；Gastrointestinal contents is first homogenized,
It is extracted with ethyl acetate again, N is used after the extract solution for merging blood plasma2N is used after drying, the extract solution for merging gastrointestinal contents2Drying；
Solid methanol is redissolved after drying, filtering with microporous membrane, HPLC are detected；
（5）Step（4）Testing result is compareed with extract finger-print, chooses Qingyang conopsea extraction finger-print, blood plasma
With the composition all having in gastrointestinal contents, what as Cynanchum otophyllum Schneid orally easily absorbed enters blood compound；
Experimental result as shown in figure 1, rat oral gavage cynanchum otophyllum saponin M1 contents are higher in stomach after 15 minutes, it is bright at 30 minutes
It is aobvious to reduce, gradually shifted to small intestine, therefore, contain M1 during small intestine 30 minutes；At 60 minutes, the M1 in small intestine disappears, but in blood
It is middle to find, therefore M1 is that the blood component that enters that we need orally easily absorbs composition；
Cynanchum otophyllum saponin M2 contents are higher in stomach after 15 minutes for rat oral gavage, significantly reduced at 30 minutes, gradually to small intestine
Transfer, therefore, contains M2 during small intestine 30 minutes；At 60 minutes, the M2 in small intestine disappears, and but finds in blood, therefore M2 is me
Need enter that blood component is i.e. oral easily to absorb composition.
Embodiment 2：The fixed point separation of blood component is participated in Qingyang and is identified
The Cynanchum otophyllum Schneid bought from Kunming chrysanthemum village medicinal material market breaks into dry powder（Medicinal material is carried out in advance cleans and crush machine）, it is blue or green
Sun ginseng root powder is soaked 24 hours with 70% ethanol, refluxing extraction three times afterwards, every time 2 hours.Ethanol extract uses rotation after merging
Turn evaporimeter in 55 degrees Celsius of temperature, pressure -0.054 is lower to reclaim ethanol, and concentrated extracting solution obtains medicinal extract, resulting medicinal extract according to
Secondary use petroleum ether, ethyl acetate and extracting n-butyl alcohol.
HPLC detections are carried out, are found into blood component in ethyl acetate extract.By Ethyl acetate fraction (45 g) through silicon
Glue column chromatography, with chloroform-methanol gradient elution（98:2、96:4、92:8、90:10、1:1）, collect each several part eluent, decompression
Concentration, concentrate is transferred in 10ml penicillin bottles, TLC detections, and the roughly the same fraction of composition is merged；Carry out HPLC
Detection, finds into blood component to chloroform：Methanol=92:8 part, to it（10g）Separated, separation method is ODS, MCI
Column chromatography, with methanol water mixed liquid:（50:50、65:35、75:25、85:15）Eluted；HPLC detections are carried out, are found into blood
Composition M1 is in methanol：Water=75:In 25 component, M2 is in methanol：Water=85:15 component.Further divided using liquid phase is prepared
From method is to methanol：Water=75:25 component methanol：Water=80:20 separation cynanchum otophyllum saponin M1, to methanol：Water=85:15
Component methanol：Water=70:30 separation cynanchum otophyllum saponin M2, collect two target chromatographic peak eluents, go out after eluent concentration
Cynanchum otophyllum saponin M1 is obtained after existing a large amount of white crystals, recrystallizing methanol（85mg）With cynanchum otophyllum saponin M2（70mg）.Through core
Magnetic resonance detection is obtained1H-NMR and13C-NMR data, cynanchum otophyllum saponin M1 with【Yin Minmin etc., the extraction of Cynanchum otophyllum Schneid ethyl acetate
The chemical composition at position, China Medicine University's journal, 2013,44 (3):213-218】Data described in one text are basically identical,
It is as follows：
1H-NMR (pyridine-d 5, 500 MHz), δ:3.87 (1H, m, H-3), 5.27 (1H, s, H-6),
5.33 (1H, dd, J=4.0, 11.0 Hz, H-12), 2.09 ( 3H, s, H-18), 1.30 (3H, s, H-19),
2.42 (3H, s, H-21), 8.30 (1H, d, J=8.5 Hz, H-3'), 7.23 (1H, d , J=8.5, H-4'),
7.23 (1H, d, J=8.5 Hz, H-6'), 8.30 (1H, dJ=8.5 Hz, H-7'), 5.48 (1H, d, J=9.5
Hz, H-1''), 4.64 (1H, m, H-3''), 3.51 (1H, m, H-4''), 4.30 (1H, m, H-5''),
1.43 (3H, d, J=6.0 Hz, H-6''), 5.17 (1H, d, J=9.5 Hz, H-1'''), 4.05 (1H, m,
H-3'''), 3.41 (1H, m, H-4'''), 4.20 (1H, m, H-5'''), 1.35 (3H, d, J=6.0 Hz,
H-6'''), 3.56 (3H, s, H-7'''), 4.75 (1H, d, J=10.0 Hz, H-1''''), 3.48 (1H, m,
H-3''''), 3.44 (1H, m, H-4''''), 3.59 (1H, m, H-5''''), 1.59 (3H, d, J=4.5
Hz, H-6''''), 3.45 (3H, s, H-7'''');
13C-NMR (pyridine-d 5, 125 MHz), δ: 39.3 (C-1), 29.9 (C-2), 77.7 (C-3),
39.0 (C-4), 139.6 (C-5), 118.9 (C-6), 34.8 (C-7), 74.4 (C-8), 44.5 (C-9),
37.4 (C-10), 25.2 (C-11), 73.4 (C-12), 58.5 (C-13), 89.6 (C-14), 33.9 (C-15),
33.2 (C-16), 92.5 (C-17), 10.8 (C-18), 18.2(C-19), 209.7 (C-20), 27.8 (C-21),
165.4 (C-1'), 122.1(C-2'), 132.4 (C-3'), 116.2 (C-4'), 163.6 (C-5'), 116.2
(C-6'), 132.4 (C-7'), 96.4 (C-1''), 39.0 (C-2''), 67.5 (C-3''), 83.4 (C-4''),
69.2 (C-5''), 18.5 (C-6''), 99.8 (C-1'''), 36.8(C-2'''), 77.8(C-3''') , 83.2
(C-4'''), 68.6 (C-5'''), 18.7 (C-6'''), 58.9 (C-7'''), 102.2 (C-1''''), 37.3
(C-2''''), 81.4 (C-3''''), 76.3 (C-4''''), 73.0 (C-5'''') , 18.7 (C-6''''),
57.1(C-7'''').According to above-mentioned spectral data, it is defined as cynanchum otophyllum saponin M1.
Cynanchum otophyllum saponin M2 with【Xiao-Xia Ma etc., Identification of new qingyangshengenin
And caudatin glycosides from the roots of Cynanchum otophyllum, Steroids, 2011,
1003-1009】Data described in one text are basically identical,1H-NMR and13C-NMR data are as follows：
1H-NMR (pyridine-d 5, 500 MHz), δ:3.84 (1H, m, H-3), 5.26 (1H, s, H-6),
5.32 (1H, dd, J=4.0, 11.5 Hz, H-12), 2.09 ( 3H, s, H-18), 1.30 (3H, s, H-19),
2.42 (3H, s, H-21), 8.30 (1H, d, J=8.0Hz, H-3'), 7.22 (1H, d , J=8.0 Hz, H-
4'), 7.22(1H, d, J=8.0 Hz, H-6'), 8.30 (1H, dJ=8.0 Hz, H-7'), 5.48 (1H, d, J=
9.5 and 1.5 Hz, H-1''), 4.64 (1H, m, H-3''), 3.52 (1H, m, H-4''), 4.30 (1H, m,
H-5''), 1.42 (3H, d, J=6.0 Hz, H-6''), 5.16 (1H, d, J=9.5 Hz, H-1'''), 4.00
(1H, m, H-3'''), 3.41 (1H, m, H-4'''), 4.17 (1H, m, H-5'''), 1.32 (3H, d, J=
6.0 Hz, H-6'''), 3.56 (3H, s, H-7'''), 4.67 (1H, d, J=10.0 Hz, H-1''''), 3.55
(1H, m, H-3''''), 3.51 (1H, m, H-4'''') , 3.52 (1H, m, H-5''''), 1.43 (3H, d,
J=4.5 Hz, H-6''''), 3.51 (3H, s, H-7''''), 5.25 (1H, d, J=9.5 Hz, H-1'''''),
3.77 (1H, m, H-3'''''), 3.54 (1H, m, H-4'''''), 4.14 (1H, m, H-5'''''), 1.54
(3H, d, J=5.5 Hz, H-6'''''), 3.46 (3H, s, H-7''''');
13C-NMR (pyridine-d 5, 125 MHz), δ: 39.2 (C-1), 29.8 (C-2), 77.7 (C-3),
39.0 (C-4), 139.4 (C-5), 119.1 (C-6) , 34.8 (C-7), 74.3(C-8), 44.5 (C-9),
37.4 (C-10), 25.2 (C-11), 73.4 (C-12), 58.4 (C-13), 89.5 (C-14), 33.9 (C-15),
33.2 (C-16), 92.5 (C-17), 10.8 (C-18), 18.1(C-19), 209.8 (C-20), 27.8 (C-21),
165.3 (C-1'), 122.0(C-2'), 132.4 (C-3'), 116.2 (C-4'), 163.6 (C -5'), 116.2
(C-6'), 132.4 (C-7'), 96.4 (C-1''), 39.0 (C-2''), 67.5 (C-3''), 83.4 (C-4''),
68.6(C-5''), 18.7 (C-6''), 99.7 (C-1'''), 36.8(C-2'''), 77.7(C-3'''), 83.2
(C-4'''), 69.2 (C-5'''), 18.5 (C-6'''), 58.7 (C-7'''), 102.2 (C-1''''), 37.7
(C-2''''), 78.9 (C-3''''), 82.6 (C-4''''), 71.8 (C-5''''), 18.7 (C-6''''),
57.3 (C-7''''), 98.5 (C-1'''''), 35.9 (C-2'''''), 79.0 (C-3'''''), 74.7 (C-
4'''''), 71.3 (C-5'''''), 19.0 (C-6'''''), 58.0 (C-7''''').According to above-mentioned spectral data,
It is defined as cynanchum otophyllum saponin M2.
Embodiment 3：The anti-epileptic group of effective components collaboration sodium phenobarbital of Cynanchum otophyllum Schneid, to anti-epileptic maximal electroshock seizure
Experiment
The foundation of epilepsy model：Maximal electroshock anti-epileptic model（MES）Optimal conditions mainly include electric stimulating time, electricity
Stimulation location（Have sharp ears, in, root）And voltage, final optimal conditions are：In electric stimulating time 0.125s, sites of electrostimulation ear
Portion, voltage 100V.Under the conditions of being somebody's turn to do, the electro photoluminescence effect of mouse is unlikely to too strong or excessively weak, and sodium phenobarbital can treat the condition
Tonic spasm caused by lower.
Sodium phenobarbital is used in combination with cynanchum otophyllum saponin M1+M2 for this experiment, to share the inhibiting rate to epileptic attack
Whether increase judges the synergy of compound；Specific method is：Kunming mouse, the animal 40 of sensitivity is filtered out using MES
Only, negative control group, phenobarbital group are randomly divided into（Positive controls）, M1+ sodium phenobarbitals group, M2+ sodium phenobarbitals group,
5 groups, every group 8 of M1+M2+ sodium phenobarbital drug combination groups etc..Sodium phenobarbital（8 mg/kg）、M1（10 mg/kg）、M2
（10 mg/kg）、M1+M2（5+5 mg/kg）It is intraperitoneal injection.When alone, tested after sodium phenobarbital administration 1h；Connection
Close in use, M1, M2 or M1+M2 is first injected intraperitoneally, 4h pneumoretroperitoneums injection sodium phenobarbital carries out MES experiments, commented after 1 hour
The inhibitory action that valency medicine is reacted epileptic caused by MES.Data statistics uses χ2Method of inspection, to examine sodium phenobarbital to close
Whether anti-epileptic curative effect is risen with M1+M2, and is compared with monomer M1, M2 effect.
As a result（Table 1）Prove that M1+M2 has shared antiepileptic action after synergy, administration with sodium phenobarbital and strengthened；And
Being compared with sodium phenobarbital with M1 or M2 combination groups also strengthens, and has significant difference, can be used as the ancillary drug for treating epilepsy.
Table 1：M1+M2 and sodium phenobarbital share the effect that mouse epilepsy is caused to MES
Note：**：Administration group and negative control group compare, P<0.01, there is significant difference；：With sodium phenobarbital group ratio
Compared with：P < 0.01.
Claims (2)
1. a kind of cynanchum otophyllum saponin composition, it is characterised in that：It includes cynanchum otophyllum saponin M1 and cynanchum otophyllum saponin M2, wherein blue or green
Sun ginseng saponin(e M1 structural formula is as follows：
；
Cynanchum otophyllum saponin M2 structural formula is as follows：
。
2. application of the cynanchum otophyllum saponin composition in antiepileptic is prepared described in claim 1.
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