CN107095878A - Application of the pedunculoside in anti-influenza virus medicament is prepared - Google Patents
Application of the pedunculoside in anti-influenza virus medicament is prepared Download PDFInfo
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- CN107095878A CN107095878A CN201710405506.4A CN201710405506A CN107095878A CN 107095878 A CN107095878 A CN 107095878A CN 201710405506 A CN201710405506 A CN 201710405506A CN 107095878 A CN107095878 A CN 107095878A
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- pedunculoside
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- WYUFTYLVLQZQNH-UHFFFAOYSA-N CCOC(C(C1O)O)OC(CO)C1O Chemical compound CCOC(C(C1O)O)OC(CO)C1O WYUFTYLVLQZQNH-UHFFFAOYSA-N 0.000 description 1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7024—Esters of saccharides
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Abstract
Purposes of the first public pedunculoside of the present invention in anti-influenza virus medicament is prepared, and application of the pedunculoside in treatment pneumonia medicine as caused by influenza virus is prepared further is disclosed.Proved through In vitro cell experiment, the IC50 values of the anti-H1N1 influenza viruses of pedunculoside are 7.6 μ g/mL, suitable with positive drug Ribavirin effect.Mouse influenza models pharmacological evaluation is confirmed, pedunculoside can significantly reduce the Lung Exponent of influenza infection mouse, and a certain amount effect feature is presented to H1N1, shows that the compound infected by influenza has preventive and therapeutic effect, the medicine for preparing resisiting influenza virus can be used for as active component.
Description
Technical field
The present invention relates to the new pharmaceutical use of pedunculoside, and in particular to pedunculoside is preparing antiviral drug for influenza
Application in thing.
Background technology
Influenza virus (abbreviation influenza virus) is a kind of to cause the animal such as people and pig, birds to suffer from influenza
RNA virus.Wherein, influenza A virus is easily morphed due to antigenic, has prevalence by Influenza A H1N1 of its initiation
The features such as wide, infectiousness is strong, the incidence of disease is high.At present, clinically for preventing and treating the antiviral agent owner of influenza virus
There are M2 inhibitors of ion channels adamantane amines, including amantadine and Rimantadine；And neuraminidase inhibitor, bag
Include Oseltamivir and zanamivir.Although they can effective symptom management, this two classes medicine long-term taking poison that easily causes a disease becomes
Different, easy resistance and there are various side effects.
(molecular formula is C to pedunculoside36H58O10) also known as Peltatin glucoside, it can extract from Aquifoliaceae Holly iron
Chinese ilex Ilex rotunda Thunb. dry bark.Belong to pentacyclic triterpenoid, with pentacyclic triterpene parent nucleus.Five rings
The general structure of triterpene compound is：
In formula, R is COOH, COO-β-D-glucosyl group or other pharmaceutically acceptable groups.
Constituted above formula, when R is COO-β-D-glucosyl group in formula, the entitled Folium Ilicis macrocarpae of compound
(Pedunculoside)。
At present, patent document CN105125567A, which discloses pedunculoside, has antiphlogistic effects.Chinese patent
CN101961340A, which discloses pedunculoside, has significant anti-arrhythmia, myocardial ischemia and Cerebral Ischemia.But not yet
See the research report acted on pedunculoside resisiting influenza virus.
The content of the invention
It is an object of the invention to provide purposes of the pedunculoside in anti-influenza virus medicament is prepared, especially in system
Purposes in standby anti-H1N1 influenza viruses.
And application of the pedunculoside in treatment pneumonia medicine as caused by influenza virus is prepared further is disclosed.It is described
Influenza virus is related to H1N1virus.
Described anti-influenza virus medicament can be made into tablet, granule, capsule or pill.
Compared with prior art, beneficial outcomes of the invention are that first public pedunculoside of the invention is preparing anti-current
Purposes in susceptible cytotoxic drug.Proved through In vitro cell experiment, the IC50 values of the anti-H1N1 influenza viruses of pedunculoside are 7.6 μ
G/mL is suitable with positive drug Ribavirin effect.Mouse influenza models pharmacological evaluation confirms that pedunculoside can be significantly reduced
The Lung Exponent of influenza infection mouse, and a certain amount effect feature is presented to H1N1, show the compound infected by influenza tool
There is preventive and therapeutic effect, the medicine for preparing resisiting influenza virus can be used for as active component.
Embodiment
Essence for a better understanding of the present invention, provides pedunculoside resisiting influenza virus with the form of embodiment below
The pharmacological results, illustrate its new application in pharmaceutical field.These embodiments of mandatory declaration simultaneously are merely to illustrate this hair
It is bright rather than limit the scope of the invention.
The preparation of the iron holly bark medicinal substances extract of embodiment 1
Take iron holly bark medicinal material appropriate, crush, cross No. 1 sieve, medicinal material adds 8 times of 70% (volume fraction) ethanol of amount, is heated to reflux
Extract 2 times, each 1h, filtering merges extract solution, puts in rotary evaporator, paste is concentrated under reduced pressure at 80 DEG C.Will concentration
Liquid transfer, which is put, to be dried under reduced pressure in case, is proceeded to dry at 80 DEG C, is crushed, produces iron holly bark medicinal substances extract (through liquid phase color
Spectrometry detects that the mass fraction of pedunculoside is 200mg/g in the extract).
The external influenza virus Inhibition test of embodiment 2
1. experiment material
1.1 test medicine：Pedunculoside (is extracted from iron holly bark and obtained, purity ＞ 98%).
1.2 control drug：Ribavirin, oleanolic acid, iron holly bark medicinal substances extract (see embodiment 1)
1.3 Strain：H1N1virus mouse lung adapted strain (FM/1/47 plants).Chicken embryo is passed on, BSL-3 (biology peaces
Full laboratory three-level) detect in laboratory, packing, -80 DEG C preserve.
1.4 cell model：MDCK mdck cell
Said medicine is saved backup for -20 DEG C after dimethyl sulfoxide (DMSO) (DMSO) fully dissolving.
2. experimental method
The measure of 2.1 virus virulences
100 μ l 10 are serially diluted to the virus liquid of 10 obtained concentration again, 8 multiple holes is set per concentration, is inoculated into successively
In 96 orifice plates for covering with MDCK cell monolayers layer, while setting cell controls.37 DEG C, 5%CO2Cultivated in Virus culture case, day by day
With inverted microscope observation cytopathy (CPE), Continuous Observation 3 days is detected with mtt assay, is surveyed in ELIASA 570nm wavelength
Determine absorbance OD values, viral 50 3nfective dose (TCID50) is calculated with Reed-Muench methods.
Measurement result：Virus virulence TCID50 is 10-5。
2.2 pedunculoside CTAs
Take mdck cell to grow up to 96 porocyte culture plates of individual layer, incline nutrient solution, washed with PBS 2 times, addition is free of
Continuous 2 times of the DMEM culture mediums of serum are serially diluted the pedunculoside decoction of (650 μ g/mL-5.07 μ g/mL), 100 μ l/ holes,
Each concentration sets 4 multiple holes, if the hole of normal cell controls 4.37 DEG C, 5%CO272h is cultivated in Virus culture case, is entered with mtt assay
Row detection, measures the trap of each experimental group and cell controls group under 570nm wavelength.Using control wells as reference, each reality is calculated
Verify the vigor ratio of cell.Cytotoxic concentration CC50 is calculated according to Reed-Muench methods, whole experiment is repeated 3 times, made even
Average.
Measurement result：The cell half toxic concentration CC50 of pedunculoside>650μg/mL.
The anti-H1N1 active testings of 2.3 pedunculosides
Take mdck cell to grow up to 96 porocyte culture plates of individual layer, incline nutrient solution, washed with PBS 2 times, added
100TCID50 virus liquids, 100 μ l/ holes, 37 DEG C, 5%CO2Adsorb 2h.Adding continuous 2 times of the DMEM culture mediums without serum is
The pedunculoside decoction of row dilution (325 μ g/mL-5.07 μ g/mL), while setting virus control group, cell controls group, positive drug
Group, iron holly bark medicinal substances extract group and oleanolic acid group.In 37 DEG C, 5%CO2Cultivate after 72h, carried out with mtt assay in incubator
Detection, the absorbance OD values surveyed with ELIASA at 570nm wavelength.Medicine is to viral inhibiting rate according to the following formula：Virus
Inhibiting rate (%)=(drug-treated group OD averages-virus control group OD averages)/(cell controls group OD averages-virus control group
OD averages) × 100%, medicine infected by influenza is calculated according to Reed-Muench methods and causes CPE to produce 50% concentration suppressed, i.e.,
Half-inhibition concentration IC50, whole experiment is repeated 3 times, and is averaged.
Experimental result：According to MTT results, the half-inhibition concentration of pedunculoside is calculated using Reed-Muench methods
IC50 is 7.6 μ g/mL, and the half-inhibition concentration IC50 of oleanolic acid is 38.6 μ g/mL, and the half of iron holly bark medicinal substances extract presses down
Concentration IC50 processed>325μg/mL.The half-inhibition concentration IC50 of positive drug Ribavirin is 6.9 μ g/mL.
Conclusion：Pedunculoside has stronger inhibitory action, its IC50 value and Ribavirin to H1N1 influenza viruses
IC50 values size is approached, and will be small than oleanolic acid and iron holly bark medicinal substances extract IC50 values, it was demonstrated that pedunculoside pair
The inhibitory action of H1N1 influenza viruses is suitable with positive control drug 'Libaweilin ', and is better than oleanolic acid and iron holly bark medicinal material is carried
Take thing.
Influenza Inhibition test in the body of embodiment 3
1. experiment material
1.1 test medicine：Pedunculoside (is extracted from iron holly bark and obtained, purity ＞ 98%).
1.2 control drug：Tamiflu, oleanolic acid, iron holly bark medicinal substances extract (embodiment 1)
1.3 it is viral：H1N1virus mouse lung adapted strain (FM/1/47 plants).Chicken embryo is passed on, BSL-3 (bio-safeties
Laboratory three-level) detect in laboratory, packing, -80 DEG C of preservations.
2. experimental animal
BALB/c mouse body weight 18g-22g, 80, purchased from Guangdong Province's Experimental Animal Center.
3. experimental method
BALB/c mouse is randomly divided into 8 groups, respectively blank control group, model control group, Tamiflu control group, olive
Sour group, iron holly bark medicinal substances extract group, high, medium and low 3 dosage groups of pedunculoside, every group 10.In addition to blank control group,
Each test group of animals ether light anesthesia, is infected, every 35 μ L with 15 LD50 FM1 influenza virus drops nose.Before infection
Daystart gastric infusion, presses 0.2ml/10g body weight gavages, 1 time a day, successive administration 5 days every time.Blank group and model comparison
Under equal conditions gavage gives isometric distilled water to group.Dissected after weighing within 6th day, take lung, weigh, calculate Lung Exponent and lung
Index inhibiting rate.
Calculation formula：Lung Exponent=lung quality (g)/body weight (g) × 100%；Lung index=(model control group is put down
The average Lung Exponent of equal Lung Exponent-experimental group) data processing of the average Lung Exponent of/model control group × 100% and statistical method：Lung
Index is represented with average value ± SD values, is compared between group and is used one-way analysis of variance；Using SPSS19.0 software data processings.
4. experiment conclusion
Lung Exponent value is bigger, represents that pneumonia is more serious.Shown by the experimental result of table 1, pedunculoside energy of the invention
The Lung Exponent of influenza infection mouse is enough significantly reduced, and a certain amount effect feature is presented to H1N1, shows pedunculoside convection current
Influenza Virus has preventive and therapeutic effect.In addition, pedunculoside is significantly stronger than oleanolic acid with rescuing for the prevention effect of influenza virus
Medicinal substances extract must be answered.Pedunculoside of the present invention can prepare the medicine for resisiting influenza virus.
The influence (n=10) of FM/1/47 plants of infecting mouse pulmonary inflammation model Lung Exponents of 1 medicine infected by influenza of table
Note：## is compared with blank control group, P<0.05, * * is compared with model control group, P<0.01.
Claims (4)
1. application of the pedunculoside in anti-influenza virus medicament is prepared.
2. application according to claim 1, it is characterised in that the influenza virus is H1N1virus.
3. application of the pedunculoside in treatment pneumonia medicine as caused by influenza virus is prepared.
4. application according to claim 3, it is characterised in that the influenza virus is H1N1virus.
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| CN201710405506.4A CN107095878B (en) | 2017-06-01 | 2017-06-01 | Application of pedunculoside in preparing anti-influenza virus medicine |
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| CN107095878A true CN107095878A (en) | 2017-08-29 |
| CN107095878B CN107095878B (en) | 2020-02-21 |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103351419A (en) * | 2013-07-09 | 2013-10-16 | 陕西中药研究所 | Two-step simultaneous preparation method for pedunculoside and syringin |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103351419A (en) * | 2013-07-09 | 2013-10-16 | 陕西中药研究所 | Two-step simultaneous preparation method for pedunculoside and syringin |
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