CN108434167A - Application of the different corilagin in preparing anti-influenza virus medicament - Google Patents
Application of the different corilagin in preparing anti-influenza virus medicament Download PDFInfo
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- CN108434167A CN108434167A CN201810144168.8A CN201810144168A CN108434167A CN 108434167 A CN108434167 A CN 108434167A CN 201810144168 A CN201810144168 A CN 201810144168A CN 108434167 A CN108434167 A CN 108434167A
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- WIGFFUXTUCLQFT-DDFJOOHZSA-N CC([C@H](C1O)[O](CCOC(c(cc2O)c(-c(c(O)c(c(O)c3)O)c3C(OC)=O)c(O)c2O)=O)C1OC(c(cc1O)cc(O)c1O)=O)O Chemical compound CC([C@H](C1O)[O](CCOC(c(cc2O)c(-c(c(O)c(c(O)c3)O)c3C(OC)=O)c(O)c2O)=O)C1OC(c(cc1O)cc(O)c1O)=O)O WIGFFUXTUCLQFT-DDFJOOHZSA-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
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
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Abstract
The invention discloses application of the different corilagin in preparing anti-influenza virus medicament, belong to pharmaceutical arts.The structural formula of the different corilagin is：Inventor, which studies, finds that different corilagin has apparent inhibiting effect to Influenza virus H1N1, and there is apparent dose relationships.Different corilagin increases the inhibiting rate of virus with the increase of concentration, to the medium effective concentration IC of H1N150It is 3.16 ± 0.81 μM.In addition, different corilagin in the concentration range of 50 μ g/ml to mdck cell almost without toxicity.The drug concentration selected in the experimental study of the present invention is in safety non-toxic concentration range within 50 μ g/ml.
Description
Technical field
The invention belongs to pharmaceutical arts, and in particular to the new application of different corilagin is that different corilagin is preparing anti-current
Application in susceptible cytotoxic drug.
Background technology
Influenza virus abbreviation influenza virus.It is divided into first (A), second (B), third (C) three type, just finds in recent years
Bovine influenza virus will be classified as fourth (D) type.Influenza virus can cause many animals such as people, fowl, pig, horse, bat to infect and fall ill, and be
The cause of disease of human influenza, bird flu, swine flu, equine influenza et al. and animal epidemic.
The typical clinical symptoms of these epidemic diseases are acute high fever, overall pain, significantly weak and respiratory symptom.Influenza disease
Contact between malicious main droplet through the air, susceptible person and the infected or with the contact of contaminated article and propagate.One
As autumn and winter be its high-incidence season.Caused by human influenza is mainly influenza A virus and influenza B virus.Flu-A disease
Malicious antigenic variation frequent occurrence, being further divided into the hypotypes such as H1N1, H3N2, H5N1, H7N9, (H and N therein are respectively represented
Two kinds of surface glycoproteins of influenza virus).Influenza virus is not strong to extraneous resistance.Animal influenza virus does not usually infect people, people
Influenza virus usually not infection animal, but outside pig comparative example.Pig can both infect human influenza virus, can also infect bird flu
Virus, but the still swine influenza virus of their main infections.After a small number of animal influenza viruses adapt to people, human influenza can be caused big
It is popular.
The common anti-influenza virus medicament in China mainly has vaccine, ion channel M2 albumen co-inhibitor and neuraminic acid at present
Enzyme inhibitor.
Vaccine：Mainly there are the three classes influenza vaccines such as viral fiery live vaccine, split vaccine and subunit vaccine in China at present.Its
Middle totivirus fire live vaccine clinical therapeutic efficacy is best, but can lure that diarrhea, abdominal pain, dizziness, head occur in 12 years old or less children into
The adverse reactions such as pain.
Ion channel M2 albumen co-inhibitors：Amantadine and Rimantadine are by blocking influenza m 2 protein and place
Host cell proteins are combined, and the release of influenza virus core RNA and relevant enzyme are blocked, to interrupt the duplication of influenza virus
Breeding acts on, and reaches antivirus action.But largely take for a long time, patient may occur in which confusion, dizziness, headache, it is drowsiness,
The adverse reactions such as nausea.
Neuraminidase inhibitor：Clinical the most commonly used neuraminidase inhibitor mainly has Oseltamivir and Zha Na meter
Wei.By inhibiting the activity of neuraminidase, the activity of influenza virus can be effectively reduced, reduces influenza virus to normal cell
Infection.Clinical research finds Oseltamivir for having a heart disease and the gerontal patient of chronic nonobstructive tuberculosis dislikes
Patient's number of cases of the adverse reactions such as the heart, vomiting is obviously higher by the patient using placebo.Zanamivir can be administered orally,
The number of ways administration such as intranasal administration and intravenous injection administration, wherein its bioavilability height, half-life short, warp is administered orally
It is low by kidney excretion rate, patient can be caused bronchial spasm occur the patient with chronic nonobstructive tuberculosis, therefore right
While the patient with asthma or chronic obstructive tuberculosis is in administration, because giving Rapid Expansion organ medicine.
Other classes：Hydrochloric acid bar can inhibit influenza virus adipose membrane and host cell surface albumen to merge to rise than Dorr
To antiviral effect, IFN-β interferon can antivirus protein gene effectively in active cell, to inhibit virus protein
Synthesis.
It is mostly chemical synthetic drug in said medicine, there is certain side effect, therefore extract anti influenza from natural materials
The active ingredient of virus is of great significance.
Invention content
The purpose of the present invention is to provide different corilagin the answering in preparing anti-influenza virus medicament for extracting from Chinese olive
With.
The technical solution used in the present invention is：
Different corilagin or its application of pharmacologically acceptable salt in preparing anti-influenza virus medicament, different Ke
Lira capital structural formula be：
The different corilagin that the present invention studies is the αisomer of corilagin (Corilagin), molecular formula：C27H22O18,
Systematic naming method：1-O- nutgall acyls -3,6- (R)-O- hexahydroxys dibenzoyl-alpha-D-glucose (1-O-galloyl-3,6- (R) -
O-hexahydroxydiphenoyl-α-D-glucose)。
Preferably, the different corilagin extracts from Chinese olive.When Chinese olive, also known as " olive " are still in dark green because of fruit
It gains the name for fresh food.It is mild-natured, it is sweet in flavor, puckery, sour.Heat-clearing, relieving sore-throat are promoted the production of body fluid, removing toxic substances.For abscess of throat, cough, polydipsia, ichthyophagy crab
Poisoning etc..Inventor extracts isolated more different corilagin (303mg) in Chinese olive chloroform extract, and content accounts for blueness
The 0.28% of fruit chloroform extract total amount.
Preferably, the influenza virus is influenza A virus.
Influenza A virus also known as influenza A, mainly hypotypes such as including H1N1, H3N2, H5N1, H7N9.
Preferably, the influenza A virus is the influenza A virus of H1N1 hypotypes.
A kind of drug of resisiting influenza virus, includes different corilagin in the active ingredient of the drug, and the different curry is drawn
The structural formula in capital is：
The different corilagin is the αisomer of corilagin (Corilagin), molecular formula：C27H22O18, systematic naming method：
1-O- nutgall acyls -3,6- (R)-O- hexahydroxys dibenzoyl-alpha-D-glucose (1-O-galloyl-3,6- (R)-O-
hexahydroxydiphenoyl-α-D-glucose)。
Preferably, the different corilagin extracts from Chinese olive.
Preferably, the influenza virus is influenza A virus.
Preferably, the influenza A virus is the influenza A virus of H1N1 hypotypes.
The beneficial effects of the invention are as follows：
Inventor extracts a kind of different corilagin of compound of resisiting influenza virus A from Chinese olive, is natural products, can make
For potential influenza virus inhibitor.
Researches show that different corilagins to have apparent inhibiting effect to Influenza virus H1N1 by inventor, and there is bright
Aobvious dose relationship.Different corilagin increases the inhibiting rate of virus with the increase of concentration, effectively dense to the half of H1N1
Spend IC50For 3.16 ± 0.81 μM (2.004 ± 0.513 μ g/mL).In addition, different corilagin is right in the concentration range of 50 μ g/ml
Mdck cell is almost without toxicity.The drug concentration selected is within 50 μ g/ml in the experimental study of the present invention, be safety without
Within the scope of toxic concentration.
Description of the drawings
Fig. 1 is different corilagin1H NMR spectras；
Fig. 2 is different corilagin13C NMR spectras；
Influence of the different corilagins of Fig. 3 to cell viability；
Inhibiting effect of the different corilagins of Fig. 4 to H1N1 cells.
Specific implementation mode
Inventor extracts isolated more different corilagin (303mg) in Chinese olive chloroform extract, and content accounts for
The 0.28% of Chinese olive chloroform extract total amount.Different corilagin molecular formula by analysis：C27H22O18, molecular weight：634.45, knot
Structure formula is：
Wherein, different corilagin1H NMR spectras are shown in Fig. 1, different corilagin13C NMR spectras are shown in Fig. 2.
With reference to embodiment, the invention will be further described, and however, it is not limited to this.
Material used in embodiment includes：Dog renal epithelial cell (mdck cell), 100U/L penicillin, streptomysin
DMEM culture mediums.Influenza A virus A/FM/1/47 (H1N1) is passed on through this laboratory SPF chicken embryos and is expanded, -80 DEG C of preservations.It is different
Corilagin is obtained by this laboratory extracting and developing, identification.
The cytotoxicity of 1 different corilagin of embodiment detects
Mdck cell presses 1 × 104/ hole is inoculated in 96 orifice plates, at 37 DEG C, 5%CO2Constant temperature cell incubator in cultivate
To single layer, the different corilagin of DMEM gradient dilutions is added in 96 orifice plates, per 200 μ l of hole, continues to cultivate 48h.Abandon culture
The DMEM culture mediums of 100 μ L MTT containing 0.5mg/ml, 37 DEG C of incubation 4h are added per hole for supernatant.Using multi-function microplate reader
(Genios Pro, Tecan, US) detects absorbance at 570nm.Using the survival rate of cell as different corilagin to mdck cell
Toxicity index.
Cell survival rate (%)=E/N × 100
E is the absorbance of medicine group, and N is the absorbance of cell controls group.
Test result is shown：Different corilagin cytotoxicity is small, and biological safety is high.
The results are shown in Figure 3, and different corilagin is in the concentration range of 50 μ g/ml to mdck cell almost without toxicity.
The different corilagin drug concentration selected in the experimental study of the present invention is in safety non-toxic concentration model within 50 μ g/ml
In enclosing.
The Activity determination of the external resisiting influenza virus A of 2 different corilagin of embodiment
The influenza virus sub-strain used in antiviral study in vitro of the present invention is A/Puterto Rico/8/34H274Y
(H1N1), mdck cell presses 2 × 104/ hole is inoculated in 96 orifice plates, at 37 DEG C, 5%CO2Constant temperature cell incubator in cultivate to
Single layer.Use 100TCID50Influenza a virus infection cell, abandon virus liquid after 37 DEG C are incubated 1h per 100 μ l of hole, be added
The different corilagin of DMEM (containing 1 μ g/ml TPCK) gradient dilution continues to cultivate 48h per 200 μ l of hole.Different corilagin resists
Virus activity further calculates medium effective concentration IC by detecting the survival rate of cell50.Ribavirin (ribavirin)
Make positive control.As a result see Fig. 4.
Fig. 4 shows that different corilagin has apparent inhibiting effect to Influenza virus H1N1, and there is apparent agent
Magnitude relation.Different corilagin increases the inhibiting rate of virus with the increase of concentration, to the medium effective concentration IC of H1N150For
3.16 ± 0.81 μM (2.004 ± 0.513 μ g/mL) are compared and reference substance Ribavirin (IC50=0.56 ± 1.11 μM) effect is micro-
It is weaker.
Comparative example 1
Prior art article Anti-influenza A Virus Activity of Dendrobine and Its
Mechanism of Action(Li R,Teng L,Liu M,et al.Anti-influenza AVirus Activity of
Dendrobine and Its Mechanism of Action[J].Journal of Agricultural&Food
Chemistry,2017,65(18):365-3674.) the IC of display dendrobine resisiting influenza virus A/FM-1/1/47 (H1N1)50Value
For 3.39 μ g/mL (12.9 μM).And we measure the IC of the different corilagin of Chinese olive50Value be 2.004 ± 0.513 μ g/mL (3.16 ±
0.81μM).Compared to the data of above-mentioned document, the inhibiting rate higher of different corilagin of the invention for influenza virus A.
Comparative example 2
Existing clinical test shows H1N1virus, and to amantadine and Rimantadine, there are drug resistances.[Zhao Hua
Outstanding person, what shields new development [J] the China biochemical drug magazine that Tamiflu inhibits influenza infection research, 2017 (5):
444-448.] and different corilagin extracts from Chinese olive, is natural products, can be used as potential anti-H1N1 lead compounds.
The above embodiment is a preferred embodiment of the present invention, but embodiments of the present invention are not by above-described embodiment
Limitation, it is other it is any without departing from the spirit and principles of the present invention made by changes, modifications, substitutions, combinations, simplifications,
Equivalent substitute mode is should be, is included within the scope of the present invention.
Claims (8)
1. different corilagin or its application of pharmacologically acceptable salt in preparing anti-influenza virus medicament, feature exist
In：The structural formula of the different corilagin is：
2. application according to claim 1, it is characterised in that：The different corilagin extracts from Chinese olive.
3. application according to claim 1, it is characterised in that：The influenza virus is influenza A virus.
4. according to claim 1 or 3 any one of them applications, it is characterised in that：The influenza A virus is H1N1 hypotypes
Influenza A virus.
5. a kind of drug of resisiting influenza virus, it is characterised in that：Include different corilagin in the active ingredient of the drug, it is described
The structural formula of different corilagin is：
6. drug according to claim 5, it is characterised in that：The different corilagin extracts from Chinese olive.
7. drug according to claim 5, it is characterised in that：The influenza virus is influenza A virus.
8. according to claim 5 or 7 any one of them drugs, it is characterised in that：The influenza A virus is H1N1 hypotypes
Influenza A virus.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109674804A (en) * | 2019-02-02 | 2019-04-26 | 武汉大学 | Corilagin is preparing the purposes in resisting myocardial fibrillation drug |
| CN111269277A (en) * | 2020-04-07 | 2020-06-12 | 云南农业大学 | Method for extracting and separating isochrysotium from garden burnet |
| CN112451534A (en) * | 2020-10-12 | 2021-03-09 | 中国医学科学院医药生物技术研究所 | Application of corilagin in inhibiting coronavirus replication to exert anti-coronavirus medicinal function |
| CN116585340A (en) * | 2023-07-19 | 2023-08-15 | 云南农业大学 | Application of isocorilagin in preparation of medicines for resisting porcine reproductive and respiratory syndrome |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109674804A (en) * | 2019-02-02 | 2019-04-26 | 武汉大学 | Corilagin is preparing the purposes in resisting myocardial fibrillation drug |
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| CN112451534A (en) * | 2020-10-12 | 2021-03-09 | 中国医学科学院医药生物技术研究所 | Application of corilagin in inhibiting coronavirus replication to exert anti-coronavirus medicinal function |
| CN112451534B (en) * | 2020-10-12 | 2021-09-17 | 中国医学科学院医药生物技术研究所 | Application of corilagin in inhibiting coronavirus replication to exert anti-coronavirus medicinal function |
| CN116585340A (en) * | 2023-07-19 | 2023-08-15 | 云南农业大学 | Application of isocorilagin in preparation of medicines for resisting porcine reproductive and respiratory syndrome |
| CN116585340B (en) * | 2023-07-19 | 2023-09-19 | 云南农业大学 | Application of isocorilagin in preparation of medicines for resisting porcine reproductive and respiratory syndrome |
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Application publication date: 20180824 |