CN110327317A - Application of the alkannin in the drug for preparing anti-rotavirus infection - Google Patents
Application of the alkannin in the drug for preparing anti-rotavirus infection Download PDFInfo
- Publication number
- CN110327317A CN110327317A CN201910684837.5A CN201910684837A CN110327317A CN 110327317 A CN110327317 A CN 110327317A CN 201910684837 A CN201910684837 A CN 201910684837A CN 110327317 A CN110327317 A CN 110327317A
- Authority
- CN
- China
- Prior art keywords
- alkannin
- rotavirus
- application
- drug
- pharmaceutically acceptable
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- 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
- A61K31/12—Ketones
- A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/222—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
The present invention relates to application of the alkannin in the drug for preparing anti-rotavirus infection, alkannin or its pharmaceutically acceptable salt, ester, solvate duplication and amplification by inhibition rotavirus, the antigen synthesis by inhibiting rotavirus, the final beneficial effect for obtaining anti-rotavirus；And alkannin or its pharmaceutically acceptable salt, ester, solvate, to normal cytotoxic side effect, safety is good, provides theoretical foundation to study the therapeutic strategy of rotavirus infection, provides an insertion point to prepare the drug of new anti-rotavirus.
Description
Technical field
The present invention relates to medicinal application fields, and in particular to alkannin answering in the drug for preparing anti-rotavirus infection
With.
Background technique
Rotavirus (Rotavirus, RV) belongs to a member of arc reovirus virus family (Reoviridae), is to cause
The main pathogens of virus diarrhea.There are about 1.1 hundred million or so newborns every year serious secretion occurs because infecting RV in the whole world
Property diarrhea, about 600,000 children because RV infect due to be dehydrated death.For other viruses or bacterial infection diarrhea, rotavirus institute
The degree and its duration of caused vomiting and diarrhea will be considerably longer than other types diarrhea, to health and the economy of the mankind
Cause tremendous influence.For preventing RV from infecting, vaccine inoculation is still most effective means.
CN106676076A discloses a kind of method that serum-free Vero cell prepares Rotavirus Vaccine stoste, comprising with
Lower step is obtained serum free medium and is adapted to cell strain with serum free medium Cultivation of Vero；Utilize the nothing of acquisition
Blood serum medium adapts to cell strain, establishes serum-free Vero cell seed bank；It is adapted to using the serum free medium of acquisition
Cell strain establishes serum-free rotavirus strain work seed bank；Use serum free medium recovery, culture, passage, amplification
Vero cell work seed bank cell, as the basal cell of bioreactor culture, after cell amplification, using bioreactor
And microcarrier, use serum free medium, continuously perfused culture high density Vero cell；It is inoculated with rotavirus strain work seed
After the seed culture of viruses of library, bioreactor microcarrier free serum culture is carried out, at virus amplification to peak, harvest virus liquid, clarified,
It is concentrated by ultrafiltration, obtains serum-free people with Rotavirus Vaccine stoste.
CN108546288A discloses a kind of human rotavirus VP8 recombinant protein, the amino acid sequence of the VP8 recombinant protein
Column include human rotavirus VP8 protein amino acid sequence and allogenic polypeptide amino acid sequence, and the isoelectric point of the allogenic polypeptide is small
In equal to 5.The present invention also provides the human rotavirus vaccines prepared based on the VP8 recombinant protein.The VP8 recombinant protein passes through
The polypeptide fragment amalgamation and expression of amino acid containing negative electrical charge in VP8 albumen and tetanus toxin and/or diphtheria toxin protein, is improved
The water solubility and yield of 8 albumen of rotavirus vp of Bacillus coli expression, and obtained fusion protein have exempt from well
Epidemic disease ability, preparation-obtained vaccine have good effect.
CN104606674A discloses rotavirus polysaccharide-protein combined vaccine, is multivalent pneumococcal polysaccharide and two
Kind or two or more carrier proteins are through conjugate vaccines made of connector, wherein connector is magnetic Nano microsphere, carrier egg
One of white is rotavirus protein.The rotavirus polysaccharide-protein combined vaccine preparation process that the invention provides is simple, using receiving
Meter Wei Qiu is that the rotavirus polysaccharide-protein combined vaccine of attachment can enhance mouse Th1 type immune response and polysaccharide is special
Immune lasting effect, specificity and the compatibility of heterogenetic antibody additionally can induce mouse and generate rotavirus antibody；Have two kinds
The preventive effect of vaccine.
But the attenuation activity of vaccine causes some cost, effects with virus shedding and propagation risk and vaccine
The problem related to safety etc. limits its popularization.Therefore, the drug for developing safely and effectively anti-rotavirus is most important.
Summary of the invention
In view of the deficiencies of the prior art, the purpose of the present invention is to provide a kind of new opplications of alkannin, and in particular to purple
Grass is plain to prepare the application in anti-rotavirus medicaments, and the present invention provides a kind of new plan for the treatment of rotavirus infection
Slightly.
In order to achieve that object of the invention, the invention adopts the following technical scheme:
In a first aspect, the present invention provides alkannin or its pharmaceutically acceptable salt, ester, solvate are preparing anti-colyliform
Application in virus drugs.
In the present invention, the duplication and amplification of the Drug inhibition rotavirus.
In the present invention, the antigen synthesis of the Drug inhibition rotavirus.
Alkannin is purple flaky crystal or crystalline powder (structural formula is as follows), is planted for Boraginaceae perennial herb
The extracted aubergine tea quinones chemical component of the dry root of object lithospermum euchromum Royle.Tcm clinical practice be mainly used for treating moist macula,
Purple factory, blood urine, stranguria with turbid discharge and bloody flux, constipation with heat retention, burn, eczema, erysipelas etc..Resist modern medical research has found that alkannin has
The extensive pharmacological action such as tumour, antibacterial, antifertility, antipyretic, hemostasis, hypoglycemic.However, for alkannin anti-rotavirus medicine
It there are no correlative study report with the effect of aspect.
The present invention creatively has found to be used to make by alkannin or its pharmaceutically acceptable salt, ester, solvate
In the drug of standby anti-rotavirus, by experiment in vitro research discovery, it has the work for inhibiting duplication and amplification to rotavirus
With, while having the function of inhibiting wheel virus antigen synthesis, and both effects are in concentration dependent, and in low concentration model
Enclose it is interior have no toxic side effect to normal cell, safety is good.Find that it can significantly mitigate rotavirus infection by In vivo study
The diarrhoea degree of suckling mouse, and restore its weight and the state of mind.
Second aspect, the present invention provide alkannin or its pharmaceutically acceptable salt, ester, solvate and inhibit wheel in preparation
Application in the drug of duplication and the amplification of shape virus.
The third aspect, the present invention provide alkannin or its pharmaceutically acceptable salt, ester, solvate and inhibit wheel in preparation
Application in the drug of the antigen synthesis of shape virus.
In the present invention, the drug further includes pharmaceutically acceptable auxiliary material.
Preferably, the auxiliary material includes any one in excipient, diluent, carrier, flavoring agent, adhesive or filler
Kind or at least two combination, the described at least two combination combination of such as excipient and diluent, carrier and flavoring agent
Combination, adhesive and combination of filler etc..
Preferably, the carrier includes liposome, micella, dendrimer, microballoon or micro-capsule.
Alkannin of the present invention or its pharmaceutically acceptable salt, ester, solvate, which can be carried on, commonly uses medicinal load
Drug on body as treatment acute myeloid leukemia, realizes better biocompatibility, targeting, biological safety and administration
Effect.
Preferably, the alkannin is the alkannin contained in pharmaceutical composition.
It preferably, include Acetylshikonin, isovaleryl shikonin or β-acetoxyl group-isovaleryl in described pharmaceutical composition
In alkannin any one or at least two combination, described at least two combination such as Acetylshikonin and isovaleryl are purple
Combination, isovaleryl shikonin and β-combination of acetoxyl group-isovaleryl shikonin, Acetylshikonin and β-acetyl oxygen of careless element
The combination of base-isovaleryl shikonin.
Reality can also be used in combination with other drugs in the alkannin or its pharmaceutically acceptable salt, ester, solvate
Now to the better therapeutic effect of rotavirus infection, such as Acetylshikonin, isovaleryl shikonin, β-acetoxyl group-isovaleryl
Alkannin etc..
In the present invention, the dosage form of the drug includes tablet, capsule, granule, powder, injection, spray, film
Agent, suppository, nasal drop or pill.It is the medicine of active constituent with alkannin or its pharmaceutically acceptable salt, ester, solvate
Object can be prepared to any of the above-described kind of pharmaceutical dosage form according to actual needs, and the drug of each dosage form can be according to pharmaceutical field
Conventional method preparation.
In the present invention, the administration route of the drug can select oral administration, sublingual administration, quiet according to actual needs
Arteries and veins injection, intraperitoneal injection, intramuscular injection, subcutaneous injection, nasal-cavity administration or percutaneous dosing any one mode.
Compared with the existing technology, the invention has the following advantages:
The present invention has found that alkannin or its pharmaceutically acceptable salt, ester, solvate pass through inhibition by vitro study
The duplication and amplification of rotavirus, the antigen synthesis by inhibiting rotavirus, the final beneficial effect for obtaining anti-rotavirus；
And alkannin or its pharmaceutically acceptable salt, ester, solvate, to normal cytotoxic side effect, safety is good；Pass through
In vivo study discovery, alkannin can significantly mitigate the diarrhoea degree of rotavirus infection suckling mouse, and make its weight and spiritual shape
State is restored.The present invention provides theoretical foundation to study the therapeutic strategy of rotavirus infection, to prepare new anti-rotavirus
Drug provide an insertion point.
Detailed description of the invention
Fig. 1 is alkannin to MA104 Cytotoxic evaluation result statistical chart；
Fig. 2 is inhibiting effect evaluation result statistical chart of the alkannin to rotavirus replication and amplification；
Fig. 3 is the inhibiting effect evaluation result statistical chart that alkannin synthesizes wheel virus antigen；
Fig. 4 is the diarrhea scoring situation statistical chart of three groups of suckling mouses；
Fig. 5 is the weight detection case statistical chart of three groups of suckling mouses；
Fig. 6 is that (a is control group to diarrhea situation schematic diagram of three groups of suckling mouses in rotavirus infection third day, and b is viral mould
Type group, c are alkannin treatment group).
Specific embodiment
The technical scheme of the invention is further explained by means of specific implementation.Those skilled in the art should be bright
, the described embodiments are merely helpful in understanding the present invention, should not be regarded as a specific limitation of the invention.
Embodiment 1
Alkannin is to MA104 Cytotoxic evaluation
The present embodiment studies alkannin to the cytotoxicity of normal cell MA104 cell strain (monkey embryonic kidney cell), specifically
Operating method are as follows: cell suspension, cell count is made after pancreatin digests de- wall in the MA104 cell strain for taking exponentially growth period
Afterwards, 1 × 10 is diluted to the DMEM in high glucose containing 10%FBS4The cell suspension of/mL, it is thin that 100 μ L are added in every hole in 96 well culture plates
Born of the same parents' suspension, 8000, every Kong Hanyue cell；Culture medium is sucked out after cell is adherent, the Asian puccoon of different final concentrations is added in each experimental group
Plain medical fluid (solvent is DMEM culture solution), respectively 0 μM (control group), 5 μM, 10 μM, 20 μM, 40 μM, 80 μM, 160 μM, 320 μ
M, control group are same volume DMEM culture solution.The each dosage of experimental group sets 6 parallel holes, and control wells equally set 6 holes；It is placed in 37
DEG C, 5%CO2Constant incubator culture 72h；After 72h, 10%CCK-8 solution, which is added, in every hole cell continues to cultivate 4h, in wavelength
Each hole absorbance value is measured on the enzyme-labeled immunity detector (Gene Company Linited company) of 450nm；Cell it is opposite
Survival rate calculates=[(OD experimental group-OD blank)/(OD control group-OD blank) × 100%] by formula.Wherein, OD is tested
Group is the absorbance value that experimental group cell measures on enzyme-labeled immunity detector, and OD control group is cellular control unit in enzyme-labeled immunity
The absorbance value measured on detector, OD blank are the suction that the blank well of any sample is not added and measures on enzyme-labeled immunity detector
Shading value.
As a result as shown in Figure 1, the cell survival rate of the MA104 cell handled with alkannin 5 μM of concentration, 10 μM, 20 μM,
Without apparent cytotoxic effect under 40 μM, 80 μM, cell survival rate is between 92.5%-99.6%.Prove alkannin to just
Normal cytotoxic side effect, safety are good.
Embodiment 2
Alkannin replicates the inhibiting effect with amplification to human rotavirus
Whether the present embodiment research alkannin to the duplication of human rotavirus and is augmented with inhibiting effect, concrete operation method
Are as follows: by MA104 cell with 1 × 104The concentration of a cells/well is seeded in 96 orifice plates and cultivates for 24 hours at 37 DEG C.It is adherent to cell
After take out tissue culture plate, PBS is washed one time.By MOI be 0.01 rotavirus liquid (100TCID50RV-Wa strain virus liquid,
Granted by Third Military Medical University is immune) act on 30min with the pancreatin of 10 μ g/mL concentration after be added in 96 well culture plates, 100
The hole μ l/.Isometric DMEM culture solution is added in normal cell controls group.All cells are at 37 DEG C, 5%CO2It is incubated for 2h, it then will be sick
Venom is sucked out, and the alkannin medical fluid of various concentration (0 μM (virus control group), 5 μM, 10 μM, 20 μM, 40 μM, 80 μM) is added,
100 holes μ L/.Isometric DMEM culture solution is added in virus control group.37 DEG C, 5%CO2It is incubated for for 24 hours.Tissue culture plate is taken out, is inhaled
Culture solution out, 10%CCK-8 solution, which is added, in every hole cell continues to cultivate 4h, in the enzyme-labeled immunity detector (Gene of wavelength 450nm
Company Linited company) on measure each hole absorbance value.Inhibiting rate=(medicine group mean OD value-virus control group is average
OD value)/(normal cell controls group mean OD value-virus control group mean OD value)) × 100%, experiment is repeated 5 times.Above-mentioned
OD value refers to the absorbance value that group of cells measures on enzyme-labeled immunity detector.
As a result as shown in Fig. 2, alkannin shows answering for significant inhibition rotavirus in 10 μM of -80 μM of concentration ranges
System and amplification effect, and this depression effect is in concentration dependent.
Embodiment 3
The inhibiting effect that alkannin synthesizes human rotavirus antigen
Whether the present embodiment research alkannin has inhibiting effect, concrete operation method to the synthesis of human rotavirus antigen
Are as follows: the MA104 cell routine for growing to single layer digestion is made after cell suspension, cell count with every hole 1 × 105Cell density
It is inoculated in 6 orifice plates, 37 DEG C, 5%CO2Under the conditions of cultivate.After cell is completely adherent, remove old culture solution in cell, toward 6 orifice plates
The middle DMEM culture solution culture 6h that serum-free is added.The DMEM culture solution of no FBS is sucked after 6h, cell is separately added by 10 μ
37 DEG C of routine culture 2h of 100TCID50RV-Wa strain virus liquid that the pancreatin of g/ml is incubated for.After 2h, virus liquid is sucked, no FBS's
DMEM culture solution washes the alkannin medical fluid of addition various concentration (5 μM, 10 μM, 20 μM, 40 μM, 80 μM) after a cell, control
Isometric DMEM culture medium without FBS is added in group, continues culture at 37 DEG C for 24 hours.After for 24 hours, cell culture fluid is collected respectively,
Then isometric DMEM culture solution without FBS is added toward intracellular again, between -20 DEG C and 4 DEG C multigelation three times, 4 DEG C,
After 6000r/min is centrifuged 15min, supernatant is collected in EP pipe.
The supernatant user's wheel virus antigen detection kit collected twice (is purchased from DRG International
Inc.；Model EIA-4455) it is detected, concrete operations are as follows: 1. take the negative controls of 100 μ L to be added in No. 1 hole,
100 μ L positive control solutions are added in No. 2 plate holes.2. each 100 μ L of each group supernatant suspension sample to be measured of 100 μ L is taken to be added to it
Yu Kongzhong after being incubated for 30min at room temperature, rinses plank with washing lotion.3. 2 drop reagent 1 (blue solution) rooms are added in each hole
Temperature is lower to be incubated for 5min, then rinses plank with washing lotion.4. 2 drops reagent 2 (red solution) are added in each hole to be incubated at room temperature
After 5min, plank is rinsed with washing lotion.5. 2 drop chromophores are added in each hole, after being incubated at room temperature 5min, 2 drops are added eventually in every hole
Only liquid mixes.6. at 450 nm, reading OD value.If value >=0.15 OD of sample, is confirmed as positive sample.Wherein, it tries
Agent 1 is the anti-rotavirus polyclonal antibody (spreading containing thiophene mercury) for dying blue；Reagent 2 is to dye red combination horseradish peroxide
The anti-mouse antibody (being spread containing thiophene mercury) of compound enzyme；Positive control solution is the wheel virus antigen (spreading containing thiophene mercury) after dilution；
Negative controls are buffer (spreading containing thiophene mercury)；Chromophore is TMB (pyridine of Magcophos methylbenzene) and hydrogen peroxide；Washing lotion is
Concentrating buffer solution and thiophene mercury are spread；Terminate liquid is 1M phosphoric acid.
As a result as shown in figure 3, ELISA is the experimental results showed that alkannin has significant suppression to the synthesis of human rotavirus antigen
Production is used, and as alkannin intervenes the increase of dosage, the expression water of the MA104 intraor extracellular viral antigen of rotavirus infection
It is flat lower, certain concentration dependent is presented.
Embodiment 4
Anti-rotavirus acts in alkannin body
The present embodiment studies the internal anti-rotavirus effect of alkannin, concrete operation method are as follows: the Kunming of 5 ages in days is small
Mouse suckling mouse 30 is only randomly divided into blank group, virus model group, alkannin treatment group, and every group 10, and distribute female rat nature lactation
It feeds.The suckling mouse stool wheel virus antigen detection of each group is feminine gender before testing.After animal packet, blank group is added using micro
Sample device is inhaled naturally by animal permits ability stomach-filling DMEM culture solution, and 150 μ L/ are only.Virus model group and alkannin treatment group suckling mouse
Give stomach-filling rotavirus liquid (100TCID50), 150 μ L/ only, after virus inoculation, each group suckling mouse and the same cage of female rat, normal breast milk
It feeds, after carrying out virus infection 2 days, the medical fluid of 0.58g/kg is administered in alkannin treatment group suckling mouse, and model group and control group are given
DMEM culture solution, every 200 μ L, 1 time a day, continuous 5 days.Groups of animals isolated rearing observation, measurement records suckling mouse daily
Weight collects the daily stool sample of infection front and back suckling mouse.After virus attack, continuous clinical observation is carried out to animal.Every
12h or so observation is primary, gently massages suckling mouse abdomen with finger every time, observes diarrhea production and scores stool,
Judgement reference literature [Boshuizen JA, et al. (2003) Changes in small intestinal of diarrhea
homeostasis,morphology,and gene expression during rotavirus infection of
Infant mice.J Virol 77:13005-13016.] in operation, score value is between 1-4 point.There is no excrement (0 point)；Brown
Excrement (1 point)；Brown soft stool (2 points)；Yellow soft stool (3 points)；Yellow watery stool (4 points).The mouse of >=2 points of scoring is considered
Diarrhea has occurred.The judgement of diarrhea is completed by same people.The suckling mouse that excrement can not be obtained is considered as no diarrhea.
As shown in Figure 4 (being counted with mean scores), the weight of each group suckling mouse detects feelings to the diarrhea scoring situation of each group suckling mouse
Condition is as shown in Figure 5 (being counted with mean scores): virus model group and alkannin treatment group after virus infection 12h to suckling mouse for 24 hours
Occur abdominal distention, it is dull, roll up, diet is reduced, tired mind, and there is suckling mouse diarrhea, the amount and number of stool occur successively
It is more than blank group.After virus attack for three days on end, diarrhoea degree most serious, excrement is in watery stool to virus model group, diarrhea occurs
Suckling mouse number ratio highest, the suckling mouse anus for loose stools occur is red and swollen, has dry skin more gauffers, spirit is lazy tired, and weight increases
Phenomena such as not increasing even slowly.Alkannin treatment group the 1st day diarrhoea degree most serious after virus attack, after medication the 3rd day
Diarrhea mitigates.Blank group has no diarrhea, and it is in khaki for defecating, and skin is flexible, and for anus without redness, body weight increase is very fast.Three
(a is control group to diarrhea situation of the group suckling mouse in virus infection third day, and b is virus model group, and c controls for alkannin as shown in Figure 6
Treatment group), as seen from the figure: blank group suckling mouse is not occur diarrhea situation, and excrement is brown；Virus model group is in virus attack the 3rd
It, diarrhoea degree most serious, excrement is in watery stool；Alkannin treatment group suckling mouse on day 3 significantly alleviated by diarrhoea degree,
Excrement is yellow soft stool.
The Applicant declares that the present invention is explained by the above embodiments, alkannin of the invention is preparing anti-rotavirus sense
Application in the drug of dye, but the present invention is not limited to the above embodiments, that is, does not mean that the present invention must rely on above-mentioned reality
Applying example could implement.It should be clear to those skilled in the art, any improvement in the present invention, each to product of the present invention
The equivalence replacement of raw material and addition, the selection of concrete mode of auxiliary element etc. all fall within protection scope of the present invention and openly
Within the scope of.
The preferred embodiment of the present invention has been described above in detail, still, during present invention is not limited to the embodiments described above
Detail within the scope of the technical concept of the present invention can be with various simple variants of the technical solution of the present invention are made, this
A little simple variants all belong to the scope of protection of the present invention.
It is further to note that specific technical features described in the above specific embodiments, in not lance
In the case where shield, can be combined in any appropriate way, in order to avoid unnecessary repetition, the present invention to it is various can
No further explanation will be given for the combination of energy.
Claims (10)
1. alkannin or its pharmaceutically acceptable salt, ester, solvate are preparing the application in anti-rotavirus medicaments.
2. application as described in claim 1, which is characterized in that the duplication and amplification of the Drug inhibition rotavirus.
3. application as claimed in claim 1 or 2, which is characterized in that the antigen of the Drug inhibition rotavirus synthesizes.
4. alkannin or its pharmaceutically acceptable salt, ester, solvate are preparing the duplication and amplification for inhibiting rotavirus
Application in drug.
5. the medicine that alkannin or its pharmaceutically acceptable salt, ester, solvate inhibit the antigen synthesis of rotavirus in preparation
Application in object.
6. application according to any one of claims 1 to 5, which is characterized in that the drug further includes pharmaceutically acceptable
Auxiliary material.
7. application as claimed in claim 6, which is characterized in that the auxiliary material include excipient, diluent, carrier, flavoring agent,
In adhesive or filler any one or at least two combination.
8. the use as claimed in claim 7, which is characterized in that the carrier includes liposome, micella, dendrimer, micro-
Ball or micro-capsule.
9. such as application of any of claims 1-8, which is characterized in that the alkannin is to contain in pharmaceutical composition
Alkannin；
It preferably, include Acetylshikonin, isovaleryl shikonin or β-acetoxyl group-isovaleryl Asian puccoon in described pharmaceutical composition
In element any one or at least two combination.
10. application as claimed in any one of claims 1-9 wherein, which is characterized in that the dosage form of the drug includes tablet, capsule
Agent, granule, powder, injection, spray, film, suppository, nasal drop or pill.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910684837.5A CN110327317B (en) | 2019-07-26 | 2019-07-26 | Application of alkannin in preparing medicine for resisting rotavirus infection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910684837.5A CN110327317B (en) | 2019-07-26 | 2019-07-26 | Application of alkannin in preparing medicine for resisting rotavirus infection |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110327317A true CN110327317A (en) | 2019-10-15 |
| CN110327317B CN110327317B (en) | 2022-09-20 |
Family
ID=68147675
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910684837.5A Active CN110327317B (en) | 2019-07-26 | 2019-07-26 | Application of alkannin in preparing medicine for resisting rotavirus infection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110327317B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113332265A (en) * | 2021-05-31 | 2021-09-03 | 大连医科大学 | IKK beta/NEMO small-molecule inhibitor and application thereof in preparation of drugs |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102048716A (en) * | 2010-12-20 | 2011-05-11 | 昆明理工大学 | New application of hydroquinone compound |
| CN104771384A (en) * | 2014-01-15 | 2015-07-15 | 中国科学院上海生命科学研究院湖州营养与健康产业创新中心 | Pharmaceutical use of alkannin |
| CN109998995A (en) * | 2018-04-27 | 2019-07-12 | 西南大学 | A kind of alkannin liposome and preparation process |
-
2019
- 2019-07-26 CN CN201910684837.5A patent/CN110327317B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102048716A (en) * | 2010-12-20 | 2011-05-11 | 昆明理工大学 | New application of hydroquinone compound |
| CN104771384A (en) * | 2014-01-15 | 2015-07-15 | 中国科学院上海生命科学研究院湖州营养与健康产业创新中心 | Pharmaceutical use of alkannin |
| CN109998995A (en) * | 2018-04-27 | 2019-07-12 | 西南大学 | A kind of alkannin liposome and preparation process |
Non-Patent Citations (4)
| Title |
|---|
| HONG GAO等: "Anti-adenovirus Activities of Shikonin, a Component of Chinese Herbal Medicine in Vitro", 《BIOL. PHARM. BULL.》 * |
| Y. ZHANG等: "Antiviral activity of shikonin ester derivative PMM-034 against enterovirus 71 in vitro", 《BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH》 * |
| YU JIANG等: "Shikonin Inhibits Intestinal Calcium-Activated Chloride Channels and Prevents Rotaviral Diarrhea", 《ORIGINAL RESEARCH》 * |
| 崔晓秋: "中药紫草化学成分及药理作用最新研究进展", 《济宁医学院学报》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113332265A (en) * | 2021-05-31 | 2021-09-03 | 大连医科大学 | IKK beta/NEMO small-molecule inhibitor and application thereof in preparation of drugs |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110327317B (en) | 2022-09-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102641298B (en) | Effector cell combination for preventing and treating tumors and preparation method thereof | |
| CN103040860A (en) | Method for initiating mammalian stem cells and application of chlorine dioxide in preparation of medicament for initiating mammalian stem cells | |
| Teng | ADENOVLRUS PNEUMONIA EPIDEMIC AMONG PEKING INFANTS AND PRESCHOOL CHILDREN IN 1958 | |
| CN101628108B (en) | Traditional Chinese medicinal granules for treating wind-cold evil and preparation method thereof | |
| CN102920729B (en) | Application of oligomerization mannuronic acid and medicinal salts of oligomerization mannuronic acid in preparing medicine for leucopenia prevention | |
| CN102727486B (en) | Application of Inula lineariifolia lactone A in preparation of medicine for treating myocarditis | |
| CN110327317A (en) | Application of the alkannin in the drug for preparing anti-rotavirus infection | |
| CN100502916C (en) | Antivirus medicinal composition and preparation method thereof | |
| CN106309455A (en) | Application of peimisine | |
| CN109820947A (en) | A kind of application of Chinese medicine composition in preparation treatment epithelium healing cough syndrome drug | |
| CN108653322A (en) | A kind of composition with the functional health product for preventing metastases | |
| CN111803484B (en) | Application of otilonium bromide in preparing antitumor drugs | |
| CN102836152B (en) | Application of physalin B in preparation of medicine for curing and/or preventing schistosomiasis | |
| CN101461817A (en) | Use of 1,2,3,4,6-five-O-gallnut acyl radical-b-D-glucose | |
| CN113521262A (en) | Lysozyme preparation with anti-inflammatory effect | |
| CN100438881C (en) | Application of crocodile blood in process for preparing anticancer antivirus and immunity improving medicine and health caring food | |
| CN112516157A (en) | Application of safflower polysaccharide in preparing medicine for treating melanoma | |
| CN106377537B (en) | Application of acetyl astragaloside | |
| CN106727495B (en) | A kind of flavanone compound is preparing the application in myocardial preservation drug | |
| CN104706836B (en) | A kind of Chinese medicine composition of eliminating chloasma and its application and preparation method | |
| CN108926583A (en) | The purposes of Zhejiang wintersweet anti-microbial infection | |
| CN102068479A (en) | Chinese medicinal composition for treating chronic urinary tract infection and preparation method thereof | |
| CN107823215A (en) | Application of the scutelloside in the medicine for preparing preventing and treating zika virus infection | |
| CN102218145B (en) | Medicinal composition for protecting optic nerve of glaucoma and preparation method thereof | |
| CN106389621A (en) | Application of combination of traditional Chinese medicinal composition and antibiotic in aspect of preparing medicines for inhibiting inflammatory factors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB02 | Change of applicant information |
Address after: 523326 No.1 Xianglong Road, Huangzhou, Shilong Town, Dongguan City, Guangdong Province Applicant after: Dongguan Songshanhu Central Hospital (Dongguan Shilong people's Hospital, Dongguan Third People's Hospital, Dongguan cardiovascular disease research institute) Address before: 523326 No.1 Xianglong Road, Huangzhou, Shilong Town, Dongguan City, Guangdong Province Applicant before: DONGGUAN THIRD PEOPLE'S HOSPITAL (DONGGUAN SHILONG PEOPLE'S Hospital) |
|
| CB02 | Change of applicant information | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |