CN106377537B - Application of acetyl astragaloside - Google Patents
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- CN106377537B CN106377537B CN201610694906.7A CN201610694906A CN106377537B CN 106377537 B CN106377537 B CN 106377537B CN 201610694906 A CN201610694906 A CN 201610694906A CN 106377537 B CN106377537 B CN 106377537B
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Abstract
The invention belongs to the technical field of medicines, and particularly relates to application of acetyl astragaloside in preparation of an enterovirus inhibitor. The invention provides an application of acetyl astragaloside in preparing a medicine for preventing and/or treating hand-foot-and-mouth diseases. Experiments prove that the acetyl astragaloside has an inhibiting effect on enterovirus-induced cytopathic effect and can improve the survival rate of virus-infected cells; meanwhile, the composition can inhibit the replication of viruses in vivo, improve the survival rate of virus-infected animals, prolong the survival time of the infected animals and relieve diseases caused by virus infection, thereby having the function and application value of treating hand-foot-and-mouth disease.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to application of acetyl astragaloside.
Background
The hand-foot-and-mouth disease is a child infectious disease caused by viruses and is a third infectious disease in China. The disease mainly infects infants of 0-6 years old, and is most common in children of 2-3 years old, herpes or ulcer is caused at the tail end of limbs and oral cavity of the children patients in the early stage of the hand-foot-and-mouth disease, and the children patients are mostly cured within 1-2 weeks. However, in a few cases, the disease progresses rapidly, meningitis, aseptic encephalitis, brainstem encephalitis, encephalomyelitis, pulmonary edema, circulatory disturbance and the like appear in about 1 to 5 days of the disease, and few cases are critical and can cause death, and survival cases can have sequelae.
According to the report of the world health organization, there are about 20 viruses causing hand-foot-and-mouth disease symptoms, wherein enterovirus 71 (enterovirus 71, EV71) and coxsackievirus A group 16 (coxsackievirus A16, CoxA16) are the most common viruses, and the number of cases caused by the infection of the two viruses accounts for more than 80% of the total cases. Other viruses that can cause hand-foot-and-mouth disease include mainly: coxsackievirus a groups 4, 5, 7, 9 and 10 (CoxA4, CoxA5, CoxA7, CoxA9 and CoxA10), coxsackievirus B groups 2 and 5 (CoxB2 and CoxB5), Echovirus (ECHO), and the like.
At present, although vaccines against the EV71 virus are already approved to be on the market, no medicine for directly targeting the virus exists, and the clinical treatment mainly adopts a strategy of symptomatic treatment; the broad-spectrum antiviral drug ribavirin has the risks of teratogenesis and growth inhibition when applied to infants. The compounds provided by the present invention are therefore able to remedy the deficiencies of the prior art in this respect.
The model is a carrier of compound activity and action mechanism, hand-foot-and-mouth virus infection can induce a plurality of apoptosis, including human malignant embryo rhabdomyoma cells (RD), neuroepithelial tumor cells (SK-N-MC), human neuroblastoma cells (SK-N-SH, SF268), African green monkey kidney cells (Vero), human microvascular endothelial cells and He L a cells, etc., in practical research, because RD cells and Vero cells have better sensitivity to viruses, the model is commonly used for antiviral research of cell level, in animal model, mice of 1-7 days age are sensitive to viruses, animal models are commonly used, 3-5 days after the mice are inoculated with viruses, symptoms such as milk refusal and weight reduction, obvious symptoms such as rigid paralysis and the like appear in four limbs 6-8 days, and the mice are self-healed or killed according to disease conditions after 9-13 days.
At present, common anti-hand-foot-and-mouth disease drugs comprise ribavirin, acyclovir, valaciclovir and the like, but the drugs have strong side effects.
In recent years, the research on the resistance of the traditional Chinese medicine to the hand-foot-and-mouth disease gradually draws attention of people, and as a plurality of traditional Chinese medicine components belong to natural extracted medicines, the traditional Chinese medicine has the advantages of small side effect and the like.
Acetylastragaloside (Acetylastragaloside) is a flavonoid component extracted from licorice (Glycyrrhiza uralensis Fisch.) and pharmacological studies show that acetylastragaloside has multiple effects of strengthening heart, promoting urination, lowering blood pressure, inhibiting bacteria, strengthening body, and the like.
At present, no report on the application of the acetyl astragaloside in the preparation of the medicine for preventing and/or treating the hand-foot-and-mouth disease is found.
Disclosure of Invention
In view of the above, the invention aims to provide the application of the acetyl astragaloside in the preparation of the inhibitor of the enterovirus.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides an application of acetyl astragaloside in preparation of an enterovirus inhibitor.
In some embodiments of the invention, the enterovirus is a coxsackievirus.
In some embodiments of the invention, the coxsackievirus is coxsackievirus type a 16;
in other embodiments of the invention, the enterovirus is enterovirus EV 71.
In some embodiments of the invention, the active dose of the acetyl astragaloside is 50-200 mg/kg/d.
The invention also provides application of the acetyl astragaloside in preparation of a medicament for preventing and/or treating or enterovirus infection diseases.
In some embodiments of the invention, the disease infected with enterovirus is hand-foot-and-mouth disease. In the present invention, the enterovirus is a coxsackievirus. Preferably, the coxsackievirus is coxsackievirus A16. The enterovirus can also be enterovirus EV71 type.
In some embodiments of the invention, the medicament comprises acetylastragaloside and a pharmaceutically acceptable excipient.
In some embodiments of the present invention, the dosage form of the drug is any one of clinically acceptable oral administration dosage forms, injection administration dosage forms or external administration preparations.
In some embodiments of the present invention, the weight fraction of the acetylastragaloside in the oral administration dosage form is 17.5-88%.
In some embodiments of the invention, the amount of the drug administered orally or by injection is 0.5-2.5 mg of acetylastragaloside per kg of body weight per day.
In some embodiments of the invention, the medicament is a tablet, capsule, granule, pill, injection, soft extract, suspension, dispersion, syrup, suppository, gel, aerosol, patch.
The invention provides application of acetyl astragaloside in preparation of an inhibitor of enteroviruses, and experimental results show that the acetyl astragaloside has an inhibiting effect on cytopathies induced by enteroviruses EV71 and Coxsackie virus A16, and can improve the survival rate of virus-infected cells; meanwhile, the composition can inhibit the replication of viruses in vivo, improve the survival rate of virus-infected animals, prolong the survival time of the infected animals, and relieve diseases caused by virus infection, thereby having the effect of treating hand-foot-and-mouth disease; and can prevent the proliferation and diffusion of virus in vivo, protect normal tissue from being damaged, and prevent virus infectious diseases.
The invention has the beneficial effects that:
1. the acetyl astragaloside is a natural small molecule compound, and can treat Coxsackie virus A16, enterovirus EV71, EC50118.61 mu mol/L and 90.32 mu mol/L are respectively 4.90 and 6.44.
2. The acetyl astragaloside can inhibit Coxsackie virus A16 and enterovirus EV71 virus infection in a dose-dependent manner, and is in a dose-dependent relationship.
3. Relieving symptoms caused by virus, and alleviating death caused by virus infection; the survival time of the virus-infected mice is prolonged, and the survival rate of the mice is improved.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below.
FIG. 1 is a graph showing the inhibitory activity of acetylastragaloside against Enterovirus 71 in example 1 of the present invention;
FIG. 2 is a graph showing the inhibitory activity of acetylastragaloside against coxsackievirus A16 type in example 1 of the present invention.
Detailed Description
The invention discloses application of acetyl astragaloside, and can be realized by appropriately improving process parameters by taking the contents of the acetyl astragaloside as reference by a person skilled in the art. It is expressly intended that all such similar substitutes and modifications which would be obvious to one skilled in the art are deemed to be included in the invention. While the methods and applications of this invention have been described in terms of preferred embodiments, it will be apparent to those of ordinary skill in the art that variations and modifications in the methods and applications described herein, as well as other suitable variations and combinations, may be made to implement and use the techniques of this invention without departing from the spirit and scope of the invention.
The invention provides an application of acetyl astragaloside in preparation of an enterovirus inhibitor.
In some embodiments of the invention, the enterovirus is a coxsackievirus. Preferably, the coxsackievirus is coxsackievirus A16.
In other embodiments of the invention, the enterovirus is enterovirus EV 71. The invention also provides application of the acetyl astragaloside in preparing a medicament for preventing and/or treating enterovirus infection diseases.
The invention provides an application of acetyl astragaloside in preparing a medicine for preventing and/or treating hand-foot-and-mouth diseases.
In the invention, the acetyl astragaloside has a structure shown in a formula I and belongs to flavonoid glycoside, and pharmacological research shows that the acetyl astragaloside has multiple functions of strengthening heart, promoting urination, reducing blood pressure, inhibiting bacteria, enhancing the body and the like.
The preferred preference of the acetyl astragaloside is an acetyl astragaloside monomer and/or an acetyl astragaloside extract, and the content of the monomer acetyl astragaloside in the acetyl astragaloside extract is more than 90 percent, and the invention can be extracted from traditional Chinese medicinal materials or traditional Chinese medicinal decoction pieces containing the acetyl astragaloside, such as liquorice, glycyrrhiza inflata or glycyrrhiza glabra according to a conventional method; commercial products of acetyl astragaloside are also available. Specifically, in the embodiments of the present invention, the astragaloside acetyl provided by the Chinese medicinal biological product assay can be used.
The invention provides an application of acetyl astragaloside in preparing a medicine for preventing and/or treating hand-foot-and-mouth diseases. Wherein the viruses causing the hand-foot-and-mouth disease comprise enteroviruses. Preferably, the viruses causing hand-foot-and-mouth disease comprise coxsackievirus A16 type and/or enterovirus EV71 type.
In the invention, the anti-hand-foot-and-mouth disease medicine comprises acetyl astragaloside and a pharmaceutically acceptable carrier. In the invention, the pharmaceutically acceptable carrier preferably comprises one or more of starch, low-substituted hydroxypropyl cellulose, aerosil, magnesium stearate, starch slurry, sucrose, dextrin, sodium carboxymethyl starch, talcum powder, polysorbate, polyethylene glycol, soybean phospholipid for injection and glycerol for injection; the anti-hand-foot-and-mouth disease drug is any one of clinically acceptable oral administration dosage forms, injection administration dosage forms or external administration preparations. Preferably, the anti-hand-foot-and-mouth disease drug is tablets, capsules, granules, pills, injections, soft extracts, suspending agents, dispersing agents, syrups, suppositories, gels, aerosols and patches. In the anti-hand-foot-and-mouth disease medicine of the oral administration dosage form, the mass fraction of the acetyl astragaloside is 17.5-88%, more preferably 20-80%, and most preferably 25-75%.
In the invention, the active dose of the acetyl astragaloside is preferably 50-200 mg/kg/d; more preferably 100-200 mg/kg/d.
In the invention, the daily oral dosage of the anti-hand-foot-and-mouth disease medicine is 0.5-2.5 mg of acetyl astragaloside/kg of human body weight, and more preferably 0.625-2.0 mg of acetyl astragaloside/kg of human body weight; the daily injection dosage of the anti-hand-foot-and-mouth disease medicine is 0.5-2.5 mg of acetyl astragaloside/kg of human body weight, and more preferably 0.625-2.0 mg of acetyl astragaloside/kg of human body weight.
The preparation method of the anti-hand-foot-and-mouth disease medicine containing the acetyl astragaloside is not particularly limited, and the preparation method can be prepared according to the common pharmaceutical method of the technical personnel in the field.
The invention provides application of acetyl astragaloside in preparing a medicine for preventing and/or treating hand-foot-and-mouth disease, wherein the MTT method is adopted to determine the inhibitory activity of the acetyl astragaloside on coxsackie virus A16 and enterovirus EV71, and the result shows that the acetyl astragaloside externally inhibits coxsackie virus A16, enterovirus EV71 and EC50118.61 mu mol/L and 90.32 mu mol/L are respectively 4.90 and 6.44.
The invention tests the curative effect of the acetyl astragaloside on mouse infection caused by enterovirus EV71 in a stomach filling (oral) mode, and the result shows that the acetyl astragaloside is administrated in a stomach filling manner for 5 days when the dosage is 50/100/200mg/kg/day, the survival rates of the mice are respectively 40%, 60% and 90%, the death protection rates are respectively 25%, 50% and 87.5%, the survival rate of the mice using the positive control medicament ribavirin is 80%, and the death protection rate is 75%;
the invention tests the curative effect of the acetyl astragaloside on mouse infection caused by coxsackie virus A16 type in an intragastric (oral) manner, and the result shows that the acetyl astragaloside is intragastric administered for 5 days when the dosage is 50/100/200mg/kg/day, the survival rates of the mice are respectively 40%, 70% and 90%, the death protection rates are respectively 33.33%, 66.67% and 88.89%, the survival rate of the mice of the positive control medicament ribavirin is 80%, and the death protection rate is 77.78%,
therefore, the effect of the acetyl astragaloside on inhibiting Coxsackie virus A16 and enterovirus EV71 is similar to that of a positive control medicament ribavirin, and the acetyl astragaloside can inhibit the replication of the virus, improve the survival rate of virus-infected animals, prolong the survival time of the infected animals, and relieve the symptoms caused by virus infection, thereby having the effect of treating the hand-foot-and-mouth disease.
The invention has the beneficial effects that:
1. the acetyl astragaloside is a natural small molecule compound, and can treat Coxsackie virus A16, enterovirus EV71, EC50118.61 mu mol/L and 90.32 mu mol/L are respectively 4.90 and 6.44.
2. The acetyl astragaloside can inhibit Coxsackie virus A16 and enterovirus EV71 virus infection in a dose-dependent manner, and is in a dose-dependent relationship.
3. Relieving symptoms caused by virus, and alleviating death caused by virus infection; the survival time of the virus-infected mice is prolonged, and the survival rate of the mice is improved.
For further illustration of the present invention, the following examples are provided to describe the application of the astragaloside provided by the present invention in the preparation of drugs for preventing and/or treating hand-foot-and-mouth disease, but should not be construed as limiting the scope of the present invention.
The raw materials and reagents used in the application of the acetyl astragaloside provided by the invention can be purchased from the market.
The invention is further illustrated by the following examples:
example 1 Activity experiment of Acetylastragaloside against hand-foot-and-mouth Virus in vitro
1. Experimental materials:
coxsackie virus A16 type (Cox A16) and enterovirus 71 type (EV71) are provided by the institute of microbiologic epidemic research immunology, national institute of military medical sciences, and stored by Jiangsu Kangyuan modern Chinese medicine institute, and are passaged in Vero cell culture at-80 ℃.
Vero cells, purchased from ATCC cell bank in usa, were maintained by the jiangsu kinawa modern chinese medicine institute.
DMEM culture medium purchased from Nanjing Kai-Kai Biotech development Co., Ltd, lot number 20141024, and cell growth medium containing 10% fetal bovine serum and 1 × 105U/L penicillin, 100 mg/L streptomycin, cell maintenance liquid, acetyl astragaloside, which is self-made by Jiangsu Kangyuan pharmaceutical industry GmbH and has the purity of 98.79%. ribavirin, which is purchased from Hayao Sanjing pharmacy, Chinese medicine standard character H199939393937, specification of 1ml:0.1g, and batch number of 140312.
Model M2e enzyme labeling instruments, Molecular Devices; pipettors, eppendorf corporation; biosafety cabinet, available from the Heal Force company, model: HFsafe-1200; carbon dioxide incubator, available from Thermo Scientific, model: FormaSteri-Cycle 371.
2. The experimental method comprises the following steps:
vero cells were cultured in DMEM medium containing 2% fetal bovine serum at 5 × 104Each well of 96-well culture plate was inoculated at a concentration of 100. mu. L per well and placed at 37 ℃ in 5% CO2The cell monolayer was formed overnight in the incubator. After discarding the supernatant, the cells were washed 1 time with PBS to wash out the remaining fetal calf serum, and diluted to 100TCID with DMEM medium without fetal calf serum50Incubating virus at 35 deg.C for 2 hr in each well of 100 μ L, removing virus liquid, preparing acetylastragaloside into different concentrations in DMEM culture medium containing 2% fetal calf serum, adding into single-layer Vero cell, and culturing at 37 deg.C and 5% CO in each of 3 multiple wells2Culturing for 48h in an incubator, observing cytopathic phenomena every day, removing supernatant after 48h, adding 100 mu L10% formaldehyde for fixing for 1h, 0.1% (w/v) crystal violet staining for 15min, measuring absorbance by an enzyme-labeling instrument at 570nm, repeating the experiment for 3 times, calculating virus inhibition rate, and calculating EC of the acetyl astragaloside on two influenza virus cells50(median effective concentration), SI (selection index).
TABLE 1 Acetylastragaloside in vitro antiviral assay (μ M)
Table 1 the results show that: the acetyl astragaloside has certain inhibition effect on enterovirus EV71 type and Coxsackie virus A16 type, and EC50Respectively 90.32 and 118.61 mu M, and respectively 6.44 and 4.90 in SI, and the experimental result shows that the acetyl astragaloside has an inhibiting effect on the in vitro replication of the strains, improves the survival rate of virus infected cells, and has an in vitro activity basis for the application in the treatment of coxsackievirus A16 and enterovirus 71 infection.
FIG. 1 shows the inhibitory activity of acetylastragaloside against Enterovirus EV71 in example 1 of the present invention; FIG. 2 is a graph showing the inhibitory activity of acetylastragaloside against coxsackievirus A16 type in example 1 of the present invention.
As can be seen from FIG. 1 and FIG. 2, the inhibitory activity of the acetyl-astragaloside on coxsackie virus A16 type is good, and the inhibitory rate on CoxA16 at 160 mu L can reach 76.8%.
Example 2 therapeutic Effect of Acetylastragaloside on Enterovirus EV71 infection
1. Experimental materials:
enterovirus 71 type (EV71) is provided by the institute of microbiologic epidemic disease research immunology, the national academy of military medical sciences, and is preserved by the Jiangsu Kangyuan modern Chinese medicine institute, and is preserved at-80 ℃ in Vero cell culture.
The SPF-level pregnant rat BA L B/c in 15-16 days of pregnancy is purchased from Qinglongshan experimental animal breeding field in Jiangning area of Nanjing city, and is raised in an IVC system (temperature is 18-28 ℃, relative humidity is 40-70%, air is mechanically sent and exhausted, light and shade period is 12h/12h, illumination is 300-300L ux at 150-.
Ribavirin, available from hayao san jing pharmaceuticals, national drug standard H19993937, specification: 1ml:0.1g, batch number: 140312.
2. the experimental method comprises the following steps:
the 3-day-old BA L B/c suckling mice are randomly divided into a normal group, a model group and a ribavirin group 100 according to litter
mg/kg/d, low dose group of acetylastragaloside 50mg/kg/d, medium dose group 100mg/kg/d, high dose group 200mg/kg/d, each group containing 10 animals except normal control group, and each group is injected with enterovirus EV71 virus solution (10 animals)7TCID50) And (3) infecting, namely 0.1m L per mouse, feeding each administration group by intragastric administration, each time being 0.1ml, continuously carrying out 5 days, spraying 75% ethanol on a suckling mouse to wrap padding after each administration or infection, putting the suckling mouse back into a cage, co-feeding the suckling mouse and a female mouse, and feeding distilled water to a normal control group and a virus control group, observing the survival state of the suckling mouse every day after infection, observing for 14 days, and calculating the severity of infection according to the following standard scores, wherein the severity is 0, the health, 1, the dorsum, the pilaris, the pilus (observation after hair growing), emaciation, reduced activity and the like, 2, the strength of hind limbs is weakened, 3, the unilateral hind limb paralysis or paralysis, 4, the bilateral paralysis or paralysis, and 5, the dying or dying, calculating the death rate and the life prolonging rate of each group, and carrying out statistical analysis by SPSS software.
TABLE 2 Effect of therapeutic administration of Acetylastragaloside on the extent of infection of Enterovirus EV71 in BA L B/c suckling mice (n ═ 10)
P comparison with model group
TABLE 3 mortality protection of Acetylastragaloside against Enterovirus EV71 infected Babl/c suckling mice (n ═ 10)
P < 0.01, P < 0.05 compared to model groups
The results in table 2 show that after therapeutic administration is carried out on each dose group of the acetyl astragaloside, symptoms such as emaciation, hind limb strength reduction, unilateral hind limb paralysis and the like caused by enterovirus EV71 infection of suckling mice can be remarkably relieved, and the infection degree integral of the acetyl astragaloside has remarkable difference compared with that of a model group; the death protection rates of the high, medium and low doses of the acetyl astragaloside are respectively 87.50%, 50.00% and 25.00%, and the life prolonging rates are respectively 71.95%, 52.39% and 31.26%, which shows that the infection degree of each dose group of the acetyl astragaloside obviously reduces the death rate and the infection degree of enterovirus EV71 infected suckling mice, prolongs the survival time of the suckling mice, has significant difference compared with a model group, and prompts that the acetyl astragaloside has a treatment effect on the enterovirus EV71 infection.
Example 3 therapeutic Effect of Acetylastragaloside on Coxsackie Virus type A16 infection
1. Experimental materials:
coxsackie virus A16 type (Cox A16) is provided by the institute of microbiologic epidemic disease research immunology, national institute of military medical science, and stored by Jiangsu Kangyuan modern Chinese medicine institute, and is subcultured in Vero cell culture and stored at-80 ℃.
An SPF-grade pregnant mouse BA L B/c in 15-16 days of pregnancy is purchased from a Qinglongshan experimental animal breeding field in Jiangning district of Nanjing city, and is raised in an IVC system (the temperature is 18-28 ℃, the relative humidity is 40-70%, the air is mechanically sent and exhausted, the light and shade period is 12h/12h, the illumination is 150-300L ux), and a 3-day-old newborn suckling mouse is taken for carrying out experiments.
Ribavirin, available from hayao san jing pharmaceuticals, national drug standard H19993937, specification: 1ml:0.1g, batch number: 140312.
2. the experimental method comprises the following steps:
the 3-day-old BA L B/c suckling mice are randomly divided into a normal group, a model group, a ribavirin group of 100mg/kg/d, an acetylastragaloside low dose group of 50mg/kg/d, a medium dose group of 100mg/kg/d and a high dose group of 200mg/kg/d according to litter, 10 mice in each group are injected with coxsackie virus A16 type (Cox A16) virus liquid (10 mice are injected into the abdominal cavity of each group except a normal control group)7TCID50) And (3) infecting, namely 0.1m L per mouse, feeding each administration group by intragastric administration, each time being 0.1ml, continuously carrying out 5 days, spraying 75% ethanol on a suckling mouse to wrap padding after each administration or infection, putting the suckling mouse back into a cage, co-feeding the suckling mouse and a female mouse, and feeding distilled water to a normal control group and a virus control group, observing the survival state of the suckling mouse every day after infection, observing for 14 days, and calculating the severity of infection according to the following standard scores, wherein the severity is 0, the health, 1, the dorsum, the pilaris, the pilus (observation after hair growing), emaciation, reduced activity and the like, 2, the strength of hind limbs is weakened, 3, the unilateral hind limb paralysis or paralysis, 4, the bilateral paralysis or paralysis, and 5, the dying or dying, calculating the death rate and the life prolonging rate of each group, and carrying out statistical analysis by SPSS software.
TABLE 4 Effect of therapeutic administration of Acetylastragaloside on the extent of infection of Coxsackie virus A16 type BA L B/c suckling mice (n ═ 10)
P comparison with model group
TABLE 5 deaths protection of Coxsackie virus A16 infected Babl/c suckling mice (n ═ 10)
P < 0.01, P < 0.05 compared to model groups
The results in tables 4 and 5 show that after the therapeutic administration of each dose group of the acetyl astragaloside, the symptoms of emaciation, weakened hind limb strength, unilateral hind limb paralysis and the like caused by coxsackie virus A16 infected suckling mice can be remarkably relieved, and the infection degree integral of the acetyl astragaloside has remarkable difference compared with that of a model group. The death protection rates of the acetyl astragaloside in high, medium and low doses are respectively 88.89%, 66.67% and 33.33%, and the life prolonging rates are respectively 66.36%, 49.87% and 30.08%, which shows that the infection degree of each dose group of the acetyl astragaloside obviously reduces the death rate and the infection degree of the coxsackie virus A16 infected suckling mice, prolongs the survival time of the suckling mice, has obvious difference compared with a model group, and prompts that the acetyl astragaloside has a treatment effect on coxsackie virus A16 infection.
Example 4 application of Acetylastragaloside in preparing Capsule medicine
350g of acetyl astragaloside, 32g of starch, 6g of low-substituted hydroxypropyl cellulose, 4.5g of aerosil, 1.5g of magnesium stearate and a proper amount of 10% starch slurry are mixed and encapsulated to obtain 1000 capsules of the acetyl astragaloside capsule preparation. The preparation is administered 1 granule 3 times daily.
Example 5 application of Acetylastragaloside in preparation of granular drug
350g of acetyl astragaloside, 1000g of sucrose and 500g of dextrin are mixed and prepared into 1000-packet acetyl astragaloside granules according to a conventional method. The preparation is administered 1 granule 3 times daily.
Example 6 application of Acetylastragaloside in the preparation of a tablet
350g of acetyl astragaloside, 50g of starch, 7.5g of sodium carboxymethyl starch, 0.8g of talcum powder, 50g of dextrin, 0.8g of magnesium stearate and a proper amount of 10% starch slurry are mixed appropriately and prepared into 1000 tablets of the acetyl astragaloside tablet according to a conventional method. The preparation is administered 1 tablet 3 times daily.
Example 7 application of Acetylastragaloside in the preparation of pill medication
Mixing 350g of acetyl astragaloside with 12g of polyethylene glycol-6000, 80.5g of polysorbate-80 and appropriate amount of liquid paraffin, and making into 1000 pills of acetyl astragaloside according to conventional method. The preparation is administered 1 granule 3 times daily.
Example 8 application of Acetylastragaloside in the preparation of injectable drugs
200g of acetyl astragaloside, 15g of soybean phospholipid for injection and 25g of glycerol for injection, wherein the volume of water for injection is fixed to 1000m L, and the acetyl astragaloside injection is prepared into 1000 times per day, 1 time per day, and at least 250m L5% glucose injection for dilution and intravenous drip.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Claims (6)
1. The application of acetyl astragaloside in preparing an inhibitor of enterovirus;
the enterovirus is Coxsackie virus A16 type or
Enterovirus EV71 type;
the acetyl astragaloside has a structure shown in a formula I:
formula I.
2. The use according to claim 1, wherein the active dose of the acetyl-astragaloside is 50-200 mg/kg/d.
3. The application of acetyl astragaloside in preparing medicines for preventing and/or treating enterovirus infection diseases; the enterovirus infection disease is hand-foot-and-mouth disease;
the enterovirus is Coxsackie virus A16 type or enterovirus EV71 type;
the acetyl astragaloside has a structure shown in a formula I:
formula I.
4. The use of claim 3, wherein the medicament comprises acetylastragaloside and a pharmaceutically acceptable excipient; the dosage form of the medicine is any clinically acceptable oral administration dosage form, injection administration dosage form or external administration preparation.
5. The use according to claim 4, wherein the mass fraction of the acetylastragaloside in the oral administration form is 17.5-88%.
6. The use according to any one of claims 3 to 5, wherein the oral or injectable dose of the medicament is 0.5 to 2.5mg of acetylastragaloside per kg of body weight per day.
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|---|---|---|---|---|
| CN1663562A (en) * | 2004-03-05 | 2005-09-07 | 惠汝太 | Application of flavone monomer in antivirus drug preparing process |
| CN101711796A (en) * | 2008-10-06 | 2010-05-26 | 大百汇生物科技（深圳）有限公司 | Application of scullcapflavone in preparing medicament for treating enterovirus infection |
| CN102180853A (en) * | 2011-03-09 | 2011-09-14 | 中国科学院昆明植物研究所 | Anti-enterovirus 71 (EV71) flavonoid compound and application thereof to pharmacy |
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|---|---|---|---|---|
| CN1663562A (en) * | 2004-03-05 | 2005-09-07 | 惠汝太 | Application of flavone monomer in antivirus drug preparing process |
| CN101711796A (en) * | 2008-10-06 | 2010-05-26 | 大百汇生物科技（深圳）有限公司 | Application of scullcapflavone in preparing medicament for treating enterovirus infection |
| CN102180853A (en) * | 2011-03-09 | 2011-09-14 | 中国科学院昆明植物研究所 | Anti-enterovirus 71 (EV71) flavonoid compound and application thereof to pharmacy |
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| 八角莲水溶性有效成分的分离与抗病毒活性的测定;姚莉韵等;《上海第二医科大学学报》;19991231;第19卷(第3期);234-237 * |
| 黄酮类化合物抗病毒活性的研究进展;龚金炎等;《中草药》;20080430;第39卷(第4期);623-627 * |
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