CN106344574B - Application of the black dragon peimine in the drug of preparation prevention and/or treatment hand-foot-and-mouth disease - Google Patents
Application of the black dragon peimine in the drug of preparation prevention and/or treatment hand-foot-and-mouth disease Download PDFInfo
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
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Abstract
The invention belongs to pharmaceutical technology fields, provide application of the black imperial peimine in preparation prevention and/or treatment hand-foot-and-mouth disease drug.Being experimentally confirmed the cytopathy that black imperial peimine induces enterovirus has inhibiting effect, can improve the survival rate of virus infected cell；The duplication that can inhibit virus in vivo simultaneously, improves the survival rate of virus-infected animal, extends the life span of infection animal, alleviates the illness that virus infection causes, to have the function for the treatment of hand-foot-and-mouth disease and application value.
Description
Technical field
The invention belongs to pharmaceutical technology fields more particularly to black imperial peimine in preparation prevention and/or treatment hand-foot-and-mouth disease
Drug in application.
Background technique
Hand-foot-and-mouth disease is children's infectious disease caused by virus, is the legal Class C infectious disease in China.Disease main infection 0-6
The infant in year, most commonly seen with 2-3 years old childhood infection, hand-foot-and-mouth disease early stage goes out in infant limb end and oral cavity etc.
Cause bleb or ulcer, infant recovery from illness mostly in 1-2 weeks.However, a small number of case disease progressions are rapid, it can be on a 1-5 days left sides of morbidity
It is right meningitis, aseptic isolator, brainstem encephalitis, encephalomyelitis, pulmonary edema and dyshaemia etc., the only a few case state of an illness occur
It is critical, it lethal can die, case can there are sequelae for survival.
According to WHO Report, about more than 20 kinds of the virus of hand-foot-and-mouth disease symptom can be caused, wherein with intestines
Road 71 types of virus (enterovirus 71, EV71) and coxsackievirus A16 (coxsachievirus A16, CoxA16)
Most commonly seen, the case load as caused by both virus infections accounts for about total 80% or more case load.Other can cause brothers mouthful
The virus of disease specifically includes that Coxsackie virus A group 4,5,7,9 and 10 types (CoxA4, CoxA5, CoxA7, CoxA9 and CoxA10),
The type of coxsackie virus group B 2 and 5 (CoxB2 and CoxB5) and echovirus (ECHO) etc..
Currently, still without the drug for being directly targeted virus, facing although being directed to the vaccine granted listing of EV71 virus
Bed mainly takes the strategy of symptomatic treatment.Clinical common anti-hand-foot-and-mouth-disease drug has Ribavirin, acyclovir, Valaciclovir
Deng, but these medicine side effects are stronger.
In recent years, the research of Chinese medicine anti-hand-foot-and-mouth-disease gradually causes the concern of people, and due to many traditional Chinese medicinal components categories
In naturally extracting drug, have many advantages, such as Small side effects.
Black dragon peimine (Hei lonine), is from fritillary bulb (Fritillaria ussuriensis), fritillaria thunbergii
The composition of alkaloids extracted in (Fritillaria thunbergii), monantha (Fritillaria monantha).
Pharmaceutical research shows that black imperial peimine has a variety of effects such as antibechic, eliminating the phlegm, antalgic and inflammation relieving, relaxation tracheal smooth muscle, antibacterial.
The report that black imperial peimine is applied in preparation prevention and/or treatment hand-foot-and-mouth disease drug is had no at present.
Summary of the invention
In view of this, the purpose of the present invention is to provide black imperial peimines in preparation prevention and/or treatment hand-foot-and-mouth disease medicine
Application in object.
The present invention is studies have shown that black dragon peimine has inhibition to the cytopathy of enterovirus, Coxsackie virus induction
Effect, can improve the survival rate of virus infected cell, antiviral activity is obvious.Therefore the present invention provides black imperial peimines to make
Application in the standby drug for preventing and/or treating hand-foot-and-mouth disease.
Preferably, the virus for causing hand-foot-and-mouth disease is enterovirus.
Preferably, the enterovirus is Coxsackie virus.Further, it is preferred that the Coxsackie virus is Coxsack
Virus A 16-type.
Preferably, the enterovirus is enterovirus EV 71 type.
Preferably, the active dose of the black imperial peimine is 50-200mg/kg/d.
Preferably, the drug includes black imperial peimine and pharmaceutically acceptable carrier.
Preferably, the drug is any one clinically-acceptable oral administered dosage form, injecting medicine-feeding form or external application
Drug-delivery preparation.
Preferably, the drug is tablet, capsule, granule, pill, liquid preparation, soft extract, suspending agent, dispersion
Agent, syrup, suppository, gelling agent, aerosol, patch.
Preferably, in the drug of the oral administered dosage form, the mass fraction of black dragon peimine is 17.5-88%.
Preferably, the daily oral dose of the oral administered dosage form is the black imperial peimine/kg body of 0.5-2.5mg
Weight.
The present invention provides application of the black imperial peimine in preparation prevention and/or treatment hand-foot-and-mouth disease drug, and the present invention is real
Test the result shows that, it is black dragon peimine to enterovirus, Coxsackie virus induction cytopathy have inhibiting effect, disease can be improved
The survival rate of malicious infection cell；The duplication that can inhibit virus in vivo simultaneously, improves the survival rate of virus-infected animal, extends
The life span of infection animal alleviates the illness that virus infection causes, to have the function for the treatment of hand-foot-and-mouth disease；And it can prevent
The proliferation and diffusion of virus in vivo, protect normal tissue from damage, play the role of preventing disease of viral infection.
The present invention has one of following beneficial effects:
1, black imperial peimine is a kind of natural small molecule compounds, to coxsackie virus A 16, enterovirus EV 71,
EC50 is respectively 116.87 μm of ol/L, 152.14 μm of ol/L, and SI is respectively 7.40,5.68.
2, black imperial peimine can inhibit to dose-dependant coxsackie virus A 16, enterovirus EV 71 virus infection, be in agent
Measure dependence.
3, black imperial peimine alleviates symptom caused by virus, mitigates death caused by virus infection；It is small to extend virus infection
Mouse life span improves mouse survival rate.
Specific embodiment
Below in conjunction with the embodiment of the present invention, technical scheme in the embodiment of the invention is clearly and completely described,
Obviously, described embodiments are only a part of the embodiments of the present invention, instead of all the embodiments.Based in the present invention
Embodiment, every other embodiment obtained by those of ordinary skill in the art without making creative efforts, all
Belong to the scope of protection of the invention.
The present invention provides a kind of application of black imperial peimine in preparation prevention and/or treatment hand-foot-and-mouth disease drug.
In the present invention, the black imperial peimine has structure shown in formula I, belongs to alkaloids, pharmacological research shows black
Imperial peimine has a variety of effects such as antibechic, eliminating the phlegm, antalgic and inflammation relieving, relaxation tracheal smooth muscle, antibacterial.
The black imperial peimine is preferably black imperial peimine monomer and/or black imperial fritillaria alkali extract, the black imperial fritillaria
In alkali extract, for the content of the black imperial peimine of monomer preferably 90% or more, the present invention can be conventionally from containing black dragon
It extracts and obtains in the Chinese medicine or the prepared slices of Chinese crude drugs of peimine, such as fritillary bulb, also can purchase the commercial goods of black imperial peimine.Tool
Body, in an embodiment of the present invention, the black imperial peimine of Nat'l Pharmaceutical & Biological Products Control Institute's offer can be used.
The present invention provides a kind of application of black imperial peimine in preparation prevention and/or treatment hand-foot-and-mouth disease drug.Its
In, the virus for causing hand-foot-and-mouth disease includes enterovirus.
Preferably, the enterovirus is Coxsackie virus.Further, it is preferred that the Coxsackie virus is Coxsack
Virus A 16-type.
Preferably, the enterovirus is enterovirus EV 71 type.
In the present invention, the prevention and/or treatment hand-foot-and-mouth disease drug include black imperial peimine and pharmaceutically acceptable
Carrier.
In the present invention, the pharmaceutically acceptable carrier.Preferably starch, low-substituted hydroxypropyl cellulose, micro mist
Silica gel, magnesium stearate, starch slurry, sucrose, dextrin, sodium carboxymethyl starch, talcum powder, polysorbate, polyethylene glycol, injection are big
One or more of Fabaceous Lecithin and glycerol for injection.
The prevention and/or treatment hand-foot-and-mouth disease can be any one clinically-acceptable oral administered dosage form, injection
Form of administration or topical administration formulations.
Preferably, the prevention and/or treatment hand-foot-and-mouth disease drug are tablet, capsule, granule, pill, liquid system
Agent, soft extract, suspending agent, dispersing agent, syrup, suppository, gelling agent, aerosol, patch.
Wherein, in the anti-hand-foot-and-mouth-disease drug of the oral administered dosage form, the mass fraction of black dragon peimine is 22.5-
88%, more preferably 20-80%, most preferably 25-75%.
In the present invention, the active dose of the black imperial peimine is preferably 50-200mg/kg/d；More preferably 100-
200mg/kg/d。
In the present invention, described to prevent and/or treat the daily oral dose of hand-foot-and-mouth disease drug to be the black dragon of 0.5-2.5mg
Peimine/kg body weight, the black imperial peimine/kg weight of more preferably 0.625-2.0mg.
The present invention does not have the preparation method of the prevention comprising black imperial peimine and/or the drug for treating hand-foot-and-mouth disease
Special limitation, according to the common pharmaceutical methods of those skilled in the art.
The present invention provides a kind of black imperial peimines to prevent and/or treat the application in hand-foot-and-mouth disease drug in preparation, this
Invention determines black imperial peimine using crystal violet method and lives to the inhibition of coxsackie virus A 16-type and enterovirus EV 71 type
Property, the results showed that, for black dragon peimine in vitro to coxsackie virus A 16, enterovirus EV 71, EC50 is respectively 116.87 μ
Mol/L, 152.14 μm of ol/L, SI are respectively 7.40,5.68.
The present invention has been carried out black imperial peimine in a manner of stomach-filling (oral) and infected enterovirus EV 71 type induced mice
Curative effect test, the results showed that, it is black dragon peimine in dosage 50/100/200mg/kg/day gastric infusion 5 days, mouse is deposited
Motility rate is respectively 30%, 40% and 70%, and Death prevention rate is respectively 70%, 40% and 30%, positive control drug Ribavirin
Mouse survival rate be 60%, Death prevention rate 60%；
The present invention has been carried out black imperial peimine in a manner of stomach-filling (oral) and infected coxsackie virus A 16-type induced mice
Curative effect test, the results showed that, it is black dragon peimine in dosage 50/100/200mg/kg/day gastric infusion 5 days, mouse is deposited
Motility rate is respectively 30%, 50% and 80%, and Death prevention rate is respectively 30%, 50% and 80%, positive control drug Ribavirin
Mouse survival rate be 60%, Death prevention rate 60%,
As it can be seen that black dragon peimine is similar to inhibitory effect of the positive control drug Ribavirin to influenza A virus, black dragon
Peimine can inhibit the duplication of virus, improve the survival rate of virus-infected animal, extend the life span of infection animal, alleviate
The illness that virus infection causes, to have the function of preventing and/or treating hand-foot-and-mouth disease.
In order to further illustrate the present invention, black imperial peimine provided by the invention is prevented in preparation with reference to embodiments
And/or the application in treatment hand-foot-and-mouth disease drug is described in detail, but cannot be understood as to the scope of the present invention
It limits.Unless otherwise specified, reagent used in following embodiment is commercially available.
The black imperial external anti-hand-foot-and-mouth-disease cytotoxic activity experiment of peimine of embodiment 1
1, experimental material:
Coxsackie virus A 16-type (CoxA16) and enterovirns type 71 (EV71), by Chinese People's Liberation Army's military medicine
Academy of sciences microorganism epidemic research immunological investigation room provides, and is saved by Jiangsu Kang Yuan R&D of modern TCM institute, thin in Vero
Passage in born of the same parents' culture, -80 DEG C of preservations.
African green monkey kidney cell (Vero cell), is purchased from U.S.'s ATCC cell bank, by Jiangsu Kang Yuan R&D of modern TCM institute
It saves.
DMEM culture medium is purchased from Nanjing KaiJi Biology Science Development Co., Ltd, lot number: 20141024, cell growth medium
In contain 10% fetal calf serum, 1 × 105U/L penicillin, 100mg/L streptomysin.In cell maintenance medium in addition to containing 2% fetal calf serum,
Other same cell growth mediums.Ribavirin refines medicine purchased from medicine three is breathed out, and national drug standard H19993937, specification: 1ml:0.1g is criticized
Number: 140312.
M2e type microplate reader, Molecular Devices；Pipettor, eppendorf company；Biohazard Safety Equipment is purchased from
Heal Force company, model: HFsafe-1200；Carbon dioxide incubator is purchased from Thermo Scientific company, type
Number: FormaSteri-Cycle 371.
2, experimental method:
Vero cell (African green monkey kidney cell) presses 5 × 10 with the DMEM culture medium containing 2% fetal calf serum4A/ml concentration
96 well culture plates are inoculated with, every 100 μ l of hole sets 37 DEG C of 5%CO2Overnight incubation forms cell monolayer in incubator.After abandoning supernatant, use
PBS washs cell 1 time, to wash away remaining fetal calf serum, is added and is diluted to the DMEM culture medium without fetal calf serum
100TCID50Each strain virus after every hole 100 μ l, 35 DEG C of incubation 2h, discards virus liquid.With the DMEM culture medium of 2% fetal calf serum
Black imperial peimine is configured to various concentration, is separately added into Vero cell monolayer, if 3 multiple holes, Vero cell in 37 DEG C,
5%CO248h is cultivated in incubator, observes cytopathic phenomena daily.After 48h, after abandoning supernatant, 100 μ l, 10% formaldehyde is added
Fixed 1h, 0.1% (w/v) violet staining 15min, microplate reader 570nm measure absorbance.Experiment is repeated 3 times altogether.Calculate black dragon
CC of the peimine to two kinds of enterovirus cells50(half toxic concentration), EC50(medium effective concentration), SI (selection index).
The black imperial peimine In vitro antibacterial test (μM) of table 1
Table 1 is as the result is shown: black dragon peimine has certain inhibiting effect to enterovirus type EV71, CoxA16 virus,
EC50Respectively 152.14 μM and 116.87, SI is respectively 5.68 and 7.40, the experimental results showed that black dragon peimine is to the above strain
Replication in vitro is inhibited, improves the survival rate of virus infected cell, has applied to coxsackie virus A 16, enteron aisle
The Pharmacodynamics in vitro basis of viral 71 type treatment of infection.
The therapeutic effect that the black imperial peimine of embodiment 2 infects enterovirus EV 71
1, experimental material:
Enterovirns type 71 (EV71) is immunized by Academy of Military Medicine, PLA's microorganism epidemic research
It learns research department to provide, is saved by Jiangsu Kang Yuan R&D of modern TCM institute, passed in Vero cell culture, -80 DEG C of preservations.
The SPF grades of pregnancies pregnant mouse of BALB/c on the 15th~16 is purchased from Jiangning county's Qinglongshan experimental animal breeding field, raising
In IVC system (18~28 DEG C of temperature, 40~70% relative humidity, mechanical supply and exhaust；The light and shade period: 12h/12h；150~
300Lux illumination), take 3 age in days Neonatal Mouses to carry out experiment.
Ribavirin is purchased from and breathes out the purification medicine of medicine three, national drug standard H19993937, specification: 1ml:0.1g, lot number:
140312。
2, experimental method:
3 age in days BALB/c suckling mouses are randomly divided into normal group, model group, Ribavirin group 100mg/kg/d, Hei Longbei by nest
Female alkali low dose group 50mg/kg/d, middle dose group 100mg/kg/d, high dose group 200mg/kg/d, every group 10, it is normal right to remove
Outer according to group, enterovirus EV 71 liquid (10 is injected intraperitoneally in remaining each group7TCID50) infected, only, each administration group is to fill by 0.1mL/
Stomach administration, each 0.1ml continuous 5 days, are put back to after 75% ethyl alcohol sprinkling suckling mouse package padding after being administered or infect every time
It is raised jointly in cage with female rat, Normal group and virus control group give distilled water.The existence of suckling mouse is observed after infection daily
State, observes 14d altogether, and according to following scale, calculates the severity of infection, and 0 point: health；1 point: the back of a bow, perpendicular hair
(being observed after growing hair), thin, activity reduction etc.；2 points: hind leg diminished strength；3 points: unilateral hindlimb paralysis or paralysis；4 points: double
Side hindlimb paralysis or paralysis；5 points: dying or dead.It calculates each group death rate and increase in life span and is united with SPSS software
Meter analysis.
Influence (n=of the black imperial peimine therapeutic administratp of table 2 to enterovirus EV 71 infection BALB/c suckling mouse gradient of infection
10)
| Group | Dosage (mg/kg) | 0 point | 1 point | 2 points | 3 points | 4 points | 5 points | P |
| Normal group | - | 10 | 0 | 0 | 0 | 0 | 0 | - |
| Model group | - | 0 | 0 | 0 | 0 | 0 | 10 | - |
| Ribavirin group | 100 | 0 | 0 | 0 | 2 | 3 | 5 | <0.01 |
| High dose group | 200 | 0 | 3 | 3 | 2 | 1 | 3 | <0.01 |
| Middle dose group | 100 | 0 | 0 | 2 | 1 | 1 | 6 | <0.01 |
| Low dose group | 50 | 0 | 0 | 0 | 1 | 2 | 7 | <0.05 |
Note: P is compared with model group
Dead protective effect of the black imperial peimine of table 3 to enterovirus EV 71 infection Babl/c suckling mouse
Note: P < 0.05 * * P < 0.01, * is compared with model group
Table 2 can significantly slow enterovirus the results show that after each dosage group progress therapeutic of black dragon peimine
EV71 infects syntexis caused by suckling mouse, hind leg diminished strength, the symptoms such as unilateral hindlimb paralysis, gradient of infection integral and model group
Compare and all has significant difference.
The Death prevention rate of the high, medium and low dosage of black dragon peimine is respectively 70%, 40%, 30%, increase in life span difference
It is 77.51%, 48.53%, 33.66%, shows that black imperial each dosage group gradient of infection of peimine significantly reduces enterovirus
EV71 infects the suckling mouse death rate and gradient of infection, extends its life span, with significant difference compared with model group, prompts black
Imperial peimine has therapeutic effect to enterovirus EV 71 infection.
The therapeutic effect that the black imperial peimine of embodiment 3 infects Coxsackie virus CoxA16
1, experimental material:
Coxsackie virus A 16-type (Cox A16), is ground by Academy of Military Medicine, PLA's microorganism epidemic disease
The offer of immunological investigation room is provided, is saved by Jiangsu Kang Yuan R&D of modern TCM institute, is passed in Vero cell culture, -80 DEG C of guarantors
It deposits.
The SPF grades of pregnancies pregnant mouse of BALB/c on the 15th~16 is purchased from Jiangning county's Qinglongshan experimental animal breeding field, raising
In IVC system (18~28 DEG C of temperature, 40~70% relative humidity, mechanical supply and exhaust；The light and shade period: 12h/12h；150~
300Lux illumination), take 3 age in days Neonatal Mouses to carry out experiment.
Ribavirin is purchased from and breathes out the purification medicine of medicine three, national drug standard H19993937, specification: 1ml:0.1g, lot number:
140312。
2, experimental method:
3 age in days BALB/c suckling mouses are randomly divided into normal group, model group, Ribavirin group 100mg/kg/d, Hei Longbei by nest
Female alkali low dose group 50mg/kg/d, middle dose group 100mg/kg/d, high dose group 200mg/kg/d, every group 10, it is normal right to remove
Outer according to group, Coxsackie virus CoxA16 liquid (10 is injected intraperitoneally in remaining each group7TCID50) infected, 0.1mL/, each administration group
With gastric infusion, each 0.1ml, continuous 5 days, after wrapping up padding with 75% ethyl alcohol sprinkling suckling mouse after being administered or infect every time,
It puts back in cage and is raised jointly with female rat, Normal group and virus control group give distilled water.Suckling mouse is observed after infection daily
Survival condition, observes 14d altogether, and according to following scale, calculates the severity of infection, and 0 point: health；1 point: hunchbacked, perpendicular
Hair (being observed after growing hair), thin, activity reduction etc.；2 points: hind leg diminished strength；3 points: unilateral hindlimb paralysis or paralysis；4 points:
Bilateral hindlimb paralysis or paralysis；5 points: dying or dead.It calculates each group death rate and increase in life span and is carried out with SPSS software
Statistical analysis.
Influence (n of the black imperial peimine therapeutic administratp of table 4 to Coxsackie virus CoxA16 infection BALB/c suckling mouse gradient of infection
=10)
| Group | Dosage (mg/kg) | 0 point | 1 point | 2 points | 3 points | 4 points | 5 points | P |
| Normal group | - | 10 | 0 | 0 | 0 | 0 | 0 | - |
| Model group | - | 0 | 0 | 0 | 0 | 0 | 10 | - |
| Ribavirin group | 100 | 0 | 0 | 0 | 2 | 4 | 4 | <0.01 |
| High dose group | 200 | 0 | 3 | 3 | 2 | 1 | 2 | <0.01 |
| Middle dose group | 100 | 0 | 0 | 2 | 1 | 1 | 6 | <0.01 |
| Low dose group | 50 | 0 | 0 | 0 | 2 | 1 | 7 | <0.05 |
Note: P is compared with model group
Dead protective effect of the black imperial peimine of table 5 to Coxsackie virus CoxA16 infection Babl/c suckling mouse
Note: P < 0.05 * * P < 0.01, * is compared with model group
Table 4 can significantly slow Coxsackie virus the results show that after each dosage group progress therapeutic of black dragon peimine
CoxA16 infects syntexis caused by suckling mouse, hind leg diminished strength, the symptoms such as unilateral hindlimb paralysis, gradient of infection integral and model
Group, which compares, all has significant difference.
The Death prevention rate of the high, medium and low dosage of black dragon peimine is respectively 80%, 50% and 30%, increase in life span point
Not Wei 89.85%, 52.82% and 34.42%, show that black imperial each dosage group gradient of infection of peimine significantly reduces Coxsack disease
The malicious CoxA16 infection suckling mouse death rate and gradient of infection, extend its life span, with significant difference compared with model group, mention
Show that black imperial peimine has therapeutic effect to Coxsackie virus CoxA16 infection.
The black imperial peimine of embodiment 4 is preparing the application in capsule medicine
The black imperial peimine of 350g and 32g starch, 6g low-substituted hydroxypropyl cellulose, 4.5g superfine silica gel powder, 1.5g is stearic
Sour magnesium and the mixing of appropriate 10% starch slurry, are packed into capsule, obtain capsule preparations 1000 of black imperial peimine.3 times a day, often
Secondary 1.
The black imperial peimine of embodiment 5 is preparing the application in granules medicine
The black imperial peimine of 350g and 1000g sucrose and 500g dextrin are mixed, 1000 Bao Heilong are conventionally made
Peimine granule.3 times a day, 1 tablet each time.
The black imperial peimine of embodiment 6 is preparing the application in tablet medicine
The black imperial peimine of 350g and 50g starch, 7.5g sodium carboxymethyl starch, 0.8g talcum powder, 50g dextrin, 0.8g is hard
Fatty acid magnesium and the suitable mixing of appropriate 10% starch slurry, are conventionally made black imperial peimine 1000, tablet.3 times a day, often
Secondary 1.
Application of the black imperial peimine of embodiment 7 in preparation pill medicine
The black imperial peimine of 350g and 12g polyethylene glycol-6000,80.5g Tween-80, appropriate liquid paraffin are mixed,
Black imperial peimine pill 1000 is conventionally made.3 times a day, 1 tablet each time.
The black imperial peimine of embodiment 8 is preparing the application in injection medicine
The black imperial peimine of 200g and 15g injection soybean lecithin, 25g glycerol for injection, water for injection are settled to
Black imperial peimine injection 1000 is conventionally made in 1000mL.One time a day, every time 1,250mL is at least used
Intravenous drip after the dilution of 5% glucose injection.
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (10)
1. application of the black dragon peimine in preparation prevention and/or treatment hand-foot-and-mouth disease drug.
2. application according to claim 1, which is characterized in that the hand-foot-and-mouth disease causes for enterovirus.
3. application according to claim 2, which is characterized in that the enterovirus is enterovirus EV 71 type.
4. application according to claim 2, which is characterized in that the enterovirus is Coxsackie virus.
5. application according to claim 4, which is characterized in that the Coxsackie virus is coxsackie virus A 16-type.
6. application according to claim 1, which is characterized in that the active dose of the black imperial peimine is 50-200mg/
kg/d。
7. application according to claim 1, which is characterized in that the drug includes black imperial peimine and pharmaceutically acceptable
Carrier；The dosage form of the drug is that any one clinically-acceptable oral administered dosage form, injecting medicine-feeding form or external application are given
Medicine preparation.
8. application according to claim 7, which is characterized in that in the drug of the oral administered dosage form, black dragon peimine
Mass fraction be 17.5-88%.
9. application according to claim 7, which is characterized in that the daily oral dose of the drug of the oral administered dosage form
For the black imperial peimine/kg body weight of 0.5-2.5mg.
10. application according to claim 7, which is characterized in that the drug be tablet, capsule, granule, pill,
Soft extract, suspending agent, syrup, suppository, gelling agent, aerosol, patch.
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|---|---|---|---|---|
| CN101721604B (en) * | 2008-10-28 | 2012-11-28 | 江苏康缘药业股份有限公司 | Application of traditional Chinese medicine composition in preparing medicine for treating hand, mouth and foot diseases |
| CN102327571B (en) * | 2011-09-30 | 2016-04-27 | 四川大学 | Bulbus Fritillariae Cirrhosae total alkaloids and contained compound are preparing the novelty teabag in cancer therapy drug |
| CN105255995B (en) * | 2015-11-23 | 2019-02-05 | 江苏康缘药业股份有限公司 | A kind of anti-hand-foot-and-mouth-disease pharmaceutical activity detection method and its kit |
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