CN106344574A - Application of heilonine in preparation of drugs for preventing and/or treating hand-foot-and-mouth disease - Google Patents

Application of heilonine in preparation of drugs for preventing and/or treating hand-foot-and-mouth disease Download PDF

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CN106344574A
CN106344574A CN201610689512.2A CN201610689512A CN106344574A CN 106344574 A CN106344574 A CN 106344574A CN 201610689512 A CN201610689512 A CN 201610689512A CN 106344574 A CN106344574 A CN 106344574A
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peimine
medicine
black dragon
foot
enterovirus
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CN106344574B (en
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萧伟
曹泽彧
丁玥
孙兰
曹亮
王振中
丁岗
胡晗绯
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Jiangsu Kanion Pharmaceutical Co Ltd
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Jiangsu Kanion Pharmaceutical Co Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/4353Heterocyclic 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
    • A61K31/4375Heterocyclic 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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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention belongs to the technical field of medicines, and provides application of heilonine in preparation of drugs for preventing and/or treating a hand-foot-and-mouth disease. Experiments prove that the heilonine has inhibiting effect on cytopathy induced by enterovirus, and the survival rate of virus infected cells can be increased; and meanwhile, copying of viruses can be inhibited in vivo, the survival rate of virus infected animals is increased, the survival time of the infected animals is prolonged, symptoms of diseases caused by virus infection are relieved, and therefore, the heilonine has effects and application value on treatment of the hand-foot-and-mouth disease.

Description

Application in the medicine of preparation prevention and/or treatment hand-foot-mouth disease for the black dragon peimine
Technical field
The invention belongs to pharmaceutical technology field, more particularly, to black dragon peimine is in preparation prevention and/or treatment hand-foot-mouth disease Medicine in application.
Background technology
Hand-foot-mouth disease is the child's infectious disease being caused by virus, is China's legal Class C infectious disease.This sick main infection 0-6 Year infant, with 2-3 year childhood infection most commonly seen, hand-foot-mouth disease their early stage goes out in infant limb end and oral cavity etc. Cause herpess or ulcer, infant was fully recovered in many weeks in 1-2.However, minority case disease progression is rapid, can be on 1-5 days left sides of morbidity Right meningitiss, aseptic isolator, brain stem encephalitis, encephalomyelitiss, pulmonary edema and circulatory disturbance etc., the only a few case state of an illness Critical, can lethal die, survival case can leave sequela.
According to WHO Report, the virus of hand-foot-mouth disease symptom kind about more than 20 can be caused, wherein with intestinal Road virus 71 types (enterovirus 71, ev71) and Coxsackie viruss a group 16 type (coxsachievirus a16, coxa16) Most commonly seen, total case load more than 80% is accounted for by the case load that both virus infection cause.Other can cause hand-foot-mouth disease The virus of disease specifically includes that Coxsackie viruss a group 4,5,7,9 and 10 type (coxa4, coxa5, coxa7, coxa9 and coxa10), Coxsackie viruss b group 2 and 5 types (coxb2 and coxb5) and echovirus (echo) etc..
At present, although the vaccine granted listing for ev71 virus, still without the medicine being directly targeted virus, face The strategy of symptomatic treatment mainly taken by bed.Clinical common anti-hand-foot-and-mouth-disease medicine has ribavirin, acyclovir, valaciclovir Deng, but these medicine side effect are stronger.
In recent years, the research of Chinese medicine anti-hand-foot-and-mouth-disease gradually causes the concern of people, and because a lot of Chinese medicinal components belong to In natural extract medicine, there are Small side effects.
Black dragon peimine (hei lonine), is from Bulbus Fritillariae Ussuriensiss (fritillaria ussuriensis), Bulbus Fritillariae Thunbergii The composition of alkaloids extracted in (fritillaria thunbergii), monantha (fritillaria monantha). Pharmaceutical research shows that black dragon peimine has antitussive, eliminating the phlegm, antalgic and inflammation relieving, lax multiple effect such as tracheal smooth muscle, antibacterial.
Have no the report of black dragon peimine application in preparation prevention and/or treatment hand-foot-mouth disease medicine at present.
Content of the invention
In view of this, it is an object of the invention to provide black dragon peimine is in preparation prevention and/or treatment hand-foot-mouth disease medicine Application in thing.
Present invention research shows, black dragon peimine all has suppression to the cytopathy of enterovirus, Coxsackie viruss induction Effect, can improve the survival rate of virus infected cell, antiviral activity is obvious.Therefore the invention provides black dragon peimine is in system Application in the medicine of standby prevention and/or treatment hand-foot-mouth disease.
Preferably, the described virus causing hand-foot-mouth disease is enterovirus.
Preferably, described enterovirus are Coxsackie viruss.Further it is preferred that described Coxsackie viruss are COxsackie Viral a16 type.
Preferably, described enterovirus are enterovirus ev71 type.
Preferably, the active dose of described black dragon peimine is 50-200mg/kg/d.
Preferably, described medicine includes black dragon peimine and pharmaceutically acceptable carrier.
Preferably, described medicine is any one clinically-acceptable oral administered dosage form, injecting medicine-feeding form or external Drug-delivery preparation.
Preferably, described medicine is tablet, capsule, granule, pill, liquid preparation, soft extract, suspending agent, dispersion Agent, syrup, suppository, gel, aerosol, patch.
Preferably, in the medicine of described oral administered dosage form, the mass fraction of black dragon peimine is 17.5-88%.
Preferably, the daily oral dose of described oral administered dosage form is 0.5-2.5mg black dragon peimine/kg body Weight.
The present invention provides application in preparation prevention and/or treatment hand-foot-mouth disease medicine for the black dragon peimine, and the present invention is real Test result to show, black dragon peimine all has inhibitory action to the cytopathy of enterovirus, Coxsackie viruss induction, can improve disease The survival rate of malicious infection cell;The duplication of virus can be suppressed simultaneously in vivo, improve the survival rate of virus-infected animal, extend The life span of infection animal, alleviates the disease that virus infection causes, thus having the effect for the treatment of hand-foot-mouth disease;And can prevent Viral propagation in vivo and diffusion, protect normal structure from damage, play the pathogenetic effect of prophylaxis of viral infections disease.
The present invention has one of following beneficial effects:
1st, black dragon peimine be a kind of natural small molecule compounds, its to Coxsackie viruss a16, enterovirus ev71, Ec50 is respectively 116.87 μm of ol/l, 152.14 μm of ol/l, and si is respectively 7.40,5.68.
2nd, black dragon peimine can suppress Coxsackie viruss a16, enterovirus ev71 virus infection, in agent in dose-dependant ground Amount dependence.
3rd, black dragon peimine is alleviated the viral symptom causing, is mitigated the death that virus infection leads to;Extend virus infection little Mus life span, improves mouse survival rate.
Specific embodiment
Below in conjunction with the embodiment of the present invention, the technical scheme in the embodiment of the present invention is clearly and completely described, Obviously, described embodiment is only a part of embodiment of the present invention, rather than whole embodiments.Based in the present invention Embodiment, the every other embodiment that those of ordinary skill in the art are obtained under the premise of not making creative work, all Belong to the scope of protection of the invention.
The invention provides a kind of application in preparation prevention and/or treatment hand-foot-mouth disease medicine for black dragon peimine.
In the present invention, described black dragon peimine has structure shown in formula, belongs to alkaloidss, pharmacological research shows, black Imperial peimine has antitussive, eliminating the phlegm, antalgic and inflammation relieving, lax multiple effect such as tracheal smooth muscle, antibacterial.
Described black dragon peimine is preferably black dragon peimine monomer and/or black dragon Bulbus Fritillariae Uninbracteatae alkali extract, described black dragon Bulbus Fritillariae Uninbracteatae In alkali extract, preferably more than 90%, the present invention can be conventionally from containing black dragon for the content of monomer black dragon peimine Extract in the Chinese crude drug of peimine or the prepared slices of Chinese crude drugs and obtain, such as Bulbus Fritillariae Ussuriensiss, also the commercial goods of commercially available black dragon peimine.Tool Body, in an embodiment of the present invention, can be using the black dragon peimine of Nat'l Pharmaceutical & Biological Products Control Institute's offer.
The invention provides a kind of application in preparation prevention and/or treatment hand-foot-mouth disease medicine for black dragon peimine.Its In, the described virus causing hand-foot-mouth disease includes enterovirus.
Preferably, described enterovirus are Coxsackie viruss.Further it is preferred that described Coxsackie viruss are COxsackie Viral a16 type.
Preferably, described enterovirus are enterovirus ev71 type.
In the present invention, described prevention and/or treatment hand-foot-mouth disease medicine include black dragon peimine and pharmaceutically acceptable Carrier.
In the present invention, described pharmaceutically acceptable carrier.It is preferably starch, low-substituted hydroxypropyl cellulose, micropowder Silica gel, magnesium stearate, starch slurry, sucrose, dextrin, carboxymethyl starch sodium, Pulvis Talci, Polysorbate, Polyethylene Glycol, injection are big One or more of fabaceous lecithin and glycerol for injection.
Described prevention and/or treatment hand-foot-mouth disease can be any one clinically-acceptable oral administered dosage form, injection Form of administration or topical administration formulations.
Preferably, described prevention and/or treatment hand-foot-mouth disease medicine are tablet, capsule, granule, pill, liquid system Agent, soft extract, suspending agent, dispersant, syrup, suppository, gel, aerosol, patch.
Wherein, in the anti-hand-foot-and-mouth-disease medicine of described 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 described black dragon peimine is preferably 50-200mg/kg/d;More preferably 100- 200mg/kg/d.
In the present invention, described prevention and/or the treatment daily oral dose of hand-foot-mouth disease medicine are the black dragon of 0.5-2.5mg Peimine/kg body weight, more preferably 0.625-2.0mg black dragon peimine/kg body weight.
The present invention does not have to the preparation method of the described prevention comprising black dragon peimine and/or the medicine for the treatment of hand-foot-mouth disease Special restriction, the pharmaceutical methods commonly used according to those skilled in the art.
The invention provides a kind of application in preparation prevention and/or treatment hand-foot-mouth disease medicine for black dragon peimine, this Invention employs crystal violet method and determines the suppression work to Coxsackie viruss a16 type and enterovirus ev71 type for the black dragon peimine Property, result shows, in vitro to Coxsackie viruss a16, enterovirus ev71, ec50 is respectively 116.87 μ to black dragon peimine Mol/l, 152.14 μm of ol/l, si is respectively 7.40,5.68.
The present invention has been carried out black dragon peimine in the way of gavage (being administered orally) and enterovirus ev71 type induced mice has been infected Curative effect test, result shows, black dragon peimine gastric infusion 5 days in dosage 50/100/200mg/kg/day, the depositing of mice 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 dragon peimine in the way of gavage (being administered orally) and Coxsackie viruss a16 type induced mice has been infected Curative effect test, result shows, black dragon peimine gastric infusion 5 days in dosage 50/100/200mg/kg/day, the depositing of mice 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%,
It can be seen that, black dragon peimine is similar to the inhibition of influenza A viruss to positive control drug ribavirin, black dragon Peimine can suppress the duplication of virus, improves the survival rate of virus-infected animal, extends the life span of infection animal, alleviates The disease that virus infection causes, thus have prevention and/or the effect for the treatment of hand-foot-mouth disease.
In order to further illustrate the present invention, the black dragon the peimine with reference to embodiments present invention being provided is in preparation prevention And/or the application in treatment hand-foot-mouth disease medicine is described in detail, but can not be understood as to the scope of the present invention Limit.If no special instructions, reagent used in following examples be commercially available.
The black dragon peimine external anti-hand-foot-and-mouth-disease cytotoxic activity experiment of embodiment 1
1st, experiment material:
Coxsackie viruss a16 type (coxa16) and enterovirns type 71 (ev71), by Chinese People's Liberation Army's military medicine Academy of science's microorganism epidemic research immunological investigation room provides, and is preserved by Jiangsu Kang Yuan R&D of modern TCM institute, thin in vero Pass 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 Preserve.
Dmem culture medium, purchased from Nanjing KaiJi Biology Science Development Co., Ltd, lot number: 20141024, cell growth medium In containing 10% hyclone, 1 × 105U/l penicillin, 100mg/l streptomycin.In cell maintenance medium in addition to containing 2% hyclone, Other same cell growth mediums.Ribavirin, refines medicine, Chinese medicines quasi-word h19993937, specification: 1ml:0.1g purchased from breathing out medicine three, criticizes Number: 140312.
M2e type microplate reader, molecular devices;Pipettor, eppendorf company;Biohazard Safety Equipment, is purchased from Heal force company, model: hfsafe-1200;CO2 gas incubator, purchased from thermo scientific company, type Number: formasteri-cycle 371.
2nd, experimental technique:
Vero cell (African green monkey kidney cell) presses 5 × 10 with the dmem culture medium containing 2% hyclone4Individual/ml concentration Inoculate 96 well culture plates, every hole 100 μ l, put 37 DEG C of 5%co2In incubator, overnight incubation forms cell monolayer.After abandoning supernatant, use Cell is washed 1 time by pbs, to wash away the hyclone of residual, adds and is diluted to the dmem culture medium without hyclone 100tcid50Each strain virus, every hole 100 μ l, after 35 DEG C of incubation 2h, discard virus liquid.Dmem culture medium with 2% hyclone By black dragon peimine be configured to variable concentrations, be separately added in monolayer vero cell, if 3 multiple holes, vero cell in 37 DEG C, 5%co248h, daily observation of cell pathological changes phenomenon is cultivated in incubator.After 48h, after abandoning supernatant, add 100 μ l 10% formaldehyde Fixing 1h, 0.1% (w/v) violet staining 15min, microplate reader 570nm mensuration absorbance.Experiment is repeated 3 times altogether.Calculate black dragon The cc to two kinds of enterovirus cells for the peimine50(half toxic concentration), ec50(medium effective concentration), si (selection index).
Black dragon peimine In vitro antibacterial test (μm) of table 1
Table 1 result shows: black dragon peimine has certain inhibitory action to enterovirus type ev71, coxa16 virus, ec50It is respectively 152.14 μm and 116.87, si and is respectively 5.68 and 7.40, test result indicate that black dragon peimine is to above strain Replication in vitro is inhibited, improves the survival rate of virus infected cell, possesses and is applied to Coxsackie viruss a16, intestinal The Pharmacodynamics in vitro basis of viral 71 type treatment of infection.
The therapeutical effect that the black dragon peimine of embodiment 2 infects to enterovirus ev71
1st, experiment material:
Enterovirns type 71 (ev71), by Academy of Military Medicine, PLA's microorganism epidemic research immunity Learning research department provides, and is preserved by Jiangsu Kang Yuan R&D of modern TCM institute, passes in vero cell culture, -80 DEG C of preservations.
The pregnant Mus of spf level pregnancy balb/c on the 15th~16, purchased from Jiangning county's Qinglongshan laboratory animal breeding field, raise (18~28 DEG C of temperature, 40~70% relative humiditys, mechanical supply and exhaust in ivc system;Light and shade cycle: 12h/12h;150~ 300lux illumination), take 3 age in days Neonatal Mouses to carry out experiment.
Ribavirin, refines medicine purchased from breathing out medicine three, Chinese medicines quasi-word h19993937, specification: 1ml:0.1g, lot number: 140312.
2nd, experimental technique:
3 age in days balb/c neonatal rats 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, except normally right Outer, remaining each group lumbar injection enterovirus ev71 liquid (10 according to group7tcid50) infected, only, each administration group is to fill for 0.1ml/ Stomach is administered, each 0.1ml, continuous 5 days, is all sprayed after neonatal rat parcel bedding and padding with 75% ethanol, put back to after being administered every time or infecting Jointly raise with dams in cage, Normal group and virus control group give distilled water.The daily existence observing neonatal rat after infection State, observes 14d altogether, and the order of severity being infected according to following scale, calculating, 0 point: health;1 point: the back of a bow, perpendicular hair (after growing hair observe), become thin, activity reduces 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.Calculate each group mortality rate and increase in life span and united with spss software Meter analysis.
The black dragon peimine therapeutic administratp of table 2 infects the impact (n=of balb/c neonatal rat gradient of infection to enterovirus ev71 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
The black dragon peimine of table 3 infects the dead protective effect of babl/c neonatal rat to enterovirus ev71
Note: * * p < 0.01, * p < 0.05 is compared with model group
Table 2 result shows, after the black dragon each dosage group of peimine carries out therapeutic, can significantly slow enterovirus What ev71 infection neonatal rat caused becomes thin, hind leg diminished strength, the symptom such as unilateral hindlimb paralysis, its gradient of infection integration and model group Relatively it is respectively provided with significant difference.
The Death prevention rate of the black dragon high, medium and low dosage of peimine is respectively 70%, 40%, 30%, and increase in life span is respectively For 77.51%, 48.53%, 33.66%, show that black dragon peimine each dosage group gradient of infection all significantly reduces enterovirus Ev71 infection neonatal rat mortality rate and gradient of infection, extend its life span, compare with model group with significant difference, point out black Imperial peimine has therapeutical effect to enterovirus ev71 infection.
The therapeutical effect that the black dragon peimine of embodiment 3 infects to Coxsackie viruss coxa16
1st, experiment material:
Coxsackie viruss a16 type (cox a16), is ground by Academy of Military Medicine, PLA's microorganism epidemic diseases Studying carefully immunological investigation room provides, and is preserved by Jiangsu Kang Yuan R&D of modern TCM institute, passes in vero cell culture, -80 DEG C of guarantors Deposit.
The pregnant Mus of spf level pregnancy balb/c on the 15th~16, purchased from Jiangning county's Qinglongshan laboratory animal breeding field, raise (18~28 DEG C of temperature, 40~70% relative humiditys, mechanical supply and exhaust in ivc system;Light and shade cycle: 12h/12h;150~ 300lux illumination), take 3 age in days Neonatal Mouses to carry out experiment.
Ribavirin, refines medicine purchased from breathing out medicine three, Chinese medicines quasi-word h19993937, specification: 1ml:0.1g, lot number: 140312.
2nd, experimental technique:
3 age in days balb/c neonatal rats 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, except normally right Outer, remaining each group lumbar injection Coxsackie viruss coxa16 liquid (10 according to group7tcid50) infected, 0.1ml/, each administration group With gastric infusion, each 0.1ml, continuous 5 days, all spray after neonatal rat parcel bedding and padding with 75% ethanol after being administered every time or infecting, Put back in cage and jointly raise with dams, Normal group and virus control group give distilled water.Daily observation neonatal rat after infection Survival condition, observes 14d altogether, and the order of severity being infected according to following scale, calculating, 0 point: health;1 point: hunchbacked, perpendicular Hair (after growing hair observe), become thin, activity reduces 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.Calculate each group mortality rate and increase in life span and carried out with spss software Statistical analysiss.
The black dragon peimine therapeutic administratp of table 4 infects the impact (n of balb/c neonatal rat gradient of infection to Coxsackie viruss coxa16 =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
The black dragon peimine of table 5 infects the dead protective effect of babl/c neonatal rat to Coxsackie viruss coxa16
Note: * * p < 0.01, * p < 0.05 is compared with model group
Table 4 result shows, after the black dragon each dosage group of peimine carries out therapeutic, can significantly slow Coxsackie viruss What coxa16 infection neonatal rat caused becomes thin, hind leg diminished strength, the symptom such as unilateral hindlimb paralysis, its gradient of infection integration and model Group compares and is respectively provided with significant difference.
The Death prevention rate of the black dragon high, medium and low dosage of peimine is respectively 80%, 50% and 30%, and increase in life span divides Not Wei 89.85%, 52.82% and 34.42%, show black dragon peimine each dosage group gradient of infection all significantly reduce COxsackie disease Malicious coxa16 infection neonatal rat mortality rate and gradient of infection, are extended its life span, are compared with model group with significant difference, carry Show that black dragon peimine has therapeutical effect to the infection of Coxsackie viruss coxa16.
Embodiment 4 black dragon application in preparing capsule medicine for the peimine
By black for 350g dragon peimine and 32g starch, 6g low-substituted hydroxypropyl cellulose, 4.5g micropowder silica gel, 1.5g Hard Fat Sour magnesium and appropriate 10% starch slurry mixing, load capsule, obtain the capsule preparations 1000 of black dragon peimine.3 times a day, often Secondary 1.
Embodiment 5 black dragon application in preparing granules medicine for the peimine
By black for 350g dragon peimine and 1000g sucrose and the mixing of 500g dextrin, conventionally make 1000 Bao Heilong Peimine granule.3 times a day, 1 every time.
Embodiment 6 black dragon application in preparing tablet medicine for the peimine
Will be hard to black for 350g dragon peimine and 50g starch, 7.5g carboxymethyl starch sodium, 0.8g Pulvis Talci, 50g dextrin, 0.8g Fatty acid magnesium and appropriate 10% starch slurry fit mixing, conventionally make black 1000, peimine tablet of dragon.3 times a day, often Secondary 1.
Application in preparation pill medicine for the black dragon peimine of embodiment 7
By black for 350g dragon peimine and 12g PEG-4000,80.5g Tween-80, the mixing of appropriate liquid Paraffin, Conventionally make black dragon peimine pill 1000.3 times a day, 1 every time.
Embodiment 8 black dragon application in preparing injection medicine for the peimine
By black for 200g dragon peimine and 15g injection soybean phospholipid, 25g glycerol for injection, water for injection is settled to 1000ml, conventionally makes black dragon peimine injection 1000.One time a day, 1 every time, at least adopts 250ml Intravenous drip after 5% Glucose Injection dilution.
The above is only the preferred embodiment of the present invention it is noted that ordinary skill people for the art For member, under the premise without departing from the principles of the invention, some improvements and modifications can also be made, these improvements and modifications also should It is considered as protection scope of the present invention.

Claims (10)

1. application in preparation prevention and/or treatment hand-foot-mouth disease medicine for the black dragon peimine.
2. application according to claim 1 is it is characterised in that the described virus causing hand-foot-mouth disease is enterovirus.
3. application according to claim 2 is it is characterised in that described enterovirus are enterovirus ev71 type.
4. application according to claim 2 is it is characterised in that described enterovirus are Coxsackie viruss.
5. application according to claim 4 is it is characterised in that described Coxsackie viruss are Coxsackie viruss a16 type.
6. application according to claim 1 is it is characterised in that the active dose of described black dragon peimine is 50-200mg/ kg/d.
7. application according to claim 1 is it is characterised in that described medicine includes black dragon peimine and pharmaceutically acceptable Carrier;Described pharmaceutical dosage form is any one clinically-acceptable oral administered dosage form, injecting medicine-feeding form or topical administration Preparation.
8. application according to claim 7 is it is characterised in that in the medicine of described oral administered dosage form, black dragon peimine Mass fraction be 17.5-88%.
9. application according to claim 7 is it is characterised in that the daily oral dose of the medicine of described oral administered dosage form For 0.5-2.5mg black dragon peimine/kg body weight.
10. according to claim 7 application it is characterised in that described medicine be tablet, capsule, granule, pill, Liquid preparation, soft extract, suspending agent, dispersant, syrup, suppository, gel, aerosol, patch.
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101721604A (en) * 2008-10-28 2010-06-09 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
CN102327571A (en) * 2011-09-30 2012-01-25 四川大学 New cancer-resisting use of fritillaria cirrhosa total alkaloids and compounds contained in fritillaria cirrhosa total alkaloids
CN105255995A (en) * 2015-11-23 2016-01-20 江苏康缘药业股份有限公司 Hand-foot-and-mouth disease resistant drug activity detection method and kit

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101721604A (en) * 2008-10-28 2010-06-09 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
CN102327571A (en) * 2011-09-30 2012-01-25 四川大学 New cancer-resisting use of fritillaria cirrhosa total alkaloids and compounds contained in fritillaria cirrhosa total alkaloids
CN105255995A (en) * 2015-11-23 2016-01-20 江苏康缘药业股份有限公司 Hand-foot-and-mouth disease resistant drug activity detection method and kit

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
KITAMURA等: "平贝母中的两种新的甾体生物碱", 《国外医药 植物药分册》 *
YUBO LI等: "Metabolomic study to discriminate the different Bulbus fritillariae species using rapid resolution liquid chromatography-quadrupole time-of-flight mass spectrometry coupled with multivariate statistical analysis", 《ANAL. METHODS》 *

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