CN106265658B - Application of the flat shellfish ketone in preparation prevention and/or treatment herpes virus hominis's infection medicine - Google Patents
Application of the flat shellfish ketone in preparation prevention and/or treatment herpes virus hominis's infection medicine Download PDFInfo
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- CN106265658B CN106265658B CN201610666822.2A CN201610666822A CN106265658B CN 106265658 B CN106265658 B CN 106265658B CN 201610666822 A CN201610666822 A CN 201610666822A CN 106265658 B CN106265658 B CN 106265658B
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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
- A61K31/437—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 five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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Abstract
The present invention relates to pharmaceutical technology field, in particular to application of the flat shellfish ketone in preparation prevention and/or treatment herpes virus hominis's infection medicine.The research of the invention finds that flat shellfish ketone can inhibit the duplication of herpes virus hominis, alleviate symptom caused by herpes virus hominis, mitigate death caused by herpes virus hominis's infection, improve survival rate and the Average Survival day of mouse, extending life rate, is in dose-dependence.Show that flat shellfish ketone can effectively prevent and/or treat to infect caused disease by herpes virus hominis.
Description
Technical field
The present invention relates to pharmaceutical technology field, in particular to flat shellfish ketone is in preparation prevention and/or treatment herpes virus hominis's sense
Contaminate the application in drug.
Background technique
Herpes simplex virus (herpes simplex virus, HSV) belongs to herpesviral α subfamily, and serotype has two
Kind human herpesvirus 1's type (HSV-1) and human herpesvirus 2's type (HSV-2).Mainly cause herpes labialis, pharynx after HSV-1 infection human body
Scorching, keratitis, or even the serious diseases such as sporadic encephalitis can be caused；HSV-2 mainly passes through damaged skin and mucosal infections cause
Genital herpes.HSV infection is a kind of common infectious disease of the mankind, and can be in body after both herpes simplex infections
Inside cause long-term latent infection.The anti-herpesvirus medicament of clinical use is mainly nucleoside analog, such as acyclovir, more former times Lip river
Wei etc..But these Antiviral Effects spectrum it is narrow, be also easy to produce drug resistance, side effect is big and expensive, make its clinical application by
Considerable restraint.In recent years, more and more researchers both at home and abroad start to filter out some efficiently anti-blebs from Chinese herbal medicine
The drug of virus, Chinese herbal medicine have many advantages, such as that from a wealth of sources, adverse reaction is few.
Fritillary bulb is the dry bulb of liliaceous plant fritillary bulb Fritillaria ussuriensis Maxim..Flat shellfish
Female also known as level ground shellfish, fritillaria, flat shellfish play the role of clearing heat and moistening lung, relieving cough and reducing sputum, are a kind of conventional Chinese medicine, with bulbus fritillariae cirrhosae, fritillaria thunbergii
Fritillaria is belonged to, but pharmaceutically has certain difference.Flat shellfish ketone (Pingbeinone), structure is shown in formula I, is from fritillary bulb
The composition of alkaloids of middle extraction, pharmacological research show that flat shellfish ketone has antiulcer, eliminating the phlegm, blood pressure lowering and CNS inhibition etc. a variety of
Effect.
The report that flat shellfish ketone is applied in preparation prevention and/or treatment herpes virus hominis's disease medicament is had no at present.
Summary of the invention
In view of this, the present invention provides flat shellfish ketone in preparation prevention and/or treatment herpes virus hominis's infection medicine
Using.Result of study shows that flat shellfish ketone can effectively prevent and/or treat to infect caused disease by herpes virus hominis.
In order to achieve the above-mentioned object of the invention, the present invention the following technical schemes are provided:
The present invention provides application of the flat shellfish ketone in the drug of preparation prevention and/or treatment herpes virus hominis's infection.
In embodiment provided by the invention, herpes virus hominis includes human herpesvirus 1's type and/or human herpesvirus 2's type.
In embodiment provided by the invention, it is herpes labialis, pharyngitis, keratitis that human herpesvirus 1's type, which infects associated diseases,
Or sporadic encephalitis.
In embodiment provided by the invention, it is genital herpes that human herpesvirus 2's type, which infects associated diseases,.
In embodiment provided by the invention, genital herpes are vaginitis caused by people's herpes virus type 2.
Preferably, the active dose of flat shellfish ketone is 20~200mg/kg/d.
Preferably, the active dose of flat shellfish ketone is 30~80mg/kg/d.
In the present invention, the drug for preventing and/or treating herpes virus hominis's infection includes flat shellfish ketone and pharmaceutically acceptable
Carrier.
In the present invention, pharmaceutically acceptable carrier include starch, it is low-substituted hydroxypropyl cellulose, superfine silica gel powder, hard
Fatty acid magnesium, starch slurry, sucrose, dextrin, sodium carboxymethyl starch, talcum powder, polysorbate, polyethylene glycol, injection soybean lecithin
One or more of with glycerol for injection.But present invention is not limited to this, and those skilled in the art think feasible carrier
Type is within the scope of the present invention.
In the present invention, the dosage form prevented and/or treat the drug of herpes virus hominis's infection is that any one clinic can connect
Oral administered dosage form, injecting medicine-feeding form or the topical application received.
Preferably, the mass fraction of flat shellfish ketone is 17.5%~88% in oral administered dosage form.
Preferably, the mass fraction of flat shellfish ketone is 20%~80% in oral administered dosage form.
It is highly preferred that the mass fraction of flat shellfish ketone is 25%~75% in oral administered dosage form.
Preferably, the mass fraction of flat shellfish ketone is 50%~90% in injecting medicine-feeding form.
Preferably, the mass fraction of flat shellfish ketone is 15%~80% in topical application.
Preferably, the dosage form of the drug of prevention and/or treatment herpes virus hominis's infection is oral administered dosage form, daily
Oral dose be the flat shellfish ketone/kg body weight of 3.6~36mg.
Preferably, prevention and/or treatment herpes virus hominis infection drug dosage form be tablet, capsule, granule,
Pill, injection, soft extract, suspending agent, dispersing agent, syrup, suppository, gelling agent, aerosol or patch.
The present invention provides application of the flat shellfish ketone in the drug of preparation prevention and/or treatment herpes virus hominis's infection.This
Invention has the following beneficial effects:
Present invention employs the flat shellfish ketone of colorimetric method for determining to the inhibitory activity of herpes virus hominis HSV-1 and HSV-2, as a result
Show that flat shellfish ketone in vitro infects herpes virus hominis HSV-1 and HSV-2, EC50Respectively 10.96 μm of ol/L, 13.45 μm of ol/
L, SI are respectively 8.7,7.0, the results showed that the cytopathy that flat shellfish ketone induces herpesviral has inhibiting effect, can improve virus
The survival rate of infection cell, antiviral activity are obvious；
The present invention determines flat shellfish ketone to herpes virus hominis in such a way that stomach-filling (oral) and external application (skin) are administered respectively
The therapeutic effect of the infection of guinea pig skin caused by HSV-1, the results showed that, flat shellfish ketone can obviously slow down guinea pig skin infection symptoms,
Shorten cure time；
The present invention also determines flat shellfish ketone to people's blister sore in such a way that stomach-filling (oral) and mucous membrane (vagina) are administered respectively
The therapeutic effect of the inflammation of mouse vagina caused by malicious HSV-2, the results showed that, flat shellfish ketone there is apparent treatment to make mouse vagina inflammation
With, and survival rate and the Average Survival day of mouse, extending life rate can be significantly improved.
By above-mentioned test result it is found that flat shellfish ketone can inhibit the duplication of HSV virus, alleviate symptom caused by HSV virus,
Mitigate death caused by HSV virus infection, improve survival rate and the Average Survival day of mouse, extending life rate, is in dose-dependant
Relationship.Show that flat shellfish ketone can effectively prevent and/or treat to infect caused disease by herpes virus hominis.
Specific embodiment
The invention discloses application of the flat shellfish ketone in preparation prevention and/or treatment herpes virus hominis's infection medicine, abilities
Field technique personnel can use for reference present disclosure, be suitably modified realization of process parameters.In particular, it should be pointed out that all similar replaces
Change and change apparent to those skilled in the art, they are considered as being included in the present invention.Side of the invention
Method and application be described by preferred embodiment, related personnel obviously can not depart from the content of present invention, spirit and
To method described herein and application is modified or appropriate changes and combinations in range, carry out implementation and application the technology of the present invention.
Flat shellfish ketone provided by the invention is used in the application in preparation prevention and/or treatment herpes virus hominis's infection medicine
Biomaterial, reagent or instrument are available on the market.
Flat shellfish ketone of the present invention is preferably flat shellfish one monomers and/or flat shellfish ketone extract.The flat shellfish ketone extracts
In object, the content of the flat shellfish ketone of monomer is preferably 90% or more.The present invention can be conventionally from the Chinese medicine for containing flat shellfish ketone
Or extract and obtain in the prepared slices of Chinese crude drugs, such as fritillary bulb, it also can purchase the commercial goods of flat shellfish ketone.Specifically, in reality of the invention
It applies in example, the flat shellfish ketone of Nat'l Pharmaceutical & Biological Products Control Institute's offer is provided.
The present invention has carried out flat shellfish ketone to guinea pig skin caused by herpes virus hominis HSV-1 in such a way that external application (skin) is administered
The curative effect of infection is tested, the results showed that, flat shellfish ketone is in dosage 20/40/80mg/kg/day percutaneous drug delivery 5 days, with smearing solvent
Dermatotome compare, apply smooth out shellfish ketone dermatotome HSV-1 infection score and recovery from illness number of days significantly reduce, present dose-dependant
Relationship.
The present invention has carried out flat shellfish ketone to guinea pig skin caused by herpes virus hominis HSV-1 in a manner of (oral) administration of stomach-filling
The curative effect of infection is tested, the results showed that, flat shellfish ketone is in dosage 25/50/100mg/kg/day gastric infusion 5 days, with placebo
The dermatotome of group is compared, and the score and recovery from illness number of days for taking orally the HSV-1 infection of flat shellfish ketone group significantly reduce, and dose-dependant is presented and closes
System.
The present invention has carried out flat shellfish ketone to guinea pig skin caused by herpes virus hominis HSV-2 in such a way that mucous membrane (vagina) is administered
The curative effect of infection is tested, the results showed that, flat shellfish ketone is in dosage 38/75/150mg/kg/day vagina administration 10 days, mouse vagina
After inoculation HSV-2 virus, compared with the control group, applies and smooth out shellfish ketone to vagina caused by mouse vagina infection HSV-2 virus
Inflammation has therapeutic effect, and is in dose-dependence.
The present invention has carried out flat shellfish ketone to guinea pig skin caused by herpes virus hominis HSV-2 in a manner of (oral) administration of stomach-filling
The curative effect of infection is tested, the results showed that, flat shellfish ketone and is compareed in dosage 50/100/200mg/kg/day gastric infusion 10 days
Group is compared, and taking orally flat shellfish ketone has therapeutic effect to vaginitis caused by mouse vagina infection HSV-2 virus, and is in dose-dependant
Relationship.
Below with reference to embodiment, the present invention is further explained:
Protective effect of the flat shellfish ketone of embodiment 1 to HSV-1 and HSV-2 infection cell lesion
1, experimental material
Cell and virus: African green monkey kidney cell (Vero cell) is purchased from U.S.'s ATCC cell bank, by the Jiangsu Kang Yuan modern times
Traditional Chinese medicine research institute saves.SM44 plants of 1 type of herpesviral (HSV-1), Sav plants of herpes virus type 2 (HSV-2), by the Chinese Academy of Sciences
Wuhan institute of viruses provides, and 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.
Reagent: acyclovir is purchased from Hubei KeYi Pharmacentic Co., Ltd..DMEM culture medium is purchased from Nanjing Kai Jisheng
Object development in science and technology Co., Ltd, lot number: 20141024,10% fetal calf serum, 1 × 10 are contained in cell growth medium5U/L penicillin,
100mg/L streptomysin.In cell maintenance medium in addition to containing 2% fetal calf serum, other same cell growth mediums.
2, experimental method:
(1) toxicity test of the flat shellfish ketone to Vero cell
Vero cell uses the DMEM culture medium containing 2% fetal calf serum to press 5 × 104A/mL concentration is inoculated with 96 well culture plates, often
100 μ L of hole, sets 37 DEG C of 5%CO2Overnight incubation forms cell monolayer in incubator.Growth-promoting media is abandoned, every hole is added 100 μ L series and passs
Than diluted concentration flat shellfish ketone (25,50,100,200,400 μM) and positive control medicine acyclovir (25,50,100,200,
400 μM) maintaining liquid, each dilution sets 4 multiple holes, while setting up normal cell controls.Set 37 DEG C, 5%CO2, see daily
Cytopathy is examined, 20 μ L MTS are added in every hole after 3d, and 2h is cultivated in 37 DEG C of incubators, and microplate reader surveys the OD value at 490nm.It presses
Following formula calculates various concentration drug to the survival rate of cell, determines the maximal non-toxic concentration and half toxic concentration CC of drug50。
Cell survival rate (%)=(experimental port OD value/control wells OD value) × 100%
(2) inhibiting effect of the flat shellfish ketone to herpes virus hominis HSV-1 and HSV-2
Vero cell uses the DMEM culture medium containing 2% fetal calf serum to press 5 × 104A/mL concentration is inoculated with 96 well culture plates, often
100 μ L of hole, sets 37 DEG C, 5%CO2Overnight incubation forms cell monolayer in incubator.After abandoning supernatant, cell is washed 1 with PBS
It is secondary, to wash away remaining fetal calf serum, the DMEM culture medium without fetal calf serum is added and is diluted to 100TCID50HSV-1/HSV-2
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 by flat shellfish ketone and sun
Property control drug acyclovir 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% are added
Formaldehyde fixes 1h, and 0.1% (w/v) violet staining 15min, microplate reader 570nm measure absorbance.Viral suppression is calculated, and
Flat shellfish ketone is calculated to two kinds of viral EC50(medium effective concentration), SI (selection index).
Viral suppression (%)=[test hole (drug+virus) be averaged A570 value-virus control wells be averaged A570 value]/
(cell control well be averaged A570 value-virus control wells be averaged A570 value) × 100%
SI=CC50/EC50
Test result is shown in Table 1:
Antiviral activity of 1 drug of table to HSV-1/HSV-2
Table 1 is as the result is shown: flat shellfish ketone in vitro has herpes virus hominis's HSV-1 and HSV-2 institute's cytopathogenic effect obvious
Inhibiting effect, EC50Respectively 10.96 μM, 13.45 μM, SI are respectively 8.7,7；Have and is applied to anti-human herpesviral HSV-1
With the Pharmacodynamics in vitro basis of HSV-2 treatment of infection.
The therapeutic effect that the flat shellfish ketone topical administration of embodiment 2 infects guinea pig skin human herpesvirus 1's type
1, experimental material
Reagent: Virless Cream is produced by Changzhou Yabang Pharmaceutical & Chemical Co., Ltd..
Animal: Dunkin-Harthey white hair cavy is purchased from Wuhan Biological Products Inst., Ministry of Public Health
Virus: SM44 plants of 1 type of herpesviral (HSV-1) is provided by Wuhan Virology Institute,Chinan academy of Sciences, by Jiang Sukang
Edge R&D of modern TCM institute saves, and passes in Vero cell culture, -80 DEG C of preservations.
2, experimental method
Dunkin-Harthey white hair cavy, weight 300-350g, male feed 3 green vegetables and feed daily.Experiment shares 12
Cavy, every group 3, is divided into 4 groups, is respectively as follows: acyclovir group, the flat high, medium and low dosage group of shellfish ketone.Every according to feelings
Condition selects 6 dermatotome modelings, administrations.After yellow Jackets anesthesia, guinea pig back is lost hair or feathers according to a conventional method, cleaned, sterilized, used
Guinea pig back is sloughed fur part and is divided into 4 dermatotomes by marker pen.Center intracutaneous injection 10 in each dermatotome7PFU/mL
HSV-1 strain virus, per injection 0.1mL.During anesthesia, animal feeding 2h in 30 DEG C of incubators.4 in acyclovir group
Dermatotome applies acyclovir, and in addition 2 dermatotomes apply the PBS solution (solvent) containing 0.1%Tween-80；The flat high, medium and low dosage of shellfish ketone
Every group of 4 dermatotome of group applies the flat shellfish ketone of various dose, and in addition 2 dermatotomes apply the PBS solution containing 0.1%Tween-80, applies every time
Smearing medical fluid is 30 μ L acyclovir, until waiting pharmaceutical dryings, smears medicine 2 times daily, successive administration 5d.Day by day cavy lesion is observed
Position recovery from illness situation.In order to which the effect of pharmaceutical is giving cavy by the score system (table 2) that Alenius and Oberg is established
After being inoculated with HSV-1 virus, the region of inoculation is pressed symptom score 1 time daily.Scoring and shown with Arabic numerals when bleb occurs,
When bleb starts dry doubling incrustation, scores and use Roman number instead, it is all to carry out with scoring equal double blind, it will be all in course of infection
Arabic and Rome scoring number is added together scoring of being accumulated.Test result is shown in Table 3.
The scoring system of 2 cavy HSV of table infection
Therapeutic effect of the flat shellfish ketone topical administration of table 3 to human simplex virus cutaneous infection of guniea pigs
Note: P < 0.05 * * * P < 0.001, * * P < 0.01, * is compared with model group
Table 3 compared with the dermatotome for smearing solvent, applies the results show that after guinea pig skin inoculation HSV-1 virus and smoothes out shellfish
The score of the HSV-1 infection in the dermatotome of ketone and recovery from illness number of days significantly reduce, and dose-dependence are presented, and have statistics poor
It is different, it prompts flat shellfish ketone that there is therapeutic effect to the HSV-1 infection of guinea pig skin, infection symptoms can be slowed down, shorten cure time.
The therapeutic effect infected guinea pig skin human herpesvirus 1's type is administered orally in the flat shellfish ketone of embodiment 3
1, experimental material
Reagent: acyclovir is purchased from Hubei KeYi Pharmacentic Co., Ltd..
Animal: Dunkin-Harthey white hair cavy is purchased from Wuhan Biological Products Inst., Ministry of Public Health
Virus: SM44 plants of 1 type of herpesviral (HSV-1) is provided by Wuhan Virology Institute,Chinan academy of Sciences, by Jiang Sukang
Edge R&D of modern TCM institute saves, and passes in Vero cell culture, -80 DEG C of preservations.
2, experimental method
Dunkin-Harthey white hair cavy, weight 300-350g, male feed 3 green vegetables and feed daily.Experiment shares 12
Cavy, is divided into 4 groups, grouping is respectively acyclovir group, and the flat high, medium and low dosage group of shellfish ketone, every according to circumstances by every group 3
Select 6 dermatotome modelings, administrations.After yellow Jackets anesthesia, guinea pig back is lost hair or feathers according to a conventional method, is cleaned, disinfection, with mark
Guinea pig back is sloughed fur part and is divided into 4 dermatotomes by note pen.Center intracutaneous injection 10 in each dermatotome7PFU/mL HSV-
1HS-1 strain virus, per injection 0.1mL.During anesthesia, animal feeding 2h in 30 DEG C of incubators.Ah former times after modeling
Luo Wei group and the flat high, medium and low dosage group of shellfish ketone are according to the progress gastric infusion of dosage described in table 4, every each 0.2mL, comfort
Agent group is replaced, successive administration 5d with the PBS solution (containing 0.1%Tween-80) of equivalent.Day by day observation cavy diseased region recovery from illness
Situation.In order to which the effect of pharmaceutical is giving cavy inoculation HSV-1 virus by the score system that Alenius and Oberg is established
Afterwards, the region of inoculation is pressed symptom score 1 time daily.Scoring when bleb occurs is shown with Arabic numerals, when bleb hops to it
And when forming a scab, scores and use Roman number instead, it is all to carry out with scoring equal double blind, by Arab all in course of infection and Rome
Scoring number is added together scoring of being accumulated.It the results are shown in Table 4.
The therapeutic effect to human simplex virus cutaneous infection of guniea pigs is administered orally in the flat shellfish ketone of table 4
Note: P < 0.05 * * * P < 0.001, * * P < 0.01, * is compared with model group
Table 4 compared with the dermatotome of placebo, takes orally Ah former times the results show that after guinea pig skin inoculation HSV-1 virus
The score of the HSV-1 infection of Luo Wei group and recovery from illness number of days significantly reduce；Similar, compared with the dermatotome of placebo, take orally
The score of the HSV-1 infection of flat shellfish ketone group and recovery from illness number of days significantly reduce, and dose-dependence are presented, and have statistics poor
It is different, it prompts flat shellfish ketone that there is therapeutic effect to the HSV-1 infection of guinea pig skin, infection symptoms can be slowed down, shorten cure time.
The treatment that the flat shellfish ketone mucosa delivery of embodiment 4 infects vaginitis caused by human herpesvirus 2's type to mouse vagina is made
With
1, experimental material
Reagent: Virless Cream is produced by Changzhou Yabang Pharmaceutical & Chemical Co., Ltd..
Animal: BALB/c mouse, female, Jiangning county Qinglongshan animal reproduction field.
Virus: Sav plants of herpes virus type 2 (HSV-2) is provided by Wuhan Virology Institute,Chinan academy of Sciences, by Jiang Sukang
Edge R&D of modern TCM institute saves, and passes in Vero cell culture, -80 DEG C of preservations.
2, experimental method
BALB/c mouse female 50, is randomly divided into 5 groups by weight, removes control group, and every group of mouse will be inhaled with ophthalmology tweezers
Gelfoam fritter with virus liquid 0.03mL (10LD50) is sent into mouse vagina, and Normal group uses sterile PBS solution instead,
Each administration group smears Virless Cream or high, medium and low dose of flat shellfish ketone in intravaginal and external genital respectively after mouse infection 2h
Amount treatment, administration number of days are 10 days, and virus control group awards smearing emulsifiable paste matrix.Dead mouse number, life number of days are observed, is calculated
Mouse survival rate, average life day, extending life rate.Test result is shown in Table 5.
The flat shellfish ketone mucosa delivery of table 5 to the therapeutic effect of Balb/c mouse HSV-2 vaginitis (n=10,)
Note: P < 0.05 * * * P < 0.001, * * P < 0.01, * is compared with model group
Table 5 compared with the control group, applies the results show that after mouse vagina inoculation HSV-2 virus and smoothes out shellfish ketone to mouse
Vaginitis caused by vagina infection HSV-2 virus has therapeutic effect, and is in dose-dependence, and each dosage group can be mentioned obviously
The survival rate of high mouse and Average Survival day, extending life rate.
The treatment that the oral administration of the flat shellfish ketone of embodiment 5 infects vaginitis caused by human herpesvirus 2's type to mouse vagina is made
With
1, experimental material
Reagent: acyclovir is purchased from Hubei KeYi Pharmacentic Co., Ltd..
Animal: BALB/c mouse, female, Jiangning county Qinglongshan animal reproduction field.
Virus: Sav plants of herpes virus type 2 (HSV-2) is provided by Wuhan Virology Institute,Chinan academy of Sciences, by Jiang Sukang
Edge R&D of modern TCM institute saves, and passes in Vero cell culture, -80 DEG C of preservations.
2, experimental method
BALB/c mouse female 50, is randomly divided into 5 groups by weight average, removes control group, every group of mouse ophthalmology tweezers
The gelfoam fritter that virus liquid 0.03mL (10LD50) will be adsorbed with is sent into mouse vagina, and Normal group uses sterile PBS instead
Solution, acyclovir and the flat high, medium and low dosage of shellfish ketone are given in stomach-filling to each administration group respectively after mouse infection 2h, and administration number of days is
10 days, physiological saline was given in virus control group stomach-filling.Dead mouse number, life number of days are observed, mouse survival rate, average life are calculated
Day, extending life rate living.Test result is shown in Table 6.
The flat shellfish ketone of table 6 be administered orally to the therapeutic effect of Balb/c mouse HSV-2 vaginitis (n=10,)
Note: P < 0.05 * * * P < 0.001, * * P < 0.01, * is compared with model group
Table 6 compared with the control group, takes orally flat shellfish ketone to mouse the results show that after mouse vagina inoculation HSV-2 virus
Vaginitis caused by vagina infection HSV-2 virus has therapeutic effect, and is in dose-dependence, and each dosage group can be mentioned obviously
The survival rate of high mouse and Average Survival day, extending life rate.
The flat shellfish ketone of embodiment 6 is preparing the application in capsule medicine
By the flat shellfish ketone of 350g and 32g starch, 6g low-substituted hydroxypropyl cellulose, 4.5g superfine silica gel powder, 1.5g magnesium stearate
And appropriate 10% starch slurry mixing, it is packed into capsule, obtains capsule preparations 1000 of flat shellfish ketone.3 times a day, 1 tablet each time.
The flat shellfish ketone of embodiment 7 is preparing the application in granules medicine
The flat shellfish ketone of 350g and 1000g sucrose and 500g dextrin are mixed, 1000 Bao Pingbei ketone are conventionally made
Granula.3 times a day, 1 tablet each time.
The flat shellfish ketone of embodiment 8 is preparing the application in tablet medicine
By the flat shellfish ketone of 350g and 50g starch, 7.5g sodium carboxymethyl starch, 0.8g talcum powder, 50g dextrin, 0.8g stearic acid
Magnesium and the suitable mixing of appropriate 10% starch slurry, are conventionally made flat 1000, shellfish ketone tablet.3 times a day, 1 tablet once.
Application of the flat shellfish ketone of embodiment 9 in preparation pill medicine
The flat shellfish ketone of 350g and 12g polyethylene glycol-6000,80.5g Tween-80, appropriate liquid paraffin are mixed, according to
Conventional method is made flat shellfish ketone pill 1000.3 times a day, 1 tablet each time.
The flat shellfish ketone of embodiment 10 is preparing the application in injection medicine
The flat shellfish ketone of 200g and 15g injection soybean lecithin, 25g glycerol for injection, water for injection are settled to 1000mL, pressed
More solito is made flat shellfish ketone injection 1000.One time a day, every time 1,5% glucose injection of 250mL is at least used
Intravenous drip after liquid dilution.
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 (9)
1. application of the flat shellfish ketone as sole active composition in preparation prevention and/or treatment herpes virus hominis's infection medicine；
The herpes virus hominis includes human herpesvirus 1's type and/or human herpesvirus 2's type.
2. application according to claim 1, which is characterized in that human herpesvirus 1's type infection associated diseases are lip blister
Rash, pharyngitis, keratitis or sporadic encephalitis.
3. application according to claim 1, which is characterized in that human herpesvirus 2's type infection associated diseases are reproduction
Device bleb.
4. application according to claim 1, which is characterized in that the active dose of the flat shellfish ketone is 20~200mg/kg/
d。
5. application according to any one of claim 1 to 4, which is characterized in that the drug includes flat shellfish ketone and pharmacy
Upper acceptable carrier.
6. application according to claim 5, which is characterized in that the dosage form of the drug is that any one is clinically-acceptable
Oral administered dosage form, injecting medicine-feeding form or topical application.
7. application according to claim 6, which is characterized in that the mass fraction of flat shellfish ketone is in the oral administered dosage form
17.5%~88%.
8. application according to claim 6 or 7, which is characterized in that the dosage form of the drug is oral administered dosage form, every
It oral dose is the flat shellfish ketone/kg body weight of 3.6~36mg.
9. application according to claim 1, which is characterized in that the dosage form of the drug be tablet, capsule, granule,
Pill, injection, soft extract, suspending agent, dispersing agent, syrup, suppository, gelling agent, aerosol or patch.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610666822.2A CN106265658B (en) | 2016-08-12 | 2016-08-12 | Application of the flat shellfish ketone in preparation prevention and/or treatment herpes virus hominis's infection medicine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201610666822.2A CN106265658B (en) | 2016-08-12 | 2016-08-12 | Application of the flat shellfish ketone in preparation prevention and/or treatment herpes virus hominis's infection medicine |
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