CN107714642A - A kind of oral solution of EV71 viruses and CVA16 viral inhibitors and preparation method thereof - Google Patents
A kind of oral solution of EV71 viruses and CVA16 viral inhibitors and preparation method thereof Download PDFInfo
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- 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
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- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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Abstract
The invention provides oral solution of EV71 viruses and CVA16 viral inhibitors (TJAB 1099) and preparation method thereof, preparation method includes:TJAB 1099 is dissolved in including polyethylene glycol, one or more combination of glycerine and tween and the in the mixed solvent of second alcohol and water, then pharmaceutically acceptable auxiliary material is added, the oral solutions of TJAB 1099 are made, this method preparation technology is simple, and the obtained oral solutions of TJAB 1099 have drug dispersion big, active ingredient is uniformly dispersed, absorb fast, effect is rapid, it is easy to divided dose, the characteristics of bioavilability is high, and the oral solution mouthfeel is good, it is convenient to take, compliance is good, suitable children and old man's medication, the antiviral drugs of hand-foot-and-mouth disease can be widely used as.
Description
Technical field
The present invention relates to field of medicaments, in particular to a kind of EV71 viruses and CVA16 viral inhibitors (TJAB-
1099) oral solution and preparation method thereof.
Background technology
People's hand-foot-and-mouth disease (Hand-foot-mouth disease, HFMD) is common acute infectious disease, and is distributed in complete
Ball.Hand-foot-and-mouth disease incubation period is 2-10 days, and average 3-5 days, the course of disease is generally 7-10 days.Occur heating paresthesia, oral cavity during onset
Mucous membrane occurs being dispersed in bleb, and maculopapule, bleb occur in brothers and buttocks, can there is inflammatory blush around bleb, and liquid is less in blister.
And with symptoms such as cough, runny nose, poor appetites.A small number of cases, particularly EV71 infect infant, may occur in which meningitis, encephalitis,
Encephalomyelitis, neurogenic pulmonary edema, dyshaemia etc., the state of an illness is dangerous, lethal can die or leave sequelae.Cause people's brothers' mouth
Disease virus be:2,4,5,7,9,10,16 types of Coxsackie virus A group (Coxasckievirus A, CVA) etc.;COxsackie disease
1,2,3,4,5 types of malicious B groups (Coxasckievirus B, CVB) etc.;Enterovirns type 71 (Human Enterovirus 71,
EV71);Echovirus (Echovirus, ECHO) etc..It is wherein relatively conventional with EV71 and CVA16 types.Existing conventional treatment brothers
The antiviral drugs of stomatosis has:ACV, GCV, interferon, Ribavirin etc., mostly broad-spectrum antiviral medicament, nothing
Specificity.
EV71 viruses and CVA16 viral inhibitors (TJAB-1099) are Tianjin International Joint Academy of Biotechnology & Medicine presidents
Rao Zi and one kind of team's research and development are for hand-foot-mouth disease EV 71 virus and the highly efficient depressor of CVA16 viruses.Pass through EV71 viruses
With the high-resolution three-dimensional structure of CVA16 viruses, have devised a kind of can suppress EV71 viruses and CVA16 viruses are undressed shell process
Novel compounds-TJAB-1099, the patent No.:CN104744433 A (data of publication of application:On July 1st, 2015).The compound
Duplication of the EV71 viruses in human body can be effectively blocked, is drawn so as to specifically treat by EV71 viruses and CVA16 viruses
The hand-foot-and-mouth disease risen.But TJAB-1099 is a kind of compound of water-insoluble, its water solubility limits its oral absorption rate,
Its clinical practice and formulation development is set to be greatly limited.
Oral solution refers to that one or more medicines are dissolved into solution supplies oral liquid preparation.Oral solution because
The decentralization of medicine is big, absorption is fast, effect is rapid, there is good bioavilability, active ingredient to be uniformly dispersed, energy correct amount
The characteristics of taking use, mouthfeel good, convenient to take, especially favored by children and gerontal patient.
The content of the invention
The problem of in correlation technique, the invention provides a kind of EV71 viruses and CVA16 viral inhibitors (TJAB-
1099) oral solution, to provide, a kind of drug dispersion is big, active ingredient is uniformly dispersed, absorbs fast, effect rapidly, raw
The high TJAB-1099 oral solutions of thing availability.
The invention provides a kind of TJAB-1099 oral solutions, including:EV71 viruses and CVA16 viral inhibitors
(TJAB-1099), shown in TJAB-1099 chemical formula such as formula (1), wherein, R is selected from H, C1-6Alkyl or C1-6Alkyl amino;It is molten
Agent, solvent include polyethylene glycol (PEG), one or more combination of glycerine and tween and second alcohol and water;And pharmaceutically
Acceptable auxiliary material.
In above-mentioned TJAB-1099 oral solutions, solvent includes ethanol, polyethylene glycol, glycerine, tween and water, wherein,
By volume fraction, ethanol proportion is 10%~50%, and polyethylene glycol proportion is 5%~25%, glycerine proportion
For 5%~30%, tween proportion is 1%~20%, and water proportion is 10%~50%.
In above-mentioned TJAB-1099 oral solutions, polyethylene glycol is polyethylene glycol 400, and tween is Tween 80, and water is steaming
Distilled water.
In above-mentioned TJAB-1099 oral solutions, 200~300mg TJAB- is dissolved with every 100mL solutions
1099。
In above-mentioned TJAB-1099 oral solutions, pharmaceutically acceptable auxiliary material includes colouring agent, flavouring and pH and adjusted
Save agent.
In above-mentioned TJAB-1099 oral solutions, colouring agent includes beta carotene, amaranth, lemon yellow or indigo,
Wherein, 0.01~0.09g colouring agent is dissolved with every 100mL solutions.
In above-mentioned TJAB-1099 oral solutions, flavouring include Sucralose, sorbierite, mannitol, saccharin sodium,
Aspartame or stevioside, wherein, the flavouring dissolved with 0.01~0.09g in every 100mL solutions.
In above-mentioned TJAB-1099 oral solutions, pH adjusting agent includes sodium hydroxide, potassium carbonate, sodium carbonate, citric acid
Potassium, sodium citrate or disodium hydrogen phosphate, wherein, the pH adjusting agent dissolved with 0.01~0.09g in every 100mL solutions.
Some embodiments of the present invention additionally provide a kind of method for preparing above-mentioned TJAB-1099 oral solutions, including:
By TJAB-1099 dissolvings in a solvent, mixed solution is made after stirring and evenly mixing, then adds pharmaceutically acceptable auxiliary material, stirs
Mix to being completely dissolved, obtain TJAB-1099 oral solutions, wherein, solvent include polyethylene glycol, glycerine and tween one kind or
A variety of combinations and second alcohol and water.
In the preparation method of above-mentioned TJAB-1099 oral solutions, pharmaceutically acceptable auxiliary material includes colouring agent, rectified
Taste agent and pH adjusting agent.
In the preparation method of above-mentioned TJAB-1099 oral solutions, by TJAB-1099 dissolvings in ethanol, stirring is extremely
After being completely dissolved, glycerine, polyethylene glycol or tween are added, after mixing, adds water, mixed solution is made.
In the preparation method of above-mentioned TJAB-1099 oral solutions, pH adjusting agent is added into mixed solution, will be mixed
The pH of solution is adjusted to 7.5~8.5, then adds colouring agent and flavouring.
Then the present invention adds pharmaceutically acceptable auxiliary material to make by the way that TJAB-1099 is dissolved in into the mixed solvent
A kind of standby TJAB-1099 oral solutions.The TJAB-1099 oral solutions have that drug dispersion is big, active ingredient is disperseed
Uniformly, infiltration rate is fast, effect is rapid, bioavilability is high, be easy to divided dose, prepares that easy, mouthfeel is good, convenient to take excellent
Point.It is especially suitable for the antiviral drugs that child patient is used as hand-foot-and-mouth disease.Because TJAB-1099 in the formulation completely with
Molecular level is dispersed in solution medium.Relative to solid dosage form formulation, the process of dissolution is eliminated so that TJAB-
1099 molecules are transported to rapidly intestinal mucosa.Due to the relative high-permeability of TJAB-1099 molecules, make its rapidly transmembrane transport
To the circulatory system, and then relative solid pharmaceutical preparation, add its bioavilability.In addition, liquid preparation divided dose is convenient, reduce
The metering difference that fuzzy application method of " children taking halves " this kind of solid pharmaceutical preparation in children is brought.So that children
Medication is more safe and effective.Further, flavouring can be conveniently added with liquid preparation, mouthfeel, convenient for children patient clothes are adjusted
With.
Brief description of the drawings
In order to illustrate more clearly about the embodiment of the present invention or technical scheme of the prior art, below will be to institute in embodiment
The accompanying drawing needed to use is briefly described, it should be apparent that, drawings in the following description are only some implementations of the present invention
Example, for those of ordinary skill in the art, on the premise of not paying creative work, can also be obtained according to these accompanying drawings
Obtain other accompanying drawings.
Fig. 1 is mean blood plasma concentration-time plot to rat intravenous injection TJAB-1099 oral solutions.
Fig. 2 is mean blood plasma concentration-time plot to rat oral gavage administration TJAB-1099 oral solutions.
Embodiment
Below in conjunction with the accompanying drawing in the embodiment of the present invention, the technical scheme in the embodiment of the present invention is carried out clear, complete
Site preparation describes, it is clear that described embodiment is only the part of the embodiment of the present invention, rather than whole embodiments.Base
Embodiment in the present invention, the every other embodiment that those of ordinary skill in the art are obtained, belongs to protection of the present invention
Scope.
The side of the oral solution provided by the invention for preparing EV71 viruses and CVA16 viral inhibitors (TJAB-1099)
Method, comprise the following steps:
First, by EV71 viruses and CVA16 viral inhibitors (TJAB-1099) dissolving in a solvent, mixed solution is made.
Wherein, solvent includes polyethylene glycol, one or more combination of glycerine and tween and second alcohol and water.In this step, lead to
Cross TJAB-1099 dissolvings in ethanol, stir to after being completely dissolved, add glycerine, polyethylene glycol or tween, after mixing, then
Water is added to dissolve TJAB-1099 in a solvent.In this step, the solvent include 5%~25% polyethylene glycol (if
Have), 5%~30% glycerine (if having) and one or more combination of 1%~20% tween (if having) and 10%~
50% ethanol and 10%~50% water.Wherein, 200~300mg TJAB-1099 is dissolved with every 100mL solvents.
Secondly, auxiliary material is added into above-mentioned mixed solution.Wherein, auxiliary material includes colouring agent, flavouring and pH adjusting agent.
In the step, pH adjusting agent is added into above-mentioned mixed solution, the pH of mixed solution is adjusted to 7.5~8.5, then added
Colouring agent and flavouring.Wherein, colouring agent includes beta carotene, amaranth, lemon yellow or indigo, and flavouring includes trichlorine sugarcane
Sugar, sorbierite, mannitol, saccharin sodium, aspartame or stevioside, pH adjusting agent include sodium hydroxide, potassium carbonate, sodium carbonate,
Potassium citrate, sodium citrate or disodium hydrogen phosphate.Wherein, 0.01~0.09g coloring is dissolved with every 100mL solvents respectively
The pH adjusting agent of agent, 0.01~0.09g flavouring and 0.01~0.09g.
Finally, by the above-mentioned packing of above-mentioned TJAB-1099 oral solutions, the labelling prepared.
The bioavilability of the TJAB-1099 oral solutions of gained is measured.
The preparation method of TJAB-1099 oral solutions provided by the invention, by the way that TJAB-1099 is dissolved in into solvent
In, pharmaceutically acceptable auxiliary material is then added to prepare TJAB-1099 oral solutions, and this method preparation technology is simple, fits
Industry's enlarging production is closed, and obtained TJAB-1099 oral solutions have that drug dispersion is big, active ingredient is scattered equal
It is even, absorb that fast, effect is rapid, is easy to divided dose, the characteristics of bioavilability is high, solve because TJAB-1099 water is insoluble
The problem of oral absorption rate is low caused by property, and the oral solution mouthfeel is good, convenient to take, compliance is good, suitable youngster
Virgin and old man's medication, the antiviral drugs of hand-foot-and-mouth disease can be widely used as.
The present invention is specifically addressed below in conjunction with specific case study on implementation, but protection scope of the present invention is not limited only to
This.
Embodiment 1:The preparation of the oral solution of EV71 viruses and CVA16 viral inhibitors (TJAB-1099)
TJAB-1099 raw material 0.25g are weighed, ethanol 42ml is added, stirs to TJAB-1099 and be completely dissolved, continuously add
Tween 14mL, stirs, and adds distilled water to 100mL, adds sodium citrate regulation pH to 8.0.Into above-mentioned solution slowly
Add 0.02g beta carotenes and 0.02g sorbierites are stirred to whole dissolvings;Packing, labelling.
Embodiment 2:The preparation of the oral solvent of EV71 viruses and CVA16 viral inhibitors (TJAB-1099)
TJAB-1099 raw material 0.25g are weighed, ethanol 42ml is added, stirs to TJAB-1099 and be completely dissolved, continuously add
Tween 80 5mL, PEG400 17mL;Stir, add distilled water to 100mL, add potassium carbonate regulation pH to 7.8.Upwards
State and 0.05g lemon yellows are slowly added in solution and 0.01g saccharin sodiums are stirred to whole dissolvings;Packing, labelling.
Embodiment 3:The preparation of the oral solvent of EV71 viruses and CVA16 viral inhibitors (TJAB-1099)
TJAB-1099 raw material 0.25g are weighed, ethanol 42mL is added, stirs to TJAB-1099 and be completely dissolved, continuously add
Glycerine 28mL, Tween 80 12mL;Stir, add distilled water to 100mL, add sodium hydroxide regulation pH to 8.5.Upwards
State and be slowly added to that 0.09g is indigo and 0.04g aspartames are stirred to whole dissolvings in solution;Packing, labelling.
Embodiment 4:The preparation of EV71 viruses and CVA16 viral inhibitors (TJAB-1099) oral solution
TJAB-1099 raw material 0.25g are weighed, ethanol 42mL is added, stirs to TJAB-1099 and be completely dissolved, continuously add
Glycerine 21mL, PEG400 17mL;Stir, add distilled water to 100mL, add sodium carbonate regulation pH to 8.2.To above-mentioned
0.06g beta carotenes are slowly added in solution and 0.09g sorbierites are stirred to whole dissolvings;Packing, labelling.
Embodiment 5:The preparation of EV71 viruses and CVA16 viral inhibitors (TJAB-1099) oral solution
TJAB-1099 raw material 0.2g are weighed, ethanol 10mL is added, stirs to TJAB-1099 and be completely dissolved, continuously add
PEG 5mL, polysorbas20 mL, glycerine 30mL;Stir, add distilled water to 100mL, add disodium hydrogen phosphate adjust pH to
7.5.0.01g amaranths are slowly added into above-mentioned solution and 0.05g mannitol is stirred to whole dissolvings;Packing, labelling.
Embodiment 6:The preparation of EV71 viruses and CVA16 viral inhibitors (TJAB-1099) oral solution
TJAB-1099 raw material 0.3g are weighed, ethanol 50mL is added, stirs to TJAB-1099 and be completely dissolved, continuously add
PEG 400 25mL, tween 1mL, glycerine 5mL;Stir, add distilled water to 100mL, add potassium citrate adjust pH to
8.0.0.06g beta carotenes are slowly added into above-mentioned solution and 0.09g sorbierites are stirred to whole dissolvings;Packing, labeling
Label.
The bioavilability of the TJAB-1099 oral solutions of gained is measured:
By the preparation method of the TJAB-1099 oral solutions described in embodiment 1, obtained 2.5mg/mL oral administration solution
Agent, rat is carried out to be injected intravenously administration and gastric infusion.
Intravenous injection administration, orbital venous plexus blood sampling time point are:0min, 2min after administration, 5min, 15min, 30min,
45min、1h、1.5h、2h、4h.Gastric infusion, orbital venous plexus blood sampling time point are:0min, 15min after administration, 30min,
45min、1h、1.5h、2h、4h、6h、8h.Centrifuged immediately after taking blood, take blood plasma to be placed in -20 DEG C of refrigerator freezings, it is to be measured.
During measure, 50 μ L plasma samples are taken, add 200 μ L IS (100ng/mL RMI 9918s, methanol/acetonitriles (1:1) it is molten
Liquid), vortex mixed 30s, centrifugation 10min (10000rpm) takes supernatant 100ul, adds 100ul methanol/waters (1:1) solution, whirlpool
Stream mixes, and takes the μ l of sample solution 5 that instrument is used in conjunction with Waters Quattro Premier XE/Acquity UPLC liquid matter and is determined
Amount analysis.
Pharmacokinetic parameter after intravenous injection administration is as shown in table 1, and the pharmacokinetic parameter after gastric infusion is such as
Shown in table 2.Mean blood plasma concentration-time graph after oral solution is injected intravenously as shown in figure 1, gastric infusion oral administration solution
Mean blood plasma concentration-time graph after agent is as shown in Figure 2.In Fig. 1, the shape of blood concentration-time curve shows TJAB-
1099 in the organ rich in blood (such as:Liver) in release rate it is fast, eliminated in peripheral tissues slower.In fig. 2, solution
Cmax reaches 118.99 μ g/L, AUC (0-t) and reaches 379.18 μ g/L*h after agent gastric infusion, compared to bulk drug gastric infusion
Afterwards entirely without exposure, significantly increase.In addition, the figure also shows that peak time is short in TJAB-1099 bodies, meets insoluble medicine
The universal law of absorption.
The pharmacokinetic parameter of table 1.TJAB-1099 solutions intravenous injection administration
It can be seen that, calculated by table 1 by pharmacokinetic parameter, the medicine of its intravenously administrable is for parameter T1/2Show TJAB-
Time required for 1099 plasma drug levels remove half is about 0.5h.Clearance values show TJAB-1099 in vivo
The speed of removing;Vd numerical value is relatively small, shows that abundances of the TJAB-1099 in peripheral organization is less.
The pharmacokinetic parameter of table 2.TJAB-1099 solution gastric infusions
By table 2, it can be seen that, the medicine of gastric infusion is for parameter Cmax、TmaxShow that TJAB-1099 peak times are short, concentration
It is low, illustrate that it is not absorbed fully.Because although the effect of the polymolecularity of solution in itself, can cause TJAB-
The absorption of 1099 solutions exposes relative to after bulk drug gastric infusion entirely without internal, there is significant raising.But due to
TJAB-1099's is insoluble, after making it into intestines and stomach, in this case it is still possible to which part separates out, and causes absorption not abundant enough.In addition,
The metabolism of complicated enzyme system and liver is even more to cause the main factor that TJAB-1099 is not fully absorbed in intestines and stomach.
We allow TJAB-1099 not soluble in water to be noted by tail vein by preparing TJAB-1099 oral solutions
Penetrate administration.TJAB-1099 adds its bioavilability after oral solution is made, and reaches its absolute bioavailability
5.84%, the effect of so as to enhance it.
Claims (12)
- A kind of 1. oral solution of EV71 viruses and CVA16 viral inhibitors TJAB-1099, it is characterised in that including:Shown in EV71 viruses and CVA16 viral inhibitors TJAB-1099, the TJAB-1099 chemical formula such as formula (1), wherein, R is selected from H, C1-6Alkyl or C1-6Alkyl amino;Solvent, the solvent include polyethylene glycol, one or more combination of glycerine and tween and second alcohol and water;And medicine Acceptable auxiliary material on.
- 2. the oral solution of EV71 viruses according to claim 1 and CVA16 viral inhibitors TJAB-1099, it is special Sign is that the solvent includes ethanol, polyethylene glycol, glycerine, tween and water, wherein, by volume fraction, ethanol institute accounting Example is 10%~50%, and the polyethylene glycol proportion is 5%~25%, and the glycerine proportion is 5%~30%, institute It is 1%~20% to state tween proportion, and the water proportion is 10%~50%.
- 3. the oral solution of EV71 viruses according to claim 1 and CVA16 viral inhibitors TJAB-1099, it is special Sign is that the polyethylene glycol is polyethylene glycol 400, and the tween is Tween 80, and the water is distilled water.
- 4. the oral solution of EV71 viruses according to claim 1 and CVA16 viral inhibitors TJAB-1099, it is special Sign is, the 200~300mg TJAB-1099 is dissolved with solution described in per 100mL.
- 5. the oral solution of EV71 viruses according to claim 1 and CVA16 viral inhibitors TJAB-1099, it is special Sign is that the pharmaceutically acceptable auxiliary material includes colouring agent, flavouring and pH adjusting agent.
- 6. the oral solution of EV71 viruses according to claim 5 and CVA16 viral inhibitors TJAB-1099, it is special Sign is that the colouring agent includes beta carotene, amaranth, lemon yellow or indigo, wherein, it is molten in solution described in per 100mL Solution has the 0.01~0.09g colouring agent.
- 7. the oral solution of EV71 viruses according to claim 5 and CVA16 viral inhibitors TJAB-1099, it is special Sign is that the flavouring includes Sucralose, sorbierite, mannitol, saccharin sodium, aspartame or stevioside, wherein, often 0.01~0.09g the flavouring is dissolved with solution described in 100mL.
- 8. the oral solution of EV71 viruses according to claim 5 and CVA16 viral inhibitors TJAB-1099, it is special Sign is that the pH adjusting agent includes sodium hydroxide, potassium carbonate, sodium carbonate, potassium citrate, sodium citrate or disodium hydrogen phosphate, Wherein, the 0.01~0.09g pH adjusting agent is dissolved with solution described in every 100mL.
- 9. a kind of prepare EV71 viruses according to any one of claims 1 to 8 with CVA16 viral inhibitors TJAB-1099's The method of oral solution, it is characterised in that including:By TJAB-1099 dissolvings in a solvent, it is molten that mixing is made after stirring and evenly mixing Liquid, pharmaceutically acceptable auxiliary material is then added, stir to being completely dissolved, obtain TJAB-1099 oral solutions, wherein, institute Stating solvent includes polyethylene glycol, one or more combination of glycerine and tween and second alcohol and water.
- 10. according to the method for claim 9, it is characterised in that the pharmaceutically acceptable auxiliary material includes colouring agent, rectified Taste agent and pH adjusting agent.
- 11. according to the method for claim 9, it is characterised in that the TJAB-1099 is dissolved in the ethanol, stirred Mix to after being completely dissolved, add the glycerine, the polyethylene glycol or the tween, after mixing, add water, be made described mixed Close solution.
- 12. according to the method for claim 10, it is characterised in that the pH adjusting agent is added into the mixed solution, The pH of the mixed solution is adjusted to 7.5~8.5, then adds the colouring agent and the flavouring.
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Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108295069A (en) * | 2018-05-10 | 2018-07-20 | 天津国际生物医药联合研究院 | A kind of application of inhibitor in the drug and sterile products for preparing anti-hand-foot-and-mouth-disease |
CN109394682A (en) * | 2018-11-21 | 2019-03-01 | 天津国际生物医药联合研究院 | It is a kind of for treating the pharmaceutical preparation and preparation method thereof of people's hand-foot-and-mouth disease |
CN109867636A (en) * | 2018-07-02 | 2019-06-11 | 北京赫尔默技术有限公司 | A kind of compound and its synthetic method of anti-CVA16 type hand-foot-and-mouth disease |
WO2019216829A1 (en) * | 2018-05-10 | 2019-11-14 | Temasek Life Sciences Laboratory Limited | Application of a food azo dye, brilliant black bn, on inhibition of infectivity of human enteroviruses causing hand foot and mouth diseases |
KR102305665B1 (en) * | 2020-08-10 | 2021-09-28 | (주)네이처페어리 | Antiviral or antibacterial compositions comprising Dendropanax morbiferus |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104744433A (en) * | 2013-12-30 | 2015-07-01 | 中国科学院生物物理研究所 | ALD and application thereof as EV71 virus and CAV16 virus inhibitor |
-
2017
- 2017-09-19 CN CN201710852008.4A patent/CN107714642A/en active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104744433A (en) * | 2013-12-30 | 2015-07-01 | 中国科学院生物物理研究所 | ALD and application thereof as EV71 virus and CAV16 virus inhibitor |
Non-Patent Citations (1)
Title |
---|
候惠民: "《药物辅料应用技术》", 31 July 2002 * |
Cited By (7)
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CN108295069A (en) * | 2018-05-10 | 2018-07-20 | 天津国际生物医药联合研究院 | A kind of application of inhibitor in the drug and sterile products for preparing anti-hand-foot-and-mouth-disease |
WO2019216829A1 (en) * | 2018-05-10 | 2019-11-14 | Temasek Life Sciences Laboratory Limited | Application of a food azo dye, brilliant black bn, on inhibition of infectivity of human enteroviruses causing hand foot and mouth diseases |
CN112384225A (en) * | 2018-05-10 | 2021-02-19 | 淡马锡生命科学实验室有限公司 | Application of edible azo dye brilliant black BN in inhibiting infectivity of human enteroviruses causing hand-foot-and-mouth disease |
CN109867636A (en) * | 2018-07-02 | 2019-06-11 | 北京赫尔默技术有限公司 | A kind of compound and its synthetic method of anti-CVA16 type hand-foot-and-mouth disease |
CN109867636B (en) * | 2018-07-02 | 2020-05-15 | 北京赫尔默技术有限公司 | Compound for resisting CVA16 type hand-foot-and-mouth disease and synthetic method thereof |
CN109394682A (en) * | 2018-11-21 | 2019-03-01 | 天津国际生物医药联合研究院 | It is a kind of for treating the pharmaceutical preparation and preparation method thereof of people's hand-foot-and-mouth disease |
KR102305665B1 (en) * | 2020-08-10 | 2021-09-28 | (주)네이처페어리 | Antiviral or antibacterial compositions comprising Dendropanax morbiferus |
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