CN110063948A - P-hydroxyphenylethanol is used to prepare the purposes for inhibiting the drug of bacterial community induction - Google Patents
P-hydroxyphenylethanol is used to prepare the purposes for inhibiting the drug of bacterial community induction Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Abstract
The purposes for inhibiting the drug of bacterial community induction is used to prepare the invention discloses p-hydroxyphenylethanol or its prodrug, the p-hydroxyphenylethanol has the structure as shown in formula (I):
Description
Technical field
The present invention relates to the purposes of p-hydroxyphenylethanol or its prodrug, especially p-hydroxyphenylethanols or its prodrug for making
The purposes of the standby drug for inhibiting bacterial community induction.
Background technique
Currently, antibiotic is all to realize anti-infectious purpose by directly killing microorganism or suppressing growth of microorganism,
Under this survival pressure, bacterium is by changing self mechanism, it is easy to generate drug resistance, this that is to say, it is bright with traditional target spot and
The antibacterials that screening technique obtains can not fundamentally solve the problems, such as that drug-resistant bacteria infects.
In recent years, bacterial community induction (Quorum Sensing, QS) system can regulate and control the existence of bacterium with it is pathogenic,
Cause the close attention of pharmacy man, it has also become the important target of pharmacy circle development of new antibacterials.Incuded with bacterial community
System is the antibacterials of target sieving, entirely different with the mechanism of action of conventional antibiotic, it does not kill bacterium or inhibits single
The growth of a bacterium, only inhibits the pathogenic behavior of bacterial community induction regulation, including reduces bacteriotoxin yield, inhibits biological quilt
Film is formed, hinder bacteria motility and adjust its excretory system etc., so that it be made to lose pathogenecity, it is prominent to be not easy inducible resistance
Become, is accordingly regarded as the novel antibacterial drug of future ideality.
P-hydroxyphenylethanol also known as 4- hydroxylphenylethyl alcohol, popular name tyrosol (Tyrosol) are mainly used as the conjunction such as medicine, fragrance
At intermediate, such as synthesis cardiovascular drug Metoprolol, times its element Luo Er etc..
CN106083533B, which discloses 4- hydroxylphenylethyl alcohol, can effectively inhibit the hatching of root-knot nematode egg, to root knot line
Egg hatch inhibiting rate is up to 95%.
CN1720802 discloses a kind of biological sprout inhibitor and its application, which is naturally to hydroxyl
Base benzyl carbinol and two kinds of benzyl carbinol.Tobacco, flower can be improved as tobacco, vegetables and flowers Suckering agents application in the biological sprout inhibitor
The yield of grass and vegetables, improving quality, sprout inhibition effective percentage are average up to 93% or more.
CN1685817 discloses a kind of tobacco and vegetable sprouting inhibitor, belongs to agricultural Suckering agents.The Suckering agents by benzyl carbinol,
Or the mixture of p-hydroxyphenylethanol or benzyl carbinol and p-hydroxyphenylethanol, it is dissolved in water and is prepared.The Suckering agents are as tobacco
And vegetable sprouting inhibitor application, the yield of tobacco and vegetables, improving quality, sprout inhibition effective percentage average reachable 90% or more can be improved.
Up to the present, there is not yet someone reports p-hydroxyphenylethanol in terms of the drug that preparation inhibits bacterial community induction
Application.
Summary of the invention
In view of this, the purpose of the present invention is to provide a kind of p-hydroxyphenylethanol or the new medical usages of its prodrug.
The present invention adopts the following technical scheme that realization above-mentioned purpose.
The present invention provides a kind of p-hydroxyphenylethanol or its prodrug is used to prepare the use for inhibiting the drug of bacterial community induction
On the way, the p-hydroxyphenylethanol has the structure as shown in formula (I):
In accordance with the purpose of the invention, it is preferable that the drug forms the pharmaceutical preparation for inhibiting bacterial community induction；The medicine
Object preparation includes the p-hydroxyphenylethanol or its prodrug, also includes pharmaceutically acceptable auxiliary material.
In accordance with the purpose of the invention, it is preferable that the drug is lived using the p-hydroxyphenylethanol or its prodrug as unique
Property ingredient.
In accordance with the purpose of the invention, it is preferable that the drug is formed for inhibiting the bacterial community of chromabacterium biolaceum to incude
Pharmaceutical preparation.
In accordance with the purpose of the invention, it is preferable that the drug forms the production for inhibiting the violacein of chromabacterium biolaceum
Measure but do not influence the pharmaceutical preparation of the normal growth of chromabacterium biolaceum.
In accordance with the purpose of the invention, it is preferable that the drug is formed for inhibiting the bacterial community of Pseudomonas aeruginosa to incude
Pharmaceutical preparation.
In accordance with the purpose of the invention, it is preferable that the drug forms pyo, elastic egg for inhibiting Pseudomonas aeruginosa
The yield of white enzyme and proteolytic enzyme but do not influence Pseudomonas aeruginosa normal growth pharmaceutical preparation.
In accordance with the purpose of the invention, it is preferable that the drug forms the pharmaceutical preparation for inhibiting bacterial community induction；Unit medicine
The content of p-hydroxyphenylethanol or its prodrug is 1~50mg in object preparation.
In accordance with the purpose of the invention, it is preferable that in unit medicament preparation the content of p-hydroxyphenylethanol or its prodrug be 5~
40mg。
In accordance with the purpose of the invention, it is preferable that in unit medicament preparation the content of p-hydroxyphenylethanol or its prodrug be 5~
20mg。
P-hydroxyphenylethanol of the invention or its prodrug can be used for preparing the drug for inhibiting bacterial community induction.The present invention
P-hydroxyphenylethanol or its prodrug the bacterial community of chromabacterium biolaceum can be inhibited to incude but do not influence the normal life of chromabacterium biolaceum
It is long.P-hydroxyphenylethanol of the invention or its prodrug can inhibit the bacterial community of Pseudomonas aeruginosa to incude but do not influence Pseudomonas aeruginosa
Normal growth.
Detailed description of the invention
Fig. 1 is the active ingredients result of p-hydroxyphenylethanol in embodiment 1.
Fig. 2 be in embodiment 1 p-hydroxyphenylethanol to the thalli growth of chromabacterium biolaceum CV026 and violacein yield
It influences.
Fig. 3 is p-hydroxyphenylethanol in embodiment 2 to Pseudomonas aeruginosa thallus, pyo, elastoser and albumen
The influence of the yield of hydrolase.
Fig. 4 A is the influence that methanol forms the biofilm of Pseudomonas aeruginosa in embodiment 3.
Fig. 4 B is the influence that azithromycin forms the biofilm of Pseudomonas aeruginosa in embodiment 3.
Fig. 4 C is the influence that p-hydroxyphenylethanol forms the biofilm of Pseudomonas aeruginosa in embodiment 3.
Fig. 5 is the binding site of receptor protein 3QP1 and signaling molecule C6HSL in embodiment 4.
Fig. 6 is the binding site of receptor protein 3QP1 and p-hydroxyphenylethanol in embodiment 4.
Fig. 7 is the hydrophobic interaction of receptor protein 3QP1 and p-hydroxyphenylethanol in embodiment 4.
Specific embodiment
The present invention is further illustrated combined with specific embodiments below, but protection scope of the present invention is not limited to
This.
The structure of p-hydroxyphenylethanol of the invention is as follows:
In the present invention, the molecular formula of the p-hydroxyphenylethanol is C8H10O2, molecular weight 138.P-hydroxyphenylethanol is
Known compound can be used and is chemically synthesized, such as according to CN101225023, CN103232328A, CN103804147A
Or method disclosed in CN104370706A etc. is prepared.P-hydroxyphenylethanol can also be obtained using the method for microbial fermentation
It obtains, such as the method according to disclosed in CN109370967A or CN108753636A etc. is prepared.
In the present invention, the prodrug of p-hydroxyphenylethanol refer in vitro it is inactive or it is active it is smaller, in vivo through enzyme or non-
The conversion of enzyme releases p-hydroxyphenylethanol and plays the compound of drug effect.
In the present invention, p-hydroxyphenylethanol or its prodrug have inhibition bacterial community induction effect, can be used for preparing tool
There is the drug for inhibiting bacterial community induction effect.According to certain embodiments of the present invention, p-hydroxyphenylethanol of the invention or
Its prodrug can inhibit the bacterial community of chromabacterium biolaceum to incude but not influence the normal growth of chromabacterium biolaceum.It is according to the present invention another
Some embodiments, p-hydroxyphenylethanol of the invention or its prodrug can inhibit the bacterial community induction of Pseudomonas aeruginosa but not shadow
Ring the normal growth of Pseudomonas aeruginosa.
In the present invention, the drug for inhibiting bacterial community induction can be using p-hydroxyphenylethanol and/or its prodrug as only
One active constituent；Also may include other has the active constituent for inhibiting bacterial community induction effect, or does not have comprising itself
Have and inhibits bacterial community induction effect but p-hydroxyphenylethanol and/or its prodrug can be assisted to play inhibition bacterial community induction
The active constituent of effect.
In the present invention, the drug for inhibiting bacterial community induction can be bulk pharmaceutical chemicals, or pharmaceutical preparation.
In the present invention, the drug, which is formed, has the pharmaceutical preparation for inhibiting bacterial community induction effect.Unit medicament preparation
In, the content of the p-hydroxyphenylethanol or its prodrug is 1~50mg, preferably 5~40mg, more preferably 5~20mg.Unit
Pharmaceutical preparation refers to the preparation an of preparation and application unit, such as one tablet, one bag of granule, a capsule, a bottleneck
Take liquid etc..The content of p-hydroxyphenylethanol or its prodrug, convenient for taking, is also convenient for sending out in above range in unit medicament preparation
It waves and bacterial community is inhibited to incude effect.
In the present invention, the dosage form of the pharmaceutical preparation is unlimited, can for tablet, granule, capsule, pill, oral solution,
Injection etc..The pharmaceutical preparation can also include pharmaceutically acceptable auxiliary material.The kind of the pharmaceutically acceptable auxiliary material
Class is with no restrictions.Auxiliary material can be filler, corrigent, lubricant etc..Filler is also known as diluent, such as wheaten starch, wood
Sweet potato starch, cornstarch, potato starch, dextrin, microcrystalline cellulose, lactose etc..The example of corrigent includes but is not limited to sweet tea
Synanthrin glycosides, glycyrrhizin, mogroside, acesulfame potassium, Aspartame, Sucralose, isomaltoketose etc..Examples of lubricant includes
But be not limited to magnesium stearate, talcum powder, superfine silica gel powder, magnesium laurylsulfate etc..
The LB culture medium that following embodiment uses is as follows:
Solid LB media: peptone 1%, yeast extract 0.5%, NaCl 1%, agar powder 2%, deionized water
100ml。
LB liquid medium: peptone 1%, yeast extract 0.5%, NaCl 1%, deionized water 100ml.
The active testing of 1 p-hydroxyphenylethanol of embodiment inhibition chromabacterium biolaceum quorum sensing
1. experimental principle
(1) bacterial community induction (QS) indicator bacteria chromabacterium biolaceum CV026 is signaling molecule C6HSL synthase gene cviI is lacked
Mutant is lost, C6HSL signaling molecule is added in external source, its quorum sensing can be induced to generate violacein.If certain compound has
There is quorum-quenching active, then the compound can be such that violacein yield reduces.
(2) synthesis of violacein is strictly to be regulated and controled by the bacterial community induction system of chromabacterium biolaceum, passes through analysis
The thalli growth of chromabacterium biolaceum and the yield of violacein, it can be determined that whether some compound has bacterial community induction suppression
System activity.
2. experimental method
2.1 chromabacterium biolaceum plate screening methods
Chromabacterium biolaceum CV026 is activated overnight.The 20mL solid LB media melted is cooled to 28 DEG C, 20 μ L cards are added
The signaling molecule C of that mycin, 100 μ L6The chromabacterium biolaceum CV026 of HSL and 400 μ L activation, is poured on plate, to plate after mixing
After solidification, 4 culture medium holes are made a call to punch, are separately added into 0.5mg/mL para hydroxybenzene in above-mentioned 3 culture medium holes
Methanol and conduct is added in ethyl alcohol, 1mg/mL p-hydroxyphenylethanol and 1.5mg/mL p-hydroxyphenylethanol, remaining 1 culture medium hole
Blank control group.After being incubated overnight at 28 DEG C, observe at above-mentioned 4 culture medium holes transparent haloing whether occur.
2.2 chromabacterium biolaceum shaking flask screening techniques
After chromabacterium biolaceum CV026 is activated overnight, it is inoculated into the LB liquid medium of the sterilizing of 20mL, chromabacterium biolaceum
The inoculum concentration of CV026 is the 2vol% of LB liquid medium volume；The signaling molecule of 20 μ L kanamycins and 100 μ L is added
C6P-hydroxyphenylethanol is added into shaking flask by HSL, formed various concentration gradient be 0.1mg/mL, 0.2mg/mL, 0.3mg/mL,
The p-hydroxyphenylethanol solution of 0.4mg/mL and 0.5mg/mL, using methanol as blank control group.150rpm is cultivated at 28 DEG C
12h.Cultivate 12h after, take 1mL chromabacterium biolaceum bacterium solution in 1.5mL centrifuge tube, 12000rpm, 10min, chromabacterium biolaceum thallus and
Violacein precipitates together, removes supernatant, and 1mL DMSO is added into centrifuge tube, re-dissolves chromabacterium biolaceum thallus and purple
Bacillin, 12000rpm, 10min are centrifuged again, and violacein is dissolved in formation violacein liquid in supernatant DMSO,
1mL ddH is added in chromabacterium biolaceum bacterial sediment for chromabacterium biolaceum bacterial sediment, Aspirate supernatant2O weight is molten, obtains chromabacterium biolaceum
Thallus liquid.The violacein liquid and chromabacterium biolaceum thallus liquid for taking 200 μ L respectively measure OD value with microplate reader in 96 microwell plates,
The wavelength of violacein is 585nm, and the wavelength of chromabacterium biolaceum thallus is 600nm.
3. experimental result
3.1 chromabacterium biolaceum plate screenings
Experimental result is referring to Fig. 1.0.5mg/mL p-hydroxyphenylethanol, 1mg/mL p-hydroxyphenylethanol and 1.5mg/mL is added
Occur the haloing of White-opalescent at the culture medium hole of p-hydroxyphenylethanol, and as the concentration of p-hydroxyphenylethanol is higher,
Haloing is also bigger.The above results show that p-hydroxyphenylethanol is able to suppress violacein synthesis, and p-hydroxyphenylethanol is to purple
The bacterial community induction system of bacillus has inhibitory activity.
3.2 chromabacterium biolaceum shaking flask is screened
Using the concentration of p-hydroxyphenylethanol as abscissa, using the absorbance at 600nm and 585nm as ordinate, analysis
P-hydroxyphenylethanol is in 0.1~0.5mg/ml concentration range, the change of the yield of chromabacterium biolaceum thalli growth and violacein
Change (referring to fig. 2).The above results show that p-hydroxyphenylethanol does not have an impact the growth of chromabacterium biolaceum, but with concentration
Increase, violacein yield is gradually reduced and in concentration dependent, when p-hydroxyphenylethanol concentration is 0.5mg/mL, to purple
The amount of suppression of color bacillin has reached 53.48%, illustrates that p-hydroxyphenylethanol has the bacterial community induction system of chromabacterium biolaceum
There is good inhibitory activity.
The active testing of 2 p-hydroxyphenylethanol of embodiment inhibition Pseudomonas aeruginosa quorum sensing
1. experimental method
1.1 pyo yield
Pseudomonas aeruginosa P.aeruginosa PA01 is activated to logarithmic phase, and is diluted to OD600It is 0.05, then average mark
For 7 groups (p-hydroxyphenylethanol groups of blank control group, positive controls and 5 various concentrations)；Wherein, it is separately added into pair for 5 groups
Hydroxylphenylethyl alcohol, forming various concentration gradient is 0.1mg/mL, 0.2mg/mL, 0.3mg/mL, 0.4mg/mL and 0.5mg/mL
P-hydroxyphenylethanol solution；In addition, using methanol as blank control group, using the azithromycin of 0.2mg/mL as positive control
Group；37 DEG C, shake culture 12h.It is centrifuged off Pseudomonas aeruginosa thallus, takes 5mL supernatant that 3mL chloroform is added, chloroform is mutually transferred to
New eppendorf pipe, and the 0.2mol/L hydrochloric acid of 1mL is added, after mixing well extraction, upper strata aqueous phase is collected by centrifugation, with enzyme mark
Instrument measures the OD value at wavelength 520nm.
1.2 elastin laminin production of enzyme
Pseudomonas aeruginosa P.aeruginosa PA01 is activated overnight.By the Pseudomonas aeruginosa P.aeruginosa after activation
PA01 is inoculated into LB liquid medium, and the inoculum concentration of Pseudomonas aeruginosa P.aeruginosa PA01 is LB liquid medium volume
1vol%；Then 7 groups (p-hydroxyphenylethanol groups of blank control group, positive controls and 5 various concentrations) are equally divided into；
Wherein, 5 groups of p-hydroxyphenylethanols for being separately added into 0.1mg/mL, 0.2mg/mL, 0.3mg/mL, 0.4mg/mL and 0.5mg/mL are molten
Liquid；In addition, using methanol as blank control group, using the azithromycin of 0.2mg/mL as positive controls；In 37 DEG C, 150rmp
Lower culture 12h.It takes bacterium solution to be centrifuged, 0.22 μm of nylon membrane of supernatant is filtered, take 100 μ L supernatants that 10mg elastin laminin-is added
Congo red and 900 μ L Na2HPO4(pH 7.0), shake culture 2h at 37 DEG C after mixing.10000rpm is centrifuged 10min, takes
Clear liquid measures absorbance at 495nm.
1.3 proteolysis production of enzyme
Pseudomonas aeruginosa P.aeruginosa PA01 is activated overnight.By the Pseudomonas aeruginosa P.aeruginosa after activation
PA01 is inoculated into LB liquid medium, and the inoculum concentration of Pseudomonas aeruginosa P.aeruginosa PA01 is LB liquid medium volume
1vol%；Then 7 groups (p-hydroxyphenylethanol groups of blank control group, positive controls and 5 various concentrations) are equally divided into；
Wherein, 5 groups of p-hydroxyphenylethanols for being separately added into 0.1mg/mL, 0.2mg/mL, 0.3mg/mL, 0.4mg/mL and 0.5mg/mL are molten
Liquid；Other 2 groups, using methanol as blank control group, using the azithromycin of 0.2mg/mL as positive controls；37 DEG C,
12h is cultivated under 150rpm.It takes bacterium solution to be centrifuged, 0.22 μm of nylon membrane of supernatant is filtered, take 100 μ L supernatants that 400 μ L are added
50mmol/L K containing 0.8% azo-casein2HPO4(pH 7.0) solution, cultivates 3h at 30 DEG C after mixing.Then it is added
The HCl solution of 1.5mol/L is placed in reacts 10min on ice, and after centrifugation, the NaOH solution of 0.5mol/L is added in supernatant；Again from
After the heart, supernatant is taken to measure absorbance at 440nm.
2. experimental result
Experimental result is referring to Fig. 3.From the figure 3, it may be seen that 4- hydroxylphenylethyl alcohol does not inhibit thallus when concentration is lower than 0.5mg/mL
Growth, and positive controls azithromycin (AZM) has apparent bacteriostasis.Compared with blank control group, with 4- hydroxy benzenes
The concentration of ethyl alcohol increases, and the yield of pyo, elastoser and proteolytic enzyme gradually decreases.Although azithromycin
It is particularly evident to the virulence factor inhibitory effect of Pseudomonas aeruginosa P.aeruginosa PA01, but it as antibiotic to bacterium
Growth also has apparent inhibitory effect, when azithromycin concentration is only 0.2mg/mL in positive controls, to the inhibiting rate of thallus
Up to 44.8%.It is above-mentioned the experiment results show that p-hydroxyphenylethanol is to the bacterial community of Pseudomonas aeruginosa P.aeruginosa PA01
Induction system has good inhibitory activity.
The analysis that 3 p-hydroxyphenylethanol of embodiment inhibits the biofilm of Pseudomonas aeruginosa to be formed
1. experimental principle
The intervention school-based of bacterium plays a significant role the formation of biofilm and stable structure, inhibits Pseudomonas aeruginosa
The intervention school-based of P.aeruginosa PA01 can effectively reduce biofilm and be formed, and improve drug susceptibility.
2. experimental method
The SEM of 2.1 biofilms is imaged
Pseudomonas aeruginosa P.aeruginosa PA01 is activated overnight.By the Pseudomonas aeruginosa P.aeruginosa after activation
PA01 is inoculated into LB liquid medium, and the inoculum concentration of Pseudomonas aeruginosa P.aeruginosa PA01 is LB liquid medium volume
1vol%；Then 3mL bacterium solution is added in six orifice plates, and is put into sterile slide, is next separately added into p-hydroxyphenylethanol
(p-hydroxyphenylethanol group), 0.2mg/mL azithromycin (positive controls) and methanol (blank control group), 37 DEG C of stationary cultures
After 48h, bacterium solution is siphoned away, and clean slide with sterile PBS, then fixed for 24 hours with 2.5% glutaraldehyde at room temperature, then used
PBS is washed, and removes glutaraldehyde, then with ethanol dehydration 15 minutes of gradient concentration (50%, 70%, 80%, 90%), finally use
100% ethanol dehydration three times, each 10min.Metal spraying observation.
3. experimental result
Experimental result A~4C referring to fig. 4.Remain unchanged surface compact, cell of the biofilm of blank control group is completely in stub
Shape is wrapped in film；The biofilm and cell of positive controls are destroyed by azithromycin, and graininess is presented；Para hydroxybenzene
The biofilm of ethanol group is destroyed by p-hydroxyphenylethanol, but the cell of bacterium is not destroyed by p-hydroxyphenylethanol, this says
Bright p-hydroxyphenylethanol can destroy biofilm, it is exposed outside make bacterium, but bacterium is complete, be normal corynebacterium, into
And illustrate p-hydroxyphenylethanol to the cell of bacterium without destructiveness, that is to say, that p-hydroxyphenylethanol does not influence bacterium and normally gives birth to
It is long, only inhibit bacterial community induction system.
The Molecular mechanism analysis on bio of bacterial community induction system is quenched in 4 p-hydroxyphenylethanol of embodiment
1. molecule simulation method
The molecule between p-hydroxyphenylethanol and receptor protein 3QP1 is carried out with molecular docking software Autodock first
Then docking determines knot with the combination of molecular dynamics software gramacs simulation p-hydroxyphenylethanol and receptor protein 3QP1 again
Coincidence point and key amino acid site.
2. sunykatuib analysis result
Sunykatuib analysis result is referring to Fig. 5~7.P-hydroxyphenylethanol and signaling molecule C6In HSL different active pockets, two
The hydrogen bond and hydrophobic forces of person is entirely different, and p-hydroxyphenylethanol is with the receptor protein 3QP1 key amino acid for forming hydrogen bond
GLU112, gLY138 and ARg163, hydrophobic forces Ser137, Met110, Arg159 and gly158.P-hydroxyphenylethanol with
The binding site of receptor protein 3QP1 is in the bond area DNA, and the Binding change of the two activity conformation of receptor protein prevents
The normal transcription of downstream gene, and then block the pathogenic behavior of quorum sensing regulation.This mechanism of action can be used for instructing new
The research and development of type antibacterials, for treating infection caused by drug tolerant bacteria.
By above-mentioned experiment it is found that p-hydroxyphenylethanol has good inhibitory activity to bacterial community induction system, but not
Influence bacterium normal growth.Above-mentioned experiment shows that p-hydroxyphenylethanol lives to bacterial community induction system with good inhibition
Property, it can be used for preparing the drug for inhibiting bacterial community induction.
Present invention is not limited to the embodiments described above, without departing from the essence of the present invention, this field skill
Any deformation, improvement, the replacement that art personnel are contemplated that each fall within the scope of the present invention.
Claims (10)
1. p-hydroxyphenylethanol or its prodrug are used to prepare the purposes for inhibiting the drug of bacterial community induction, the para hydroxybenzene second
Alcohol has the structure as shown in formula (I):
2. purposes according to claim 1, which is characterized in that the drug forms the drug system for inhibiting bacterial community induction
Agent；The pharmaceutical preparation includes the p-hydroxyphenylethanol or its prodrug, also includes pharmaceutically acceptable auxiliary material.
3. purposes according to claim 1, which is characterized in that the drug is made with the p-hydroxyphenylethanol or its prodrug
For sole active agent.
4. purposes according to claim 1, which is characterized in that the drug forms the bacterial flora for inhibiting chromabacterium biolaceum
The pharmaceutical preparation that body-sensing is answered.
5. purposes according to claim 4, which is characterized in that the drug forms the purple bar for inhibiting chromabacterium biolaceum
The yield of rhzomorph but do not influence chromabacterium biolaceum normal growth pharmaceutical preparation.
6. purposes according to claim 1, which is characterized in that the drug forms the bacterial flora for inhibiting Pseudomonas aeruginosa
The pharmaceutical preparation that body-sensing is answered.
7. purposes according to claim 6, which is characterized in that the drug forms the green pus bacterium for inhibiting Pseudomonas aeruginosa
Element, elastoser and proteolytic enzyme yield but do not influence Pseudomonas aeruginosa normal growth pharmaceutical preparation.
8. described in any item purposes according to claim 1~7, which is characterized in that the drug, which is formed, inhibits bacterial flora body-sensing
The pharmaceutical preparation answered；The content of p-hydroxyphenylethanol or its prodrug is 1~50mg in unit medicament preparation.
9. purposes according to claim 8, which is characterized in that p-hydroxyphenylethanol or its prodrug in unit medicament preparation
Content is 5~40mg.
10. purposes according to claim 8, which is characterized in that p-hydroxyphenylethanol or its prodrug in unit medicament preparation
Content be 5~20mg.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105663244A (en) * | 2016-01-04 | 2016-06-15 | 中国石油大学(华东) | Fig leaf extract with bacterium colony induction quenching activity, and use thereof |
| CN105899221A (en) * | 2013-12-23 | 2016-08-24 | 医疗品牌研究有限公司 | Dermatological composition based on algae and olive leaf extracts |
| CN107473980A (en) * | 2017-08-28 | 2017-12-15 | 浙江工业大学 | A kind of application of amides compound in bacterial community sensing activity inhibitor is prepared |
| CN107595822A (en) * | 2017-08-24 | 2018-01-19 | 广东省微生物研究所（广东省微生物分析检测中心） | Farnesol is preparing the application in suppressing the generation of pseudomonas aeruginosa pyo and biofilm formation medicine |
| CN107841523A (en) * | 2017-10-19 | 2018-03-27 | 浙江大学 | Triterpene substance method is extracted from Inonotus obliquus using the induction of quorum sensing molecule |
| CN107929742A (en) * | 2017-12-18 | 2018-04-20 | 海南大学 | The anti-infective pharmaceutical applications of hordenine or its joint antibiotic |
-
2019
- 2019-05-14 CN CN201910398611.9A patent/CN110063948A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105899221A (en) * | 2013-12-23 | 2016-08-24 | 医疗品牌研究有限公司 | Dermatological composition based on algae and olive leaf extracts |
| CN105663244A (en) * | 2016-01-04 | 2016-06-15 | 中国石油大学(华东) | Fig leaf extract with bacterium colony induction quenching activity, and use thereof |
| CN107595822A (en) * | 2017-08-24 | 2018-01-19 | 广东省微生物研究所（广东省微生物分析检测中心） | Farnesol is preparing the application in suppressing the generation of pseudomonas aeruginosa pyo and biofilm formation medicine |
| CN107473980A (en) * | 2017-08-28 | 2017-12-15 | 浙江工业大学 | A kind of application of amides compound in bacterial community sensing activity inhibitor is prepared |
| CN107841523A (en) * | 2017-10-19 | 2018-03-27 | 浙江大学 | Triterpene substance method is extracted from Inonotus obliquus using the induction of quorum sensing molecule |
| CN107929742A (en) * | 2017-12-18 | 2018-04-20 | 海南大学 | The anti-infective pharmaceutical applications of hordenine or its joint antibiotic |
Non-Patent Citations (5)
| Title |
|---|
| AIPING CHANG等: "Tyrosol from marine Fungi, a novel Quorum sensing inhibitor against Chromobacterium violaceum and Pseudomonas aeruginosa", 《BIOORGANIC CHEMISTRY》 * |
| DIANA MARTÍNEZ-MATAMOROS等: "BÚSQUEDA DE BACTERIAS MARINAS COMO FUENTE DE INHIBIDORES DE QUORUM SENSING (IQS): PRIMER ESTUDIO QUIMICO DE Oceanobacillus profundus(RKHC-62B)", 《VITAE, REVISTA DE LA FACULTAD DE CIENCIAS FARMACÉUTICAS Y ALIMENTARIAS》 * |
| FASEELA HAMZA等: "Chapter 16 Marine Biodiversity As a Resource for Bioactive Molecules As Inhibitors of Microbial Quorum Sensing Phenotypes", 《BIOTECHNOLOGICAL APPLICATIONS OF QUORUM SENSING INHIBITORS》 * |
| JIN-WEI ZHOU等: "Hordenine: A Novel Quorum Sensing Inhibitor and Antibiofilm Agent against Pseudomonas aeruginosa", 《J. AGRIC. FOOD CHEM.》 * |
| SHAYMAA HASSAN ABDEL-RHMAN等: "Effect of Tyrosol and Farnesol on Virulence and Antibiotic Resistance of Clinical Isolates of Pseudomonas aeruginosa", 《BIOMED RESEARCH INTERNATIONAL》 * |
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