CN108101796A - A kind of tertiary amine compounds and application thereof - Google Patents
A kind of tertiary amine compounds and application thereof Download PDFInfo
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- CN108101796A CN108101796A CN201711177085.0A CN201711177085A CN108101796A CN 108101796 A CN108101796 A CN 108101796A CN 201711177085 A CN201711177085 A CN 201711177085A CN 108101796 A CN108101796 A CN 108101796A
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- methyl
- tertiary amine
- compound according
- antibacterial
- compound
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C219/00—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C219/02—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C219/04—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C219/08—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having at least one of the hydroxy groups esterified by a carboxylic acid having the esterifying carboxyl group bound to an acyclic carbon atom of an acyclic unsaturated carbon skeleton
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K6/00—Preparations for dentistry
- A61K6/80—Preparations for artificial teeth, for filling teeth or for capping teeth
Abstract
, can be under the action of acidogenic bactria the present invention provides a kind of tertiary amines noval chemical compound, environmental pH reduces, and plays antibacterial action, has pH sensitivity characteristics, solves the problems, such as classical antibacterial agents due to a lack of selectivity and cause flora imbalance.
Description
Technical field
The present invention relates to a kind of new tertiary amine compounds and application thereof.
Background technology
Dental caries are one of most common chronic diseases, as a kind of bacterial plaque disease, the bacterium in the generation and oral cavity of dental caries
Spot biomembrane has close relationship.Plaque bio-film is colonized in tooth Acquired Pellicle surface, and cell is generated using carbohydrate
Epimatrix, and further growth wherein is ripe, microenvironment pH value continuously decreases, and microbe species are shifted to production acid, acid fast bacteria,
Tooth demineralization is caused to generate dental caries bad.
For many years, have a large amount of for the correlative studys for inhibiting plaque bio-film, such as Chlorhexidine, hydrogen peroxide, fluoride preparation, receive
Rice material etc., there is apparent effect in the form of solution, suspension, gel etc. in the study on prevention of dental caries；However there is also
Some problems, such as Chlorhexidine, hydrogen peroxide substantially weaken for the effect into membrane micro.It is controlled when dental caries patient completes filling
After treatment, once Micro blazed-grating occurs in resin edge, bacterial plaque is easy to assemble, and generates secondary caries, and said medicine is in secondary caries prevention
Effect it is limited.In recent years, there is the research of many modified resin fillers, such as quaternary ammonium salt-modified resin filling material system
System, has more apparent effect for the biomembrane for being adhered to resin, tooth and bonding plane surface.
However, also there is substantial amounts of oral cavity resident bacteria in oral cavity, with safeguarding that oral health, Oral health behaviours balance have
Close relationship, the studies above material have comparatively ideal as a result, but for micro- in the generation of antibacterial, anti-dental caries or secondary caries
The effect of biology lacks selectivity, has the possibility for causing flora imbalance, leads to the problem of new.Nowadays it is much sensitive on preventing decayed tooth pH
Nano material research, under low ph value state have antibacterial activity be one of effective ways to solve the above problems.It is but right
In can modified resin filler system, and be still short of with the investigations of materials of pH sensitivity characteristics.
The content of the invention
Based on the above problem, the present invention provides a kind of tertiary amines noval chemical compounds, can resist oral cavity acidogenic bactria.
Specifically, the present invention provides tertiary amine compounds shown in formula I：
Wherein, R1, R2 are respectively and independently selected from H, C1-C4 alkyl；
R3 is selected from C1-C4 alkyl；
N is selected from the integer of 12-16.
Heretofore described C1-C4 alkyl not only including straight chained alkyl, but also can include branched alkyl.Can be methyl, second
Base, n-propyl, isopropyl, normal-butyl, isobutyl group etc..
Further, R1, R2 are respectively and independently selected from methyl or ethyl.In a specific embodiment of the invention, R1, R2 points
Methyl is not independently selected from it.
Further, R3 is selected from methyl or ethyl.In a specific embodiment of the invention, R3 is selected from methyl.
Further, n is selected from the integer of 13-15, such as 13,14,15.In a specific embodiment of the invention, n 14.
Following experimental study is carried out to such compound in the present invention, to illustrate the advantageous effect of the compound：
1st, under difference pH minimal inhibitory concentration (MIC) measure
16 chain tertiary amines, 16 chain quaternary ammonium salts are dissolved in the BHI culture mediums (pH=5, pH=7.4) of different pH value, pH=7
In Mcbain culture mediums with neutral buffer systems, insert 96 orifice plates and carry out gradient dilution, will be cultivated in BHI culture mediums
24H (37 DEG C, 90%N2, 5%CO2, 5%H2) Streptococcus mutans suspension add in gradient dilution antibacterials culture medium and
In (concentration 107CFU/ml) cultivate 24H (37 DEG C, 90%N2, 5%CO2, 5%H2) according to the muddy feelings of culture medium in 96 orifice plates
Condition judges MIC.
2nd, experiment sample preparation and Streptococcus mutans biology Membrance cuiture
Experiment packet be bonding agent group (control group), 5%16 chain quaternary ammonium salts+bonding agent group (5%16 chain quaternary ammoniums
Salt group), 5%16 chain tertiary amines+bonding agent group (5%16 chain tertiary amine group), wherein, 16 chain tertiary amines are methacrylic acid methyl hexadecane
Base aminoethyl.
The circular resin sheet of a diameter of 1.2cm is prepared, with even spread thin layer of adhesive posterior photocuring on resin sheet.
By each group resin sheet as in 24 orifice plates after 37 DEG C of oxirane disinfections, in culture variation hammer in thin layer of adhesive
Bacterium (Streptococcus mutans UA159).By anaerobic environment (90%N in Streptococcus mutans and BHI culture mediums2, 5%
CO2, 5%H2) after culture 24H, equal proportion, which is mixed in BHI containing 1% sucrose and neutralizes the Mcbain with neutral buffer systems, to be trained
Support in base, after be incorporated in above-mentioned 24 orifice plate that (three strain concentration are 107CFUs/ml), per hole 2ml, anaerobic environment culture
48H。
3rd, MTT method (mtt assay) detects
The resin sheet (every group 6) for having cultivated 48H biomembranes is moved into 24 new orifice plates, is respectively put into 1ml MTT dyestuffs
In (0.5mg/ml, PBS dissolve), after 37 DEG C of Anaerobic culturel 1H, resin sheet is transferred to 24 new orifice plates, is separately added into 1ml bis-
Methyl sulfoxide (DMSO) room temperature is protected from light after prevention 20min takes 200ul to be placed in 96 orifice plates per hole, the number of degrees under OD values 540nm.
4th, lactic acid is tested
The resin sheet (every group 6) for having cultivated 48H biomembranes is moved into 24 new orifice plates, 1.5ml is respectively put into and contains
The buffering peptone water (BPW) of 0.2% sucrose, the lactic acid producing amount detected using lactic dehydrogenase enzyme process after 37 DEG C of Anaerobic culturel 3H, with OD
It is worth for the number of degrees under 340nm.
Result of the test is referring to table 1, Fig. 1, Fig. 2.
Table 1
As shown above, in acid medium, the antibacterial action of 16 chain tertiary amines is remarkably reinforced, and the quaternary ammonium salt of 16 chains resists
Bacterium effect variation is little, it can be seen that tertiary amine is in the antibacterial potential with pH sensibility.
Attached drawing, which is shown in different culture media, contains same concentrations quaternary ammonium salt (dimethylamino cetyl methacrylic acid
Ester DMAHDM), effect of the tertiary amine of the present invention to 48 biomembranes of Streptococcus mutans when small.In BHI culture mediums it can be seen from attached drawing
In (after culture pH value be 4.1) same concentrations quaternary ammonium salt it is similar for the antibacterial action of 48 biomembranes when small with tertiary amine.And
(pH value is 6.1 after culture) tertiary amine does not have apparent antibacterial action for biomembrane in McBain culture mediums.The above results
It is also demonstrated that, tertiary amine compound provided by the invention has pH sensibility, and DMAHDM does not have above-mentioned performance.
Based on above-mentioned activity experiment, the present invention also provides above-claimed cpds to prepare with antibacterial or antibacterium biomembrane
Purposes in the drug or material of activity.
Further, the bacterium is acidogenic bactria.
Wherein, the bacterium is Streptococcus mutans.
Being used to prepare in acid condition the present invention also provides above-claimed cpd, there is antibacterial or antibacterium biomembrane to live
Purposes in the drug of property, pro-drug or material.
The present invention also provides a kind of antibacterials or materials, it is that compound described above is active ingredient.
The tertiary amine compounds that the present invention synthesizes, under the action of acidogenic bactria, environmental pH reduces, and plays antibacterial and makees
With, have pH sensitivity characteristics, compared with DMAHDM, solve quaternary ammonium salt antiseptic due to a lack of selectivity and cause flora imbalance
Problem.
Said medicine or material can be used for biomedical material (such as dentistry), can also be used for other field.The present invention
In one specific embodiment, the material is biomedical material, particularly dental material.
Dental material of the present invention is also referred to as oral cavity material, is one of biomedical material, for oral cavity biocycle
In border, tooth or replacement defect, the denture of missing available for repairing defect make its recover anatomic form, function and beauty, with
And rescue a variety of materials waited used in items medical treatment in oral health and to deformity.
In use, in order to meet the actual needs, can be used with other auxiliary material combinations, such as dental cement
Deng.
In addition, pro-drug of the present invention, refer to inactive in vitro or active smaller, being converted into through enzyme or non-enzymatic in vivo
Active medicine and the compound for playing drug effect.Due to tertiary amine compound provided by the invention, without anti-under normal neutral environment
Bacterium activity, but in acid condition or acid-producing bacteria it is existing under the conditions of can generate antibacterial activity, therefore, the present invention is also
It can be used as pro-drug.
Description of the drawings
Results of the Fig. 1 in BHI culture mediums
Results of the Fig. 2 in McBain culture mediums
The nuclear magnetic spectrum of Fig. 3 methacrylic acid methyl hexadecylamine base ethyl esters
Specific embodiment
1 synthesizing methyl propylene acid methyl hexadecylamine base ethyl ester of embodiment (Pro B, the present invention in again referred to as 16 chain uncles
Amine)
(1) synthesis of compound B2：In the round-bottomed flask of 250ml, addition compound bromohexadecane (0.1mol,
25g, 25ml) and compound A2 (N- methylethanolamines) (5.0eq, 0.5mol, 32g, 34ml), and the isopropanol for adding in 80ml is made
For solvent, flow back 8-10h at 85 DEG C, finds have a large amount of products to generate through thin-layer chromatography (TLC) detection.System is cooled down and is recovered
To room temperature, system is poured into 150mL ether and is diluted, and washed with water (3*150ml), saturated salt solution (2*150ml) washing,
Organic phase is collected, through anhydrous Na2SO4Dry, decompression obtains colorless oil B (24g, up to 99%yield) except solvent.
(2) synthesis of compound Pro B:B2 (0.1mol, 24g) and metering system are added in the round-bottomed flask of 100ml
Sour methyl esters (3.0eq, 0.3mol, 31.8ml), stirs evenly.Add in catalyst CAA (0.4mol%, 0.107g) and inhibition
Agent p-hydroxyanisole (2mol%, 100mg), stirs evenly.Reaction system is in 100-110 DEG C of reaction, in atmospheric distillation plant
Under can steam a little methyl methacrylate.When reacting 12h, system is become yellow and is gradually deepened from colourless, adds urge at this time
Agent CAA (0.6mol%, 150mg), the reaction was continued 12h, after system is restored to room temperature, yellow transparent oily is obtained through column chromatography
Object methacrylic acid methyl hexadecylamine base ethyl ester (Pro B) (4.2g, 14%yield).
2 dentistry antibacterial material of embodiment
Suitable methacrylic acid methyl hexadecylamine base ethyl ester is taken, after adhesive mixing, you can press down as dentistry
Bacterium materials'use.
Signified dentistry antibacterial material of the invention, can be methacrylic acid methyl hexadecylamine base ethyl ester and adhesive
Mixed product can also be separated product.
Claims (10)
1. tertiary amine compounds shown in formula I：
Wherein, R1, R2 are respectively and independently selected from H, C1-C4 alkyl；
R3 is selected from C1-C4 alkyl；
N is selected from the integer of 12-16.
2. compound according to claim 1, it is characterised in that：R1, R2 are respectively and independently selected from methyl or ethyl.
3. compound according to claim 2, it is characterised in that：R1, R2 are respectively and independently selected from methyl.
4. compound according to claim 1, it is characterised in that：R3 is selected from methyl or ethyl.
5. compound according to claim 4, it is characterised in that：R3 is selected from methyl.
6. compound according to claim 1, it is characterised in that：N is selected from the integer of 13-15.
7. compound according to claim 6, it is characterised in that：N is 14.
8. compound described in claim 1-7 any one is preparing the drug with antibacterial or antibacterium biomembrane activity, preceding
Purposes in body drug or material.
9. purposes according to claim 8, it is characterised in that：The bacterium is acidogenic bactria；Further, the bacterium
For Streptococcus mutans.
10. a kind of antibacterials or material, it is characterised in that：It is using compound described in claim 1-7 any one as work
Property ingredient.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710331112 | 2017-05-11 | ||
| CN2017103311129 | 2017-05-11 |
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| CN108101796A true CN108101796A (en) | 2018-06-01 |
| CN108101796B CN108101796B (en) | 2020-11-24 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113975281A (en) * | 2021-12-03 | 2022-01-28 | 四川大学 | Application of tertiary amine monomer in preparation of medicine for inhibiting helicobacter pylori in oral cavity and stomach |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1386132A (en) * | 2000-05-22 | 2002-12-18 | 可乐丽股份有限公司 | Antimicrobial composition |
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2017
- 2017-11-22 CN CN201711177085.0A patent/CN108101796B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1386132A (en) * | 2000-05-22 | 2002-12-18 | 可乐丽股份有限公司 | Antimicrobial composition |
Non-Patent Citations (2)
| Title |
|---|
| STN: "RN 29538-06-5", 《REGISTRY》 * |
| STN: "RN 778532-86-8", 《REGISTRY》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113975281A (en) * | 2021-12-03 | 2022-01-28 | 四川大学 | Application of tertiary amine monomer in preparation of medicine for inhibiting helicobacter pylori in oral cavity and stomach |
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| CN108101796B (en) | 2020-11-24 |
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