CN100502890C - Amoxicillin antibacterial agent containing nano silver, and its preparing method - Google Patents
Amoxicillin antibacterial agent containing nano silver, and its preparing method Download PDFInfo
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- CN100502890C CN100502890C CNB2006100243085A CN200610024308A CN100502890C CN 100502890 C CN100502890 C CN 100502890C CN B2006100243085 A CNB2006100243085 A CN B2006100243085A CN 200610024308 A CN200610024308 A CN 200610024308A CN 100502890 C CN100502890 C CN 100502890C
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- amoxicillin
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Abstract
The present invention relates to an amoxicillin antimicrobial containing nano silver. its preparation method and application. At the normal temperature the nano silver and amoxicillin are uniformly mixed so as to obtain the invented amoxicillin antimicrobial containing nano silver. The tests show that said invention has stronger antimicrobial effect.
Description
Technical field
The invention belongs to the biological medicine technology field, be specifically related to a kind of amoxicillin antibacterial agent that contains nanometer silver and preparation method thereof.
Background technology
(β-lactam) and sulfonamides compound are broad-spectrum antibiotics comparatively to β-lactams.Because long-time application repeatedly causes a large amount of antibacterials to the strong Drug resistance of this type of antibacterial generation, thereby in life neutralization medical treatment, adopts the antimicrobial dosage of increase to reach satisfied antibacterial effect usually.The consequence of doing like this can only be the Drug resistance that constantly increases antibacterial, and the Drug resistance of antibacterial more and more becomes the serious problems that influence human health and life.In recent years, people study the drug-fast mechanism of antibacterial, (amount of β-lactamases) is relevant to the Drug resistance of β-lactams and the beta-lactam hydrolytic enzyme of its generation to find antibacterial, beta-lactam hydrolytic enzyme hydrolyzable 'beta '-lactam antibiotic, make it can not destroy the synthetic of cell wall, thereby make its forfeiture drug effect.In order to satisfy medical treatment and needs in life, medicament scholar and physician are constantly developed new 'beta '-lactam antibiotic from various different angles, as the part-structure of the non-effective site by changing beta-lactam, make medicament present inertia, thereby avoid hydrolysis and lost efficacy hydrolytic enzyme; (or replacing) uses two kinds of antibiotics simultaneously, and its principle is after antibacterial develops immunity to drugs to a kind of antibiotics, another antibiotic kills antibacterial; Add some auxiliary Organic substances in antibiotics, as clavulanic acid (Clavulanic acid), these auxiliary elements can suppress β-lactams fermentoid, thereby the drug effect of antibiotics is brought into play.These methods have solved drug-fast problem to a certain extent, but the drug effect of the antibacterial of failing to improve significantly, and particularly along with the entering of some organic component, medicine also increases the side effect of human body thereupon.In human with natural fight, find to have material in many mineral and the biology, as sulfur, silver, chitosan, hydroxyapatite or the like with antibacterial action.Over nearly 20 years, along with the birth and the development of nanosecond science and technology, the pleasantly surprised discovery of people has multiple nano-particle also to have antibacterial action preferably, as nanometer gold, nanometer silver, nano titanium oxide, nanometer hydroxyapatite.Therefore, biodegradable nontoxic nano grade biological antibacterial or inorganic low (or do not have) toxic nano-particle and the associating of conventional antibiotic is antibiotic, be those skilled in the art's goal in research with the antibiotic poor efficiency of effective solution.
Summary of the invention
The objective of the invention is to propose a kind of amoxicillin antibacterial agent that contains nanometer silver and preparation method thereof.
A kind of amoxicillin antibacterial agent that contains nanometer silver that the present invention proposes, amoxicillin solution and nanometer silver mix, wherein, the solution of the powder preparation in the Amoxicillin Capsules is adopted in the amoxicillin, the nanometer silver particle diameter is 10-50nm, and the mass ratio of amoxicillin and nanometer silver is 50: 1-10: 1.
The preparation method of the amoxicillin antibacterial agent that contains nanometer silver that the present invention proposes at normal temperatures, is mixed in proportion the solution of the preparation of the powder in the Amoxicillin Capsules and the silver colloid dispersion liquid of nanometer silver, stirs 8-20 minute, promptly gets required product.
Among the present invention, described nanometer silver can utilize soluble silver salt, adopts several different methods such as sol-gel processing, microemulsion method, reverse micelle method, vapour deposition process to obtain, and is easy to prepare, also can be by commercially available acquisition (commercialization).Used nanometer silver prepares by following method among the present invention:
Adopt soluble silver salt, at normal temperatures and pressures, inject ammonia in concentration is the silver salt of 0.01-0.1mol/L, stir, keeping the solution pH value is 11-12, and the response time is 10-15 minutes, obtains silver-colored ammonia ([Ag (NH
3)
2]
+) solution, [Ag (NH
3)
2]
+The sodium lauryl sulphate of solution and 5wt% (SDS) aqueous solution with the volume ratio of 1:0.9-1:1.1 in reaction bulb behind the uniform mixing, placing temperature is on the 60-80 ℃ of magnetic stirring apparatus, dropwise add vitamin C with medical Transfusion device, ascorbic concentration is 0.02mol/L, and the maintenance speed of agitator is 100-130 rev/min, react 1.5-2.5 hour (amount that is slightly larger than in the stoichiometry with ascorbic consumption is as the criterion), obtain the precipitate of black, with ethanol is solvent, the centrifuge washing precipitate to remove surfactant, reduces pressure or vacuum distilling then, temperature is 50-80 ℃, promptly gets nanometer silver.
Among the present invention, the block and the powder body of argent also can be adopted in the silver-colored source of described preparation nanometer silver.As: block or powder body silver are prepared nanometer silver by physical methods such as induced with laser vapour deposition process, mixing plasma method, sputtering method, high-energy ball milling methods.
The amoxicillin antibacterial agent that contains nanometer silver of the present invention is used for escherichia coli, the application that also can be used for Hemolytic streptococcus, streptococcus pneumoniae, do not produce penicillinase gold Portugal bacterium or hemophilus influenza, antibacterials such as proteus mirabilis, Enterococcus presses down (resisting) bacterium.
The method of testing of general anti-biotic material anti-microbial property is adopted in the test of the anti-microbial property of the amoxicillin antibacterial agent that contains nanometer silver that the present invention obtains.In amount of bacteria is 5.0 * 10
6Under the CFU, detect the minimal inhibitory concentration of amoxicillin, nanometer silver respectively; Under same condition, add respectively nanometer silver and amoxicillin the variable concentrations mixed solution and and their compare during use separately.According to the method that Sondi describes, set up their growth curve.
With example, concrete method of testing is to adopt the general antibacterial antiplaque agent performance test methods of microbiology with the test escherichia coli, and test strain (escherichia coli F220) is activated under 37 ℃ in the LB culture medium, is cultured to amount of bacteria then and reaches 10
8～10
9CFU.Then inoculum is carried out sterile working's filtration washing, strain is diluted to obtains 5.0 * 10 in the sterilized water
6The bacteria sample of CFU.
These antibacterials are divided into equal some five equilibriums, add 0mg/ml respectively, 0.150mg/ml, 0.300mg/ml, 0.375mg/ml, the amoxicillin solution of 0.450mg/ml and 0.525mg/ml and 0 μ g/ml, 5 μ g/ml, 10 μ g/ml, 15 μ g/ml, 20 μ g/ml, 25 μ g/ml, 30 μ g/ml, 35 μ g/ml, the nano silver dispersion of 40 μ g/ml was cultivated 24 hours down for 37 ℃ in temperature then.Can detect in amount of bacteria respectively like this is 5.0 * 10
6Under the CFU, the minimal inhibitory concentration of amoxicillin, nanometer silver is about MIC=40 μ g/ml.According to the Sondi method, set up their growth curve.Escherichia coli are added to and contain the 0.15mg/ml amoxicillin respectively, in the 100ml LB fluid medium of 5 μ g/ml nanometer silvers and 0.15mg/ml amoxicillin and 5 μ g/ml nanometer silver mixing antibacterial.The growth curve of antibacterial OD value of bacterial concentration when detecting different time is come definite.
The present invention has the following advantages:
1, the invention provides a kind of to conventional antibacterial, particularly antibacterial to the improvement of its anti-(going out) microbial inoculum that develops immunity to drugs and new approaches, the new way of optimization.That is, on the basis of original medicament, add a small amount of nanometer grade inorganic antibacterial material, implement Synergistic antimicrobial.So not only greatly reduce the dosage of original medicine artificial increase, and, also can reach comparatively ideal sterilization (or antibacterial) effect under the lower situation of original pharmaceutical quantities in order to overcome Drug resistance.
2, the present invention has realized the optimum organization of two kinds of antibacterial, and the two effect sum when using separately that the Synergistic antimicrobial effect significantly is better than Isodose is opportunities of shining new vigor to traditional antibacterials.
3, the present invention is the theme with antibacterial amoxicillin commonly used and the nanometer silver Synergistic antimicrobial that is easy to get, sets forth in detail the theory of Synergistic antimicrobial, the foundation of antibiotic novel pharmaceutical formulation had uses for reference and directive significance.
5, related amoxicillin and nanometer silver Synergistic antimicrobial among the present invention can be prepared into complex antimicrobials comparatively easily, and has raw material and be easy to get, and production technology is simple, and is easy to operate, helps advantages such as industrialization and commercialization.Have the disinfectant that is used for household, medicine, environment, chemical industry and public place and (or) potentiality of antibacterial.Thereby comparatively vast potential for future development and application space arranged.
Description of drawings
The TEM photo of Fig. 1 nanometer silver and ED figure.
The amoxicillin antimicrobial effect curve chart of Fig. 2 variable concentrations.
The nanometer silver antimicrobial effect curve figure of Fig. 3 variable concentrations.
Concentration amoxicillin that Fig. 4 is different and nanometer are separately antibiotic and unite antimicrobial controlled trial figure.Wherein Fig. 4 (A) represents the antibacterial effect block diagram.Fig. 4 (B) is and the corresponding outdoor scene photo of experiment, a among the figure, 5 μ g/ml nanometer silvers, b, 0.15mg/ml amoxicillin, c, 0.15mg/ml amoxicillin+5 μ g/ml nanometer silvers, d, 0.15mg/ml amoxicillin+10 μ g/ml nanometer silvers.
Fig. 5 is the growth curve chart of antibacterial in containing different antibacterial LB culture fluid.Wherein ▲, 5 μ g/ml nanometer silvers, ●, 0.15mg/ml amoxicillin, ■, 0.15mg/ml amoxicillin+5 μ g/ml nanometer silvers.
The specific embodiment
(1) preparation of nanometer silver
At normal temperatures and pressures, to concentration 0.01mol/L AgNO
3Solution injects ammonia, keeps pH value of solution=12, then [Ag (NH
3)
2]+solution and 5% (wt%) sodium lauryl sulphate (SDS) aqueous solution equal-volume is mixed into triangular flask, and placing temperature is on 70 ℃ of magnetic stirring apparatuss.Dropwise add vitamin C (concentration 0.01mol/L) with medical Transfusion device, the rotating speed that keeps stirrer simultaneously is 120 rev/mins, reacts 2 hours.Do solvent centrifuge washing precipitation (repeated several times is removed surfactant) with ethanol, vacuum drying promptly gets nanometer silver then.
(2) nanometer silver and amoxicillin anti-microbial property test (minimal inhibitory concentration test)
In antibacterial test, test strain (escherichia coli F220) is activated under 37 ℃ in the LB culture medium, is cultured to amount of bacteria then and reaches 108～109CFU.Then inoculum is carried out sterile working's filtration washing, strain is diluted to obtains 5.0 * 10 in the sterilized water
6The bacteria sample of CFU.
These antibacterials are divided into equal some five equilibriums, add 0mg/ml respectively, 0.150mg/ml, 0.300mg/ml, 0.375mg/ml, the amoxicillin solution of 0.450mg/ml and 0.525mg/ml and 0 μ g/ml, 5 μ g/ml, 10 μ g/ml, 15 μ g/ml, 20 μ g/ml, 25 μ g/ml, 30 μ g/ml, 35 μ g/ml, the nano silver dispersion of 40 μ g/ml was cultivated 24 hours down for 37 ℃ in temperature then.Can detect in amount of bacteria respectively like this is 5.0 * 10
6Under the CFU, the minimal inhibitory concentration of amoxicillin, nanometer silver.From Fig. 2 and 3 minimal inhibitory concentration MIC=0.525mg/ml of amoxicillin as can be seen; The minimal inhibitory concentration of nanometer silver is about MIC=40 μ g/ml.
(3) nanometer silver and amoxicillin Synergistic antimicrobial performance test and comparison
Under same condition, in the aliquot bacterial strain, add the nanometer silver of 1ml and the variable concentrations mixed solution of amoxicillin respectively, 0.15mg/ml amoxicillin+5 μ g/ml nanometer silvers, as seen in Figure 4, the effect of amoxicillin and nanometer silver Synergistic antimicrobial is far superior to amoxicillin and the independent effect of using of nanometer silver.
(4) antibiotic kinetic test
According to the method that Sondi describes, set up their growth curve.Escherichia coli are added to and contain the 0.15mg/ml amoxicillin respectively, in the 100ml LB fluid medium of 5 μ g/ml nanometer silvers and 0.15mg/ml amoxicillin and 5 μ g/ml nanometer silver mixing antibacterial.The growth curve of antibacterial OD value of bacterial concentration when detecting different time is come definite.
Embodiment 2
Under same condition, in the aliquot bacterial strain, add the nanometer silver of 1ml and the variable concentrations mixed solution of amoxicillin respectively, 0.15mg/ml amoxicillin+10 μ g/ml nanometer silvers, stir and obtained product in 10 minutes, as seen in Figure 4, the effect of amoxicillin and nanometer silver Synergistic antimicrobial is far superior to amoxicillin and the independent effect of using of nanometer silver.
Embodiment 3
(particle diameter is 30-40nm) to be mixed with the silver colloid dispersion liquid of 10 μ g/ml and solution that the powder in the commercially available Amoxicillin Capsules (specification 0.125g/ grain) is mixed with 0.25mg/ml is mixed to utilize commercially available nanometer silver, the mass ratio of nanometer silver and amoxicillin is 1:10, stirred 8 minutes, obtain product, the enforcement associating is antibiotic also to realize satisfactory results.
(particle size range 25-30nm) is mixed with the silver colloid dispersion liquid of 10 μ g/ml and solution that the powder in the commercially available Amoxicillin Capsules (specification 0.125g/ grain) is mixed with 0.25mg/ml is mixed to utilize commercially available nanometer silver, the mass ratio of nanometer silver and amoxicillin is 1:20, stirred 15 minutes, obtain product, the enforcement associating is antibiotic also to realize satisfactory results.
(particle size range 35-40nm) is mixed with the silver colloid dispersion liquid of 10 μ g/ml and solution that the powder in the commercially available Amoxicillin Capsules (specification 0.125g/ grain) is mixed with 0.25mg/ml is mixed to utilize commercially available nanometer silver, the mass ratio of nanometer silver and amoxicillin is 1:40, stirred 25 minutes, obtain product, the enforcement associating is antibiotic also to realize satisfactory results.
(particle size range 25-30nm) is mixed with the silver colloid dispersion liquid of 10 μ g/ml and solution that the powder in the commercially available Amoxicillin Capsules (specification 0.125g/ grain) is mixed with 0.25mg/ml is mixed to utilize commercially available nanometer silver, the mass ratio of nanometer silver and amoxicillin is 1:50, stirred 30 minutes, obtain product, the enforcement associating is antibiotic also to realize satisfactory results.
Claims (2)
1, a kind of amoxicillin antibacterial agent that contains nanometer silver, it is characterized in that mixing by amoxicillin solution and nanometer silver, wherein, the solution of the powder preparation in the Amoxicillin Capsules is adopted in the amoxicillin, the nanometer silver particle diameter is 10-40nm, and the mass ratio of amoxicillin and nanometer silver is 50:1-10:1; Nanometer silver adopts silver nitrate to prepare by following step: at normal temperatures and pressures, inject ammonia in concentration is the silver nitrate of 0.01-0.1mol/L, stir, keeping the solution pH value is 11-12, and the response time is 10-15 minutes, obtains silver-colored ammonia [Ag (NH
3)
2]
+Solution is [Ag (NH
3)
2]
+In reaction bulb behind the uniform mixing, place temperature is on the 60-80 ℃ of magnetic stirring apparatus to the lauryl sodium sulfate aqueous solution of solution and 5wt%, ascorbinate with the volume ratio of 1:0.9-1:1.1, ascorbic concentration is 0.02mol/L, and to keep speed of agitator be 100-130 rev/min, reacted 1.5-2.5 hour, obtains the precipitate of black, with ethanol is solvent, the centrifuge washing precipitate is removed surfactant, then decompression or vacuum distilling, temperature is 50-80 ℃, promptly gets nanometer silver.
2, a kind of preparation method that contains the amoxicillin antibacterial agent of nanometer silver as claimed in claim 1, it is characterized in that at normal temperatures, the solution of the preparation of the powder in the Amoxicillin Capsules and the silver colloid dispersion liquid of nanometer silver are mixed in proportion, stirred 8-20 minute, promptly get required product;
Wherein, nanometer silver adopts silver nitrate to prepare by following step: at normal temperatures and pressures, inject ammonia in concentration is the silver nitrate of 0.01-0.1mol/L, stir, keeping the solution pH value is 11-12, and the response time is 10-15 minutes, obtains silver-colored ammonia [Ag (NH
3)
2]
+Solution is [Ag (NH
3)
2]
+In reaction bulb behind the uniform mixing, place temperature is on the 60-80 ℃ of magnetic stirring apparatus to the lauryl sodium sulfate aqueous solution of solution and 5wt%, ascorbinate with the volume ratio of 1:0.9-1:1.1, ascorbic concentration is 0.02mol/L, and to keep speed of agitator be 100-130 rev/min, reacted 1.5-2.5 hour, obtains the precipitate of black, with ethanol is solvent, the centrifuge washing precipitate is removed surfactant, then decompression or vacuum distilling, temperature is 50-80 ℃, promptly gets nanometer silver.
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| CN103042227B (en) * | 2012-12-18 | 2014-12-31 | 广东省微生物研究所 | Nano-silver sol antibacterial agent and preparation method thereof |
| CN103142649B (en) * | 2013-03-01 | 2014-08-20 | 赵华文 | Preparation method of amylose-coated I3<->-complexed silver-coated iron composite nanoparticles |
| CN103933066B (en) * | 2014-03-12 | 2017-05-24 | 同济大学 | Method for improving antibacterial activity of cephalexin through synergy of nanometer copper oxide |
| CN109632661B (en) * | 2018-11-02 | 2021-09-17 | 中南大学 | Gold nanoparticle probe for visually detecting amoxicillin, preparation method and application thereof |
| CN113427015B (en) * | 2021-06-18 | 2022-11-01 | 上海交通大学 | Preparation method and application of novel silver nano material AgNFs |
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| CN1672689A (en) * | 2004-03-26 | 2005-09-28 | 深圳市爱杰特医药科技有限公司 | Nano silver antiseptic gel for treating women's genital tract infection and its prepn and application |
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|---|---|---|---|---|
| CN1672689A (en) * | 2004-03-26 | 2005-09-28 | 深圳市爱杰特医药科技有限公司 | Nano silver antiseptic gel for treating women's genital tract infection and its prepn and application |
Non-Patent Citations (2)
| Title |
|---|
| 纳米以银抗菌材料研发现状. 张文钲，王广文.化工新型材料，第31卷第2期. 2003 * |
| 纳米银材料抗菌效果研究及其安全性初步评价. 钟金栋，夏雪山，张若愚，高毅颖.昆明理工大学学报(理工版)，第30卷第5期. 2005 * |
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