CN102205126B - Application of combined catechin matters together with antibacterial agents - Google Patents
Application of combined catechin matters together with antibacterial agents Download PDFInfo
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Abstract
The invention relates to application of combination of two or three of catechin matters with antibiotics in preparing antibacterial agents. The combined catechin matters applied to the field of anti-methicillin-resistant staphylococcus aureus (MRSA) together with antibiotics provides antibacterial and sensitivity enhancing effects of medicaments, so that the application of the catechin matters is widened, the application scheme of the catechin matters is widened, and the phenomenon that the MRSA resists medicaments due to antibacterial agent abuse can be lightened.
Description
Technical field
The present invention relates to the medicinal application field, relate in particular in catechin and epigallo catechin or the L-Epicatechin gallate arbitrarily after both or the three kinds of associatings again and antibiotic application of uniting in the preparation antibacterials.
Background technology
After finding the first strain methicillin-resistant staphylococcus aureus (Methicillin-resistantStaphylococcus aureus, MRSA) in 1961, the eighties in 20th century, MRSA became the important pathogen of global hospital infection so far.There is in various degree drug resistance to comprising in MRSA to beta-lactam antibiotic, aminoglycoside, quinolones even glycopeptide class antibacterials such as penicillin, cephalosporin and cephamycin-types.Therefore, seek the way overcome resistance mechanism, find new target site and develop new antibiotic extremely urgent.
The special penicillin-binding protein 2a (PBP2a) that the drug resistance of MRSA is main and a kind of affinity of its generation is low is relevant, exist at the antibiotic of antibiotic concentration and can substitute other several PBP performance physiological functions that suppressed by antibiotic in the situation, keeping the normal growth of antibacterial, thereby show the drug resistance to Multiple Classes of Antibiotics.Therefore, present external many pharmacy corporations are all with the target spot of PBP2a as new antibacterials exploitation.
Catechins is extensively to be present in a class material that has extensive biologic activity in the natural plants such as tea, mainly comprises catechin (C), epicatechin (EC), nutgall catechin (GC), epigallo catechin (EGC), L-Epicatechin gallate (ECG), nutgall catechin gallic acid ester (GCG), epigallocatechin gallate (EGCG) (EGCG).Studies show that catechins has the various biological functions such as antitumor, anti-gene mutation, antibiotic, antiinflammatory, atherosclerosis.
A large amount of studies show that, the catechin that derives from the tea has certain fungistatic effect in the high concentration situation.Catechin can suppress glucosyltransferase, reduces the growing amount of glucosan, disturbs thalline to need sugar to stick and connects, and the Various Diseases indigenous bacterias such as Bacillus typhi, Salmonella paratyphi, yellow staphylococcus haemolyticus, golden yellow streptococcus and dysentery are had obvious inhibitory action.
The applicant take PBP2a as target spot, adopts biosensor technology to screen the material that obtains having antibiotic sensitizing activity from kind more than 100 has the Chinese medicine of infection and antiinflammatory action in early-stage Study; And from the Fructus Crataegi component, be purified into a component with remarkable antibiotic sensitization, it is carried out finding that it is comprised of three materials, is respectively catechin, epigallo catechin, L-Epicatechin gallate after the component analysis.Bibliographical information was once arranged, use a kind of catechins and Antibiotic combination to use and can be used for the MRSA treatment, but its effect is all bad, has limited the popularization of catechins in antibiotic enhanced sensitivity application facet.
Summary of the invention
The purpose of this invention is to provide in a kind of catechin, epigallo catechin and the catechin acid esters arbitrarily after both or the three kinds of associatings again and antibiotic application of uniting in the preparation antibacterials.The catechins associating is arrived anti-MRSA field with antibiotic use in conjunction again, the antibiotic sensitization of medicine can be provided, not only widen the purposes of catechins, widen its application scheme, and can alleviate the abuse of existing antibacterials and cause methicillin-resistant staphylococcus aureus to produce the phenomenon of drug resistance.
Technical scheme of the present invention is:
Unite in the application of preparation in the antibacterials with antibiotic again after any two or three associating in the catechins.
The mass ratio of catechin and epigallo catechin is 2: 1～8: 1, the mass ratio of catechin and L-Epicatechin gallate is 1: 1～8: 1, and the mass ratio of catechin, epigallo catechin and L-Epicatechin gallate is 1: 1: 1～8: 1: 1.
Described catechins is catechin, epigallo catechin and L-Epicatechin gallate.
Described antibiotic is any one of penicillins, cephalosporin apoplexy due to endogenous wind.
Described penicillin antibiotic is benzylpenicillin, ampicillin, oxazacillin, ampicillin sodium-sulbactam sodium.
Described cephalosporins comprises cefuroxime, cefpiramide.
Based on above-mentioned purpose, the technical scheme that the present invention uses be with two kinds in the catechins with anti-MRSA medicine in a kind of use in conjunction of carrying out, this application is not the application as the Therapeutic Method of disease, but the application in the medicine that is equipped with treatment disease (anti-MRSA), wherein the mass ratio of catechin and epigallo catechin is 2: 1～8: 1, the mass ratio of catechin and L-Epicatechin gallate is 1: 1～8: 1, and the mass ratio of catechin, epigallo catechin and L-Epicatechin gallate is 1: 1: 1～8: 1: 1.When the mass ratio of catechin and epigallo catechin is 2: 1, the mass ratio of catechin and L-Epicatechin gallate is 2: 1, when the mass ratio of catechin, epigallo catechin and L-Epicatechin gallate is can with the medication amount of minimum obtain optimum antibiotic effect of enhanced sensitivity at 1: 1: 1.Upper three kinds of compositions can be prepared into compositions, also can be three kinds of independent medicaments.Mentioned component can produce collaborative anti-MRSA and render a service, and can reduce the minimum inhibitory concentration (MIC) of anti-MRSA medicine.
The associating of uniting the associating, catechin and the epigallo catechin that comprise catechin and L-Epicatechin gallate of above-mentioned catechins, the associating of catechin, epigallo catechin and L-Epicatechin gallate; Above-mentioned antibiotic is the beta-lactam antibiotic antibiotic, such as penicillins, cephalosporins.In a preferred embodiment, above-mentioned antibacterials are benzylpenicillin, ampicillin, oxazacillin, cefuroxime, cefpiramide, ampicillin sodium-sulbactam sodium, are preferably oxazacillin and ampicillin.
The independent use of catechin can suppress the growth of part gram-negative bacteria and gram positive bacteria, and with the antibacterial efficacy that can obviously strengthen antibacterials after the antibacterials use in conjunction, but this antibiotic enhanced sensitivity does not have good effect at MRSA.By experiment, the applicant finds when coupling catechin and L-Epicatechin gallate, or coupling catechin and epigallo catechin, or behind coupling catechin, epigallo catechin and the L-Epicatechin gallate again with the antibiotic coupling, can obviously reduce the using dosage of anti-MRSA medicine; Simultaneously experiment also shows catechin coupling L-Epicatechin gallate, or catechin coupling epigallo catechin, or can obviously reduce the MRSA bacterium with the antibiotic coupling again behind catechin coupling epigallo catechin and the L-Epicatechin gallate and attack the mouse death rate that causes, significantly suppress the content of antibacterial in the Mouse Blood.
Therefore, the present invention has widened the new purposes of catechin, L-Epicatechin gallate, epigallo catechin, has improved the antibacterial efficacy of antibacterials, the drug resistance phenomenon that has alleviated the antibacterials abuse and caused by the antibacterials abuse.
The applicant finds in experiment when any two or three in catechin, epigallo catechin, the L-Epicatechin gallate combined, beta-lactam antibiotic is had obvious enhancement effect to the antibacterial effect of MRSA, but with its separately after antibiotic enhancement effect then substantially disappear.We further find by experiment, simple a kind of catechins and Antibiotic combination can not be obtained good antibiotic sensitization, but then have very strong antibiotic sensitization behind wherein any two or three catechins and Antibiotic combination, above-mentioned achievement in research had no any report in the past in present patent application.
Because there is in various degree drug resistance in MRSA to many antibacterials, therefore, any two or three catechins associating of employing of the present invention again with Antibiotic combination, can strengthen antibacterials to the antibacterial activity of MRSA.After the catechins of the present invention associating and uniting of antibacterials have very strong antibiotic sensitization, so that adopt the natural medicine with antibiotic sensitizing activity to strengthen antibacterials the antibacterial activity of MRSA is had more very important clinical value.
Description of drawings
Fig. 1 is that the collaborative ampicillin (AMP) of C associating ECG, oxazacillin (OXA) are to the Combination curve of Methicillin-resistant Staphylococcus aureus WHO-2.
Fig. 2 is that the collaborative ampicillin (AMP) of C associating EGC, oxazacillin (OXA) are to the Combination curve of Methicillin-resistant Staphylococcus aureus WHO-2.
Fig. 3 is that C, EGC, ECG three's combination and cooperation ampicillin (AMP), oxazacillin (OXA) are to the Combination curve of Methicillin-resistant Staphylococcus aureus WHO-2.
The protective effect of when Fig. 4 is C associating ECG and the collaborative use of OXA MRSA WHO-2 being attacked mice
The protective effect of when Fig. 5 is C associating EGC and the collaborative use of OXA MRSA WHO-2 being attacked mice
The protective effect of when Fig. 6 is C associating ECG, EGC and the collaborative use of OXA MRSA WHO-2 being attacked mice
The impact of when Fig. 7 is C associating EGC and the collaborative use of OXA MRSA WHO-2 being attacked bacterial number in the Mouse Blood
The impact of when Fig. 8 is C associating ECG and the collaborative use of OXA MRSA WHO-2 being attacked bacterial number in the Mouse Blood
The impact of when Fig. 9 is the collaborative use of C, ECG, EGC and OXA MRSA WHO-2 being attacked bacterial number in the Mouse Blood
The specific embodiment
The present invention is further illustrated below in conjunction with embodiment, but described embodiment only is used for explanation the present invention rather than restriction the present invention.
When the mass ratio of catechin and epigallo catechin is 2: 1～8: 1, the mass ratio of catechin and L-Epicatechin gallate is 1: 1～8: 1, and the mass ratio of catechin, epigallo catechin and L-Epicatechin gallate is 1: 1: 1～8: 1: 1.Especially the mass ratio when catechin and epigallo catechin is 2: 1, the mass ratio of catechin and L-Epicatechin gallate is 2: 1, can obtain with the medication amount of minimum optimum antibiotic effect of enhanced sensitivity when the mass ratio of catechin, epigallo catechin and L-Epicatechin gallate is 1: 1: 1.
The present embodiment is to study catechins and multiple beta-lactam antibiotic to MIC (minimum inhibitory concentration) and the MBC (minimum bactericidal concentration) of MRSAWHO-2.
Adopt the micropore dilution method, adjusting bacterial concentration is 10
5CFU/ml is inoculated in the 96 hole aseptic culture plates.13 kinds of medicines such as C, ECG, EGC, penicillin sodium, ampicillin are respectively take normal saline dilution as 5.12mg/ml.Add various medicines to containing in the antibacterial culturing hole, doubling dilution successively, the ultimate density of the 1st～11 hole medicine is followed successively by 512,256,128,64,32,16,8,4,2,1,0.5ug/ml.Put 37 ℃ of incubators and hatch 24h and 48h, read the positive and negative control hole, negative control hole is limpid, and the positive control hole is muddy.Medicine is the lowest concentration of drug of anti-bacteria naked eyes visible growth behind the 24h to the MIC of antibacterial, and medicine is the lowest concentration of drug of anti-bacteria naked eyes visible growth behind the 48h to the MBC of antibacterial.This time experimental result shows fully bacteria growing inhibiting of C, ECG, the independent use of EGC, and has observed the inhibitory effect of different pharmaceutical to this antibacterial.(seeing Table 1).
During independent use of 13 kinds of antibiotic of table 1 and catechins to MIC and the MBC of MRSA WHO-2
The present embodiment be to study C, ECG, EGC respectively with the OXA use in conjunction after on the impact of MRSA WHO-2MIC and MBC.
Adopt checkerboard type micropore dilution method, adjusting bacterial concentration is 10
5CFU/ml is inoculated in the 96 hole aseptic culture plates, and the medicine behind the observation compatibility is to MIC and the MBC of WHO-2.This time experimental result shows that C, ECG, EGC all can not obviously reduce MIC and the MBC of antibacterials respectively with after the OXA use in conjunction, or lower enhancement effect (such as OXA+C 64 μ g/ml, OXA+ECG 16 μ g/ml, FICI is 0.5) is only arranged.(seeing Table 2).
OXA MIC/MBC after table 2 C, ECG, EGC work in coordination with OXA respectively
The present embodiment be to study after C and ECG, C and EGC two medicine associatings or C, ECG and the associating of EGC three medicines and after the OXA use in conjunction on the impact of MRSA WHO-2 MIC.
Adopt checkerboard type micropore dilution method, adjusting bacterial concentration is 10
5CFU/ml is inoculated in the 96 hole aseptic culture plates, and the medicine behind the observation compatibility is to the MIC of WHO-2.Although this time no matter experimental result shows it is to use separately C, ECG, EGC, perhaps they all can not reduce the MIC of antibacterials respectively with after the OXA use in conjunction, but again with after the OXA use in conjunction MIC of MRSA WHO-2 are had significant reduction effect after C and ECG, C and EGC two medicine associatings or C, ECG and the associating of EGC three medicines.(seeing Table 3,4,5)
Antibacterials are to the MIC (μ g/ml) of MRSA WHO-2 when table 3 variable concentrations C associating ECG and the collaborative use of OXA
Antibacterials are to the MIC (μ g/ml) of MRSA WHO-2 when table 4 variable concentrations C associating EGC and the collaborative use of OXA
Antibacterials were to the MIC (μ g/ml) of MRSA WHO-2 when table 5 variable concentrations C, EGC, ECG united rear and the collaborative use of OXA
The present embodiment is to study after C and ECG, C and the EGC associating and benzylpenicillin, ampicillin, cefuroxime, cefpiramide, ampicillin sodium-sulbactam sodium use in conjunction after on the impact of MRSA WHO-2 MIC.
Adopt checkerboard type micropore dilution method, adjusting bacterial concentration is 10
5CFU/ml is inoculated in the 96 hole aseptic culture plates, and the medicine behind the observation compatibility is to MIC and the MBC of WHO-2.
5 kinds of antibiotic of table 6 and two kinds of catechins are united when using the MIC to MRSA WHO-2
Embodiment 5
The present embodiment is to study C and ECG use in conjunction beta-lactam antibiotic are attacked mice to WHO-2 protective effect.
Cleaning level 90 of the kind white mice in Kunming (Third Military Medical University's Experimental Animal Center provides), body weight 19.9 ± 0.5g/ only, male and female half and half, be divided at random matched group, WHO-2 group, WHO-2+OXA group, the WHO-2+C group, the WHO-2+ECG group, WHO-2+C+ECG group, WHO-2+OXA+C group, WHO-2+OXA+ECG group, WHO-2+OXA+C+ECG group.Every group of 10 animals.Matched group does not give any antibacterial or medicine; The WHO-2 group gives 6 * 10
9The WHO-2 bacterium that/kg lives; The WHO-2+OXA group begins to give the OXA200mg/kg/day intramuscular injection to 4h behind the bacterium; The WHO-2+C group begins to give the C80mg/kg/day intramuscular injection to 4h behind the bacterium; The WHO-2+ECG group begins to give the ECG40mg/kg/day intramuscular injection to 4h behind the bacterium; The WHO-2+C+ECG group begins to give C80mg/kg/day, ECG 40mg/kg/day intramuscular injection to 4h behind the bacterium; The WHO-2+OXA+C group begins to give OXA200mg/kg/day, the C80mg/kg/day intramuscular injection to 4h behind the bacterium; The WHO-2+OXA+ECG group begins to give OXA200mg/kg/day, the ECG40mg/kg/day intramuscular injection to 4h behind the bacterium; The WHO-2+OXA+C+ECG group: 4h begins 200mg/kg/day, C 80mg/kg/day, ECG40mg/kg/day intramuscular injection after giving bacterium.All medicine administrations every day 2 times, per 12 hours once, until dead mouse or ended by the 7th day.Give normal diet and drinking-water, observe mice ordinary circumstance and mortality rate in 7 days.No matter the result shows it is to use separately C, ECG, perhaps they all can not reduce the death toll of mice respectively with after the OXA use in conjunction, but C unite with ECG after again with the OXA use in conjunction after (seeing Table 7) then obviously reduce the mortality rate of mice.
The protective effect of when table 7 C associating ECG and the collaborative use of OXA MRSA WHO-2 being attacked mice
This experimental example is to study C and EGC use in conjunction beta-lactam antibiotic are attacked mice to WHO-2 protective effect.
90 of cleaning level Kunming kind white mice, body weight 19.9 ± 0.5g/, male and female half and half, be divided at random matched group, WHO-2 group, WHO-2+OXA group, the WHO-2+C group, WHO-2+EGC group, WHO-2+C+EGC group, WHO-2+OXA+C group, WHO-2+OXA+EGC group, WHO-2+OXA+C+EGC group.Every group of 10 animals.Matched group does not give any antibacterial or medicine; The WHO-2 group gives 6 * 10
9The WHO-2 bacterium that/kg lives; The WHO-2+OXA group begins to give the OXA200mg/kg/day intramuscular injection to 4h behind the bacterium; The WHO-2+C group begins to give C 40mg/kg/day intramuscular injection to 4h behind the bacterium; The WHO-2+EGC group begins to give the EGC80mg/kg/day intramuscular injection to 4h behind the bacterium; The WHO-2+C+EGC group begins to give C40mg/kg/day, EGC 80mg/kg/day intramuscular injection to 4h behind the bacterium; The WHO-2+OXA+C group begins to give OXA 200mg/kg/day, C 40mg/kg/day intramuscular injection to 4h behind the bacterium; The WHO-2+OXA+EGC group begins to give OXA 200mg/kg/day, the EGC80mg/kg/day intramuscular injection to 4h behind the bacterium; The WHO-2+OXA+C+EGC group: 4h begins to give OXA200mg/kg/day, C 40mg/kg/day, EGC 80mg/kg/day intramuscular injection after giving bacterium.All medicine administrations every day 2 times, per 12 hours once, until dead mouse or ended by the 7th day.Give normal diet and drinking-water, observe mice ordinary circumstance and mortality rate in 7 days.No matter the result shows it is to use separately C, EGC, perhaps they all can not reduce the death toll of mice respectively with after the OXA use in conjunction, but C unite with EGC after again with the OXA use in conjunction after (seeing Table 8) then obviously reduce the mortality rate of mice.
The protective effect of when table 8C associating EGC and the collaborative use of OXA MRSA WHO-2 being attacked mice
Embodiment 7
This experimental example is to study C, ECG, EGC use in conjunction beta-lactam antibiotic are attacked mice to WHO-2 protective effect.
Cleaning level 110 of the kind white mice in Kunming (Third Military Medical University's Experimental Animal Center provides), body weight 19.9 ± 0.5g/ only, male and female half and half, be divided at random matched group, WHO-2 group, WHO-2+OXA group, the WHO-2+C group, the WHO-2+ECG group, WHO-2+EGC group, WHO-2+C+ECG+EGC group, WHO-2+OXA+C group, WHO-2+OXA+ECG group, WHO-2+OXA+EGC group, WHO-2+OXA+C+EGC+ECG group.Every group of 10 animals.Matched group does not give any antibacterial or medicine; The WHO-2 group gives 6 * 10
9The WHO-2 bacterium that/kg lives; The WHO-2+OXA group begins to give the OXA200mg/kg/day intramuscular injection to 4h behind the bacterium; The WHO-2+C group begins to give the C80mg/kg/day intramuscular injection to 4h behind the bacterium; The WHO-2+ECG group begins to give ECG 20mg/kg/day intramuscular injection to 4h behind the bacterium; The WHO-2+EGC group: 4h begins to give EGC 20mg/kg/day intramuscular injection after giving bacterium; The WHO-2+C+ECG+EGC group begins to give C 80mg/kg/day, ECG 20mg/kg/day, EGC 20mg/kg/day intramuscular injection to 4h behind the bacterium; The WHO-2+OXA+C group begins to give OXA200mg/kg/day, the C80mg/kg/day intramuscular injection to 4h behind the bacterium; The WHO-2+OXA+ECG group begins to give OXA200mg/kg/day, the ECG20mg/kg/day intramuscular injection to 4h behind the bacterium; The WHO-2+OXA+EGC group: 4h begins to give OXA200mg/kg/day, EGC20mg/kg/day after giving bacterium; WHO-2+OXA+C+EGC+ECG group: OXA200mg/kg/day, ECG20mg/kg/day, C80mg/kg/day, EGC20mg/kg/day intramuscular injection.All medicine administrations every day 2 times, per 12 hours once, until dead mouse or ended by the 7th day.Give normal diet and drinking-water, observe mice ordinary circumstance and mortality rate in 7 days.No matter the result shows it is to use separately C, ECG, EGC, perhaps they all can not reduce the death toll of mice respectively with after the OXA use in conjunction, but after C, ECG, the EGC associating again with the OXA use in conjunction after (seeing Table 9) then obviously reduce the mortality rate of mice.
Table 9C, ECG, the protective effect that the EGC associating is rear and mice is attacked in the collaborative use of OXA to MRSA WHO-2
This experimental example is to study C and ECG use in conjunction antibacterials are attacked bacterial number in the blood of mice on WHO-2 impact.
54 of cleaning level Kunming kind white mice, body weight 20.3 ± 0.9g/, male and female half and half, be divided at random matched group, WHO-2 group, WHO-2+OXA group, the WHO-2+C group, WHO-2+ECG group, WHO-2+C+ECG group, WHO-2+OXA+C group, WHO-2+OXA+ECG group, WHO-2+OXA+C+ECG group.Every group of 6 animals.Drug treating is with experimental example 4, and 12 hours mouse orbits are aseptic after the administration gets blood and be applied on the agar plate that contains OXA100 μ g/ml, and in the 24th hour counting clump count.No matter it is to use separately C, ECG that the result shows, perhaps they can reduce bacterial number in the mouse blood respectively with after the OXA use in conjunction slightly, but after C and the ECG associating again with the OXA use in conjunction after (seeing Table 10) then can obviously reduce bacterial number in the mouse blood.
The collaborative impact of using bacterial number in the MRSA WHO-2 attack Mouse Blood of table 10C associating ECG and OXA
This experimental example is to study C and EGC use in conjunction antibacterials are attacked bacterial number in the blood of mice on WHO-2 impact.
54 of cleaning level Kunming kind white mice, body weight 19.5 ± 0.8g/, male and female half and half, be divided at random matched group, WHO-2 group, WHO-2+OXA group, the WHO-2+C group, WHO-2+EGC group, WHO-2+C+EGC group, WHO-2+OXA+C group, WHO-2+OXA+EGC group, WHO-2+OXA+C+EGC group.Every group of 6 animals.Drug treating is with experimental example 4, and 12 hours mouse orbits are aseptic after the administration gets blood and be applied on the agar plate that contains OXA100 μ g/ml, and in the 24th hour counting clump count.No matter it is to use separately C, EGC that the result shows, perhaps they can reduce bacterial number in the mouse blood respectively with after the OXA use in conjunction slightly, but after C and the EGC associating again with the OXA use in conjunction after (seeing Table 10) then can obviously reduce bacterial number in the mouse blood.
The collaborative impact of using bacterial number in the MRSA WHO-2 attack Mouse Blood of table 11C associating EGC and OXA
This experimental example is to study C, ECG, EGC use in conjunction antibacterials are attacked bacterial number in the blood of mice on WHO-2 impact.
54 of cleaning level Kunming kind white mice, body weight 18.8 ± 0.9g/ only, male and female half and half, WHO-2 group, WHO-2+OXA group, WHO-2+C group, WHO-2+ECG group, WHO-2+EGC group, WHO-2+C+ECG group, WHO-2+C+EGC group, WHO-2+OXA+C group, WHO-2+OXA+ECG group, WHO-2+OXA+EGC group, WHO-2+OXA+C+ECG group, WHO-2+OXA+C+EGC group, WHO-2+OXA+C+ECG+EGC group, every group of 6 animals.Drug treating is with experimental example 4, and 12 hours mouse orbits are aseptic after the administration gets blood and be applied on the agar plate that contains OXA100 μ g/ml, and in the 24th hour counting clump count.No matter it is to use separately C, EGC, EGC that the result shows, perhaps they can reduce bacterial number in the mouse blood respectively with after the OXA use in conjunction slightly, but after C and the EGC associating again with the OXA use in conjunction after (seeing Table 10) then can obviously reduce bacterial number in the mouse blood.
The collaborative impact of using bacterial number in the MRSAWHO-2 attack Mouse Blood of table 11C, ECG, EGC and OXA
Claims (3)
- After catechin in the catechins, epigallo catechin and the L-Epicatechin gallate associating again with any one antibiotic application of uniting in the preparation antibacterials of penicillins, cephalosporin apoplexy due to endogenous wind, the mass ratio of described catechin, epigallo catechin and L-Epicatechin gallate is 1:1:1～8:1:1.
- 2. application according to claim 1 is characterized in that: described Penicillin antibiotics is selected from benzylpenicillin, ampicillin, oxazacillin, ampicillin sodium-sulbactam sodium.
- 3. application according to claim 1 is characterized in that: described cephalosporins is selected from cefuroxime, cefpiramide.
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| EP1663124A4 (en) * | 2003-09-12 | 2009-04-29 | Mitsui Norin Kk | Antimicrobial compositions and methods of use |
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2010
- 2010-07-23 CN CN 201010234990 patent/CN101940574A/en active Pending
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2011
- 2011-07-19 CN CN 201110201611 patent/CN102205126B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5807564A (en) * | 1995-09-06 | 1998-09-15 | Mitsui Norin Co., Ltd. | Method of strengthening antibacterial action of antibiotics |
| CN101351198A (en) * | 2005-12-29 | 2009-01-21 | 三井农林株式会社 | Combination and method for ensuring dimethoxyphenecillin resistance staphylococcus aureus to be sensitive to benzoxazole cillin |
Non-Patent Citations (2)
| Title |
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| Paul D.Stapleton et al.Modulation of β-lactam resistance in Staphylococcus aureus by catechins and gallates.《International journal of antimicrobial agents》.2004,第462-467页. * |
| 华德兴等.绿茶及其提取物抗耐甲氧西林金黄色葡萄球菌作用研究.《中国抗生素杂志》.2010,第35卷(第3期),第228-233页. * |
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| Publication number | Publication date |
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| CN101940574A (en) | 2011-01-12 |
| CN102205126A (en) | 2011-10-05 |
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