CN109568318A - A kind of synergy system of the plant extracts with antibacterial activity - Google Patents

A kind of synergy system of the plant extracts with antibacterial activity Download PDF

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CN109568318A
CN109568318A CN201811577943.5A CN201811577943A CN109568318A CN 109568318 A CN109568318 A CN 109568318A CN 201811577943 A CN201811577943 A CN 201811577943A CN 109568318 A CN109568318 A CN 109568318A
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calcium salt
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向飞
萨拉肯特·L
李斯匹朋·H
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    • A—HUMAN NECESSITIES
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    • A61K31/00—Medicinal preparations containing organic active ingredients
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/47—Quinolines; Isoquinolines
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    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • 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
    • A61P31/10—Antimycotics

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Abstract

The present invention provides a kind of combined system being made of 2- cyclopropyl -4- phenylchinoline compound, which can enhance the fungistatic effect of the root Leutea avicennia Mozaff. acetone extract by synergistic effect.

Description

A kind of synergy system of the plant extracts with antibacterial activity
Technical field
The invention belongs to biomedicine technical fields, and in particular to a kind of to enhance Leutea by synergistic effect The combined system of avicennia Mozaff. extract antibacterial effect.
Background technique
Infectious diseases is the major class disease caused by the microorganism infections such as bacterium, helminth, fungi or virus, can be passed through Various approach are directly or indirectly propagated between human body.It is posted including antibiotic, antiviral agent, antifungal with anti-although having at present A variety of anti-infectives such as infested medicine can be used for the treatment of infectious diseases, cause a disease in this disease still global range or lethal One of the main reason for.2010, there are about 15,000,000 to die of infectious diseases in the whole world.
Although the antibiotic such as penicillins, cephalosporins, quinolones and synthetic antibacterial drug are applied in the mankind and thin Huge effect has been played in the struggle of bacterium sexuality dye, has effectively contained the propagation of bacterial infection.But with above-mentioned antibacterial The continuous of the application of medicine is popularized, and the bacterial drug resistance problem caused because of Irrational Use of Drugs becomes increasingly conspicuous.Therefore still having needs Developing has the active drug of high-efficiency antimicrobial for partial resistance bacterium.
Quinoline is structure parent nucleus common to a variety of compounds with antibacterial activity, such as SG10201405650S, DE102010051391 etc. discloses the quinolines with antibacterial activity in the prior art.
Being rich in plant has the ingredient with antibacterial activity, for example the present inventor has found in its pre-stage test, originates from her The acetone extract of the root of the Leutea avicennia Mozaff. in bright western part is to methicillin sensitive S grape The common human pathogen such as coccus has certain bacteriostasis, but it is staphylococcic to methicillin-resistant S Biocidal property is poor (not to reach IC50)。
Summary of the invention
The purpose of the present invention is to provide a kind of combined system being made of 2- cyclopropyl -4- phenylchinoline compound, The combined system can enhance the antibacterial effect of the root Leutea avicennia Mozaff. acetone extract by synergistic effect Fruit.
To achieve the goals above, one aspect of the present invention provides a kind of different, and molar ratio 0.01~100 it Between the combination that is constituted of the first 2- cyclopropyl -4- phenylchinoline compound and the 2nd 2- cyclopropyl -4- phenylchinoline compound System, the first 2- cyclopropyl -4- phenylchinoline compound is selected from shows one of compound A~E or its medicine as described below Acceptable salt on, the 2nd 2- cyclopropyl -4- phenylchinoline compound are selected from one of compound 1~9 as follows Or its pharmaceutically acceptable salt:
2- cyclopropyl -4- phenylchinoline compound of the present invention is the compound for being seen in prior art record, Specifically, 1~compound of compound 4 is seen in American Journal of Analytical Chemistry, 2010,2, 83~90 record；Compound 4~8 is seen inhttp://shodhganga.inflibnet.ac.in/bitstream/ 10603/22707/13/13_chapter%208.pdfThe record of one text；Compound 9 is seen in, pharmacy and clinical research, 2017,25 (4): 286~288 record；Compound A~compound F is seen in Chinese Journal of Pharmaceuticals, 2009,39 (11): 846~848 record.
On the one hand preferred, pharmaceutically acceptable salt of the present invention is calcium salt.
On the one hand preferred, the 2nd 2- cyclopropyl -4- phenylchinoline compound of the present invention is selected from as previously described Compound 1, compound 3, the calcium salt of compound 4, the calcium salt of compound 5, the calcium salt of compound 6, compound 7, is changed compound 2 Close one of the calcium salt of object 8 and compound 9.
According to the strong and weak sequence to act synergistically in bacteriostatic test, the preferably following combined system of combined system of the present invention One of (CI < 0.1):
The combined system that compound B and compound 8 are constituted with 75 molar ratio,
The combined system that compound C and compound 7 are constituted with 0.25 molar ratio,
The combined system that compound C and 5 calcium salt of compound are constituted with 100 molar ratio,
The combined system that compound E and compound 2 are constituted with 25 molar ratio,
The combined system that compound C and 6 calcium salt of compound are constituted with 0.01 molar ratio,
The combined system that compound B and 5 calcium salt of compound are constituted with 0.01 molar ratio,
The combined system that compound C and compound 3 are constituted with 0.75 molar ratio,
The combined system that compound D and compound 2 are constituted with 0.50 molar ratio,
The combined system that compound C and compound 2 are constituted with 75 molar ratio,
The combined system that compound B and 5 calcium salt of compound are constituted with 75 molar ratio,
The combined system that compound B and 5 calcium salt of compound are constituted with 100 molar ratio,
The combined system that compound E and compound 3 are constituted with 0.75 molar ratio,
The combined system that compound A and 5 calcium salt of compound are constituted with 75 molar ratio,
The combined system that compound C and 5 calcium salt of compound are constituted with 0.50 molar ratio,
The combined system that compound B and compound 8 are constituted with 0.25 molar ratio,
The combined system that compound D and 9 calcium salt of compound are constituted with 100 molar ratio,
The combined system that compound C and 5 calcium salt of compound are constituted with 75 molar ratio,
The combined system that compound B and compound 7 are constituted with 1 molar ratio,
The combined system that compound B and compound 2 are constituted with 100 molar ratio,
The combined system that compound E and 9 calcium salt of compound are constituted with 100 molar ratio,
The combined system that compound A and compound 7 are constituted with 0.25 molar ratio,
The combined system that compound A and compound 3 are constituted with 0.75 molar ratio,
The combined system that compound E and 6 calcium salt of compound are constituted with 0.25 molar ratio,
The combined system that compound C and compound 7 are constituted with 75 molar ratio,
The combined system that compound D and compound 7 are constituted with 0.01 molar ratio,
The combined system that compound D and 5 calcium salt of compound are constituted with 75 molar ratio,
The combined system that compound B and 6 calcium salt of compound are constituted with 0.25 molar ratio,
The combined system that compound E and compound 2 are constituted with 1 molar ratio,
The combined system that compound E and 5 calcium salt of compound are constituted with 25 molar ratio,
The combined system that compound D and compound 3 are constituted with 0.01 molar ratio,
The combined system that compound C and 9 calcium salt of compound are constituted with 0.75 molar ratio,
The combined system that compound B and compound 3 are constituted with 0.75 molar ratio,
The combined system that compound A and 5 calcium salt of compound are constituted with 50 molar ratio,
The combined system that compound B and compound 3 are constituted with 0.25 molar ratio,
The combined system that compound C and compound 3 are constituted with 25 molar ratio.
It is furthermore preferred that combined system of the present invention is selected from one of following combined system:
The combined system that compound B and compound 8 are constituted with 75 molar ratio,
The combined system that compound C and compound 7 are constituted with 0.25 molar ratio,
The combined system that compound C and 5 calcium salt of compound are constituted with 100 molar ratio,
The combined system that compound E and compound 2 are constituted with 25 molar ratio,
The combined system that compound C and 6 calcium salt of compound are constituted with 0.01 molar ratio,
The combined system that compound B and 5 calcium salt of compound are constituted with 0.01 molar ratio,
The combined system that compound C and compound 3 are constituted with 0.75 molar ratio,
The combined system that compound D and compound 2 are constituted with 0.50 molar ratio,
The combined system that compound C and compound 2 are constituted with 75 molar ratio,
The combined system that compound B and 5 calcium salt of compound are constituted with 75 molar ratio,
The combined system that compound B and 5 calcium salt of compound are constituted with 100 molar ratio,
The combined system that compound E and compound 3 are constituted with 0.75 molar ratio,
The combined system that compound A and 5 calcium salt of compound are constituted with 75 molar ratio,
The combined system that compound C and 5 calcium salt of compound are constituted with 0.50 molar ratio,
The combined system that compound B and compound 8 are constituted with 0.25 molar ratio,
The combined system that compound D and 9 calcium salt of compound are constituted with 100 molar ratio,
The combined system that compound C and 5 calcium salt of compound are constituted with 75 molar ratio,
The combined system that compound B and compound 7 are constituted with 1 molar ratio.
Most preferably, combined system of the present invention is selected from one of following combined system (CI < 0.02):
The combined system that compound B and compound 8 are constituted with 75 molar ratio,
The combined system that compound C and compound 7 are constituted with 0.25 molar ratio,
The combined system that compound C and 5 calcium salt of compound are constituted with 100 molar ratio,
The combined system that compound E and compound 2 are constituted with 25 molar ratio,
The combined system that compound C and 6 calcium salt of compound are constituted with 0.01 molar ratio,
The combined system that compound B and 5 calcium salt of compound are constituted with 0.01 molar ratio,
The combined system that compound C and compound 3 are constituted with 0.75 molar ratio,
Another aspect of the present invention provides the composition containing combined system as previously described.
Preferably, composition of the present invention can be made into selected from one of tablet, capsule and granule dosage form Oral preparation.
It is furthermore preferred that the oral preparation further contains diluent and lubricant.
It is further preferred that diluent of the present invention is fine selected from pregelatinized starch, starch, dextrin, sucrose, crystallite Tie up one of element, sorbierite, mannitol, lactose, calcium sulfate, calcium monohydrogen phosphate and calcium phosphate；Lubricant of the present invention is Selected from sodium stearyl fumarate, stearic acid, magnesium stearate, calcium stearate, paraffin oil, paraffin, glycerin monostearate, single palmitinic acid Glyceride, sodium acetate, sodium chloride, DL-leucine, sldium lauryl sulfate, magnesium laurylsulfate, polyethylene glycol, polyoxyethylene list One of stearate and Brij30.
Most preferably, preparation of the present invention can further containing Leutea avicennia Mozaff. rhizome third Ketone extract.
Oral solid formulation of the present invention can be used method well known to those of ordinary skill in the art and be prepared, The method that specific method can refer to but be not limited in " pharmacy " (the 8th edition) that Fang Liang is edited, People's Health Publisher publishes.This The preparation method of the invention granule be by combined system, diluent, mix lubricant to get.
The preparation method of capsule of the present invention is the filling glue by after combined system, diluent, mix lubricant Capsule to get.
The preparation method of tablet of the present invention is to carry out tabletting for after combined system, diluent, mix lubricant, To obtain the final product.
The content of combined system in oral solid formulation of the present invention and the dosage being thus related to can lead to It crosses pharmacological testing well known to those of ordinary skill in the art to be screened and optimized, the present invention is to this without specifically limited.
Supplementary product consumption in oral solid formulation of the present invention can be by well known to those of ordinary skill in the art Formulation method is screened and is optimized, and the present invention is to this without specifically limited.
Extracorporeal bacteria inhibitor test is the results show that of the present invention by the first 2- cyclopropyl -4- phenylchinoline compound and The combined system and Leutea avicennia Mozaff. rhizome acetone that two 2- cyclopropyl -4- phenylchinoline compounds are constituted Extract can generate the bacteriostasis of collaboration when 0.5 quality is than drug combination.
Specific embodiment
Below with reference to the embodiment of the present invention, clear, complete description is carried out to technical solution of the present invention, it is clear that retouched The embodiment stated is only a part of the embodiments of the present invention, instead of all the embodiments.Based on the embodiments of the present invention, Every other embodiment obtained by those of ordinary skill in the art without making creative efforts, belongs to this hair The range of bright protection.
The combined system that test example 1 is made of 2- cyclopropyl -4- phenylchinoline compound makees the In Vitro Bacteriostasis of tested bacterium Evaluation
Measure the combination of the present invention being made of 2- cyclopropyl -4- phenylchinoline compound respectively using filter paper enzyme In Vitro Bacteriostasis of the system to each tested bacterium.Specifically, with liquid-transfering gun draw prepared bacterial suspension (1 × 105Preparation method: MRSA ATCC43300 kind is activated [37 ± 1 DEG C, 3 days], recycling connects by/mL on TSB culture medium Kind ring beats easily a small amount of lawn from culture medium, is respectively added in the conical flask for being contained with 50mL sterile saline), uniformly apply It is put on agar plate surface after cooling, plate containing bacterium is made.Sterilizing filter paper piece is taken, lets off 2 times of incremental 6 kind concentration ladders respectively 1h is impregnated in the tested material methanol solution of degree, the 6mm circular filter paper piece impregnated is attached on the above-mentioned plate containing bacterium made, often A culture dish (diameter 90mm) sticks the filter papers of 3 dipped same mass concentration tested material methanol solutions, and (filter paper is as far as possible It is spaced identical), using 50% methanol solution as blank control.Processed plate containing bacterium is placed in 37 DEG C of insulating boxs and is cultivated For 24 hours, colony diameter is measured using crossing method, and calculates inhibiting rate (IR) according to following formula.
Using inhibiting rate (IR) to the first 2- cyclopropyl -4- phenylchinoline compound and the 2nd 2- cyclopropyl in combined system The logarithm (log (c)) of the total concentration (μ g/mL) of base -4- phenylchinoline compound is mapped, and carries out linear regression with Excel, First 2- cyclopropyl -4- phenylchinoline chemical combination in combined system when extrapolating generation specific depression effect (fa) according to regression equation The total concentration of object and the 2nd 2- cyclopropyl -4- phenylchinoline compound, i.e. ICfa(A)。
The evaluation of test example 2Leutea avicennia Mozaff. extract In Vitro Bacteriostasis effect
It is equally had rated using filter paper enzyme and is prepared according to method well known to those of ordinary skill in the art The In Vitro Bacteriostasis effect of Leutea avicennia Mozaff. acetone extract.Wherein, the preparation method of the extract is such as It is lower described:
Leutea avicennia Mozaff. rhizome is weighed, takes 20g fine powder that 15 times of 85% acetone, reflux is added after grinding 3h, filtering are extracted, filter residue is added second of 10 times of 85% acetone extraction, filtered, filtrate, rotary evaporation are concentrated into twice for merging In paste, vacuum oven low temperature drying is set to get spare.
Prepared bacterial suspension (1 × 10 is drawn with liquid-transfering gun5/ mL, preparation method: by MRSA ATCC43300 kind is activated [37 ± 1 DEG C, 3 days] on TSB culture medium, and oese is recycled to beat easily from culture medium on a small quantity Lawn is respectively added in the conical flask for being contained with 50mL sterile saline), uniformly it is applied to agar plate table after cooling Plate containing bacterium is made in face.Sterilizing filter paper piece is taken, lets off in the tested material methanol solution of 2 times of incremental 6 kind concentration gradients and soaks respectively 1h is steeped, the 6mm circular filter paper piece impregnated is attached on the above-mentioned plate containing bacterium made, each culture dish (diameter 90mm) is sticked The filter paper (filter paper is spaced identical as far as possible) of 3 dipped same mass concentration tested material methanol solutions, it is molten with 50% methanol Liquid is as blank control.Processed plate containing bacterium is placed in 37 DEG C of insulating boxs and is cultivated for 24 hours, bacterium is measured using crossing method Diameter is fallen, and calculates inhibiting rate (IR) according to following formula.
Using inhibiting rate (IR) to the logarithm of the concentration (μ g/mL) of the Leutea avicennia Mozaff. extract It is worth (log (c)) mapping, and carries out linear regression with Excel, when extrapolates specific depression effect (fa) of generation according to regression equation The concentration of the Leutea avicennia Mozaff. extract, i.e. ICfa(B)。
3 2- cyclopropyl -4- phenylchinoline compound combination system of test example is mentioned with Leutea avicennia Mozaff. Take the evaluation of the collaboration bacteriostasis of object drug combination
For every kind of 2- cyclopropyl -4- phenylchinoline compound combination system and the Leutea avicennia Mozaff. the drug combination of extract repeats test corresponding to test example 1 and test example 2 in parallel.
Specific 2- cyclopropyl -4- phenylchinoline compound combination system is taken, with the Leutea avicennia Mozaff. extract is dissolved in methanol after being mixed with 0.5 mass ratio, wherein 2- cyclopropyl -4- phenylchinoline compound combination The molal quantity of system with the gross mass of 2- cyclopropyl -4- phenylchinoline compound in combined system, then successively 2 times be diluted to 6 The solution of concentration gradient, it is spare.
Prepared bacterial suspension (1 × 10 is drawn with liquid-transfering gun5/ mL, preparation method: by MRSA ATCC43300 kind is activated [37 ± 1 DEG C, 3 days] on TSB culture medium, and oese is recycled to beat easily from culture medium on a small quantity Lawn is respectively added in the conical flask for being contained with 50mL sterile saline), uniformly it is applied to agar plate table after cooling Plate containing bacterium is made in face.Sterilizing filter paper piece is taken, lets off in the tested material methanol solution of 2 times of incremental 6 kind concentration gradients and soaks respectively 1h is steeped, the 6mm circular filter paper piece impregnated is attached on the above-mentioned plate containing bacterium made, each culture dish (diameter 90mm) is sticked The filter paper (filter paper is spaced identical as far as possible) of 3 dipped same mass concentration tested material methanol solutions, it is molten with 50% methanol Liquid is as blank control.Processed plate containing bacterium is placed in 37 DEG C of insulating boxs and is cultivated for 24 hours, bacterium is measured using crossing method Diameter is fallen, and calculates inhibiting rate (IR) according to following formula.
Using inhibiting rate (IR) to the total concentration (μ g/mL) of 2- cyclopropyl -4- phenylchinoline compound in mixed system Logarithm (log (c)) mapping, and linear regression is carried out with Excel, it is extrapolated according to regression equation and generates specific depression effect (fa) when in mixed system 2- cyclopropyl -4- phenylchinoline compound total concentration, i.e. ICfa(mixA), use ICfa(mixA)× 2, i.e., Obtain ICfa(mixB)。
It is calculated according to the following formula by the first 2- cyclopropyl -4- phenylchinoline compound and the 2nd 2- cyclopropyl -4- phenylchinoline The combined system and the extract drug combination index CI that compound is constituted.
As CI < 1, synergistic effect is indicated, and the smaller representative synergistic effect of CI is stronger, the results are shown in Table 1.
Table 1
Although as it can be seen from table 1 combined system of the present invention (highest inhibiting rate lower to the inhibitory activity of MRSA 5% or so), when it is with 0.5 mass ratio and the described extract drug combination, it but can significantly increase highest inhibition Rate, and the CI as fa ≈ 5% is < 1.
Embodiment 1 contains by the first 2- cyclopropyl -4- phenylchinoline compound and the 2nd 2- cyclopropyl -4- phenylchinoline Close the preparation of the tablet for the combined system that object is constitutedPrescription
Preparation method
The combined system and diluent, lubricant for taking recipe quantity, after being sufficiently mixed, tabletting, both.
Embodiment 2 contains by the first 2- cyclopropyl -4- phenylchinoline compound and the 2nd 2- cyclopropyl -4- phenylchinoline Close the preparation of the capsule for the combined system that object is constitutedPrescription
Preparation method
The combined system, diluent and lubricant for taking recipe quantity, be sufficiently mixed rear filling capsule to get.
Embodiment 3 contains by the first 2- cyclopropyl -4- phenylchinoline compound and the 2nd 2- cyclopropyl -4- phenylchinoline Close the preparation of the granule for the combined system that object is constitutedPrescription
Preparation method
The combined system, diluent and lubricant for taking recipe quantity, after being sufficiently mixed dispense to get.

Claims (10)

1. by different, and first 2- cyclopropyl -4- phenylchinoline compound and of the molar ratio between 0.01~100 The combined system that two 2- cyclopropyl -4- phenylchinoline compounds are constituted, which is characterized in that the first 2- cyclopropyl -4- benzene Base quinoline compound is selected from shows one of compound A~E or its pharmaceutically acceptable salt, the 2nd 2- cyclopropyl as described below Base -4- phenylchinoline compound is selected from one of compound 1~9 as follows or its pharmaceutically acceptable salt:
2. combined system according to claim 1, which is characterized in that the pharmaceutically acceptable salt is calcium salt.
3. combined system according to claim 1, which is characterized in that the 2nd 2- cyclopropyl -4- phenylchinoline compound It is the calcium for being selected from compound 1 as previously described, compound 2, compound 3, the calcium salt of compound 4, the calcium salt of compound 5, compound 6 One of salt, compound 7, compound 8 and calcium salt of compound 9.
4. combined system according to claim 1, which is characterized in that one in the preferably following combined system of the combined system Kind:
The combined system that compound B and compound 8 are constituted with 75 molar ratio,
The combined system that compound C and compound 7 are constituted with 0.25 molar ratio,
The combined system that compound C and 5 calcium salt of compound are constituted with 100 molar ratio,
The combined system that compound E and compound 2 are constituted with 25 molar ratio,
The combined system that compound C and 6 calcium salt of compound are constituted with 0.01 molar ratio,
The combined system that compound B and 5 calcium salt of compound are constituted with 0.01 molar ratio,
The combined system that compound C and compound 3 are constituted with 0.75 molar ratio,
The combined system that compound D and compound 2 are constituted with 0.50 molar ratio,
The combined system that compound C and compound 2 are constituted with 75 molar ratio,
The combined system that compound B and 5 calcium salt of compound are constituted with 75 molar ratio,
The combined system that compound B and 5 calcium salt of compound are constituted with 100 molar ratio,
The combined system that compound E and compound 3 are constituted with 0.75 molar ratio,
The combined system that compound A and 5 calcium salt of compound are constituted with 75 molar ratio,
The combined system that compound C and 5 calcium salt of compound are constituted with 0.50 molar ratio,
The combined system that compound B and compound 8 are constituted with 0.25 molar ratio,
The combined system that compound D and 9 calcium salt of compound are constituted with 100 molar ratio,
The combined system that compound C and 5 calcium salt of compound are constituted with 75 molar ratio,
The combined system that compound B and compound 7 are constituted with 1 molar ratio,
The combined system that compound B and compound 2 are constituted with 100 molar ratio,
The combined system that compound E and 9 calcium salt of compound are constituted with 100 molar ratio,
The combined system that compound A and compound 7 are constituted with 0.25 molar ratio,
The combined system that compound A and compound 3 are constituted with 0.75 molar ratio,
The combined system that compound E and 6 calcium salt of compound are constituted with 0.25 molar ratio,
The combined system that compound C and compound 7 are constituted with 75 molar ratio,
The combined system that compound D and compound 7 are constituted with 0.01 molar ratio,
The combined system that compound D and 5 calcium salt of compound are constituted with 75 molar ratio,
The combined system that compound B and 6 calcium salt of compound are constituted with 0.25 molar ratio,
The combined system that compound E and compound 2 are constituted with 1 molar ratio,
The combined system that compound E and 5 calcium salt of compound are constituted with 25 molar ratio,
The combined system that compound D and compound 3 are constituted with 0.01 molar ratio,
The combined system that compound C and 9 calcium salt of compound are constituted with 0.75 molar ratio,
The combined system that compound B and compound 3 are constituted with 0.75 molar ratio,
The combined system that compound A and 5 calcium salt of compound are constituted with 50 molar ratio,
The combined system that compound B and compound 3 are constituted with 0.25 molar ratio,
The combined system that compound C and compound 3 are constituted with 25 molar ratio.
5. combined system according to claim 4, which is characterized in that the combined system is one in following combined system Kind:
The combined system that compound B and compound 8 are constituted with 75 molar ratio,
The combined system that compound C and compound 7 are constituted with 0.25 molar ratio,
The combined system that compound C and 5 calcium salt of compound are constituted with 100 molar ratio,
The combined system that compound E and compound 2 are constituted with 25 molar ratio,
The combined system that compound C and 6 calcium salt of compound are constituted with 0.01 molar ratio,
The combined system that compound B and 5 calcium salt of compound are constituted with 0.01 molar ratio,
The combined system that compound C and compound 3 are constituted with 0.75 molar ratio,
The combined system that compound D and compound 2 are constituted with 0.50 molar ratio,
The combined system that compound C and compound 2 are constituted with 75 molar ratio,
The combined system that compound B and 5 calcium salt of compound are constituted with 75 molar ratio,
The combined system that compound B and 5 calcium salt of compound are constituted with 100 molar ratio,
The combined system that compound E and compound 3 are constituted with 0.75 molar ratio,
The combined system that compound A and 5 calcium salt of compound are constituted with 75 molar ratio,
The combined system that compound C and 5 calcium salt of compound are constituted with 0.50 molar ratio,
The combined system that compound B and compound 8 are constituted with 0.25 molar ratio,
The combined system that compound D and 9 calcium salt of compound are constituted with 100 molar ratio,
The combined system that compound C and 5 calcium salt of compound are constituted with 75 molar ratio,
The combined system that compound B and compound 7 are constituted with 1 molar ratio.
6. combined system according to claim 5, which is characterized in that the combined system is in following combined system It is a kind of:
The combined system that compound B and compound 8 are constituted with 75 molar ratio,
The combined system that compound C and compound 7 are constituted with 0.25 molar ratio,
The combined system that compound C and 5 calcium salt of compound are constituted with 100 molar ratio,
The combined system that compound E and compound 2 are constituted with 25 molar ratio,
The combined system that compound C and 6 calcium salt of compound are constituted with 0.01 molar ratio,
The combined system that compound B and 5 calcium salt of compound are constituted with 0.01 molar ratio,
The combined system that compound C and compound 3 are constituted with 0.75 molar ratio.
7. the composition containing combined system according to claim 1~any one of 6.
8. composition according to claim 7, which is characterized in that the composition can be made into selected from tablet, capsule and particle The oral preparation of one of agent dosage form.
9. composition according to claim 8, which is characterized in that the oral preparation further contains diluent and lubricant.
10. composition according to claim 9, which is characterized in that the preparation can further contain Leutea The acetone extract of avicennia Mozaff. rhizome.
CN201811577943.5A 2018-12-22 2018-12-22 A kind of synergy system of the plant extracts with antibacterial activity Withdrawn CN109568318A (en)

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