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CN109646428A - Vanillic acid is inhibiting the application in multidrug resistant staphylococcus aureus growth - Google Patents

Vanillic acid is inhibiting the application in multidrug resistant staphylococcus aureus growth Download PDF

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Publication number
CN109646428A
CN109646428A CN201910151567.1A CN201910151567A CN109646428A CN 109646428 A CN109646428 A CN 109646428A CN 201910151567 A CN201910151567 A CN 201910151567A CN 109646428 A CN109646428 A CN 109646428A
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staphylococcus aureus
resistant staphylococcus
multidrug
vanillic acid
drug
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CN201910151567.1A
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Inventor
钱卫东
沈兰芳
王婷
刘婵婵
刘淼
张家宁
孙照欢
杨敏
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Shaanxi University of Science and Technology
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Shaanxi University of Science and Technology
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/192Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents

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  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

本发明公开了香草酸在抑制多重耐药金黄色葡萄球菌生长中的应用,根据香草酸对耐利奈唑胺、甲氧苄啶、庆大霉素、环丙沙星、青霉素、头孢唑啉、克林霉素、万古霉素、苯唑西林、哌拉西林人源多重耐药金黄色葡萄球菌具有较好的体外杀灭作用,能够抑制多重耐药金黄色葡萄球菌的生长,且最低杀菌浓度为2.4mg/mL,最小抑菌浓度为0.3mg/mL,本发明提出了香草酸对人源多重耐药金黄色葡萄球菌的抑制作用。本发明可有效缓解或解决多重耐药金黄色葡萄球菌的耐药感染问题,降低病死率,为抑制人源多重耐药金黄色葡萄球菌提出新的思路,具有重要的实践意义。The invention discloses the application of vanillic acid in inhibiting the growth of multi-drug resistant Staphylococcus aureus. Clindamycin, vancomycin, oxacillin, piperacillin human multi-drug resistant Staphylococcus aureus have good in vitro killing effect, can inhibit the growth of multi-drug resistant Staphylococcus aureus, and the minimum bactericidal concentration It is 2.4 mg/mL, and the minimum inhibitory concentration is 0.3 mg/mL. The invention proposes the inhibitory effect of vanillic acid on human multidrug-resistant Staphylococcus aureus. The invention can effectively alleviate or solve the drug-resistant infection problem of multi-drug-resistant Staphylococcus aureus, reduce the fatality rate, and propose a new idea for inhibiting human-derived multi-drug-resistant Staphylococcus aureus, which has important practical significance.

Description

Vanillic acid is inhibiting the application in multidrug resistant staphylococcus aureus growth
Technical field
The present invention relates to effective component of chinese medicine vanillic acids as the research and development of the inhibitor of staphylococcus aureus and to answer With, and in particular to vanillic acid is inhibiting the application in multidrug resistant staphylococcus aureus growth.
Background technique
Staphylococcus aureus (Staphylococcus aureus) is the principal causative for causing human infectious disease Bacterium can cause many severe infections, can also cause pneumonia, pseudomembranous enteritis, pericarditis etc..Antibiotic is widely used, excessively Using bacterial drug resistance is continuously increased, cause bacterial drug resistance in global constantly diffusion, " superbacteria " continuously emerges, become The focus of global concern.The generation of multi-drug resistant bacteria brings huge challenge to clinical treatment, for example, invalid treatment not only promotees Postpone the state of an illness, and consumes social resources, aggravates national public finance burden.
On the problem of enhancing in face of bacterial drug resistance, Chinese herbal medicine shows advantageous advantage, for example, having poison secondary Act on the advantage and characteristic that small, medicine source is extensive, cheap.Thus, safely and effectively it is efficiently low to become people's searching for Chinese herbal medicine The new sources of the bacterial inhibitor of poison.
Vanillic acid as one of effective components of plants such as vanilla beans, vanilla pod and Radix picrorrhizae, both at home and abroad to its Antibacterial anti-inflammatory, it is anti-oxidant, inhibit tyrosinase activity, allelopathy, adjust nerve and procoagulant activity in terms of have it is certain Research, but report is less in terms of vanillic acid inhibits bacterial growth.
(Huang Yuqian, Yang Jingfeng, Liang Chunhao, old Shen put down one, Liu Xinyu to document, and honest and just clod of earth is farsighted, Yao Yuchen, Zhang Yu, Han Xiao Vanillic acid is to Germinating Peanut Seeds, growth of seedling and the influence of rhizosphere microflora [J] Scientia Agricultura Sinica, and 2018,51 (09): 1735-1745. the vanilla acid solution for) reporting various concentration can be such that the quantity of peanut rhizosphere bacteria and actinomyces drops It is low, inhibit the growth and breeding of bacterium and actinomyces in rhizosphere soil, and low rush high the phenomenon that pressing down is presented in the influence to soil fungi, The growth of fungi i.e. in the vanilla acid solution promotion peanut rhizosphere soil of low concentration, and the vanilla acid solution of high concentration is then to fungi Growth has certain inhibiting effect.About using vanillic acid as the report for inhibiting multidrug resistant staphylococcus aureus active constituent Road is not yet found.
Summary of the invention
The present invention is directed to the clinical drug-resistant problem of above-mentioned elaboration, starts with from existing resources of medicinal plant library, excavates potential Drug resistance bacteria inhibitor, and it is an object of the present invention to provide vanillic acid inhibit multidrug resistant staphylococcus aureus growth in application, be It develops novel antibiotic substitute and the multidrug resistant predicament offer practical basis of resistant Staphylococcus aureus is provided.
To achieve the goals above, the technical solution adopted by the present invention are as follows:
Vanillic acid is inhibiting the application in multidrug resistant staphylococcus aureus growth.
Preferably, the resistant Staphylococcus aureus is the resistance to Linezolid of source of people, trimethoprim, gentamicin, cyclopropyl Sha Xing, penicillin, cephazoline, clindamycin, vancomycin, oxacillin, in Piperacillin Multiple Classes of Antibiotics golden yellow Staphylococcus.
Preferably, the vanillic acid minimum bactericidal concentration is 2.4mg/mL, minimal inhibitory concentration 0.3mg/mL.
The beneficial effects of the present invention are embodied in:
Research the present invention is based on vanillic acid to the effect of source of people multidrug resistant staphylococcus aureus, is pressed down using vanillic acid The growth of multidrug resistant staphylococcus aureus processed is the research and development and application of multidrug resistant staphylococcus aureus inhibitor New thinking is provided, is with a wide range of applications in fields such as food, drugs.
It is husky to antibiotic-resistant Linezolid, trimethoprim, gentamicin, cyclopropyl that the present invention has further clarified vanillic acid Star, penicillin, cephazoline, clindamycin, vancomycin, oxacillin, the source of people staphylococcus aureus of Piperacillin are resistance to The inhibiting effect of pharmacological property is effectively relieved or solves the problems, such as the drug resistant infection of multidrug resistant staphylococcus aureus, reduces case fatality rate.
Specific embodiment
The present invention is described in further details below with reference to embodiment.It is described that the examples are only for explaining the invention, and Non- limiting the scope of the invention.
1, the drug sensitive experiment of source of people staphylococcus aureus
The present invention is bacterium germination with 10 plants of source of people staphylococcus aureuses (bacterial strain sample is derived from disease prevention and control center) Strain, select Linezolid, trimethoprim, gentamicin, Ciprofloxacin, penicillin, cephazoline, clindamycin, vancomycin, The drug susceptability test paper piece progress drug sensitive test of 10 kinds of oxacillin, Piperacillin common antibiotics.
The pure bacterium colony uniform dissolution of picking culture 18~for 24 hours adjusts its turbidity and 0.5 in 2~5mL sterile saline Maxwell opacity tube equal turbidity.50~200 μ L bacterium solutions of sterile absorption, even spread plate place 3~5min at room temperature.With sterile tweezer Drug sensitive test paper (diameter 6mm) is tightly attached to planar surface as required by son, and every kind susceptibility piece three parallel.By inoculated plate Be placed in 36~37 DEG C be incubated for 16~for 24 hours.Antibacterial circle diameter is measured with the vernier caliper of 0.02mm precision, with the diameter of inhibition zone To judge that the sensibility of drug, antibacterial result are marked according to U.S. clinical trial room national standardization administration committee (CLSl2017) Standard determines that criterion is shown in Table 1.Experimental result is shown in Table 2, faces the results show that 2# source of people staphylococcus aureus can be resistant to 8 kinds Common antibiotic on bed, therefore as the research object of next step experiment.
Table 1. U.S. clinical trial room national standardization administration committee (CLSl2017) standard determination result
Antibacterial circle diameter result in the drug sensitive experiment of 2. source of people staphylococcus aureus of table
Note: the unit of antibacterial circle diameter is mm in table 2, and numerical value is three parallel average values;
2, inhibiting effect of the vanillic acid to multiple antibiotic resistant strain
In order to fully consider drug safety, the present invention is using vanillic acid single active ingredient as research object, with vancomycin As positive control, the research of drug resistance inhibiting effect is carried out.The pure bacterium colony uniform dissolution of picking culture 18~for 24 hours is in 2~5mL In LB liquid medium, its turbidity and 0.5 Maxwell opacity tube equal turbidity are adjusted, and measure its OD with microplate reader600Value.Use dimethyl The vanillic acid that sulfoxide compound concentration is 30mg/mL is trained medical fluid, bacterium solution and LB liquid as medical fluid, using test tube doubling dilution Support base and be added in 96 well culture plates and is incubated overnight, the medical fluid group of various concentration is three parallel, it is ensured that experimental data can Reliability.
Using microplate reader measurement vanillic acid to the minimal inhibitory concentration (MIC) of multidrug resistant staphylococcus aureus.And it will Culture solution under MIC concentration, which is placed in sterile LB liquid medium, to be continued to cultivate, using microplate reader measurement vanillic acid to multiple The minimum bactericidal concentration (MBC) of resistant Staphylococcus aureus, experimental result is shown in Table 3.
The suppression result of 3. vanillic acid of table and vancomycin to source of people multidrug resistant staphylococcus aureus
As shown in Table 3, vanillic acid is mould to resistance to trimethoprim, gentamicin, Ciprofloxacin, penicillin, cephazoline, crin Element, oxacillin, Piperacillin multidrug resistant staphylococcus aureus inhibiting effect it is preferable, MIC be 300 μ g/mL, MBC is 2400 μ g/mL.
According to the above experimental result, the drug resistance feature of pathogenic bacteria of drug-resistant is solved in conjunction with Chinese herbal medicine, it can be by obtaining activity Single-item ingredient vanillic acid plays inhibiting effect directly against clinical main multidrug resistant staphylococcus aureus, can effectively delay Solution or the drug resistant infection for solving the problems, such as multidrug resistant staphylococcus aureus reduce case fatality rate, to inhibit source of people multidrug resistant gold Staphylococcus aureus proposes new thinking, has important practice significance.

Claims (10)

1.香草酸在抑制多重耐药金黄色葡萄球菌生长中的应用。1. Application of vanillic acid in inhibiting the growth of multidrug-resistant Staphylococcus aureus. 2.根据权利要求1所述的应用,其特征在于:所述多重耐药金黄色葡萄球菌为人源金黄色葡萄球菌。2 . The application according to claim 1 , wherein the multidrug-resistant Staphylococcus aureus is human Staphylococcus aureus. 3 . 3.根据权利要求1所述的应用,其特征在于:所述金黄色葡萄球菌的耐药性是通过纸片扩散法确定的。3 . The application according to claim 1 , wherein the drug resistance of the Staphylococcus aureus is determined by a paper sheet diffusion method. 4 . 4.根据权利要求1所述的应用,其特征在于:所述多重耐药金黄色葡萄球菌耐受的抗生素选自利奈唑胺、甲氧苄啶、庆大霉素、环丙沙星、青霉素、头孢唑啉、克林霉素、万古霉素、苯唑西林、哌拉西林中的多种。4. application according to claim 1 is characterized in that: the antibiotic that described multidrug-resistant staphylococcus aureus is resistant to is selected from linezolid, trimethoprim, gentamicin, ciprofloxacin, penicillin , Cefazolin, Clindamycin, Vancomycin, Oxacillin, Piperacillin. 5.根据权利要求1所述的应用,其特征在于:所述多重耐药金黄色葡萄球菌选自耐利奈唑胺、甲氧苄啶、庆大霉素、环丙沙星、青霉素、头孢唑啉、克林霉素、万古霉素、苯唑西林及哌拉西林的人源金黄色葡萄球菌。5. application according to claim 1, is characterized in that: described multidrug-resistant staphylococcus aureus is selected from linezolid resistance, trimethoprim, gentamicin, ciprofloxacin, penicillin, cefazole chlorin, clindamycin, vancomycin, oxacillin, and piperacillin of human Staphylococcus aureus. 6.根据权利要求5所述的应用,其特征在于:所述香草酸对所述人源金黄色葡萄球菌的最低杀菌浓度为2.4mg/mL,最小抑菌浓度为0.3mg/mL。The application according to claim 5, wherein the minimum bactericidal concentration of the vanillic acid to the human Staphylococcus aureus is 2.4 mg/mL, and the minimum inhibitory concentration is 0.3 mg/mL. 7.根据权利要求1所述的应用,其特征在于:所述香草酸对多重耐药金黄色葡萄球菌具有体外杀灭作用,以及抑制多重耐药金黄色葡萄球菌的体外生长。7 . The application according to claim 1 , wherein the vanillic acid has an in vitro killing effect on multidrug-resistant Staphylococcus aureus, and inhibits the in vitro growth of multidrug-resistant Staphylococcus aureus. 8 . 8.香草酸在制备抗多重耐药金黄色葡萄球菌的药物中的应用。8. The application of vanillic acid in the preparation of medicines against multidrug-resistant Staphylococcus aureus. 9.根据权利要求8所述的应用,其特征在于:所述多重耐药金黄色葡萄球菌为人源金黄色葡萄球菌。9 . The application according to claim 8 , wherein the multidrug-resistant Staphylococcus aureus is human Staphylococcus aureus. 10 . 10.根据权利要求8所述的应用,其特征在于:所述多重耐药金黄色葡萄球菌选自对利奈唑胺、甲氧苄啶、庆大霉素、环丙沙星、青霉素、头孢唑啉、克林霉素、万古霉素、苯唑西林、哌拉西林中多种抗生素耐药的人源金黄色葡萄球菌。10. application according to claim 8, is characterized in that: described multidrug-resistant staphylococcus aureus is selected from linezolid, trimethoprim, gentamicin, ciprofloxacin, penicillin, cefazole A variety of antibiotic-resistant human Staphylococcus aureus bacteria including chlorin, clindamycin, vancomycin, oxacillin, and piperacillin.
CN201910151567.1A 2019-02-28 2019-02-28 Vanillic acid is inhibiting the application in multidrug resistant staphylococcus aureus growth Pending CN109646428A (en)

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CN103087001A (en) * 2011-11-03 2013-05-08 南京大学 Vanillic acid 1,3,4-oxadiazole derivatives, and preparation methods and uses thereof
US20140315788A1 (en) * 2013-04-19 2014-10-23 Board Of Trustees Of The University Of Arkansas Methods for improving heart function
US20170000755A1 (en) * 2015-07-02 2017-01-05 Novus International Inc. Antimicrobial compositions and uses thereof

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103044284A (en) * 2011-10-13 2013-04-17 南京大学 Vanillic acid acylhydrazone derivatives, and preparation method and application thereof
CN103087001A (en) * 2011-11-03 2013-05-08 南京大学 Vanillic acid 1,3,4-oxadiazole derivatives, and preparation methods and uses thereof
US20140315788A1 (en) * 2013-04-19 2014-10-23 Board Of Trustees Of The University Of Arkansas Methods for improving heart function
US20170000755A1 (en) * 2015-07-02 2017-01-05 Novus International Inc. Antimicrobial compositions and uses thereof

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Title
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