CN110237058A - Citral is inhibiting the application in the growth of multidrug resistant Huo Shi enterobacteria - Google Patents
Citral is inhibiting the application in the growth of multidrug resistant Huo Shi enterobacteria Download PDFInfo
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- CN110237058A CN110237058A CN201910614507.9A CN201910614507A CN110237058A CN 110237058 A CN110237058 A CN 110237058A CN 201910614507 A CN201910614507 A CN 201910614507A CN 110237058 A CN110237058 A CN 110237058A
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- huo shi
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- shi enterobacteria
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/11—Aldehydes
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- 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
- A61P31/04—Antibacterial agents
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Abstract
The invention discloses citrals to inhibit the application in the growth of multidrug resistant Huo Shi enterobacteria, there is preferable killing in vitro effect according to multidrug resistant Huo Shi enterobacteria of the citral to resistance to Piperacillin, bromine lattice door spit of fland, Imipenem, Ofloxacin, furantoin, cephalo thiophene quinoline, acidum nalidixicum, it is able to suppress the growth of multidrug resistant Huo Shi enterobacteria, and minimum bactericidal concentration is 2.8mg/mL, minimal inhibitory concentration is 2.4mg/mL, the invention proposes citrals to the inhibiting effect of multidrug resistant Huo Shi enterobacteria, is with a wide range of applications in field of medicaments.
Description
Technical field
Research and development and application the present invention relates to effective component of chinese medicine citral as bacterial inhibitor, and in particular to lemon
Lemon aldehyde is inhibiting the application in the growth of multidrug resistant Huo Shi enterobacteria.
Background technique
Huo Shi enterobacteria (Enterobacter hormaechei) is a kind of Gram-negative bacteria, and amphimicrobian is easy
It is grown on ordinary culture medium, is present in humans and animals enteron aisle.Huo Shi enterobacteria can cause animal and people to infect under given conditions,
It is conditioned pathogen, can be separated to from infection animal or animal wound, case caused by infecting includes brain soldier's (pleasant virtue
Research [J] the China nosocomial infection of pine, Zhu Yan, Xie Zunjin patients with cerebral apoplexy phlegm Dorothy Holman enterobacteria drug resistance and resistance mechanism
Learn magazine, 2011,21 (05): 1025-1026.), premature labor and the bacteremia of weak baby etc..Currently, the domestic research to the bacterium
Very few (the research of Li Luyao, Liu Mengjia, Teng Mingming, Wang Le, Zhang Yaoxiang, Liu Ping Qi Huo Shi enterobacteria biological characteristics of report
[J] animal and veterinary magazine, 2017,36 (04): 1-2+6.), and Huo Shi enterobacteria multidrug resistant and Chinese medical extract inhibit it
The report of aspect is less.
In recent years, as the kind of antibacterials, especially antibiotic increases and is widely used, bacterial drug resistance problem day
It is beneficial serious, seriously affect the therapeutic effect of infectious diseases and the rehabilitation of patient.Using Chinese medicine treatment bacterium infected with long
History, the researchers of many traditional Chinese medicines done relevant research for the antibacterial therapy of Chinese medicine, proposed Chinese medicine in anti-infective side
Face has many advantages, such as the broad-spectrum antimicrobial effect of low drug resistance, multiaction target position, and medicine source is extensive, cheap (Lu Penglei, Cai
Few flat TCM in Vitro drug sensitive test present Research [J] laboratory medicine and clinical, 2018,15 (15): 2339-2342.).
The litsea citrate oil extracted from the fruit of a cubeb litsea tree is a kind of natural perfume material of complicated component, wherein citral be mainly at
Point, general content between 60%~80%, research shows that citral treatment cardiovascular disease, antiallergy of relievining asthma, it is antibacterial, control
Treat colonic diarrhea etc. effectively (research [J] of Zhang Shengqiang, Zhang Qi, Wang Suling, He Lin citral Benexate Hydrochloride
China Medicine University's journal, 1999 (06): 37-39.).
(state's grain husk, Zhou Yuhui, Wang Peng, Chen Shang Xing, Fan Guorong, Wang Zongde citral and its derivative are to oil tea for state's grain husk et al.
Bacteriostatic activity [J] the Jiangsu's agriculture science of anthrax bacteria, 2016,44 (12): 167-171.) it is ground using mycelial growth rate method
Study carefully the influence that 10 kinds of compounds such as citral and its derivative grow Oil Tea Anthracnose bacterium, finds citral and its derivative
There is certain inhibiting effect to Oil Tea Anthracnose bacterium, and inhibitory effect increases with concentration and enhanced.Li Zhaoshuan et al. (Li Zhao
It is double, Wang Xinan, Wang Peng, Chen Shang Xing, Fan Guorong, inhibitory activity of the Wang Zongde natural lemon aldehyde derivatives to food spoilage bacterium
[J] Zhejiang Agriculture journal, 2016,28 (11): 1928-1933.) inhibition zone method and Double broth dilution method are used, test 12
Kind of natural lemon aldehyde derivative compound to escherichia coli, staphylococcus aureus, staphylococcus epidermis, Pseudomonas aeruginosa it is antibacterial
Activity finds that 12 kinds of natural lemon aldehyde derivative compounds have certain fungistatic effect to 4 kinds of bacteriums.Tang Huan et al. (Tang Huan, king
Spring, Zhou Likun, five kinds of Extracts from Plant Recourses of model essay surprise protect inhibitory effect [J] the historical relic of l Museum Exhibition Hal air source bacterium
Shield and archaeology science, 2019,31 (01): 50-57.) using 5 kinds of Extracts from Plant Recourses as cleanser, in l Museum Exhibition Hal
The gas phase that collected air microbe carries out planar surface is stifling, and then by viable bacteria counting method and is based on bacterial 16 S r RNA
Polymerase chain reaction-denaturing gradient gel electrophoresis technique of gene, the best Extracts from Plant Recourses of discovery fungistatic effect are lemon
Lemon aldehyde, it is most weak for geranium oil.But not yet find the research report for inhibiting Huo Shi enterobacteria about citral.
Summary of the invention
The purpose of the present invention is to provide citrals to inhibit the application in the growth of multidrug resistant Huo Shi enterobacteria, for exploitation
Novel antibiotic substitute provides practical basis.
To achieve the goals above, the technical solution adopted by the present invention are as follows:
Determine that Huo Shi enterobacteria to the drug resistance of antibiotic, determines citral by doubling dilution using disk diffusion method
To the minimum bactericidal concentration and minimal inhibitory concentration of Huo Shi enterobacteria.The result shows that: non-antibiotic class compound citral is to more
Weight drug resistance Huo Shi enterobacteria has preferable bacteriostasis, can be used for inhibiting the growth of multidrug resistant Huo Shi enterobacteria.
Preferably, the multidrug resistant Huo Shi enterobacteria is source of people or the resistance to Piperacillin of animal sources, bromine lattice door spit of fland, imines training
South, Ofloxacin, furantoin, cephalo thiophene quinoline, in acidum nalidixicum Multiple Classes of Antibiotics Huo Shi enterobacteria.
Preferably, the minimum bactericidal concentration of the citral is 2.8mg/mL, minimal inhibitory concentration 2.4mg/mL.
Preferably, the citral is to resistance to Piperacillin, bromine lattice door spit of fland, Imipenem, Ofloxacin, furantoin, head
The Huo Shi enterobacteria of spore thiophene quinoline and acidum nalidixicum is inhibited.
The beneficial effects of the present invention are embodied in:
The present invention starts with from existing resources of medicinal plant library, excavates potential drug resistance bacteria inhibitor, is based on citral pair
The Effect study of multidrug resistant Huo Shi enterobacteria inhibits the growth of multidrug resistant Huo Shi enterobacteria using citral, is multiple resistance to
The research and development of medicine Huo Shi enterobacteria inhibitor and application provide new thinking, and provide for solution antibiotics drug resistance beneficial
It helps, is with a wide range of applications in field of medicaments.
Further, the present invention is directed to clinical drug-resistant problem, the inhibition using citral to multidrug resistant Huo Shi enterobacteria
Effect, as the substitute of antibiotic, can be relieved or solve the problems, such as the drug resistant infection of multidrug resistant Huo Shi enterobacteria, reduce
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 Huo Shi enterobacteria
Using 2 plants of source of people Huo Shi enterobacterias as starting strain, (bacterial strain sample is derived from the Chinese People's Liberation Army and always cures the present invention
Institute), select Piperacillin, gentamicin, bromine lattice door spit of fland, Imipenem, Ofloxacin, furantoin, cephalo thiophene quinoline, acidum nalidixicum
The drug susceptability test paper piece of 8 kinds of antibiotic carries out drug sensitive test.
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 susceptability test paper piece (diameter 6mm) is tightly attached to planar surface as required by son, and every kind drug susceptability test paper piece three parallel.It will be inoculated with
Plate 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 straight of inhibition zone
Diameter judges source of people Huo Shi enterobacteria to the sensibility of drug, and antibacterial result is according to the national standardization management of U.S. clinical trial room
The committee (CLSl2017) standard determination, criterion are shown in Table 1.Experimental result is shown in Table 2, the results show that wherein one plant of source of people is suddenly
Family name enterobacteria (1# bacterial strain) can be resistant to 7 kinds of antibiotic clinically used.
Table 1. U.S. clinical trial room national standardization administration committee (CLSl2017) standard determination result
The drug sensitive experiment antibacterial circle diameter result of 2. source of people Huo Shi enterobacteria of table
Note: the unit of antibacterial circle diameter is mm, and numerical value is three parallel average values
2, inhibiting effect of the citral to multiple antibiotic resistant strain
In order to fully consider drug safety, the present invention is using citral single active ingredient as research object, with gentamicin
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 citral that sulfoxide compound concentration is 50mg/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 it is credible
Degree.
Using microplate reader measurement citral to the minimal inhibitory concentration of multidrug resistant Huo Shi enterobacteria (1# bacterial strain, 2# bacterial strain)
(MIC).And the culture solution under MIC concentration is transferred and continues to cultivate in sterile LB liquid medium, it is measured using microplate reader
For citral to the minimum bactericidal concentration (MBC) of multidrug resistant Huo Shi enterobacteria, experimental result is shown in Table 3.
Suppression result of 3. citral of table to source of people multidrug resistant Huo Shi enterobacteria
As shown in Table 3, citral is to resistance to Piperacillin, bromine lattice door spit of fland, Imipenem, Ofloxacin, furantoin, cephalo
The inhibiting effect of the multidrug resistant Huo Shi enterobacteria of thiophene quinoline, acidum nalidixicum is preferable, by taking 1# bacterial strain as an example, MIC 2.4mg/mL,
MBC is 3.2mg/mL.
According to the above experimental result, the features such as Chinese herbal medicine is not likely to produce drug resistance is integrated, can pass through and obtain citral activity
Single-item ingredient plays inhibiting effect directly against multidrug resistant Huo Shi enterobacteria, is effectively relieved or solves multidrug resistant Huo Shi intestines
The drug resistance of bacillus, infection, the problems such as causing a disease, effectively performance inhibiting effect, reduce pathogenicity rate and case fatality rate, to inhibit multidrug resistant
Huo Shi enterobacteria proposes new thinking, has established solid foundation to develop the inhibitor of multidrug resistant Huo Shi enterobacteria.
Claims (10)
1. citral is inhibiting the application in the growth of multidrug resistant Huo Shi enterobacteria.
2. application according to claim 1, it is characterised in that: the multidrug resistant Huo Shi enterobacteria is source of people or animal sources
Huo Shi enterobacteria.
3. application according to claim 1, it is characterised in that: the Huo Shi enterobacteria is to pass through to the drug resistance of antibiotic
What disk diffusion method determined.
4. application according to claim 1, it is characterised in that: the antibiotic choosing of the multidrug resistant Huo Shi enterobacteria tolerance
From a variety of in Piperacillin, bromine lattice door spit of fland, Imipenem, Ofloxacin, furantoin, cephalo thiophene quinoline, acidum nalidixicum.
5. application according to claim 4, it is characterised in that: minimum bactericidal of the citral to the Huo Shi enterobacteria
Concentration is 2.8mg/mL, minimal inhibitory concentration 2.4mg/mL.
6. application according to claim 1, it is characterised in that: the multidrug resistant Huo Shi enterobacteria is selected from resistance to piperazine and draws west
Woods, bromine lattice door spit of fland, Imipenem, Ofloxacin, furantoin, cephalo thiophene quinoline and acidum nalidixicum Huo Shi enterobacteria.
7. application according to claim 1, it is characterised in that: the citral has body to multidrug resistant Huo Shi enterobacteria
Outer killing effect, and inhibit the growth in vitro of multidrug resistant Huo Shi enterobacteria.
8. application of the citral in the drug for preparing anti-multidrug resistant Huo Shi enterobacteria.
9. application according to claim 8, it is characterised in that: the multidrug resistant Huo Shi enterobacteria is source of people or animal sources
Huo Shi enterobacteria.
10. application according to claim 8, it is characterised in that: the multidrug resistant Huo Shi enterobacteria, which is selected from, draws west to piperazine
Woods, bromine lattice door spit of fland, Imipenem, Ofloxacin, furantoin, cephalo thiophene quinoline, the drug resistant Huo Shi of Multiple Classes of Antibiotics in acidum nalidixicum
Enterobacteria.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201910614507.9A CN110237058B (en) | 2019-07-09 | 2019-07-09 | Application of citral in inhibition of growth of multidrug-resistant enterobacter heumakii |
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| CN201910614507.9A CN110237058B (en) | 2019-07-09 | 2019-07-09 | Application of citral in inhibition of growth of multidrug-resistant enterobacter heumakii |
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| CN110237058B CN110237058B (en) | 2022-04-29 |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017006252A1 (en) * | 2015-07-08 | 2017-01-12 | Rheinisch-Westfaelische Technische Hochschule Aachen (Rwth) | Extracellular production of designer hydroxyalkanoyloxy alkanoic acids with recombinant bacteria |
| CN106566845A (en) * | 2016-11-10 | 2017-04-19 | 南京农业大学 | Biological surfactant produced by Enterobacter hormaechei and applications thereof |
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2019
- 2019-07-09 CN CN201910614507.9A patent/CN110237058B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017006252A1 (en) * | 2015-07-08 | 2017-01-12 | Rheinisch-Westfaelische Technische Hochschule Aachen (Rwth) | Extracellular production of designer hydroxyalkanoyloxy alkanoic acids with recombinant bacteria |
| CN106566845A (en) * | 2016-11-10 | 2017-04-19 | 南京农业大学 | Biological surfactant produced by Enterobacter hormaechei and applications thereof |
Non-Patent Citations (3)
| Title |
|---|
| BIWEI YANG ET AL.: "Occurrence of Enterobacter hormaechei carrying blaNDM-1 and blaKPC-2", 《DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE》 * |
| I.G. SANDRI ET AL.: "Antimicrobial activity of the essential oils of Brazilian species of the genus Cunila against foodborne pathogens and spoiling bacteria", 《FOOD CHEMISTRY》 * |
| 冯婷婷等: "阴沟肠杆菌感染与耐药机制的研究进展", 《中国人兽共患病学报》 * |
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