CN106798746A - Ursolic acid new application and the composition containing ursolic acid and application thereof - Google Patents
Ursolic acid new application and the composition containing ursolic acid and application thereof Download PDFInfo
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Abstract
The invention belongs to biomedicine field, and in particular to the new application of ursolic acid and the composition containing ursolic acid and application thereof, more particularly to ursolic acid is suppressing the purposes that Staphylococcus Aureus Biofilm is formed.Experiment proves that ursolic acid can suppress the formation of Staphylococcus Aureus Biofilm in vitro, and it can make the Forming ability reduction by 8~32.8% of Staphylococcus Aureus Biofilm.Present invention also offers a kind of composition, it includes ursolic acid and antibiotic, on the one hand both combination can improve inhibitory action of the ursolic acid to Staphylococcus Aureus Biofilm, on the other hand the effective dose of antibiotic can substantially be reduced, bacterial drug resistance can be suppressed simultaneously, be suitable to popularization and application on a large scale.
Description
Technical field
The invention belongs to biomedicine field, and in particular to ursolic acid new application and composition and its use containing ursolic acid
On the way.
Background technology
Staphylococcus aureus is the common field planting bacterium of human body skin and nasal cavity, while being also cause clinical infection common
Pathogenic bacteria, can both cause local pyogenic infection, such as pyogenic infection of carbuncle, furuncle, epifolliculitis, paronychia and surgical incision part,
Also the systemic infections such as pneumonia, osteomyelitis, meningitis, pyogenic arthritis, endocarditis and pyemia, septicemia can be caused.
Bacterial biof iotalm is also referred to as biofilm, is bacterial adhesion on tissue or medical material surface, by discharge polysaccharide and
The population of cells with stereochemical structure that albumen forms hydrated matrix wrapping thalline and constitutes is bacterium in order to adapt to living environment
And the existence form a kind of corresponding with planktonic cells for being formed.Now, clinically many chronic infections have with bacterial biof iotalm
Very big association.Biomembrane wraps up whole thalline, causes antibiotic to be difficult to contact thalline, it is impossible to directly to kill thalline, very big shadow
Ring the therapeutic effect of antibiotic.Antibiotic-Antibiotic combination effect is clinically frequently used, bacterium is killed, but up to not
To the effect of anticipation.
Ursolic acid, it is very wide in distributed in nature, can be natural from honeysuckle, dark plum and hawthorn, Fructus Corni, rose hip etc.
In plant, there are some researches show ursolic acid has various pharmacological activity such as calmness, anti-inflammatory, antibacterial, anti-diabetic, anticancer.At present,
It is reported that ursolic acid can obtain good bactericidal effect with antibiotic combination.Such as Chinese patent application CN101543499A
In the application of antibiosis, it is related to be combined ursolic acid and penicillin in overriding resistance golden yellow a kind of natural compound ursolic acid
Application in terms of staphylococcus, the invention points out that ursolic acid has preferably to staphylococcus aureus in vitro with penicillin combination
Antibacterial activity, minimum inhibitory concentration be 1.3 μ g/disc.But, research of the invention to ursolic acid is only lived in its in-vitro antibacterial
Property aspect, be not directed to whether it can in vitro suppress or prevent Staphylococcus Aureus Biofilm from being formed.
In addition, at present due to antibiotic dosage it is excessive caused by the internal organs such as human nerve, marrow, liver, kidney produce compared with
The event of big adverse reaction is more and more.Renal toxicity reaction is easily caused as gentamicin is excessively used, animal experiments prove that,
Gentamicin can cause a small number of proximal tubulars damages, detection of glomeruli filtration function obstacle and glomerulus ultrastructure exception and work(
Can step-down.In addition, the event of the human body serious adverse reaction caused by Cefradine is also more and more, it is bad anti-in national drug
Answer what inspection center issued《Adverse drug reaction communication》In point out, because of the severely adverse event that Cefradine causes
It is 15.0%, wherein, the Adverse Event about blood urine accounts for 97.63%.Therefore, how the validity of antibiotic is being kept
The consumption of antibiotic is controlled simultaneously as the technical problem of current urgent need to resolve.
The content of the invention
In order to solve technical problem present in prior art, it is an object of the invention to provide a kind of new use of ursolic acid
Way and have composition of ursolic acid and application thereof, to solve disadvantages described above.
One of the object of the invention is to provide a kind of composition containing ursolic acid preparing for suppressing or preventing golden yellow
Purposes in color Staphylococcus Biofilm growth medicine.
Further, the composition includes ursolic acid and antibiotic, and the content of ursolic acid is 1.83 in the composition
~10.05 μ g/ml.
Further, the antibiotic is selected from lavo-ofloxacin, ROX, Cefradine, gentamicin and A Moxi
One kind in woods.
Further, the antibiotic is selected from lavo-ofloxacin, and the content of ursolic acid is 5.93 μ g/ml in the composition
~10.05 μ g/ml, the content of the lavo-ofloxacin is 0.03 μ g/ml~0.12 μ g/ml.
Further, the content of ursolic acid is 10.05 μ g/ml in the composition, and the content of the lavo-ofloxacin is
0.12μg/ml。
Further, the content of ursolic acid is 5.93 μ g/ml in the composition, and the content of the lavo-ofloxacin is
0.12μg/ml。
Further, the content of ursolic acid is 7.76 μ g/ml in the composition, and the content of the lavo-ofloxacin is
0.12μg/ml.。
Further, the antibiotic be selected from ROX, in the composition content of ursolic acid be 5.93 μ g/ml~
10.05 μ g/ml, the content of the ROX is 0.15 μ g/ml.
Further, the content of ursolic acid is 10.05 μ g/ml in the composition, and the content of the ROX is
0.15μg/ml。
Further, the antibiotic be selected from Cefradine, in the composition content of ursolic acid be 3.65 μ g/ml~
10.05 μ g/ml, the content of the Cefradine is 0.3 μ g/ml~1.2 μ g/ml.
Further, the content of ursolic acid is 10.05 μ g/ml in the composition, and the content of the Cefradine is 0.3
μg/ml。
Further, the content of ursolic acid is 7.76 μ g/ml in the composition, and the content of the Cefradine is 0.6 μ
g/ml。
Further, the content of ursolic acid is 10.05 μ g/ml in the composition, and the content of the Cefradine is 0.6
μg/ml。
Further, the antibiotic be selected from gentamicin, in the composition content of ursolic acid be 5.93 μ g/ml~
10.05 μ g/ml, the content of the gentamicin is 0.03 μ g/ml~0.125 μ g/ml.
Further, the content of ursolic acid is 5.93 μ g/ml~10.05 μ g/ml, the gentamicin in the composition
Content be 0.06 μ g/ml~0.123 μ g/ml.
Further, the content of ursolic acid is 10.05 μ g/ml in the composition, and the content of the gentamicin is
0.123μg/ml。
Further, the content of ursolic acid is 7.76 μ g/ml in the composition, and the content of the gentamicin is
0.123μg/ml。
Further, the content of ursolic acid is 10.05 μ g/ml in the composition, and the content of the gentamicin is
0.061μg/ml。
Further, the content of ursolic acid is 7.76 μ g/ml in the composition, and the content of the gentamicin is
0.061μg/ml。
Further, the content of ursolic acid is 5.93 μ g/ml in the composition, and the content of the gentamicin is
0.123μg/ml。
Further, the antibiotic be selected from Amoxicillin, in the composition content of ursolic acid be 3.65 μ g/ml~
10.05 μ g/ml, the content of the Amoxicillin is 0.015 μ g/ml~0.06 μ g/ml.
Further, the content of ursolic acid is 5.93 μ g/ml in the composition, and the content of the Amoxicillin is 0.06
μg/ml。
Further, the content of ursolic acid is 3.65 μ g/ml in the composition, and the content of the Amoxicillin is 0.03
μg/ml。
Further, the content of ursolic acid is 5.93 μ g/ml in the composition, and the content of the Amoxicillin is 0.06
μg/ml。
Further, the composition is oral formulations or external preparation.
Further, the oral formulations include tablet, capsule, powder, dripping pill, pill, granule, supensoid agent, spraying
Agent, suppository or elixir；The external preparation includes creme or paste.
Another goal of the invention of the invention is to provide a kind of suppression or prevent what Staphylococcus Aureus Biofilm from growing
Composition, the composition includes ursolic acid and antibiotic.
Further, the antibiotic is selected from lavo-ofloxacin, ROX, Cefradine, gentamicin and A Moxi
One kind in woods.
Except, preparing suppression or preventing Staphylococcus Aureus Biofilm from giving birth to present invention also offers combinations of the above thing
Purposes in medicine long.
The molecular formula of ursolic acid that the present invention is provided is：C30H48O3, No. CAS is：77-52-1.
The current research to ursolic acid is not directed to whether it can suppress in vitro only in terms of its antibacterial activity in vitro
Or prevent Staphylococcus Aureus Biofilm from being formed.Inventors be surprised to learn that, ursolic acid is to Staphylococcus Aureus Biofilm
It is formed with suppression and prevents effect, experiment proves that concentration is the ursolic acid of 1.83~10.05 μ g/ml in vitro to golden yellow Portugal
The formation of grape coccus biomembrane has inhibitory action, its can make staphylococcus aureus biofilm formation ability reduction by 8~
32.8%.Biomembrane envelope Observation On The Morphology is drawn, add ursolic acid, biofilm formation amount is significantly reduced, and structure
It is loose, wherein during with concentration as 10.05 μ g/ml, inhibition is most strong, biofilm formation ability reduction by 32.8% can be made.Although
Inventor's ursolic acid that stumbles on can significantly inhibit the formation of biomembrane, but its mechanism for suppressing biomembrane is failed to understand, need into
One step research.
On the other hand, inventor attempts ursolic acid is big mould with lavo-ofloxacin, ROX, Cefradine, celebrating respectively
Element and Amoxicillin combination, investigate its influence formed to Staphylococcus Aureus Biofilm.Result shows, ursolic acid respectively with
The combination of lavo-ofloxacin, ROX, Cefradine, gentamicin and Amoxicillin can improve ursolic acid to golden yellow colour biological
The inhibitory action that film is formed, when such as ursolic acid is combined with Cefradine, lavo-ofloxacin and ROX respectively, can make golden yellow
The inhibiting rate of staphylococcic biomembrane is up to 90%, better than ursolic acid independent medication effect.In addition, the presence of ursolic acid
Can also substantially reduce the consumption of each antibiotic, such as ursolic acid respectively with lavo-ofloxacin, ROX, Cefradine and A Moxi
Woods combination can make the effective dose of each antibiotic be reduced to the 1/2~1/8 of former effective dose；Ursolic acid joins surely with gentamicin
With 1/8~1/32 that its effective dose can be made to be reduced to former effective dose.
Compared with prior art, the present invention has the advantage that：
1) the invention provides ursolic acid in preparing suppression or preventing Staphylococcus Aureus Biofilm from growing medicine
Purposes, for treatment infection of staphylococcus aureus patient provides a kind of new medicine, and to the development of clinical medicine
Obvious impetus is arrived.
2) present invention also offers a kind of high-efficiency low-toxicity medicine, it includes ursolic acid and antibiotic, and the medicine can not only be carried
Ursolic acid high can substantially reduce the effective dose of antibiotic to suppressing the inhibitory action of biofilm formation, so as to reduce bad
The generation of reaction.
Brief description of the drawings
Fig. 1 is that suppression of the ursolic acid of various concentrations on the growing amount of Staphylococcus Aureus Biofilm influences；
Fig. 2 is influence of the ursolic acid of various concentrations to Staphylococcus Aureus Biofilm morphosis.
Specific embodiment：
Below by way of the description of specific embodiment, the invention will be further described, but this is not to limit of the invention
System, those skilled in the art's basic thought of the invention, various modifications may be made or improves, but without departing from this
The basic thought of invention, within the scope of the present invention.
The preparation of embodiment 1, ursolic acid and lavo-ofloxacin dry suspensoid agent
| Ursolic acid | 1005μg |
| Lavo-ofloxacin | 12μg |
| Beta cyclodextrin | 10g |
| Sodium carboxymethylcellulose | 5g |
| Glycerine | 25ml |
A) take after ursolic acid, lavo-ofloxacin, beta cyclodextrin and sodium carboxymethylcellulose cross 80 mesh sieves respectively and mix, obtain mixed
Close powder；
B) mixed powder is added into glycerine softwood, crosses 80 DEG C of drying after 30 mesh sieves, cross 30 mesh sieve whole grains, packaging obtains dry
Supensoid agent.
When taking, 100ml water is added, shaken up, obtain final product liquid suspension.
The preparation of embodiment 2, ursolic acid and Dried Roxithromycin Suspension
| Ursolic acid | 1005μg |
| ROX | 15μg |
| Beta cyclodextrin | 12g |
| Sodium carboxymethylcellulose | 5g |
| Glycerine | 23ml |
Preparation method such as embodiment 1.
The preparation of embodiment 3, ursolic acid and cefradine for suspension
| Ursolic acid | 1005μg |
| Cefradine | 15μg |
| Beta cyclodextrin | 16g |
| Sodium carboxymethylcellulose | 5g |
| Glycerine | 20ml |
Preparation method such as embodiment 1.
The preparation of embodiment 4, ursolic acid and cefradine for suspension
| Ursolic acid | 776μg |
| Cefradine | 60μg |
| Beta cyclodextrin | 6g |
| Sodium carboxymethylcellulose | 5g |
| Glycerine | 15ml |
Preparation method such as embodiment 1.
The preparation of embodiment 5, ursolic acid and gentamicin dry suspensoid agent
| Ursolic acid | 1005μg |
| Gentamicin | 12.3μg |
| Beta cyclodextrin | 12g |
| Sodium carboxymethylcellulose | 5g |
| Glycerine | 20ml |
Preparation method such as embodiment 1.
The preparation of embodiment 6, ursolic acid and gentamicin dry suspensoid agent
| Ursolic acid | 776μg |
| Gentamicin | 12.3μg |
| Beta cyclodextrin | 8g |
| Sodium carboxymethylcellulose | 5g |
| Glycerine | 10ml |
Preparation method such as embodiment 1.
The preparation of embodiment 7, ursolic acid and gentamicin dry suspensoid agent
Preparation method such as embodiment 1.
The preparation of embodiment 8, ursolic acid and Amoxicillin dry suspension
| Ursolic acid | 593μg |
| Amoxicillin | 6μg |
| Beta cyclodextrin | 20g |
| Sodium carboxymethylcellulose | 5g |
| Glycerine | 20ml |
Preparation method such as embodiment 1.
The influence that test example one, various concentrations ursolic acid are formed to Staphylococcus Aureus Biofilm
1.1 test methods
Take test tube slant plus fluid nutrient medium is diluted to 1 × 107CFU/ml, takes 95 μ l bacterium solutions and adds 96 orifice plates, ursolic acid
0.087 μm of ol/ml, 0.17 μm of ol/ml, 0.263 μm of ol/ml, 0.35 μm of ol/ml, 0.438 μm of ol/ml plus 5 μ l are diluted to successively
To 96 orifice plates so that final volume is 100 μ l, separately does the solvent control of DMSO.After being put into 37 DEG C of biochemical cultivation cases and carrying out culture 14h
Take out, aseptic 0.9% sodium chloride is rinsed, after air-drying, add 0.1% violet staining 30min, rinse after air-drying and add 95% second
Alcohol carries out decolouring 15min, surveys A values in 570nm wavelength, and observe the ursolic acid of each concentration to Staphylococcus Aureus Biofilm shape
The change of state structure.
1.2 the results are shown in Table 1, Fig. 1 and Fig. 2, by Fig. 1 (* significant difference (P ＜ 0.05) compared with blank group；* and blank group
Compared to difference extremely significantly (P ＜ 0.01)) understand, the bear estimation of 5 concentration gradients is formed to Staphylococcus Aureus Biofilm
There is inhibitory action, and with the increase of black bearberry acid concentration, biomembrane inhibitory action is stronger, when black bearberry acid concentration is 10.05 μ g/
During ml, it can make Staphylococcus Aureus Biofilm Forming ability reduction by 32.8%.From Fig. 2 (A negative control groups, B.0.004 μ
Mol/ml, C.0.008 μm ol/ml, D.0.13 μm ol/ml, E.0.17 μm ol/ml, F.0.022 μm ol/ml) understand, ursolic acid
Can significantly reduce the forming amount of Staphylococcus Aureus Biofilm, the biofilm structure after being acted on through the ursolic acid of various concentrations
Loose, this explanation, various concentrations ursolic acid has inhibitory action to Staphylococcus Aureus Biofilm.
Influence of the ursolic acid of table 1 to Staphylococcus Aureus Biofilm
| Black bearberry acid concentration | 0μg/ml | 3.65μg/ml | 5.93μg/ml | 7.76μg/ml | 10.05μg/ml |
| Biomembrane growing amount (%) | 100±8.16 |
Compared with 0 μ g/ml ursolic acid,**P ＜ 0.01,*P ＜ 0.05.
The influence of test example two, ursolic acid and antibiotic combination to Staphylococcus Aureus Biofilm
1. material
1.1 medicine ursolic acid (Shanghai Jing Chun biochemical technologies limited company, analyze pure, lot number U107243), head
Spore draws fixed (Guangzhou Baiyunshan Pharmaceutical Group Co., Ltd., lot number：2160005), lavo-ofloxacin (the one or three republicanism pharmacy
Co., Ltd, batch number BP009A1), Amoxicillin (Guangzhou Baiyunshan Pharmaceutical Group Co., Ltd., batch number：
4150095), gentamicin (Guangzhou Baiyunshan Tianxin Pharmaceutical Co., Ltd., batch number：1640401), ROX glue
(Tianjin all generations Chemical Co., Ltd., analyzes pure, criticizes for capsule (Yangzijiang Pharmaceutical Group Co., Ltd, lot number 15112041), sodium chloride
Number 20130322), nutrient agar (Huankai Microbes Tech Co., Ltd., Guangdong, biochemical pure, lot number 3103128), nutrient broth
(Huankai Microbes Tech Co., Ltd., Guangdong, biochemical pure, lot number 3104063), crystal violet (Tianjin great Mao chemical reagent factories,
Lot number 20160103), dimethyl sulfoxide (DMSO) (DMSO, IGMA-ALDDICH, lot number WXBB3106V), water be purified water.
1.2 instrument ultraviolet-uisible spectrophotometers (Japanese Shimadzu UV-2450 types), Portable pressure steam sterilizing pot (north
Jing Shi bright Medical Instruments Co., Ltd GMSX-280 forever), biochemical cultivation case (Shanghai Medical Equipment Plant of Bo Xun Industrial Co., Ltd.s
SPX-150B-Z series), clean bench (Shanghai Su Jing Industrial Co., Ltd.s model SW-CJ-1D), electronic balance (Changshu City
Shuan Jie testers factory model JJ323BC), electric heating constant-temperature blowing drying box (deeply convince laboratory apparatus Co., Ltd, model in Shanghai
DGG-9203A), ultra low temperature freezer (middle U.S. of section water chestnut low temperature science and technology limited Company, model DW-HI388), ELIASA (Shanghai
Yong Chuan Medical Devices Co., Ltd.s, model M-600), inverted microscope (Chongqing Ao Te optical instruments Co., Ltd, model
MIT100)。
1.3 strain golden color staphylococcuses (Staphylococcus aureus, S.a, bacterial strain number:ATCC25923).
2. method
2.1 bacterium solutions are prepared S. aureus Inoculate in MH broth bouillons, prepare single bacterium colony.After Amplification Culture,
2 × 10 are eluted and are diluted to SPSS7CFU/ml, it is standby.
5 kinds of antibiotic are configured to 2.2 antibiotic the solution of 7.16mmol/L respectively for reagent liquid preparation sterilized water,
It is standby.
The measure of 2.3 minimal inhibitory concentrations determines ursolic acid to the minimum antibacterial of staphylococcus aureus using MP method
Concentration (MIC).Take and freeze bacterium and be inoculated in nutrient agar solid culture plate, after culture 24h, picking single bacterium falls within solid slope culture
Base, 37 DEG C of culture 24h of biochemical cultivation case, is eluted with nutrient broth, is diluted to 1 × 107CFU/ml (OD=0.05) bacterium is hanged
Liquid is standby.On aseptic 96 orifice plate, in 1~8 each μ l meat soups of Kong Zhongjia 100 of row.It is each in 1st row hole to add concentration for 8.77 μm of ol/
The μ l of ml black bearberries acid solution 100, using coubling dilution, are diluted in the 2nd~8 row hole successively.Then the bacterium solution that will be prepared is successively
Each hole is added, per the μ l of hole 100.The μ l of the bacterium solution 100 and μ l of nutrient solution 100 are added in 9th row hole, liquid is not added with, as negative control
Group；Final concentration of 2.19 μm of ol/ml in each hole, 1.09 μm of ol/ml, 0.54 μm of ol/ml, 0.27 μm of ol/ml, 0.13 μm of ol/ml,
0.068 μm of ol/ml and 0.034 μm of ol/ml, 0.017 μm of ol/ml.37 DEG C of constant temperature quiescent culture 24h of biochemical cultivation case, take out with
Visually observe, the minimum inhibitory concentration MIC of the least concentration without bacterial growth, i.e. medicine to tested bacterium.The minimum of each antibiotic
Mlc refers to the above method.
2.4 ursolic acid and antibiotic be combined influence to golden yellow biofilm formation according to the above-mentioned ursolic acid for measuring with it is each
The minimum inhibitory concentration of antibiotic, takes the ursolic acid of different MIC concentration respectively from the antibiotic of different MIC concentration by 1:1 body
Product ratio is separately added into hole, adds 90 μ l bacterium solutions, after culture, after crystal violet method dyeing, A values is surveyed in 570nm wavelength.
As a result 2.5 result of the tests show that ursolic acid is combined with each antibiotic as shown in table 2~5, on the one hand can be obvious
Improve the inhibitory action to Staphylococcus Aureus Biofilm of ursolic acid；On the other hand the consumption of antibiotic is can obviously reduce,
Both effects of combination with Synergistic.
The ursolic acid of table 2 is combined the influence to biomembrane forming amount with lavo-ofloxacin
Note：Compared with blank group,**P ＜ 0.01,*P ＜ 0.05.
As shown in Table 2, the μ g/ml~0.12 μ g/ml of the μ g/ml~10.05 μ g/ml of ursolic acid 5.93 and lavo-ofloxacin 0.03
Compatibility is used has inhibition to biofilm formation, wherein with the μ g/ml~10.05 μ g/ml of ursolic acid 5.93 and levofloxacin
The μ g/ml effects of star 0.12 are most obvious, and more than 70% is up to biofilm formation inhibiting rate, particularly as the μ of ursolic acid 10.05
G/ml is optimal with the μ g/ml effects of lavo-ofloxacin 0.12, and 90% is up to biofilm formation inhibiting rate.
The ursolic acid of table 3 is combined the influence to biomembrane forming amount with ROX
Note：Compared with blank group,**P ＜ 0.01,*P ＜ 0.05.
As shown in Table 3, the μ g/ml~10.05 μ g/ml of ursolic acid 5.93 and the μ g/ml compatibilities of ROX 1.44 are using having
Effect, wherein it is optimal with the μ g/ml of ursolic acid 10.05 and the μ g/ml effects of ROX 1.44, to biofilm formation inhibiting rate
Up to 80%.
The ursolic acid of table 4 is combined the influence to biomembrane forming amount with Cefradine
Note：Compared with blank group,**P ＜ 0.01,*P ＜ 0.05.
As shown in Table 4, the μ g/ml~10.05 μ g/ml of ursolic acid 3.65 and the μ g/ml~1.2 μ g/ml compatibilities of Cefradine 0.3
Using effective, wherein it is optimal with the μ g/ml~10.05 μ g/ml of ursolic acid 7.76 and the μ g/ml effects of Cefradine 0.6,
80% is above to biofilm formation inhibiting rate.
The ursolic acid of table 5 is combined the influence to biomembrane forming amount with gentamicin
Note：Compared with blank group,**P ＜ 0.01,*P ＜ 0.05.
As shown in Table 5, the μ g/ml~0.123 μ g/ml of the μ g/ml~10.05 μ g/ml of ursolic acid 5.93 and gentamicin 0.031
Compatibility use is effective, wherein it is optimal with the μ g/ml of ursolic acid 7.76 and the μ g/ml effects of gentamicin 0.123, to biology
Film forms inhibiting rate and is up to 90%.
The ursolic acid of table 6 is combined the influence to biomembrane forming amount with Amoxicillin
Note：Compared with blank group,**P ＜ 0.01,*P ＜ 0.05.
As shown in Table 6, the μ g/ml~0.060 μ g/ml of the μ g/ml~10.05 μ g/ml of ursolic acid 3.65 and Amoxicillin 0.015
Compatibility use is effective, wherein it is optimal with the μ g/ml of ursolic acid 5.93 and the μ g/ml effects of Amoxicillin 0.06, to biology
Film forms inhibiting rate and is up to 45%.
Test example three, clinical practice
1. case selection selects 250 respiratory infection patient volunteers caused by staphylococcus aureus, man 120
Example, female 130,20~46 years old age, average age 26 ± 1.5 years old is randomly divided into 5 groups, is respectively 1 group of embodiment, embodiment 2
Group, 3 groups of embodiment, 6 groups of embodiment, 8 groups of embodiment.
1.2 treatment methods
1 group of embodiment：Supensoid agent described in the embodiment of the present invention 1, plus 100ml water are taken, is shaken up, take 3d, 1 time/d；
2 groups of embodiment：Supensoid agent described in the embodiment of the present invention 2, plus 100ml water are taken, is shaken up, take 3d, 1 time/d；
3 groups of embodiment：Supensoid agent described in the embodiment of the present invention 3, plus 100ml water are taken, is shaken up, take 3d, 1 time/d；
6 groups of embodiment：Supensoid agent described in the embodiment of the present invention 6, plus 100ml water are taken, is shaken up, take 3d, 1 time/d；
8 groups of embodiment：Supensoid agent described in the embodiment of the present invention 8, plus 100ml water are taken, is shaken up, take 3d, 1 time/d.
1.3 efficacy assessment standards
It is effective：24~38 hours after medication, temperature recovery is normal, and no longer gos up, and other symptoms take a turn for the better or disappear；
Effectively：48~72 hours after medication, temperature recovery is normal, and other symptoms take a turn for the better；
It is invalid：More than 72 hours body temperature does not recover normal yet after medication, and other symptoms are again multiple quickly after mitigating or mitigating
Originator.
2. result is as shown in table 7.
The clinical efficacy result of table 7
| Group | Number of cases | Effective (rate) | Effectively (rate) | Invalid (rate) | Total effective rate |
| 1 group of embodiment | 50 | 35 (70.0%) | 12 (24%) | 3 (6%) | 94.0% |
| 2 groups of embodiment | 50 | 36 (72.0%) | 12 (24%) | 2 (4%) | 96.0% |
| 3 groups of embodiment | 50 | 36 (72.0%) | 13 (26%) | 1 (2%) | 98.0% |
| 6 groups of embodiment | 50 | 38 (76.0%) | 12 (24%) | 0 | 100.0% |
| 8 groups of embodiment | 50 | 35 (70.0%) | 13 (26%) | 2 (4%) | 96.0% |
As seen from the above table, in 250 respiratory infection patients, more than 90.0% patient takes 24 after medicine of the present invention~
38 hours, temperature recovery was normal, and no longer gos up, and other symptoms take a turn for the better or disappear, wherein, joined with gentamicin and ursolic acid
With best results, total effective rate reaches 100.0%, and after taking, each patient has no adverse reaction generation.This explanation, bear of the present invention
Tartaric acid can not only substantially reduce the effective dose of antibiotic with antibiotic combination, and can reduce the generation of adverse reaction.
Claims (9)
1. the composition containing ursolic acid is in preparing for suppressing or preventing Staphylococcus Aureus Biofilm from growing medicine
Purposes.
2. purposes as claimed in claim 1, it is characterised in that the composition includes ursolic acid and antibiotic, the combination
The content of ursolic acid is 1.83~10.05 μ g/ml in thing.
3. purposes as claimed in claim 2, it is characterised in that the antibiotic is selected from lavo-ofloxacin, ROX, cephalo
Draw the one kind in fixed, gentamicin and Amoxicillin.
4. purposes as claimed in claim 3, it is characterised in that the antibiotic is selected from lavo-ofloxacin, in the composition
The content of ursolic acid is 5.93 μ g/ml~10.05 μ g/ml, and the content of the lavo-ofloxacin is 0.03 μ g/ml~0.12 μ g/
ml。
5. purposes as claimed in claim 3, it is characterised in that the antibiotic is selected from ROX, bear in the composition
The content of tartaric acid is 5.93 μ g/ml~10.05 μ g/ml, and the content of the ROX is 0.15 μ g/ml.
6. purposes as claimed in claim 3, it is characterised in that the antibiotic is selected from Cefradine, bear in the composition
The content of tartaric acid is 3.65 μ g/ml~10.05 μ g/ml, and the content of the Cefradine is 0.3 μ g/ml~1.2 μ g/ml.
7. purposes as claimed in claim 3, it is characterised in that the antibiotic is selected from gentamicin, bear in the composition
The content of tartaric acid is 5.93 μ g/ml~10.05 μ g/ml, and the content of the gentamicin is 0.03 μ g/ml~0.123 μ g/ml.
8. purposes as claimed in claim 3, it is characterised in that the antibiotic is selected from Amoxicillin, bear in the composition
The content of tartaric acid is 3.65 μ g/ml~10.05 μ g/ml, and the content of the Amoxicillin is 0.015 μ g/ml~0.06 μ g/ml.
9. it is a kind of for suppress or prevent Staphylococcus Aureus Biofilm grow composition, it is characterised in that including black bearberry
Acid and antibiotic, the content of ursolic acid is 1.83~10.05 μ g/ml in the composition.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112704663A (en) * | 2020-12-18 | 2021-04-27 | 吉林农业科技学院 | Preparation method of loquat leaf ursolic acid cream |
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| CN101578045A (en) * | 2006-12-26 | 2009-11-11 | 斯特里莱克斯科技有限责任公司 | Antimicrobial compositions |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101578045A (en) * | 2006-12-26 | 2009-11-11 | 斯特里莱克斯科技有限责任公司 | Antimicrobial compositions |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN112704663A (en) * | 2020-12-18 | 2021-04-27 | 吉林农业科技学院 | Preparation method of loquat leaf ursolic acid cream |
| CN112704663B (en) * | 2020-12-18 | 2022-07-19 | 吉林农业科技学院 | Preparation method of loquat leaf ursolic acid cream |
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