CN106420872A - Panax pseudo ginseng leaves extract and fluconazole composition of anti-candida albicans drug-resistant strain and application thereof - Google Patents
Panax pseudo ginseng leaves extract and fluconazole composition of anti-candida albicans drug-resistant strain and application thereof Download PDFInfo
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- CN106420872A CN106420872A CN201610876465.2A CN201610876465A CN106420872A CN 106420872 A CN106420872 A CN 106420872A CN 201610876465 A CN201610876465 A CN 201610876465A CN 106420872 A CN106420872 A CN 106420872A
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- fluconazole
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
- A61K36/258—Panax (ginseng)
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4196—1,2,4-Triazoles
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Abstract
The invention relates to a panax pseudo ginseng leaves extract and fluconazole composition of an anti-candida albicans drug-resistant strain and application thereof. The composition is prepared from fluconazole and the panax pseudo ginseng leaves extract, wherein the weight ratio of the fluconazole to the panax pseudo ginseng leaves extract is 1 to 0.25-8. The fluconazole and the panax pseudo ginseng leaves extract are used in a combined mode and have the remarkable synergic antibacterial effect on the candida albicans, meanwhile an antifungal effect is remarkably strengthened, and the composition clinically has a wide application prospect.
Description
Technical field
The present invention relates to the related pharmaceutical composition of a kind of Chinese medical extract, specifically, be that a kind of antifungal is resistance to
The composition of the ginsenoside of medicine bacterial strain and Fluconazole and application thereof.
Background technology
Candida albicans is a kind of pathomycete important clinically, and candida albicans disease spectrum of causing a disease is very wide, can cause skin, mucous membrane and
The infection of gut system.In recent years, due to tumour, the increasing of AIDS patient, the incidence of disease of monilial infection is in rising trend.?
In one investigation of the U.S., the discovery microbial nosocomial infection of beads occupies the 4th.Candida albicans is to cause deep clinically true
Bacterium infects common pathogen, accounts for more than 80%.Traditional antifungal drug clinical cure rate is relatively low, resistance easily occur,
Some drugs bad reaction is obvious.Tool State Statistics Bureau numerical monitor, annual about 300,000,000,000 yuan of whole nation drugs consumption, medical insurance is annual
Disbursement is at about 80,000,000,000 yuan, and wherein medicine accounts for 50,000,000,000 yuan.Therefore the antifungal drug how developing high-efficiency low-toxicity is near
Study hotspot problem over Nian.And China's traditional Chinese medicine is with a long history to the treatment of fungal infection, have accumulated rich experiences, great Liang Zhong
The research of herbal medicine antifungic action shows, from conventional medicament, developing new drug holds out broad prospects.Therefore the traditional Chinese medical science how is played special
Look advantage, fully excavates valuable Chinese herbal medicine resource, partly substitutes Western medicine, thus reduce Western medicine consumption, reduces the secondary work of Western medicine poison
It is the developing direction that antimycotic is treated with producing with drug resistance.
Fluconazole is a kind of antifungal drug disturbing fungal cell membrane lipid synthesis, but easily produces drug resistance and make
Curative effect is greatly lowered, and owing to fungal cell is similar to the cell membrane component of human host cell or has much common metabolism
Feature, while using Fluconazole antimycotic, has a certain degree of toxic and side effect to human body cell.And at present with regard to fluorine
Health azoles is antimycotic with Chinese medicine combination, and especially fluconazole ginsenoside produces to reduce its toxic and side effect and drug resistance
Correlative study have not been reported.
Content of the invention
It is an object of the invention to, for deficiency of the prior art, provide the ginseng stem of a kind of antifungal antibody-resistant bacterium
Leaf saponin(e and the composition of Fluconazole.
Another purpose of the present invention is to provide the purposes of described composition.
Another the purpose of the present invention is to provide a kind of pharmaceutical composition.
For realizing above-mentioned first purpose, the present invention adopts the technical scheme that：
The ginsenoside of a kind of antifungal antibody-resistant bacterium and the composition of Fluconazole, described composition is by fluorine
Health azoles and ginsenoside composition, the weight ratio of described Fluconazole and ginsenoside is 1:(0.25-8).
Preferably, the weight ratio of described Fluconazole and ginsenoside is 1:1.
For realizing above-mentioned second purpose, the present invention adopts the technical scheme that：
As above application in preparing antimycotic medicine for arbitrary described composition.
As above application in the medicine preparing antifungal for arbitrary described composition.
As above application in the medicine preparing antifungal antibody-resistant bacterium for arbitrary described composition.
For realizing above-mentioned 3rd purpose, the present invention adopts the technical scheme that：
A kind of pharmaceutical composition, it contains as above arbitrary described composition, and conventional pharmaceutical carrier.
The invention has the advantages that：
Present inventor selects ginsenoside from numerous known Chinese medical extracts, resists very known to numerous
Bacterium Western medicine selects Fluconazole, by the CLSIM27-A3 scheme ginsenoside associating Fluconazole generally acknowledged in the world to facing
The candida albicans of the 19 strain fluconazole resistant that bed separates carries out In vitro chemo-drug sensitive test, is found surprisingly that the two drug combination to resistance
Candida albicans there is significant synergetic antibacterial effect, especially when the two concentration ratio is 1:Synergetic antibacterial effect when 1 is the most
Significantly.Ginsenoside part so not only can be used to substitute Fluconazole secondary to reduce Fluconazole consumption and reduction Fluconazole poison
Effect and drug resistance produce, and also significantly enhance anti-mycotic efficiency, possess wide application prospect clinically.
Detailed description of the invention
The detailed description of the invention providing the present invention below elaborates.
Embodiment 1
1 experiment material
1.1 bacterium source
19 strain clinical Candida separation strains come from dept. of dermatology of Shanghai Tongji Hospital Mycology Lab, respectively sputum (7 strain),
Vaginal fluid (5 strain), ight soil (4 strain), urine (3 strain).Medicaments insensitive Quality-control strains is CLSI (the Clinical and
Laboratory Standards Institute) the Candida parapsilosis ATCC22019 that specifies and candida krusei
ATCC6258.
1.2 main agents and instrument
Dimethyl sulfoxide (DMSO) (Amerseo company of the U.S.), RPMI 1640 powder (Gibco company of the U.S.), sabouraud culture medium is former
Material (Shanghai branch company of Chemical Reagent Co., Ltd., Sinopharm Group), electronic analytical balance (MettlerT01edo company of Switzerland), electricity
Hot constant incubator (above Nereid's grand experimental facilities Co., Ltd), Biohazard Safety Equipment (Li Kang bio tech ltd).
1.3 test medicine
Fluconazole (FLC) powder (content 99.9%) is purchased from Shanghai Sunve Pharmaceutical Co., Ltd., during stem and leaf of Radix Ginseng saponin is purchased from
State's medicine biological products assay institute, specification numbering 1553.
2 methods
Herbs By Broth Microdilution (M27-A3) scheme recommended according to CLSI is implemented.
2.1 medicines store the preparation of liquid
Water miscible Fluconazole is dissolved in sterilizing distilled water, and stem and leaf of Radix Ginseng saponin is dissolved in dimethyl sulfoxide (DMSO), is prepared as medicine storage
Liquid storage.
The preparation of 2.2 drug sensitive reaction plates
Mother liquid medicine RPMI 1640 fluid nutrient medium is carried out 10 grades of doubling dilutions, the medicine final concentration model of Fluconazole
Enclosing for 64-0.125 μ g/ml, the final concentration scope of ginsenoside is：256-0.5μg/ml.Drug sensitive plate is in often arranging 1～10 hole
Doubling specific concentration liquid 100 μ 1 (combination drug sensitive plate then adds each 50 μ l of two kinds of medicines respectively) respectively, the 11st hole adds 100 μ l liquid trainings
Foster base is growth control, and it is blank that the 12nd hole adds 200 μ l fluid nutrient mediums.Block Quality Control is all prepared every time during preparation drug sensitive plate
Bacterium drug sensitive plate.
The preparation of 2.3 bacteria suspensions
Strain subject is inoculated on SDA, makes bacteria suspension with 3ml physiological saline after 35 DEG C of cultivation 24h or 48h, use wheat
Family name's opacity tube is adjusted to 0.5 Maxwell unit, counts suspension and be adjusted to 1 × 10 on blood cell counting plate6～5 × 106CFU/
Ml, is then 1 × 10 with RPMI 1640 culture medium by bacteria suspension concentration dilution3～5 × l03CFU/ml (diluting 1000 times) (2 times
Working concentration).
The inoculation of 2.4 bacteria suspensions
Freezing drug sensitive plate is melted on rearmounted superclean bench by the thawing program of 4 DEG C, each 1h of room temperature, adds with pipettor
Place 35 DEG C of insulating boxs after bacteria suspension to cultivate.
2.5 incubate and terminal point determining
Postvaccinal medicaments insensitive test board is placed in 35 DEG C of constant incubators cultivation 24h and 48h, uses visual method to judge
Terminal.Medicaments insensitive terminal interpretation is with reference to the standard to micro liquid media dilution method, azole in M27-A3 scheme in the world
Medicine is using 80% suppression as observation terminal, it is judged that minimum inhibitory concentration (minimum inhibitory concentration,
MIC).The result of ginsenoside judges to carry out with reference to azole drug.
The effect assessment of 2.6 drug combinations
Part Mlc index (fractional inhibitory concentration index, FICI) is to comment
The major parameter of two medicine interaction modes of valency drug combination.Mlc fraction (FIC) is that each is medication combined antibacterial
The ratio of Shi Suoxu MIC and MIC when alone, FIC index (FICI) is then equal to two kinds of medicine FIC sums.When MIC value is higher than inspection
Survey the highest prescribing a time limit with the highest twice value limiting concentration in order to calculate FICI.When FICI≤0.5, the interaction of two medicines is defined as
Synergy；0.5<It is unrelated effect during FICI≤4；Work as FICI>When 4, two medicines produce antagonism.
2.7 statistical analysis
Use SPSS 17.0 analyzing and processing data.It is laggard that two groups of MIC value when using each prescription and be combined are converted to logarithm
Row t checks, P<0.05 when side thinks there is significant difference.
3 results and analysis
MIC value when the experimental result display Fluconazole of table 1 and ginsenoside drug combination is single significantly lower than the two
The MIC value of private medicine.By the calculating of FICI value it can be seen that this 19 strain candida albicans fluconazole resistant strain passes through Fluconazole
Equal with FICI after ginsenoside drug combination<0.5, show that the two combination antibody-resistant bacterium to experiment has significantly collaborative
Antibacterial action.And from table 1 data it can be seen that working as Fluconazole and ginsenoside concentration ratio is 1:When 1, Synergistic antimicrobial
Act on the most notable.
Table 1 Fluconazole and ginsenoside are individually and the MIC value that is used in combination and the interaction of the two
The above is only the preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
Member, on the premise of without departing from the inventive method, can also make some improvement and supplementary, and these improve and supplement and also should be regarded as
Protection scope of the present invention.
Claims (6)
1. the composition of the ginsenoside of an antifungal antibody-resistant bacterium and Fluconazole, it is characterised in that described
Composition is made up of Fluconazole and ginsenoside, and the weight ratio of described Fluconazole and ginsenoside is 1:(0.25-
8).
2. composition according to claim 1, it is characterised in that the weight ratio of described Fluconazole and ginsenoside
It is 1:1.
3. application in preparing antimycotic medicine for the composition described in claim 1 or 2.
4. application in the medicine preparing antifungal for the composition described in claim 1 or 2.
5. application in the medicine preparing antifungal antibody-resistant bacterium for the composition described in claim 1 or 2.
6. a pharmaceutical composition, it is characterised in that it contains the composition described in claim 1 or 2, and conventional medicinal load
Body.
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| CN201610876465.2A CN106420872B (en) | 2016-09-30 | 2016-09-30 | A kind of composition and its application of the ginsenoside and Fluconazole of antifungal antibody-resistant bacterium |
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| CN106420872B CN106420872B (en) | 2019-07-09 |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070286812A1 (en) * | 2006-06-09 | 2007-12-13 | Toutounghi Camille | Nasal formulation |
| CN101816646A (en) * | 2010-04-27 | 2010-09-01 | 中国人民解放军第二军医大学 | Application of theaflavin as synergist of antifungal medicine |
| CN102274215A (en) * | 2010-06-10 | 2011-12-14 | 吉林大学 | Synergist with synergetic antifungal effect with fluconazole |
| CN104188962A (en) * | 2014-08-14 | 2014-12-10 | 东南大学 | Application of magnolol and azole medicines to preparation of antifungal combined medicines |
| CN105663126A (en) * | 2016-03-29 | 2016-06-15 | 山东省千佛山医院 | Antifungal product combining ambroxol hydrochloride with fluconazole and application thereof |
-
2016
- 2016-09-30 CN CN201610876465.2A patent/CN106420872B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070286812A1 (en) * | 2006-06-09 | 2007-12-13 | Toutounghi Camille | Nasal formulation |
| CN101816646A (en) * | 2010-04-27 | 2010-09-01 | 中国人民解放军第二军医大学 | Application of theaflavin as synergist of antifungal medicine |
| CN102274215A (en) * | 2010-06-10 | 2011-12-14 | 吉林大学 | Synergist with synergetic antifungal effect with fluconazole |
| CN104188962A (en) * | 2014-08-14 | 2014-12-10 | 东南大学 | Application of magnolol and azole medicines to preparation of antifungal combined medicines |
| CN105663126A (en) * | 2016-03-29 | 2016-06-15 | 山东省千佛山医院 | Antifungal product combining ambroxol hydrochloride with fluconazole and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| KEYAL,UMA等: "Drug interaction of traditional Chinese medicines with fluconazole against fluconazole resistant strains of Candida albicans", 《INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE》 * |
| 姜淼等: "2种中药单体对念珠菌的体外药敏研究", 《中国真菌学杂志》 * |
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