CN106880832A - The new application of glutathione - Google Patents
The new application of glutathione Download PDFInfo
- Publication number
- CN106880832A CN106880832A CN201710170722.5A CN201710170722A CN106880832A CN 106880832 A CN106880832 A CN 106880832A CN 201710170722 A CN201710170722 A CN 201710170722A CN 106880832 A CN106880832 A CN 106880832A
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- Prior art keywords
- glutathione
- beta
- antibacterial
- lactam antibiotic
- bacterium
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/06—Tripeptides
-
- 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
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
-
- 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
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
- A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
- A61K31/546—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine containing further heterocyclic rings, e.g. cephalothin
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention discloses the application respectively in preparing the antibacterial or germ killing drugs containing beta-lactam class antibiotic, can improve the antibacterial or germ killing drugs of beta-lactam class antibiotic removing pathogen ability, can reduce antibacterial or germ killing drugs of the bacterium to beta-lactam class antibiotic resistance in preparation in preparation of the new application of glutathione, i.e. glutathione.Beneficial effects of the present invention are：Glutathione can significantly improve sensitiveness of the bacterium to beta-lactam class antibiotic, and glutathione is used with beta-lactam class Antibiotic combination, and the beta-lactam class antibiotic than Isodose is used alone has stronger fungistatic effect.
Description
Technical field
The present invention relates to antibiotic restraining and sterilizing bacteria technical field, and in particular to the new application of glutathione.
Background technology
The discovery and application of antibiotic are a great revolutions of the mankind, there is for being resisted with Death from this mankind
Big weapon, because the first big killer of human death is exactly bacterium infection.However, in the middle of actual life, due to such antibiotic
Abuse abuse, cause antibody-resistant bacterium to increase year by year, significantly reduce the drug effect of antibiotic.Beta-lactam antibiotic is to control
More the common antibiotics of bacteriosis, therefore such antibiotic produce the bacterium of drug resistance especially prevalent.Drug resistance is current
One of most urgent public health problem in the whole world.In September, 2014, the U.S. is reply antimicrobial resistance, once disclosed one and schedules to last
The national strategy of 5 years.And in China, 80,000 people are just had more than every year and dies from drug resistant infection.Assessed according to Britain's antibiotic resistance
The committee estimates, if present case can not be improved, to the year two thousand fifty, China will have 1,000,000 people, the whole world will to have 10,000,000
People meets with antibiotic resistance problems, and the loss for causing is up to 100 trillion dollars.
One of which technical method, is the sensitiveness by adjusting bacterium to beta-lactam antibiotic, is not changing anti-
In the case that raw element dosage even reduces dosage, the bacteriostasis of beta-lactam antibiotic is improved.Thus, it is found that
Molecular substance of the bacterium to beta-lactam antibiotic sensitiveness can be improved, it is combined with beta-lactam antibiotic and is prepared into
Compound preparation, the infection to controlling bacterium particularly drug-fast bacteria is particularly significant.
Glutathione is the tripeptide compound being combined into by glutamic acid, cysteine and glycine, its major physiological work(
Can remove free radical, anti-oxidant, anti-aging.It is a kind of small-molecule substance, and the molecular formula of the small-molecule substance is
C10H17N3O6S, molecular weight is 307.32.Many free radicals that metabolism is produced in body can damaging cells film, invasion and attack life
The generation of life macromolecular, promotion body aging, and induced tumor or atherosclerosis.Because containing in the structure of glutathione
One active sulfydryl-SH is easily oxidized dehydrogenation, and this specific structure just becomes free radical scavenger main in vivo.Paddy
The sweet peptide of Guang not only removes human free radical, can also improve body immunity.It can not only promote blood cell manufacture Protective substances
Function, Protective substances refer to the material that can protect the body from infection, meanwhile, the total content of internal inflammation material can be also reduced, this
A little inflammation materials are to be made to come by cell.However, on glutathione regulation bacterium beta-lactam antibiotic sensitiveness
There is not been reported for research.
The content of the invention
The purpose of the present invention is aiming at above-mentioned defect of the prior art, there is provided glutathione can be carried as one kind
Beta-lactam antibiotic high removes the small-molecule substance of pathogen ability, and preparation can efficiently suppress the new use of the medicine of bacterium
On the way.
To achieve these goals, the technical scheme of present invention offer is：Glutathione contains beta-lactam in preparation
Application in the antibacterial or germ killing drugs of antibiotic.
Second object of the present invention there is provided glutathione and can improve beta-lactam antibiotic removing in preparation
Application in the antibacterial or germ killing drugs of pathogen ability.
Third object of the present invention there is provided glutathione and can reduce bacterium to beta-lactam antibiosis in preparation
Application in the antibacterial or germ killing drugs of plain drug resistance.
Further, above-mentioned application, it is described antibacterial or sterilized to suppress or kill staphylococcus aureus, stop newborn hammer
Bacterium, Escherichia coli and/or Streptococcusagalactiae.
Bacterium includes but is not limited to staphylococcus aureus, streptococcus dysgalactiae, Escherichia coli and Streptococcusagalactiae.These are thin
Bacterium is the encountered pathogenic bacteria of the mankind and economic animal.Cover gram-positive bacterium（Staphylococcus aureus, stop newborn hammer
Bacterium, Streptococcusagalactiae）And negative bacteria（Escherichia coli）；Coccus（Staphylococcus aureus）, streptococcus（Streptococcus dysgalactiae, nothing
Streptococcus lactis）And bacillus（Escherichia coli）.These bacteriums can be the sensitive strain of penicillin or ampicillin, or resistance to
Medicine bacterial strain.These pathogens are relatively conventional, and common its antibody-resistant bacterium, while Escherichia coli are again the moulds for studying bacterial resistance
Formula bacterium, therefore these bacteriums can be used as sensitive strain and the Typical Representative of antibody-resistant bacterium.
Further, above-mentioned application, described beta-lactam antibiotic is penicillin, ampicillin and/or cephalo
Thiophene.
Antibiotic includes but is not limited to penicillin, ampicillin and cefoxitin.Because penicillin, ampicillin and cephalo
Thiophene belongs to beta-lactam antibiotic, and the mechanism of action of these antibiotic is similar, can suppress cell wall mucopeptide synzyme,
I.e. PBP, so that block cell wall mucopeptide synthesizes, makes bacterial cell wall defect, and thalline expansion is cracked, therefore these
Antibiotic can be used as the Typical Representative of beta-lactam antibiotic.
Further, above-mentioned application, in described antibacterial or germ killing drugs, glutathione and beta-lactam antibiotic
Dose ratio is calculated as 1 by weight：（0.002-5）.
Further, above-mentioned application, in described antibacterial or germ killing drugs, the usage amount of glutathione is 0.6 mg/mL-
3.2 mg/mL。
Beneficial effects of the present invention are：
The present invention is by after addition glutathione by a certain percentage, having found penicillin to the minimum antibacterial dense of staphylococcus aureus
Degree is significantly reduced, and illustrates that glutathione can improve sensitiveness of the staphylococcus aureus to penicillin.It has furthermore been found that paddy
The sweet peptide of Guang can equally reduce the minimum suppression of beta-lactam antibiotic ampicillin and cefoxitin to staphylococcus aureus
Bacteria concentration.
Experiment also found that glutathione can improve streptococcus dysgalactiae, Escherichia coli and Streptococcusagalactiae respectively to mould
Element, the sensitiveness of ampicillin cefoxitin.The above results are shown, can be joined by glutathione and beta-lactam antibiotic
Close to use and strengthen the fungistatic effect of beta-lactam antibiotic, to reach the purpose for the treatment of bacteriosis, be to treat resistance
The disease that bacterium triggers provides a kind of new technical method.
By content disclosed in this invention, a kind of new antibacterial or bactericide can be also prepared, the agent contains gluathione
Peptide and beta-lactam antibiotic；Or a kind of raising beta-lactam antibiotic is antibacterial to drug-fast bacteria or system of bactericidal action
Agent, its main component is glutathione and beta-lactam antibiotic.
Specific embodiment
Embodiment 1：
Glutathione improves the sensitivity of staphylococcus aureus, streptococcus dysgalactiae, Escherichia coli and Streptococcusagalactiae to penicillin
Property：
1. experiment material
（1）Bacterial strain：Staphylococcus aureus, streptococcus dysgalactiae, Escherichia coli and Streptococcusagalactiae are both from Chinese agriculture section
Institute's Lanzhou herding and microorganism seminar of veterinary drug research institute.
（2）Glutathione：It is Sigma Co., USA's product, article No. is G4251.Weigh pulvis and be dissolved in ultra-pure water, 0.2 is micro-
4 DEG C of preservations after rice filter filtering.
（3）Caseinhydrolysate agar medium：It is Britain's Oxoid Products, article No. is CM0337B.Weigh pulvis molten
In ultra-pure water, 121 DEG C of autoclavings, to 50-60 DEG C or so of room temperature to entering disposable 90mm culture dishes and be made caseinhydrolysate to put down
Plate.
（4）Penicillin E-test strips：It is French Mei Liai Products, article No. is 502618.
2. experimental technique：
Use phosphate buffer（PBS, PH：7.4）The bacterial strain bacterial concentration that will be isolated and purified is adjusted to 0.5 maxwell unit, bacterial concentration
It is 5 × 107-5×108CFU/mL.The caseinhydrolysate agar medium 20mL containing glutathione is prepared under aseptic condition（Chain
The aseptic de- fine Sheep Blood that coccus need to add 5%）, the content of glutathione is respectively 0（Control group）, 0.75,1.5 and 3mg/mL.With
In the cotton stick swab immersion bacterial suspension of sterilizing, unnecessary bacterium solution is extruded in tube wall, be then uniformly coated on corresponding hydrolysis junket
On albumen flat board（The de- fine Sheep Blood that streptococcus need to add 5%）, after being stored at room temperature 3-5mim, sterile working is by penicillin E-test
Strip is affixed on above-mentioned culture medium, and 37 DEG C of culture 24h read the minimum inhibitory concentration of penicillin on each caseinhydrolysate flat board
（MICs）.As shown in table 1, compared with control group, penicillin is minimum antibacterial dense in the glutathione addition group of various concentrations for result
Degree is substantially reduced, and with the increase of glutathione concentrations, the amplitude of penicillin minimum inhibitory concentration reduction also increases.Explanation
Glutathione can improve the sensitiveness of staphylococcus aureus, streptococcus dysgalactiae, Escherichia coli and Streptococcusagalactiae to penicillin,
And with glutathione concentrations effect.Table 1 is shown as glutathione to staphylococcus aureus, streptococcus dysgalactiae, Escherichia coli
With the regulation of the penicillin sensitivity of Streptococcusagalactiae.
Table 1
Wherein, GSH represents glutathione.
Embodiment 2：
Glutathione improves staphylococcus aureus, streptococcus dysgalactiae, Escherichia coli and Streptococcusagalactiae to the quick of ampicillin
Perception：
1. experiment material：
（1）Bacterial strain：Staphylococcus aureus, streptococcus dysgalactiae, Escherichia coli and Streptococcusagalactiae are both from Chinese agriculture section
Institute's Lanzhou herding and microorganism seminar of veterinary drug research institute.
（2）Glutathione：It is Sigma Co., USA's product, article No. is G4251.Weigh pulvis and be dissolved in ultra-pure water, 0.2 is micro-
4 DEG C of preservations after rice filter filtering.
（3）Caseinhydrolysate agar medium：It is Britain's Oxoid Products, article No. is CM0337B.Weigh pulvis molten
In ultra-pure water, 121 DEG C of autoclavings, to 50-60 DEG C or so of room temperature to entering disposable 90mm culture dishes and be made caseinhydrolysate to put down
Plate.
（4）Ampicillin E-test strips：It is French Mei Liai Products, article No. is 501518.
2. experimental technique：
Use phosphate buffer（PBS, PH：7.4）The bacterial strain bacterial concentration that will be isolated and purified is adjusted to 0.5 maxwell unit, bacterial concentration
It is 5 × 107-5×108CFU/mL.The caseinhydrolysate agar medium 20mL containing glutathione is prepared under aseptic condition（Chain
The aseptic de- fine Sheep Blood that coccus need to add 5%）, the content of glutathione is respectively 0（Control group）, 0.75,1.5 and 3mg/mL.With
In the cotton stick swab immersion bacterial suspension of sterilizing, unnecessary bacterium solution is extruded in tube wall, be then uniformly coated on corresponding hydrolysis junket
On albumen flat board（The de- fine Sheep Blood that streptococcus need to add 5%）, after being stored at room temperature 3-5mim, sterile working is by ampicillin E-
Test strips are affixed on above-mentioned culture medium, 37 DEG C of culture 24h, read the minimum antibacterial of ampicillin on each caseinhydrolysate flat board
Concentration（MICs）.As shown in table 2, compared with control group, ampicillin is minimum in the glutathione addition group of various concentrations for result
Mlc is substantially reduced, and with the increase of glutathione concentrations, the amplitude of ampicillin minimum inhibitory concentration reduction
Increase.Illustrate that glutathione can improve staphylococcus aureus, streptococcus dysgalactiae, Escherichia coli and Streptococcusagalactiae to ammonia benzyl west
The sensitiveness of woods, and with glutathione concentrations effect.Table 2 be shown as glutathione to staphylococcus aureus, stop newborn hammer
The regulation of the ampicillin sensitive of bacterium, Escherichia coli and Streptococcusagalactiae.
Table 2
Wherein, GSH represents glutathione.
Embodiment 3：
Glutathione improves staphylococcus aureus, streptococcus dysgalactiae, Escherichia coli and Streptococcusagalactiae to the quick of cefoxitin
Perception：
1. experiment material：
（1）Bacterial strain：Staphylococcus aureus, streptococcus dysgalactiae, Escherichia coli and Streptococcusagalactiae are both from Chinese agriculture section
Institute's Lanzhou herding and microorganism seminar of veterinary drug research institute.
（2）Glutathione：It is Sigma Co., USA's product, article No. is G4251.Weigh pulvis and be dissolved in ultra-pure water, 0.2 is micro-
4 DEG C of preservations after rice filter filtering.
（3）Caseinhydrolysate agar medium：It is Britain's Oxoid Products, article No. is CM0337B.Weigh pulvis molten
In ultra-pure water, 121 DEG C of autoclavings, to 50-60 DEG C or so of room temperature to entering disposable 90mm culture dishes and be made caseinhydrolysate to put down
Plate.
（4）Cefoxitin E-test strips：It is French Mei Liai Products, article No. is 503518.
2. experimental technique：
Use phosphate buffer（PBS, PH：7.4）The bacterial strain bacterial concentration that will be isolated and purified is adjusted to 0.5 maxwell unit, bacterial concentration
It is 5 × 107-5×108CFU/mL.The caseinhydrolysate agar medium 20mL containing glutathione is prepared under aseptic condition（Chain
The aseptic de- fine Sheep Blood that coccus need to add 5%）, the content of glutathione is respectively 0（Control group）, 0.75,1.5 and 3mg/mL.With
In the cotton stick swab immersion bacterial suspension of sterilizing, unnecessary bacterium solution is extruded in tube wall, be then uniformly coated on corresponding hydrolysis junket
On albumen flat board（The de- fine Sheep Blood that streptococcus need to add 5%）, after being stored at room temperature 3-5mim, sterile working is by cefoxitin E-
Test strips are affixed on above-mentioned culture medium, 37 DEG C of culture 24h, read the minimum antibacterial of cefoxitin on each caseinhydrolysate flat board
Concentration（MICs）.As shown in table 3, compared with control group, cefoxitin is minimum in the glutathione addition group of various concentrations for result
Mlc is substantially reduced, and with the increase of glutathione concentrations, the amplitude of cefoxitin minimum inhibitory concentration reduction
Increase.Illustrate that glutathione can improve staphylococcus aureus, streptococcus dysgalactiae, Escherichia coli and Streptococcusagalactiae to cephalo thiophene
The sensitiveness of fen, and with glutathione concentrations effect.Table 3 be shown as glutathione to staphylococcus aureus, stop newborn hammer
The regulation of the cefoxitin sensitiveness of bacterium, Escherichia coli and Streptococcusagalactiae.
Table 3
Wherein, GSH represents glutathione.
Finally it should be noted that：The preferred embodiments of the present invention are the foregoing is only, are not intended to limit the invention,
Although being described in detail to the present invention with reference to the foregoing embodiments, for a person skilled in the art, it still may be used
Modified with to the technical scheme described in foregoing embodiments, or equivalent is carried out to which part technical characteristic.
All any modification, equivalent substitution and improvements within the spirit and principles in the present invention, made etc., should be included in of the invention
Within protection domain.
Claims (7)
1. application of the glutathione in the antibacterial or germ killing drugs containing beta-lactam antibiotic are prepared.
2. glutathione is in the antibacterial or germ killing drugs that can improve beta-lactam antibiotic removing pathogen ability are prepared
Application.
3. glutathione is in preparation can reduce antibacterial or germ killing drugs of the bacterium to beta-lactam antibiotic drug resistance
Using.
4. according to any described applications of claim 1-3, it is characterised in that described antibacterial or sterilized golden yellow to suppress or killing
Color staphylococcus, streptococcus dysgalactiae, Escherichia coli and/or Streptococcusagalactiae.
5. according to any described applications of claim 1-3, it is characterised in that described beta-lactam antibiotic is mould
Element, ampicillin and/or cefoxitin.
6. according to any described applications of claim 1-3, it is characterised in that in described antibacterial or germ killing drugs, glutathione
Dose ratio with beta-lactam antibiotic is calculated as 1 by weight：（0.002-5）.
7. according to any described applications of claim 1-3, it is characterised in that in described antibacterial or germ killing drugs, glutathione
Usage amount be 0.6 mg/mL-3.2 mg/mL.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710170722.5A CN106880832A (en) | 2017-03-21 | 2017-03-21 | The new application of glutathione |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710170722.5A CN106880832A (en) | 2017-03-21 | 2017-03-21 | The new application of glutathione |
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| CN106880832A true CN106880832A (en) | 2017-06-23 |
Family
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109224062A (en) * | 2018-09-30 | 2019-01-18 | 浙江肽明生物科技有限公司 | A kind of novel polypeptide high-efficiency antimicrobial element and preparation method thereof |
| CN109966473A (en) * | 2019-05-14 | 2019-07-05 | 南京医科大学 | A kind of reduced form Glutathione combines antifungal products and its application of ascorbic acid and/or Caspofungin |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102973542A (en) * | 2012-12-04 | 2013-03-20 | 中山大学 | Micromolecular substance for improving sensitivity of bacteria to antibiotics |
-
2017
- 2017-03-21 CN CN201710170722.5A patent/CN106880832A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102973542A (en) * | 2012-12-04 | 2013-03-20 | 中山大学 | Micromolecular substance for improving sensitivity of bacteria to antibiotics |
Non-Patent Citations (3)
| Title |
|---|
| GOSWAMI M等: "Glutathione-mediated augmentation of β-lactam antibacterial activity against Escherichia coli", 《JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY》 * |
| YANG F等: "Short communication: N-Acetylcysteine-mediated modulation of antibiotic susceptibility of bovine mastitis pathogens", 《 JOURNAL OF DAIRY SCIENCE》 * |
| 张亚妮: "谷胱甘肽与铜绿假单胞菌致病性及抗生素抗性的关系研究", 《中国博士学位论文全文数据库（医药卫生科技辑）》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109224062A (en) * | 2018-09-30 | 2019-01-18 | 浙江肽明生物科技有限公司 | A kind of novel polypeptide high-efficiency antimicrobial element and preparation method thereof |
| CN109966473A (en) * | 2019-05-14 | 2019-07-05 | 南京医科大学 | A kind of reduced form Glutathione combines antifungal products and its application of ascorbic acid and/or Caspofungin |
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