CN106668011A - New application of vitamin C - Google Patents

New application of vitamin C Download PDF

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Publication number
CN106668011A
CN106668011A CN201710170255.6A CN201710170255A CN106668011A CN 106668011 A CN106668011 A CN 106668011A CN 201710170255 A CN201710170255 A CN 201710170255A CN 106668011 A CN106668011 A CN 106668011A
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CN
China
Prior art keywords
vitamin
beta
antibacterial
lactam antibiotic
bacterium
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201710170255.6A
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Chinese (zh)
Inventor
杨峰
李宏胜
王旭荣
王玲
罗金印
李新圃
张世栋
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Lanzhou Institute of Animal Husbandry and Veterinary Medicine CAAS
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Lanzhou Institute of Animal Husbandry and Veterinary Medicine CAAS
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Publication date
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Priority to CN201710170255.6A priority Critical patent/CN106668011A/en
Publication of CN106668011A publication Critical patent/CN106668011A/en
Pending legal-status Critical Current

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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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
    • 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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention discloses new application of vitamin C, i.e., application of the vitamin C respectively to preparation of a bacteriostatic or antiseptic medicament containing beta-lactam antibiotics, preparation of a bacteriostatic or antiseptic medicament capable of improving sensitivity of bacteria to the beta-lactam antibiotics and preparation of a bacteriostatic or antiseptic medicament capable of reducing drug resistance of the bacteria to the beta-lactam antibiotics. The new application of the vitamin C, which is disclosed by the invention, has the beneficial effects that the vitamin C can obviously improve the sensitivity of the bacteria to the beta-lactam antibiotics so as to reduce probability that the drug resistance occurs to the bacteria; combined use of the vitamin C and the beta-lactam antibiotics has a better bacteriostatic effect than separate use of the beta-lactam antibiotics.

Description

Ascorbic new application
Technical field
The present invention relates to antibiotic restraining and sterilizing bacteria technical field, and in particular to ascorbic new application.
Background technology
Pathogen is the arch-criminal of numerous infectious diseases, the sustainable development of serious harm animal husbandry and the body of the mankind Body health.Especially beta-lactam antibiotic is the common antibiotics for curing bacteriosis to antibiotic.However, actual life It is central, because the abuse of such antibiotic is abused, cause antibody-resistant bacterium to increase year by year, significantly reduce the drug effect of antibiotic. At present, beta-lactam antibiotic drug resistance occurs all over the world, and is rising to risk altitude.New resistance mechanism is just Occurring and in global spread, threatening the ability for the treatment of common transmittable disease.Because beta-lactam antibiotic validity declines, Increasing infection becomes increasingly difficult to treatment, even pasts medical help sometimes.Therefore, it is bacillary using new approach prevention and treatment It is very urgent and important that disease shows.
One of which technical method, is the susceptibility by strengthening 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 for being particularly drug-fast bacteria to control bacterium is particularly significant.
Vitamin C is a compound containing sulfydryl, in the past many as mucolytic, is that a kind of curative effect is good And the expectorant in the respiratory tract infection medication of safety.Its mechanism of action is that the sulfydryl in its molecule can be by mucoprotein in sputum Disulfide bond (- S-S-) fracture, decompose mucin, so as to reduce the viscosity of phlegm, be allowed to easy expectoration and improve symptom.Dimension Element C is used as a kind of sulfydryl donor for life, in addition to above-mentioned effect, main or a kind of antioxidant, with interference free radical Generate, remove the free radical for having generated, adjust the metabolic activity of cell, prevent the damage of DNA, adjust expression and the signal of gene Transduction system, anti-apoptotic, Anti- angiogenesis, suppress malignant progression, and suppress it is neoplastic generation and shift Effect.However, with regard to vitamin C adjust bacterium beta-lactam antibiotic sensitiveness research there is not been reported.
The content of the invention
The purpose of the present invention is aiming at above-mentioned defect of the prior art, there is provided vitamin C improves disease as a kind of Small molecule metabolites of the opportunistic pathogen to beta-lactam antibiotic sensitiveness, 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：Vitamin C is anti-containing beta-lactam in preparation Application in the antibacterial or germ killing drugs of raw element.
Second object of the present invention there is provided vitamin C and can improve bacterium to beta-lactam antibiotic in preparation Application in the antibacterial or germ killing drugs of sensitiveness.
Third object of the present invention there is provided vitamin C and can reduce bacterium to beta-lactam antibiotic in preparation Application in the antibacterial or germ killing drugs of 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, the mechanism of action all similar of these antibiotic, can suppress cell wall mucopeptide synzyme, I.e. PBP, so as to the synthesis of block cell wall mucopeptide, cracks bacterial cell wall defect, thalline expansion, 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, vitamin C and beta-lactam antibiotic Dose ratio is calculated as by weight 1：（0.002-4）.
Further, above-mentioned application, in described antibacterial or germ killing drugs, ascorbic usage amount is 0.18mg/mL- 1.75 mg/mL。
Beneficial effects of the present invention are：
The present invention has found penicillin to the minimum antibacterial dense of staphylococcus aureus by adding by a certain percentage after vitamin C Degree is significantly reduced, and illustrates that vitamin C can improve sensitiveness of the staphylococcus aureus to penicillin.It has furthermore been found that dimension life Plain C can equally reduce beta-lactam antibiotic ampicillin and cefoxitin to the minimum antibacterial dense of staphylococcus aureus Degree.
Test also finds that vitamin C 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 with beta-lactam antibiotic by vitamin C Close using strengthening the fungistatic effect of beta-lactam antibiotic, be to treat resistance to reach the purpose for the treatment of bacteriosis The disease that bacterium causes 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 vitamin C And beta-lactam antibiotic；Or a kind of raising beta-lactam antibiotic is antibacterial to drug-fast bacteria or preparation of bactericidal action, Its main component is vitamin C and beta-lactam antibiotic.
Specific embodiment
Embodiment 1：
Vitamin C 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）Vitamin C：For Sigma Co., USA's product, article No. is A7250.Weigh pulvis and be dissolved in ultra-pure water, 0.2 micron 4 DEG C preserve after filter is filtered.
（3）Caseinhydrolysate agar medium：For Britain's Oxoid Products, article No. is CM0337B.Weigh pulvis molten In ultra-pure water, 121 DEG C of autoclavings, to room temperature 50-60 DEG C or so to entering disposable 90mm culture dishes and make caseinhydrolysate to put down Plate.
（4）Penicillin E-test strips：For French Mei Liai Products, article No. is 502618.
2. experimental technique：
Use phosphate buffer（PBS, PH：7.4）The bacterial strain bacterial concentration for isolating and purifying is adjusted to into 0.5 maxwell unit, bacterial concentration For 5 × 107-5×108CFU/mL.Prepare under aseptic condition and contain ascorbic caseinhydrolysate agar medium 20mL（Hammer The aseptic de- fine Sheep Blood that bacterium need to add 5%）, ascorbic content is respectively 0（Control group）, 0.41,0.83 and 1.75mg/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 On casein plate（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 strips are affixed on above-mentioned culture medium, 37 DEG C of culture 24h, read the minimum antibacterial dense of penicillin on each caseinhydrolysate flat board Degree（MICs）.As a result as shown in table 1, compared with control group, penicillin is minimum antibacterial dense in the vitamin C addition group of variable concentrations Degree is substantially reduced, and with the increase of vitamin C concentration, the amplitude that penicillin minimum inhibitory concentration is reduced also increases.Explanation Vitamin C can improve the sensitiveness of staphylococcus aureus, streptococcus dysgalactiae, Escherichia coli and Streptococcusagalactiae to penicillin, And with vitamin C concentration effect.Table 1 be shown as vitamin C to staphylococcus aureus, streptococcus dysgalactiae, Escherichia coli and The regulation of the penicillin sensitivity of Streptococcusagalactiae.
Table 1
Wherein, Vc represents vitamin C.
Embodiment 2：
Vitamin C improves the sensitivity of staphylococcus aureus, streptococcus dysgalactiae, Escherichia coli and Streptococcusagalactiae to ampicillin 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）Vitamin C：For Sigma Co., USA's product, article No. is A7250.Weigh pulvis and be dissolved in ultra-pure water, 0.2 micron 4 DEG C preserve after filter is filtered.
（3）Caseinhydrolysate agar medium：For Britain's Oxoid Products, article No. is CM0337B.Weigh pulvis molten In ultra-pure water, 121 DEG C of autoclavings, to room temperature 50-60 DEG C or so to entering disposable 90mm culture dishes and make caseinhydrolysate to put down Plate.
（4）Ampicillin E-test strips：For French Mei Liai Products, article No. is 501518.
2. experimental technique：
Use phosphate buffer（PBS, PH：7.4）The bacterial strain bacterial concentration for isolating and purifying is adjusted to into 0.5 maxwell unit, bacterial concentration For 5 × 107-5×108CFU/mL.Prepare under aseptic condition and contain ascorbic caseinhydrolysate agar medium 20mL（Hammer The aseptic de- fine Sheep Blood that bacterium need to add 5%）, ascorbic content is respectively 0（Control group）, 0.41,0.83 and 1.75mg/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 On casein plate（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 a result as shown in table 2, compared with control group, the minimum suppression in ampicillin in the vitamin C addition group of variable concentrations Bacteria concentration is substantially reduced, and with the increase of vitamin C concentration, the amplitude that ampicillin minimum inhibitory concentration is reduced also increases Greatly.Illustrate that vitamin C can improve staphylococcus aureus, streptococcus dysgalactiae, Escherichia coli and Streptococcusagalactiae to ampicillin Sensitiveness, and with vitamin C concentration effect.Table 2 is shown as vitamin C to staphylococcus aureus, streptococcus dysgalactiae, big The regulation of the ampicillin sensitive of enterobacteria and Streptococcusagalactiae.
Table 2
Wherein, Vc represents vitamin C.
Embodiment 3：
Vitamin C improves the sensitivity of staphylococcus aureus, streptococcus dysgalactiae, Escherichia coli and Streptococcusagalactiae to cefoxitin 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）Vitamin C：For Sigma Co., USA's product, article No. is A7250.Weigh pulvis and be dissolved in ultra-pure water, 0.2 micron 4 DEG C preserve after filter is filtered.
（3）Caseinhydrolysate agar medium：For Britain's Oxoid Products, article No. is CM0337B.Weigh pulvis molten In ultra-pure water, 121 DEG C of autoclavings, to room temperature 50-60 DEG C or so to entering disposable 90mm culture dishes and make caseinhydrolysate to put down Plate.
（4）Cefoxitin E-test strips：For French Mei Liai Products, article No. is 503518.
2. experimental technique：
Use phosphate buffer（PBS, PH：7.4）The bacterial strain bacterial concentration for isolating and purifying is adjusted to into 0.5 maxwell unit, bacterial concentration For 5 × 107-5×108CFU/mL.Prepare under aseptic condition and contain ascorbic caseinhydrolysate agar medium 20mL（Hammer The aseptic de- fine Sheep Blood that bacterium need to add 5%）, ascorbic content is respectively 0（Control group）, 0.41,0.83 and 1.75mg/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 On casein plate（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 a result as shown in table 3, compared with control group, the minimum suppression of cefoxitin in the vitamin C addition group of variable concentrations Bacteria concentration is substantially reduced, and with the increase of vitamin C concentration, the amplitude that cefoxitin minimum inhibitory concentration is reduced also increases Greatly.Illustrate that vitamin C can improve staphylococcus aureus, streptococcus dysgalactiae, Escherichia coli and Streptococcusagalactiae to cefoxitin Sensitiveness, and with vitamin C concentration effect.Table 3 is shown as vitamin C to staphylococcus aureus, streptococcus dysgalactiae, big The regulation of the cefoxitin sensitiveness of enterobacteria and Streptococcusagalactiae.
Table 3
Wherein, VC represents vitamin C.
Finally it should be noted that：The preferred embodiments of the present invention are the foregoing is only, the present invention is not limited to, 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 To modify 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 the present invention's Within protection domain.

Claims (7)

1. application of the vitamin C in the antibacterial or germ killing drugs containing beta-lactam antibiotic are prepared.
2. vitamin C can improve answering in antibacterial or germ killing drugs of the bacterium to beta-lactam antibiotic sensitiveness in preparation With.
3. vitamin C can reduce answering in antibacterial or germ killing drugs of the bacterium to beta-lactam antibiotic drug resistance in preparation With.
4. according to the arbitrary described application 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 the arbitrary described application of claim 1-3, it is characterised in that described beta-lactam antibiotic is mould Element, ampicillin and/or cefoxitin.
6. according to the arbitrary described application of claim 1-3, it is characterised in that in described antibacterial or germ killing drugs, vitamin C with The dose ratio of beta-lactam antibiotic is calculated as by weight 1：（0.002-4）.
7. according to the arbitrary described application of claim 1-3, it is characterised in that ascorbic in described antibacterial or germ killing drugs Usage amount is 0.18mg/mL-1.75 mg/mL.
CN201710170255.6A 2017-03-21 2017-03-21 New application of vitamin C Pending CN106668011A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
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Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
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Country Status (1)

Country Link
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Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
A. RAMESH等: "Ascorbic acid-induced loss of a pediocin-encoding plasmid in Pediococcus acidilactici CFR K7", 《WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY》 *
ARCHANA CHATTERJEE等: "Antimicrobial effects of antioxidants with and without clarithromycin on Helicobacter pylori", 《MOLECULAR AND CELLULAR BIOCHEMISTRY》 *
F. YANG等: "Short communication: N-Acetylcysteine-mediated modulation of antibiotic susceptibility of bovine mastitis pathogens", 《JOURNAL OF DAIRY SCIENCE》 *
LINDA EJIM等: "Combinations of antibiotics and nonantibiotic drugs enhance antimicrobial efficacy", 《NATURE CHEMICAL BIOLOGY》 *
SUHIRA M.ABURAWI等: "Effect of Vitamin C on Penicillin G Efficacy to Inhibit Bacterial Populations", 《TRIPOLITANA MEDICAL JOURNAL》 *

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