CN110946870A - Antibacterial pharmaceutical composition and application thereof - Google Patents
Antibacterial pharmaceutical composition and application thereof Download PDFInfo
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- CN110946870A CN110946870A CN201910854851.5A CN201910854851A CN110946870A CN 110946870 A CN110946870 A CN 110946870A CN 201910854851 A CN201910854851 A CN 201910854851A CN 110946870 A CN110946870 A CN 110946870A
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- Prior art keywords
- fosfomycin
- cryptotanshinone
- antibacterial
- pharmaceutical composition
- drug
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- 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.)
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- 230000000844 anti-bacterial effect Effects 0.000 title claims abstract description 29
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 14
- YMDXZJFXQJVXBF-STHAYSLISA-N fosfomycin Chemical compound C[C@@H]1O[C@@H]1P(O)(O)=O YMDXZJFXQJVXBF-STHAYSLISA-N 0.000 claims abstract description 57
- 229960000308 fosfomycin Drugs 0.000 claims abstract description 53
- GVKKJJOMQCNPGB-JTQLQIEISA-N Cryptotanshinone Chemical compound O=C1C(=O)C2=C3CCCC(C)(C)C3=CC=C2C2=C1[C@@H](C)CO2 GVKKJJOMQCNPGB-JTQLQIEISA-N 0.000 claims abstract description 39
- GVKKJJOMQCNPGB-UHFFFAOYSA-N Cryptotanshinone Natural products O=C1C(=O)C2=C3CCCC(C)(C)C3=CC=C2C2=C1C(C)CO2 GVKKJJOMQCNPGB-UHFFFAOYSA-N 0.000 claims abstract description 39
- 239000003814 drug Substances 0.000 claims abstract description 27
- 241000191967 Staphylococcus aureus Species 0.000 claims abstract description 11
- 241000894006 Bacteria Species 0.000 claims abstract description 9
- 229940124350 antibacterial drug Drugs 0.000 claims abstract description 6
- 239000000203 mixture Substances 0.000 claims abstract description 5
- 208000035473 Communicable disease Diseases 0.000 claims description 5
- 239000003242 anti bacterial agent Substances 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- 208000015181 infectious disease Diseases 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000004615 ingredient Substances 0.000 claims description 2
- 239000000463 material Substances 0.000 claims description 2
- 230000000845 anti-microbial effect Effects 0.000 claims 1
- 239000004599 antimicrobial Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 229940079593 drug Drugs 0.000 abstract description 16
- 230000005764 inhibitory process Effects 0.000 abstract description 8
- 210000002421 cell wall Anatomy 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 6
- 230000001580 bacterial effect Effects 0.000 abstract description 5
- 230000002924 anti-infective effect Effects 0.000 abstract description 4
- 238000000034 method Methods 0.000 abstract description 4
- 238000011282 treatment Methods 0.000 abstract description 4
- 206010059866 Drug resistance Diseases 0.000 abstract description 3
- 210000002390 cell membrane structure Anatomy 0.000 abstract description 3
- 238000000338 in vitro Methods 0.000 abstract description 3
- 239000002547 new drug Substances 0.000 abstract description 3
- 238000011160 research Methods 0.000 abstract description 3
- 238000012827 research and development Methods 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000007788 liquid Substances 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 241000192125 Firmicutes Species 0.000 description 2
- 241000187747 Streptomyces Species 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000011146 sterile filtration Methods 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- UDPGUMQDCGORJQ-UHFFFAOYSA-N (2-chloroethyl)phosphonic acid Chemical compound OP(O)(=O)CCCl UDPGUMQDCGORJQ-UHFFFAOYSA-N 0.000 description 1
- 238000009631 Broth culture Methods 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000588747 Klebsiella pneumoniae Species 0.000 description 1
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 1
- 208000011948 Multi-organ disease Diseases 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 241000304195 Salvia miltiorrhiza Species 0.000 description 1
- 235000011135 Salvia miltiorrhiza Nutrition 0.000 description 1
- 206010062255 Soft tissue infection Diseases 0.000 description 1
- 241000187398 Streptomyces lividans Species 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000008236 biological pathway Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000004690 coupled electron pair approximation Methods 0.000 description 1
- 235000019788 craving Nutrition 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 108091008053 gene clusters Proteins 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229960003085 meticillin Drugs 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 238000001668 nucleic acid synthesis Methods 0.000 description 1
- 229930029653 phosphoenolpyruvate Natural products 0.000 description 1
- DTBNBXWJWCWCIK-UHFFFAOYSA-N phosphoenolpyruvic acid Chemical compound OC(=O)C(=C)OP(O)(O)=O DTBNBXWJWCWCIK-UHFFFAOYSA-N 0.000 description 1
- 230000004260 plant-type cell wall biogenesis Effects 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/665—Phosphorus compounds having oxygen as a ring hetero atom, e.g. fosfomycin
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides an antibacterial pharmaceutical composition and application thereof. The antibacterial pharmaceutical composition consists of fosfomycin and cryptotanshinone. The cryptotanshinone and the fosfomycin are scientifically and reasonably combined, the cryptotanshinone and the fosfomycin are used together, the antibacterial activity of the fosfomycin is enhanced through the function that the cryptotanshinone destroys the cell wall and the cell membrane structure of bacteria, a good inhibition effect is generated for the staphylococcus aureus with fosfomycin resistance, a specific and effective treatment scheme is provided for treating the fosfomycin resistance strain, and a brand-new way is provided for the increasingly serious problem of bacterial drug resistance. Compared with the traditional new drug research and development, the antibacterial drug composition and the combined drug method provided by the invention have the advantages of high efficiency, rapidness, low cost, multiple optional combinations and the like, and show good antibacterial activity in-vitro anti-infection research.
Description
Technical Field
The invention relates to the field of pharmacy, and particularly relates to an antibacterial pharmaceutical composition and application thereof.
Background
Infectious diseases are common frequently-occurring diseases threatening human life and health, and are also one of the important complications and death causes of multi-organ diseases. The use of anti-infective drugs greatly reduces the mortality of infectious diseases. The major mechanisms of antibiotics currently include inhibition of cell wall synthesis, inhibition of certain functions of cell membranes, inhibition of protein synthesis, inhibition of nucleic acid synthesis, inhibition of folic acid synthesis, and the like.
Fosfomycin is an earlier discovered antibiotic produced by pseudomonas of streptomyces, was co-developed by merck and spain CEPA in 1969, and in 2006, Woodyer et al reported the cloning and characterization of the complete fosfomycin biosynthesis gene cluster isolated from streptomyces neomycin and its homolog streptomyces lividans in strain 1, thus opening a new perspective of fosfomycin biosynthesis and the door to the creation of new homologs of fosfomycin by molecular biological pathway engineering. Today, fosfomycin has been artificially synthesized.
The spatial structure of the phosphomycin is similar to that of phosphoenolpyruvate which is an essential substance for the synthesis of bacterial cell walls, and the phosphomycin can be covalently combined with the pyruvyltransferase in the early stage of the synthesis of the cell walls to irreversibly inactivate the pyruvyltransferase so as to inhibit the biosynthesis of the bacterial cell walls, so that the phosphomycin has good antibacterial activity on gram-positive bacteria and gram-negative bacteria, and is mainly used for soft tissue infection and simple urinary tract infection caused by staphylococcus aureus, escherichia coli, klebsiella pneumoniae and the like.
However, with the widespread clinical use of fosfomycin, drug resistance has gradually developed. The treatment of drug resistant strains is extremely tricky, which causes a dramatic increase in the mortality rate of the infection, constituting a serious threat to the health of the whole human being. It is therefore imperative to provide a reasonable treatment regimen against fosfomycin-resistant strains. However, in recent decades, few new antibiotics are available, and the combined administration of fosfomycin and other bioactive molecules as antibacterial adjuvants may provide a new idea for the development of novel antibacterial drugs.
Cryptotanshinone is a fat-soluble effective component extracted from traditional Chinese medicine salvia miltiorrhiza, and reportedly, cryptotanshinone has an obvious inhibiting effect on staphylococcus aureus, methicillin-resistant staphylococcus aureus and β -lactamase positive staphylococcus aureus.
The combined medication can realize the minimum dosage of antibiotics and improve the curative effect as far as possible, is the idea of developing novel drug-resistant bacteria resistant drugs in the future and is also the craving of patients. The combined medication of fosfomycin and cryptotanshinone has not been reported.
Disclosure of Invention
The invention aims to provide an antibacterial pharmaceutical composition and application thereof.
The invention provides an antibacterial pharmaceutical composition, which consists of fosfomycin and cryptotanshinone.
Further, the weight ratio of the cryptotanshinone to the fosfomycin is 1 (16-128).
The invention also provides a preparation method of the antibacterial pharmaceutical composition, and the antibacterial pharmaceutical composition is prepared according to the following steps: taking fosfomycin and cryptotanshinone according to a proportion, preparing the fosfomycin and the cryptotanshinone into a solution, and mixing the solution.
The invention also provides an antibacterial medicinal preparation which is prepared by taking the antibacterial medicinal composition as an active ingredient and adding pharmaceutically acceptable auxiliary materials or auxiliary ingredients.
The invention also provides an antibacterial combined medicament which contains the same or different specifications of fosfomycin and cryptotanshinone which are simultaneously or respectively administered, and a pharmaceutically acceptable carrier.
Further, the weight ratio of the cryptotanshinone to the fosfomycin is 1 (16-128).
The invention also provides application of the combination of the fosfomycin and the cryptotanshinone in preparing antibacterial drugs or antibacterial infectious diseases.
Further, the weight ratio of the cryptotanshinone to the fosfomycin is 1 (16-128).
Further, the antibacterial agent is an agent against gram-positive bacteria; the antibacterial infectious disease is a gram-positive bacterial infectious disease.
Further, the gram-positive bacterium is staphylococcus aureus.
The cryptotanshinone and the fosfomycin are scientifically and reasonably combined, the cryptotanshinone and the fosfomycin are used together, the antibacterial activity of the fosfomycin is enhanced through the function that the cryptotanshinone destroys the cell wall and the cell membrane structure of bacteria, a good inhibition effect is generated for the staphylococcus aureus with fosfomycin resistance, a specific and effective treatment scheme is provided for treating the fosfomycin resistance strain, and a brand-new way is provided for the increasingly serious problem of bacterial drug resistance. Compared with the traditional new drug research and development, the antibacterial drug composition and the combined drug method provided by the invention have the advantages of high efficiency, rapidness, low cost, multiple optional combinations and the like, and show good antibacterial activity in-vitro anti-infection research.
Obviously, many modifications, substitutions, and variations are possible in light of the above teachings of the invention, without departing from the basic technical spirit of the invention, as defined by the following claims.
The present invention will be described in further detail with reference to the following examples. This should not be understood as limiting the scope of the above-described subject matter of the present invention to the following examples. All the technologies realized based on the above contents of the present invention belong to the scope of the present invention.
Detailed Description
Example 1 preparation of drug combination of cryptotanshinone and fosfomycin
Method (A)
1, weighing a plurality of fosfomycin, and carrying out sterile filtration after the volume is fixed by RO water to obtain the fosfomycin with corresponding concentration.
Weighing a plurality of cryptotanshinone, diluting to a constant volume with DMSO, and performing sterile filtration to obtain cryptotanshinone with corresponding concentration.
3, mixing the fosfomycin and the cryptotanshinone according to different proportions to prepare mixed liquid medicine with different concentrations and compatibility.
4, the phosphomycin-resistant Staphylococcus aureus strains numbered 1 to 7 were inoculated in 1mL of MH broth and cultured overnight at 37 ℃.
5, the overnight-cultured broth was adjusted to 0.5 McLeod (about 1.0X 10)8CFU/mL), and then diluted with a 20-fold concentration gradient to give an inoculum concentration of 10. mu.l/well and 5.0X 105CFU/mL。
6, mixing the mixed liquid medicine with different concentrations and MH broth culture medium, adding into a 96-well plate, and finally adding 10 mul of inoculated bacterial liquid for mixing. So that the final concentration range of fosfomycin is 16-2048g/mL and the final concentration range of cryptotanshinone is 0.5-8g/mL, and a chessboard dilution method MIC is implemented.
7, properly wrapping the 96-well culture plate to prevent the liquid from being excessively evaporated, and culturing at 37 ℃ for 16-18 h.
And 8, taking out the 96-well plate, and observing and detecting. The minimum antibiotic Concentration for aseptic growth is the Minimum Inhibitory Concentration (MIC). The Fractional Inhibitory Concentration Index (FICI) is an index for determining the interaction effect of drugs. The total FICI is the sum of the FICI of each medicine, namely the MIC of the A medicine combined with the A medicine and the MIC of the B medicine combined with the B medicine. The total FICI: synergy, < 0.5; partial synergy, 0.5-0.75; adding, 0.76-1.0; independently, > 1.0-4.0; antagonism, > 4.0.
(II) results
As can be seen from Table 1, when 7 fosfomycin-resistant strains are subjected to combined administration of fosfomycin and cryptotanshinone, 5 strains have a synergistic effect, and 2 strains have a partial synergistic effect. Cryptotanshinone can increase the sensitivity of the drug-resistant strain to fosfomycin by about 2-16 times.
Table 1: effect of combined medication of fosfomycin and cryptotanshinone on fosfomycin-resistant staphylococcus aureus
Total FICI: synergy, < 0.5; partial synergy, 0.5-0.75; adding, 0.76-1.0; independently, > 1.0-4.0; antagonism, > 4.0.
The results show that the fosfomycin and cryptotanshinone combined drug can play a role in synergy, increase the sensitivity of the drug-resistant bacteria and more effectively inhibit the drug-resistant bacteria under the condition of lower drug dosage. The fosfomycin and cryptotanshinone combined medicine has great application value in the aspects of bacteriostasis and infection resistance.
In conclusion, the cryptotanshinone and the fosfomycin are scientifically and reasonably combined, the cryptotanshinone and the fosfomycin are used together, the antibacterial activity of the fosfomycin is enhanced through the function that the cryptotanshinone destroys the cell wall and the cell membrane structure of bacteria, a good inhibition effect is generated for the staphylococcus aureus with fosfomycin resistance, a specific and effective treatment scheme is provided for treating the fosfomycin resistance strain, and a new way is provided for the increasingly serious problem of the bacterial resistance. Compared with the traditional new drug research and development, the antibacterial drug composition and the combined drug method provided by the invention have the advantages of high efficiency, rapidness, low cost, multiple optional combinations and the like, and show good antibacterial activity in-vitro anti-infection research.
Claims (10)
1. An antibacterial pharmaceutical composition, characterized in that: it is composed of fosfomycin and cryptotanshinone.
2. The antibacterial pharmaceutical composition according to claim 1, characterized in that: the weight ratio of the cryptotanshinone to the fosfomycin is 1 (16-128).
3. A process for preparing an antibacterial pharmaceutical composition according to claim 1 or 2, characterized in that: the antibacterial pharmaceutical composition is prepared according to the following steps: taking fosfomycin and cryptotanshinone according to a proportion, preparing the fosfomycin and the cryptotanshinone into a solution, and mixing the solution.
4. An antimicrobial pharmaceutical formulation characterized by: the preparation is prepared by taking the antibacterial medicine composition as an active ingredient according to claim 1 or 2 and adding pharmaceutically acceptable auxiliary materials or auxiliary ingredients.
5. An antibacterial combination, characterized in that: it contains fosfomycin and cryptotanshinone which are in the same or different specifications and are simultaneously or respectively administrated, and a pharmaceutically acceptable carrier.
6. The combination according to claim 5, wherein: the weight ratio of the cryptotanshinone to the fosfomycin is 1 (16-128).
7. The application of the combination of fosfomycin and cryptotanshinone in preparing antibacterial drugs or resisting bacterial infectious diseases.
8. Use according to claim 7, characterized in that: the weight ratio of the cryptotanshinone to the fosfomycin is 1 (16-128).
9. Use according to claim 7, characterized in that: the antibacterial agent is an anti-gram-positive-bacteria agent; the antibacterial infectious disease is a gram-positive bacterial infectious disease.
10. Use according to claim 9, characterized in that: the gram-positive bacterium is staphylococcus aureus.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811125781 | 2018-09-26 | ||
| CN2018111257811 | 2018-09-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110946870A true CN110946870A (en) | 2020-04-03 |
Family
ID=69976273
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910854851.5A Pending CN110946870A (en) | 2018-09-26 | 2019-09-10 | Antibacterial pharmaceutical composition and application thereof |
Country Status (1)
| Country | Link |
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| CN (1) | CN110946870A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111588749A (en) * | 2020-06-05 | 2020-08-28 | 首都医科大学附属北京中医医院 | New application of traditional Chinese medicine composition |
| CN112999230A (en) * | 2021-02-18 | 2021-06-22 | 浙江中医药大学 | Application of cryptotanshinone in preparation of bacterial respiratory chain inhibitor |
-
2019
- 2019-09-10 CN CN201910854851.5A patent/CN110946870A/en active Pending
Non-Patent Citations (3)
| Title |
|---|
| JEONG-DAN CHA等: "Synergistic Effect between Cryptotanshinone and Antibiotics against Clinic Methicillin and Vancomycin-Resistant Staphylococcus aureus", 《EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE》 * |
| ZIJING RUAN: "Synergistic Effects from Combination of Cryptotanshinone and Fosfomycin Against Fosfomycin-Susceptible and Fosfomycin-Resistant Staphylococcus aureus", 《INFECTION AND DRUG RESISTANCE》 * |
| 傅瑞春: "8种植物抗菌成分与抗菌剂联用抗耐药菌作用的研究", 《中国优秀硕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 |
|---|---|---|---|---|
| CN111588749A (en) * | 2020-06-05 | 2020-08-28 | 首都医科大学附属北京中医医院 | New application of traditional Chinese medicine composition |
| CN112999230A (en) * | 2021-02-18 | 2021-06-22 | 浙江中医药大学 | Application of cryptotanshinone in preparation of bacterial respiratory chain inhibitor |
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Application publication date: 20200403 |