CN105030819A - Use of 3-hydroxy-4-pyridone high-molecular iron chelating agent - Google Patents
Use of 3-hydroxy-4-pyridone high-molecular iron chelating agent Download PDFInfo
- Publication number
- CN105030819A CN105030819A CN201510395542.8A CN201510395542A CN105030819A CN 105030819 A CN105030819 A CN 105030819A CN 201510395542 A CN201510395542 A CN 201510395542A CN 105030819 A CN105030819 A CN 105030819A
- Authority
- CN
- China
- Prior art keywords
- chelating agent
- iron chelating
- pyridone
- macromolecule
- hydroxy
- 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.)
- Granted
Links
- 0 CC(C1=CC=CCC1)=* Chemical compound CC(C1=CC=CCC1)=* 0.000 description 5
Abstract
The invention discloses a use of a 3-hydroxy-4-pyridone high-molecular iron chelating agent. The 3-hydroxy-4-pyridone high-molecular iron chelating agent has antibacterial effects and can be used as an antibacterial material. The 3-hydroxy-4-pyridone high-molecular iron chelating agent has excellent effects of resisting methicillin-resistant staphylococcus aureus. According to a mechanism of cation simulative antibacterial peptide formation from tertiary amine or secondary amine positive ion structures in a high-molecular iron chelating agent, interaction between a positive charge area and a negative charge area on a cell membrane, and iron chelating effects of an iron chelating agent, the normal growth environment around bacteria is destroyed and bacterium growth is inhibited so that bacteria cannot normally grow. The 3-hydroxy-4-pyridone high-molecular iron chelating agent cannot be absorbed by skin because of macro-molecule characteristics, does not produce toxic or side effects and can be used as an antibacterial material with dual antibiosis effects.
Description
One, technical field
The present invention relates to a kind of purposes of chelating agen, specifically a kind of purposes of 3-hydroxyl-4-pyridinone macromolecule iron chelating agent.
Two, background technology
Anti-biotic material refers to the class new function material self having killing or suppress microbial function, extremely wide application prospect is had in fields such as medical field, household supplies, household electrical appliance, packagings for foodstuff, people, environmental health is required to the today of day by day improving, the application of anti-biotic material is subject to paying close attention to more widely.Current domestic antibacterial, sterilization material generally uses antibiotic, as o-phenyl phenol, Methylisothiazolinone and triclosan etc., although antibiotic has higher antibacterial activity for wildtype bacterium, its for drug-fast strain without any effect.Now, antibiotic abuse has reached very serious stage, and superbacteria that antibiotic abuse can cause Drug resistance extremely strong produces, if this situation continued worsens, when probably making facing mankind infect without medicine can condition.Antibiotic is owing to being micromolecule in addition, and it along with blood circulation is to some positions be not infected by bacterial of human body, thus can bring larger toxic and side effects.Antibiotic has for the person with idiosyncrasy and easily produces anaphylaxis, may be fatal when anaphylaxis is serious.And used antibiotics antibacterial to enter water circulation system be also secondary pollution.After suppressing by antibacterials or killing responsive antibacterial, the but continued growth breeding of some insensitive antibacterial or mycete, causes new infection, i.e. " superinfection ", this much sees in the patient of long-term Domain of Abuse Antibiotics, and treatment difficulty, case fatality rate can be caused high.
Microorganism needs the iron ion in absorbing environmental to ensure the carrying out of a series of physiological activities in its body, and the reduction of oxygen in such as ATP building-up process, the reduction of DNA prerequisite material nucleotide, the synthesis of haemachrome and other a series of important reaction all need the participation of ferrum.Meanwhile, ferrum is also the important nutrient of one of microorganism, and it is essential for keeping the activity of many enzymes in cell.In order to obtain the necessary ferrum element of the activity of sustaining life, microbes synthesizes in vivo and secretes a class to Fe
3+there is organic micromolecule compound---the siderophore of stronger complexation power, if compete ferrum so have in surrounding to the siderophore of the very high chelating agen of ferrum affinity and microorganism, make antibacterial can not obtain enough ferrum element, its growth will be suppressed, just can not growth and breeding.So synthesize a kind of have be not absorbed by the body, there is high affine ferrum ability, ferrum macromolecule capacious iron chelating agent will to treatment microbial infectious diseases have certain application prospect.From the sixties in 20th century since first America and Europe has found methicillin-resistant staphylococcus aureus (MRSA) hospital infection, its ratio shared in infection of staphylococcus aureus is more and more higher, has become one of important pathogenic bacterium of hospital infection.Because its route of transmission is extensive, outbreak of epidemic in Yi Zhi institute; Again because it is by force pathogenic, become the difficult point of clinical treatment in multidrug resistant.Therefore, the infection of prevention and therapy MRSA is the important topic that Nosocomiology faces.
Antibacterial peptide is a kind of polypeptide produced through biological Immune inducing in vivo, is the ingredient of innate immunity response.It has heat stability and high-efficiency antimicrobial is active.2003 start, and the state such as the U.S., Japan starts have seminar to be engaged in the research of poly-polypeptide class artificial antimicrobial peptide successively; 2005, the Wong teach problem group of UCLA university of the U.S. took to the research of polymer electrolyte artificial antimicrobial peptide; 2009, Univ Michigan-Ann Arbor USA Kuroda seminar started from the research of molecular biology angle to polymer electrolyte artificial antimicrobial peptide, and has inquired into the impact of chemical environment for antibacterial effect of functional groups in detail.Utilize the hands section of Polymer Synthesizing, the molecular structure of simulation natural antibacterial peptide, cheapness can be synthesized and the polymer of not easily biodegradable synthetic, the cation type polymer obtained especially by structural design can interact with surface of cell membrane, make the permeability changes of bacterial membrane, negative charge regional interaction on positive charge region wherein and cell membrane, high molecular hydrophobic side is made to insert in the lipid film of cell membrane, and then change lipid membrane structure, transmembrane potential is formed with after cell membrane effect, break acid-base balance, affect osmotic balance, suppress Repiration, then good antibacterial action is played.
No matter be gram positive bacteria or gram negative bacteria, their growth all needs ferrum, if in conjunction with the ferrum affinity of macromolecule iron chelating agent and macromole not by characteristic that human body skin absorbs, add the positive charge Antibacterial mechanism utilizing antibacterial peptide, a kind of very effective dual anti-biotic material will be obtained.
Three, summary of the invention
The present invention aims to provide a kind of purposes of 3-hydroxyl-4-pyridinone macromolecule iron chelating agent, wherein 3-hydroxyl-4-pyridinone macromolecule iron chelating agent is obtained by polymethylacrylic acid (+)-2,3-Epoxy-1-propanol ether-ether and the 3-hydroxyl-4-pyridine compounds generation ring-opening reaction containing amido, utilize the positron structure of tertiary amine in 3-hydroxyl-4-pyridinone macromolecule iron chelating agent or secondary amine, negative charge regional interaction on positive charge region and bacterial cell membrane, high molecular hydrophobic side is made to insert in the lipid film of cell membrane, and then change lipid membrane structure, transmembrane potential is formed with after cell membrane effect, break acid-base balance, affect osmotic balance, suppress Repiration, add the high ferro affinity of 3-hydroxyl-4-pyridine compounds, absorb the trace element of bacterium surface, especially ferric iron element, make it grow to be suppressed.
The structural formula of 3-hydroxyl-4-pyridinone macromolecule iron chelating agent of the present invention is as follows:
The span 20-200 of n.
3-hydroxyl-4-pyridinone macromolecule iron chelating agent of the present invention is by polymethylacrylic acid (+)-2,3-Epoxy-1-propanol ether-ether and the 3-hydroxyl-4-pyridine compounds containing amido and epoxide group generation ring-opening reaction, 3-hydroxyl-4-pyridine compounds is covalently attached to macromolecule ferrum (III) chelating agen that polymethylacrylic acid glycidyl ether ester side chain obtains, concrete preparation process is as follows:
By the polymethylacrylic acid (+)-2,3-Epoxy-1-propanol ether-ether (M of 100 mass parts
n=1000-10000) join in single port bottle, then the anhydrous N of 200-300 mass parts is added, dinethylformamide dissolves, add the 3-hydroxyl-4-pyridine compounds that 50-100 mass parts triethylamine and 100-1000 mass parts contain amido again, 55-80 DEG C is kept to react 2-36 hour, the ether sedimentation products of 2000-3000 mass parts is added in reactant liquor, dry after filtering-depositing, add the anhydrous N of 200-300 mass parts subsequently, dinethylformamide dissolves, then put into bag filter and dialyse that (every day changed No. four distilled water in 3-5 days, bag filter molecular cut off is 3000) remove the excessive 3-hydroxyl-4-pyridine compounds containing amido, obtain macromolecule ferrum (III) chelating agen.
The described 3-hydroxyl-4-pyridine compounds containing amido is selected from 1-(amino-4,7,10-tri-oxygen tridecyl)-2-methyl-3-hydroxyl-4-(1H)-pyridone (1), 1-amino-ethyl-2-methyl-3-hydroxyl-4-(1H)-pyridone (2), 1-methylaminopropyl-2-methyl-3-hydroxyl-4-(1H)-pyridone (3) or 2-methyl-3-hydroxyl-4-(1H)-5-Methyaminomethyl-pyridone (4), its structural formula is as follows:
3-hydroxyl-4-pyridinone macromolecule iron chelating agent of the present invention has antibacterial action, can be used as anti-biotic material and uses, wherein have excellent antibacterial effect to methicillin-resistant staphylococcus aureus especially.
The present invention compared with prior art has the following advantages:
1,3-hydroxyl-4-pyridinone macromolecule iron chelating agent of the present invention, not only combine the cationic antimicrobial mechanism of natural antibacterial peptide, also in conjunction with the chelation of iron chelating agent for ferrum element, destroy antibacterial surrounding normal growing environment, can as a kind of anti-biotic material of dual function.
2, present invention incorporates the nontoxic, good with material compatibility of polymethylacrylic acid (+)-2,3-Epoxy-1-propanol ether-ether, the material ferrum chelating capacity obtained promotes greatly, be 1196 μm of ol/g to the maximum, bacterial growth necessary ferrum element effectively can be absorbed when using as anti-biotic material, cause the growth of antibacterial to be suppressed, make it can not growth and breeding.
3,3-hydroxyl-4-pyridinone macromolecule iron chelating agent of the present invention, utilize the tertiary amine in structure or secondary amine cationic structural, be adsorbed on the bacterial cell membrane with negative charge, just as carpet, film surface is covered when quantity acquires a certain degree, attack with the model of action targeting of " detergent ", destroy bacterial cell membrane and cause cell death, utilize carpet model (carpet-like) function cells film.This model mechanism of action can not have any effect to close to electroneutral human body cell film, test through hemolytic experiment, epithelial cell is had no side effect, and good water solubility, antiseptic solution can be configured to widely use, its macromole characteristic is not absorbed by the skin, and does not produce toxic and side effects, can solve if added in material with antibacterial additives the problem that current micromolecule antibacterial adds macromolecular material resistance to migration difference to.
Four, accompanying drawing explanation
Fig. 1 is the absorbance graph of a relation of the macromolecule iron chelating agent 8K21 aqueous solution using ultraviolet visible spectrophotometry mensuration ferric ion content and the embodiment of the present invention 1 to prepare.
Fig. 2 is macromolecule iron chelating agent 7K21 and 7TD that prepare of the embodiment of the present invention 1 and embodiment 2 block diagram to methicillin-resistant staphylococcus aureus sterilizing rate and concentration relationship after air couveuse hatches 24 hours.
Fig. 3 is the epithelial cell Toxic test results figure of macromolecule iron chelating agent 7K21 and 7TD prepared by the embodiment of the present invention 1 and embodiment 2.
Five, detailed description of the invention
Embodiment 1:
By 0.2g polymethylacrylic acid (+)-2,3-Epoxy-1-propanol ether-ether PGMA1 (M
n=12800gmol
-1) and 1.3g1-(amino-4, 7, 10-tri-oxygen tridecyl)-2-methyl-3-hydroxyl-4-(1H)-pyridone joins in single port bottle, then the anhydrous N of 8mL is added, dinethylformamide dissolves, add 1mL triethylamine again, 55 DEG C are kept to react 36 hours, 80mL ether sedimentation products is added in reactant liquor, dry after filtering-depositing, (every day changed four water in 3 days to put into bag filter dialysis, bag filter molecular cut off is 3000) remove excessive monomer and obtain macromolecule iron chelating agent 7K21, wherein the content of small molecule chelators in macromolecule iron chelating agent is about 70wt%.Get 0.1 gram of 7K21 to be dissolved in respectively in 1mL water and acetone, butanone, DMF, dimethyl sulfoxine, can solution be formed, leave in the solution without any insoluble matter.Calculate repetitive number in polymethylacrylic acid (+)-2,3-Epoxy-1-propanol ether-ether by proton nmr spectra, calculate the number-average molecular weight M of macromolecule iron chelating agent
n=50100.
If keep other condition constant, 0.2gPGMA1 in reactant is replaced by 0.2g polymethylacrylic acid (+)-2,3-Epoxy-1-propanol ether-ether PGMA2 (M
n=10300gmol
-1), can obtain macromolecule iron chelating agent 8K21, wherein the content of small molecule chelators in macromolecule iron chelating agent is about 70wt%.
Embodiment 2:
By 0.2g polymethylacrylic acid (+)-2,3-Epoxy-1-propanol ether-ether PGMA2 (M
n=10300gmol
-1) and 0.29g1-methylaminopropyl-2-methyl-3-hydroxyl-4-(1H)-pyridone join in single port bottle, then the anhydrous N of 8mL is added, dinethylformamide dissolves, then 1mL triethylamine is added, 80 DEG C are kept to react 2 hours, 80mL ether sedimentation products is added in reactant liquor, dry after filtering-depositing, (every day changed No. four distilled water in 3 days to put into bag filter dialysis, bag filter molecular cut off is 3000) remove excessive monomer and obtain macromolecule iron chelating agent 8K41, wherein the content of small molecule chelators in macromolecule iron chelating agent is about 58wt%.
If keep other condition constant, 0.2gPGMA2,0.29g1-methylaminopropyl-2-methyl-3-hydroxyl-4-(1H)-pyridone in reactant is replaced by respectively 0.2g polymethylacrylic acid (+)-2,3-Epoxy-1-propanol ether-ether PGMA1,0.24g2-methyl-3-hydroxyl-4-(1H)-5-Methyaminomethyl-pyridone, can obtain macromolecule iron chelating agent 7TD, wherein the content of small molecule chelators in macromolecule iron chelating agent is about 70wt%.Calculate repetitive number in polymethylacrylic acid (+)-2,3-Epoxy-1-propanol ether-ether by proton nmr spectra, calculate the number-average molecular weight M of macromolecule iron chelating agent
n=33100.
Application Example:
Above-described embodiment 1 is selected to synthesize the mensuration that the 8K21 obtained carries out ferrum chelating capacity, to probe into the chelated iron macromolecule of different molecular weight length, iron ion (III) chelating capacity of the macromolecule iron chelating agent that different ligands is formed.Concrete operations are as follows: get dried chelated iron fractionated polymer another name and measure (5.39mg8K21), add 0.4mL dimethyl sulfoxide and form solution, getting the above-mentioned solution of 5 μ L again and join the 1.4mL water formation high molecular aqueous solution of chelated iron (amount of dimethyl sulfoxide is ignored), is 48.13 μ g/mL by calculating the concentration of macromolecular compound 8K21.This experiment adopts ferric chloride in aqueous solution (0.8953mM, FeCl
3) carry out titration, every 5 minutes titration 5 microlitre ferric chloride in aqueous solution, measured by the ferrum chelating capacity of ultraviolet-visible absorption spectroscopy (250-600nm) to compound, because after macromolecular compound and iron ion chelating, absorption is had in visible-range, along with the increase of iron chelating agent concentration, UV-visible absorbance increases, when the chelating agen that iron ion and macromolecule are formed is saturated, absorbance will no longer change, now can obtain high molecular ferrum chelating capacity according to the cubage dripping iron ion in ferrous solution, the ferrum chelating capacity finally recording 8K21 is 1196 μm of ol/g.Fig. 1 is the absorbance graph of a relation of the macromolecule iron chelating agent 8K21 aqueous solution using ultraviolet visible spectrophotometry mensuration ferric ion content and the embodiment of the present invention 1 to prepare.
Inoculation is frozen in (TSB, 2.5mL) at fresh soybean protein, cultivates 18 hours in the constant incubator of 37 DEG C afterwards.Therefrom get 40 μ L culture fluid, be diluted in the TSB containing 100 μ g/mL ampicillin (4mL), then in the constant incubator of 37 DEG C, cultivate about 3 hours.Centrifugally make bacterial strain sedimentation (staphylococcus aureus rotating speed is 10000rpm, other strain is 5000rpm, centrifugal 5min), removing supernatant, utilize 2-[4-(2-ethoxy)-1-piperazinyl] esilate (HEPES) buffer (10mMHEPES afterwards, 150mMNaCl, pH7.4) wash remaining bacterial strain twice.The bacterium liquid obtained is put into 96 microwell plates and is carried out sterilization experiment, utilizes the method for doubling dilution, is added in 96 microwell plates by the HEPES buffer of 3-hydroxyl-4-pyridinone macromolecule iron chelating agent.Utilized by macromolecule iron chelating agent HEPES to be diluted to 150 μ L, add 50 μ L bacterium liquid.Microwell plate is positioned in the constant incubator of 37 DEG C and cultivates 3 hours, antibacterial is diluted in 96 microwell plates by 10 times of dilution methods, cultivate 12 hours in M ü eller-Hinton (MH) agar plate afterwards, control the number of strains of reference (PC) between 80 ~ 120.The macromolecule iron chelating agent concentration data table that table 1 uses for this antibacterial experiment.Fig. 2 is macromolecule iron chelating agent 7K21 and 7TD that prepare of the embodiment of the present invention 1 and embodiment 2 block diagram to methicillin-resistant staphylococcus aureus sterilizing rate and concentration relationship after air couveuse hatches 24 hours.
Table 1
Table 2 for macromolecule iron chelating agent 7K21 and 7TD of variable concentrations after air couveuse hatches 24 hours to methicillin-resistant staphylococcus aureus sterilizing rate tables of data.As can be seen from the table, macromolecule iron chelating agent 7K21 and 7TD just can have the sterilizing rate of 99.9% respectively under the concentration of 6 μMs (0.301mg/mL) and 12 μMs (0.397mg/mL).
Table 2
Utilize 2 times of dilution methods, in 96 microwell plates, prepare the PBS buffer solution of 3-hydroxyl-4-pyridinone macromolecule iron chelating agent.Get 0.1mL mouse epithelial cells liquid afterwards, utilize phosphate buffered saline (PBS) (PBS) buffer solution Mouse Blood cell.Utilize PBS by Mouse Blood cell dilution afterwards, ensure that Mouse Blood cell concentration is about 2.5 × 10
4cells/ μ L.The PBS buffer solution of 160 μ L Mouse Blood cell dispersal liquid and 40 μ L3-hydroxyl-4-pyridinone macromolecule iron chelating agents is mixed, reference mixes with mouse cell with 50% QULA pine, cultivate 1 hour in the constant incubator of 37 DEG C, it is 200rpm that control shaking table rocks speed.Then by the mixed liquor in microwell plate with the centrifugal 5min of the rotating speed of 800rcf, get 50 μ L and add in 96 microwell plates, under 414nm wavelength, survey its absorbance, and be defined as 100% with 50% QULA pine with the absorbance of mouse cell biased sample.Fig. 3 is the epithelial cell Toxic test results figure of macromolecule iron chelating agent 7K21 and 7TD prepared by the embodiment of the present invention 1 and 2.This figure shows that macromolecule iron chelating agent 7TD has less cytotoxicity compared with 7K21, and 7TD does not have cytotoxicity substantially.
Claims (3)
1. a purposes for 3-hydroxyl-4-pyridinone macromolecule iron chelating agent, is characterized in that: described macromolecule iron chelating agent uses as anti-biotic material;
Described macromolecule iron chelating agent is:
2. purposes according to claim 1, is characterized in that: described macromolecule iron chelating agent has dual antibacterial action, on the one hand the Repiration of anti-bacteria, and the ferric iron element on the other hand by absorbing bacterium surface makes the growth of antibacterial be suppressed.
3. purposes according to claim 1 and 2, is characterized in that:
Described macromolecule iron chelating agent has excellent antibacterial effect to methicillin-resistant staphylococcus aureus.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510395542.8A CN105030819B (en) | 2015-07-06 | 2015-07-06 | A kind of purposes of 3- hydroxyl -4- pyridinone macromolecule iron chelating agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510395542.8A CN105030819B (en) | 2015-07-06 | 2015-07-06 | A kind of purposes of 3- hydroxyl -4- pyridinone macromolecule iron chelating agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105030819A true CN105030819A (en) | 2015-11-11 |
| CN105030819B CN105030819B (en) | 2019-04-05 |
Family
ID=54438184
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510395542.8A Active CN105030819B (en) | 2015-07-06 | 2015-07-06 | A kind of purposes of 3- hydroxyl -4- pyridinone macromolecule iron chelating agent |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105030819B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107574581A (en) * | 2017-08-03 | 2018-01-12 | 天津大学 | A kind of antibiotic property poly- (ε caprolactones)/simulation antibacterial peptide electrospun fiber membrane and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1926135A (en) * | 2003-11-20 | 2007-03-07 | 阿普泰克斯公司 | Cycloalkyl derivatives of 3-hydroxy-4-pyridinones |
| CN103228653A (en) * | 2010-09-24 | 2013-07-31 | 盐野义制药株式会社 | Substituted polycyclic carbamoyl pyridone derivative prodrug |
-
2015
- 2015-07-06 CN CN201510395542.8A patent/CN105030819B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1926135A (en) * | 2003-11-20 | 2007-03-07 | 阿普泰克斯公司 | Cycloalkyl derivatives of 3-hydroxy-4-pyridinones |
| CN103228653A (en) * | 2010-09-24 | 2013-07-31 | 盐野义制药株式会社 | Substituted polycyclic carbamoyl pyridone derivative prodrug |
Non-Patent Citations (1)
| Title |
|---|
| 马越等: "3-羟基-4-吡啶酮衍生物的合成及与Fe3+螯合性能", 《精细化工》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107574581A (en) * | 2017-08-03 | 2018-01-12 | 天津大学 | A kind of antibiotic property poly- (ε caprolactones)/simulation antibacterial peptide electrospun fiber membrane and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105030819B (en) | 2019-04-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| UA53683C2 (en) | Bactericidal composition | |
| CN106146835B (en) | A kind of high molecular quaternary Antibacterial agent preparation method and application | |
| CN104984384A (en) | Medical antibacterial dressing and preparation method thereof | |
| CN105475359A (en) | Application of two-dimensional lysozyme nanometer film as antibacterial material | |
| Flynn | Povidone-iodine as a topical antiseptic for treating and preventing wound infection: a literature review | |
| Kenawy et al. | Synthesis and biocidal activity of modified poly (vinyl alcohol) | |
| CN103893022A (en) | Application of antibacterial peptide as preservative in preparing cosmetics | |
| CN104784103B (en) | Based on oligomeric amino acid amphiphile, amphiphilic molecule injectable anti-bacterial hydrogel | |
| CN102675674A (en) | Self-assembled modified polylactic acid material of lysozyme and mushroom polysaccharide sulfate and preparation method thereof | |
| CN102405935B (en) | Protamine compounded preparation, preparation method and application thereof | |
| CN107099031B (en) | A kind of heat resist modification polyhexamethylene guanide and its preparation method and application | |
| CN105030819A (en) | Use of 3-hydroxy-4-pyridone high-molecular iron chelating agent | |
| CN106366333B (en) | A method of oxidation chitosan quaternary ammonium salt crosslinked with collagen | |
| CN102450973A (en) | Multifunctional wet tissue containing orange essence | |
| CN111714455A (en) | Quaternary ammonium salinization chitin anti-pathogenic microorganism spray, preparation method and application thereof | |
| CN102977392A (en) | Preparation method of bacterial cellulose capable of removing endotoxin | |
| JPH0338504A (en) | Improving method of antibacterial property of silver-containing compound | |
| CN111303413A (en) | Tetrahydropyrimidinyl cationic antibacterial polymer, and preparation method and application thereof | |
| CN103329942B (en) | Compound disinfectant, and preparation method and applications thereof | |
| CN103784968B (en) | A kind of antibiotic-chitosan covalent complex and its preparation method and application | |
| CN109912729A (en) | A kind of preparation method of antibacterial chitosan and its application as liquid treatment dressing | |
| CN103735570A (en) | Oral care solution for preventing oral fungal infection | |
| Tülü et al. | Dendrimers as antibacterial agents | |
| Rathinam et al. | Effects of antibiotics upon quorum sensing regulated characters: a propitious scheme against device associated infections | |
| CN103109869A (en) | All-natural special disinfectant for aquaculture |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |