CN105456233B - A kind of long-acting slow-release antibacterial film of high drug load and preparation method thereof - Google Patents
A kind of long-acting slow-release antibacterial film of high drug load and preparation method thereof Download PDFInfo
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Abstract
Long-acting slow-release antibacterial film the present invention relates to a kind of high drug load and preparation method thereof, belongs to pharmaceutical carrier technical field.The antibacterial film structure is (PO/PAA/peptide GO/PAA)n、(peptide‑GO/PAA/PO/PAA)n、(PAA/peptide‑GO/PAA/PO)nOr (PAA/PO/PAA/peptide GO)n；Wherein described PO is cationic polymer, and the PAA is polyacrylic acid, and the peptide GO are antibacterial peptide/graphene oxide composite hybridization body structure that antibacterial peptide molecule is formed with graphene oxide by electrostatical binding, and the n is the self assembly number of plies；The present invention also provides the preparation method of the long-acting slow-release antibacterial film of the high drug load, the long-acting slow-release antibacterial film of the high drug load obtained using the present invention, its mechanical strength, durability and antibacterial effect greatly improve, and load capacity of the medicine in layer assembly film is high.
Description
Technical field
Long-acting slow-release antibacterial film the present invention relates to a kind of high drug load and preparation method thereof, belongs to pharmaceutical carrier technology
Field.
Background technology
Various medical sanitary apparatus can be used in the medical procedures such as wound processing, operation, can also be used in tissue reparation
To various interventional medicine devices.In actual mechanical process, these apparatuses and device will inevitably expose in atmosphere, its
Surface is easily polluted by harmful bacteria, further causes wound or the bacterial cross-infection of tissue, this is modern medicine
One of main problem, also often restricts the main reason for treating success or failure.Come in interventional treatment usually using heavy dose antibiotic
It is anti-infective, but since intervention device surface is covered by the biomembrane that multiple proteins in human body are formed quickly, medicine is difficult to
The film layer is crossed, thus curative effect is little, frequently even needs to remove the device of oneself implantation and is implanted into again.Therefore, closed using one kind
Suitable method prepares long acting antibiotic coating in these medical instruments and intervention device surface has particularly important meaning, this side
Face can inhibit bacteria the growth on surface, while also reduce bacterial resistance occurred possibility.
Common antibacterials area load method mainly has several, including adsorption, covalent bond, medicine and base material
Blending etc..The method of wherein (1) adsorption is to be immersed in device in the solution of antibacterials to make adsorption have medicine point
Son prepares antimicrobial surface.The method is easy to operate, but defect is that drug molecule is easy to depart from from surface, while surface is only
There is one layer of very thin medicine, the medication amount loaded is limited.The method is relatively adapted to the absorption of the less medicine of solubility, such as cloudy
The silver salt of ion antibiotic is more difficult to dissolve than sodium salt, can prepare antimicrobial surface by the adsorption of silver salt.(2) covalent bond
Method be medicine to be fixed on by covalent bond the surface of device so that sustained drug play a role.It is compared to table
The method of face absorption, covalent coupling method has the advantages of firm drug loading, long action time, but this technology also has its limitation
Property, it is limited to be used for covalently bound medicament categories first, and since the characteristics of covalent bond determines that medicine can not be from dress
Put and be discharged into neighbouring liquid or tissue, thus its antibacterial ability is often confined to the region of device contact, drug effect scope
It is smaller.(3) medicine and base material blending are another important methods of medical surfaces load, and this method can greatly improve medicine
Useful load, and in apparatus surface or nearby can provide antibiotic property, but if be difficult reality using traditional blending method
The controlled release of existing medicine, therefore still need and this technology is improved, for example the active force of base material and medicine is adjusted, control
Make technique of blending etc..
LBL self-assembly (Layer-by-layer) technology is also used for the preparation of antimicrobial surface in recent years, its principle be by
Substrate with specific function site is immersed in the solution containing antibacterials, is reacted by the physical/chemical of solid liquid interface, profit
With the different modes of action, such as chemical bond (ionic bond, covalent bond, hydrogen bond), Van der Waals force, dipole-dipole interaction etc.
Drug molecule is loaded into formation antibacterial surface coating in layer assembly film.Layer-by-layer method is simple, of low cost,
It can assemble and form a film in body surface of different shapes, and the thickness of film can be controlled on a molecular scale, layer by layer
The convenient composition and structure to film of assemble method regulates and controls, it is possible to achieve the slow control release of medicine, and be advantageously implemented
The preparation of multifunctional unit property film.But there are the following problems for current LBL self-assembly antibacterial film：(1) medicine is generally with list
Molecular state is attached in layer assembly film, and individual layer drug loading is relatively low, and the raising of assembling film entirety drug loading is very big
Dependent on the increase of the assembling number of plies, time and effort consuming；(2) layer assembly film is mainly by forming based on polyelectrolyte molecules, mechanics
Intensity is poor；(3) although layer assembly film can be by the regulation and control of its composition, for example degradable polymer molecule is introduced, come real
The slow control release of existing institute's carrying medicament, but due to polymer molecule degraded generally require specific condition (such as specific pH,
Ionic strength etc.), often it is difficult to realize in real process, therefore the simple Controlled release effect for relying on polymer molecule degraded has
Limit and be generally extremely difficult to longer slow-release time.
The content of the invention
The object of the present invention is to provide a kind of long-acting slow-release antibacterial film of high drug load, realizes the high of antibacterial film and carries
Dose and long-acting slow-release effect.Present invention also offers the preparation method of the antibacterial film.
The technical scheme is that：
A kind of long-acting slow-release antibacterial film of high drug load, its structure are (PO/PAA/peptide-GO/PAA)n；Wherein
The PO is cationic polymer, and the PAA is polyacrylic acid, the peptide-GO for antibacterial peptide molecule (peptide) with
The antibacterial peptide that graphene oxide (GO) is formed by electrostatical binding/graphene oxide composite hybridization body structure, the n are self assembly
The number of plies.
The structure of the antibacterial film is realized by the form of LBL self-assembly, since LBL self-assembly is a circulation
Process, therefore in the structure expression, the order of PO and peptide-GO can be exchanged mutually, be after exchange
(peptide-GO/PAA/PO/PAA)n, similarly its structure expression can also be (PAA/peptide-GO/PAA/PO)nWith
(PAA/PO/PAA/peptide-GO)n。
The antibacterial peptide molecule (peptide) is positively charged antibacterial peptide molecule, preferably G4Or Nap-FF-R9, its molecule knot
Structure formula is respectively：
(1)G4Molecular structure：
(2)Nap-FF-R9Molecular structure：
The self assembly number of plies n chooses the integer between 10-100, the integer between preferably 30-60.
The cationic polymer (PO) is selected from poly- beta-amino ester (PAE), polyethyleneimine (PEI), polydiene base the third two
One or more kinds of combinations in ammonio methacrylate (PDDA), kayexalate (PSS), cation between layers
Polymer (PO) is identical or different.
A kind of preparation method of the long-acting slow-release antibacterial film of high drug load, comprises the following steps：
(1) compound concentration is the antibacterial peptide molecular solution of 2.0-15.0mmol/L, and adjusting pH value of solution is 4-6, stands, makes it
Self assembly is nanometer corynebacterium or filamentary structure；
(2) compound concentration is graphene oxide (GO) solution of 0.1-1.0mg/mL, and adjusting pH value of solution is 7-9；
(3) the antibacterial peptide molecular solution after step (1) processing is mixed with the graphene oxide solution that step (2) obtains,
In mixing match, the antibacterial peptide liquor capacity is 2-5 times of the graphene oxide solution volume；Ultrasound mixes, and is resisted
Bacterium peptide/graphene oxide composite hybridization body structure-solution, i.e. peptide-GO solution；
(4) cationic polymer (PO) solution is prepared, concentration 0.5-2.0mg/mL, adjusting pH value of solution is 4.0-5.0；
(5) polyacrylic acid (PAA) solution is prepared, concentration 0.5-2.0mg/mL, adjusting pH value of solution is 8.5-9.5；
(6) substrate is selected, substrate is immersed in step (3), (4) or (5) either step resulting solution, soaks 5-
10min, then takes out, immerses pure water, taking-up, drying；It is then immersed in another non-first time leaching obtained by step (3), (4) or (5)
5-10min in the solution entered, then takes out, immerses pure water, taking-up, drying；When substrate is adsorbed in immersion solution repeatedly,
Cationic polymer solution and peptide-GO solution are unable to tandem immersion, it is necessary to molten using polyacrylic acid between
Liquid interval；Often immerse 1 cationic polymer solution, 1 peptide-GO solution and 2 polyacrylic acid solutions and form a group
Layer, is moved in circles n times using above-mentioned immersion process, that is, obtains the long-acting slow-release antibacterial film of high drug load of the present invention.
Such as：Substrate is immersed in the PO solution that step (4) obtains and soaks 5-10min, is taken out, immerses pure water 5-10s,
Take out, nitrogen purging surface is dried；Place into the PAA solution that step (5) obtains and soak 5-10min, take out, immerse pure
Water 5-10s, takes out, and nitrogen purging surface is dried；Then the peptide-GO composite hybridization bodies that step (3) obtains are placed into
5-10min is soaked in structure-solution, is taken out, immerses pure water 5-10s, is taken out, nitrogen purging surface is dried；Finally put again
Enter in the PAA solution that step (5) obtains and soak 5-10min, take out, immerse pure water 5-10s, take out, nitrogen purging surface carries out
It is dry；It is so a layer group, is moved in circles n times using above-mentioned soaking step, you can obtain high drug load of the present invention
Long-acting slow-release antibacterial film.
In the step (1), the antibacterial peptide molecular solution concentration of preparation is on its self assembly concentration.
In the step (1), adjust pH after, placed 1-5 days under room temperature, the solution can self assembly be nanometer corynebacterium
Or filamentary structure.
In the step (3), when antibacterial peptide molecular solution is mixed with GO solution, the two ratio is dense according to antibacterial peptide solution
Degree change can difference, the purpose of the two mixing be the positively charged quantity of antibacterial peptide molecule institute in system is substantially exceeded GO tables
The negatively charged quantity of face institute, so as to ensure peptide/GO mixed solution stably dispersings, does not have Precipitation, peptide-GO
Hybrid surface carries positive charge.
In the step (3), the ultrasonic condition is：Ultrasonic power is 90-110W, ultrasonic time 10-20min.
In the step (6), the preferred silicon dioxide substrate of substrate is as model.
In the step (6), using identical solution immersion order when preferably each layer of group is soaked.
The present invention is by selecting the positively charged antibacterial peptide molecule with stronger self assembly ability, in its critical self assembly
The Nanoscale assemblies for making its self assembly be supramolecular aggregation form on concentration, are then mixed to form with graphene oxide layer
Composite hybridization body structure.It is to improve medicine to select specific antibacterial peptide molecule and carry out drug loading by supermolecule nano assembly
The key of thing load capacity, and assembly structure can guarantee that the positive charge of peptide molecule being exposed to assembly surface, with aoxidizing stone
Cause the charge reversal on hybrid surface during black alkene hydridization, so as to ensure peptide/graphene oxide composite hybridization body in layer assembly
During combination between negatively charged polymer molecule, smoothly form multilayer film.
In addition, peptide/graphene oxide composite hybridization body structure is in the solution since the interaction between colloidal solid is easy
Separate out, to carry out supersound process in advance when carrying out layer assembly film preparation makes its dispersed suspension in the solution, so
It just can guarantee that the multilayer film for preparing that thickness is homogeneous and property is controllable.
Compared with prior art, beneficial effects of the present invention are：
(1) graphene oxide layer structure of the present invention can greatly improve the mechanical strength of face coat, carry
Its high durability；
(2) antibacterial peptide molecule selected by can be combined using self assembly as supermolecule nano assembly in the form of molecule aggregate
Into layer assembly film, the drug loading of either as singular molecular entities is compared to, it is negative in layer assembly film to substantially increase medicine
Carrying capacity；
(3) antibacterial peptide molecular assembly is combined with surface of graphene oxide by non-covalent bonds such as electrostatic/hydrophobic effects,
Be conducive to it and discharge active material from the disengaging on surface；
(4) during layer assembly PO layers can add a kind of degradable polymer point according to selection is actually needed
Son, it is ensured that it degrades under suitable conditions, and (such as poly- beta-amino ester (PAE) can be in pH>Hydrolyzed under the conditions of 7.0), it will wrap up
Surface reactive material exposure in the solution, discharged；
(5) carry out hybrid using self assembly antibacterial peptide to construct, the poly- of peptide assembly and its either as singular molecular entities can be utilized
Collection and dissociation equilibrium, slowly release antibacterial peptide molecule, have extremely prolonged antibacterial effect.
Brief description of the drawings
Fig. 1：Antibacterial peptide molecule G4Atomic force microscope (AFM) figure of composite construction is formed with graphene oxide (GO)
Piece,
Fig. 2：(PAE/PAA/G in silica substrate4-GO/PAA)50The scanning electron microscopic picture of layer assembly film,
Fig. 3：(PAE/PAA/G in silica substrate4-GO/PAA)50Layer assembly film is (at 0.05% sodium hydroxide solution
Reason peel off) stretch modulus test curve.
Embodiment
The technology contents of the present invention are described in detail with specific embodiment below in conjunction with the accompanying drawings.
Embodiment 1：
1st, the long-acting slow-release antibacterial film of a kind of high drug load, structure are (PO/PAA/peptide-GO/PAA)50, wherein
The PO selects poly- beta-amino ester (PAE), and the PAA is polyacrylic acid, and peptide-GO is antibacterial peptide molecule G4Pass through electrostatic
With reference to the antibacterial peptide formed with GO/graphene oxide composite hybridization body structure.
2nd, the preparation method of the long-acting slow-release antibacterial film of the high drug load is：
(1) G is prepared4Solution, concentration 4.0mmol/L, (concentration is on its self assembly concentration), using 1.0mol/L
NaOH solution adjust pH value of solution be 4.5, place 3 days, it is nanometer corynebacterium structure to make its self assembly；
(2) compound concentration is graphene oxide (GO) solution of 1.0mg/mL, is adjusted using the NaOH solution of 1.0mol/L
PH value of solution is 8；
(3) G for obtaining step (1)4The GO solution that solution is obtained with step (2) is according to volume ratio 3:1 mixing, ultrasound
Mix, ultrasonic power 100W, ultrasonic time 15min, obtains G4- GO composite hybridization body structure-solutions, as shown in Figure 1；
(4) poly- beta-amino ester (PAE) solution is prepared, concentration 1.0mg/mL, pH is adjusted using the HCl solution of 1.0mol/L
For 4.5；
(5) polyacrylic acid (PAA) solution is prepared, concentration 1.0mg/mL, pH is adjusted using the NaOH solution of 1.0mol/L
For 9；
(6) silicon dioxide substrate is selected, silicon dioxide substrate is immersed in the PAE solution that step (4) obtains and is soaked
10min, takes out, and immerses pure water 5s, takes out nitrogen purging surface and is dried；Place into the PAA solution that step (5) obtains and soak
10min is steeped, is taken out, immerses pure water 5s, nitrogen purging surface is taken out and is dried；Then place into what step (3) obtained
10min is soaked in peptide-GO composite hybridization body structure-solutions, is taken out, immerses pure water 5s, nitrogen purging surface is taken out and carries out
It is dry；Finally it is placed again into the PAA solution that step (5) obtains and soaks 10min, take out, immerse pure water 5s, takes out nitrogen purging
Surface is dried；Is so a layer group, high drug load of the present invention is obtained 50 times using above-mentioned immersion sequential loop
Long-acting slow-release antibacterial film (PAE/PAA/G4-GO/PAA)50, layer assembly film is referred to as, its Cross Section Morphology is as shown in Figure 2.
Fig. 1 is antibacterial peptide molecule G4Atomic force microscope (AFM) figure of composite construction is formed with graphene oxide (GO)
Piece；It can be seen from the figure that G4A nanometer corynebacterium structure is assembled into, these structures are attached to GO sheet surfaces and form G4- GO is compound
Hybrid structure.
Fig. 2 is (PAE/PAA/G in the present embodiment gained silicon dioxide substrate4-GO/PAA)50The scanning electricity of layer assembly film
Mirror picture.Picture shows that above-mentioned species after 50 circulations of layer assembly on solid substrate surface by can effectively form a film, shape
It is about 2 μm of film layer into thickness, there is certain layer structure.
Fig. 3 is (PAE/PAA/G in silica substrate4-GO/PAA)50Layer assembly film (0.05% sodium hydroxide solution
Processing peel off) stretch modulus test curve.The long-acting slow-release antibacterial film for the high drug load that the present embodiment obtains, passes through mechanics
Extension test, its tensile modulus of elasticity are 8~10Gpa, its vertical spring modulus is 1.5~4Gpa.
The long-acting slow-release antibacterial film for the high drug load that the present embodiment obtains, is measured, antibacterial activity by thermal weight loss method
Component (G4) content in multilayer film is 23.2wt%；Antibacterial film long-acting slow-release more than 45 days in aqueous.
3rd, antibacterial experiment：
40 μ L strains (Escherichia coli, Escherichia coli) are added in 2mL culture mediums (LB) solution, are shaken at 37 DEG C
After swinging overnight incubation, centrifuging and taking lower floor, is rinsed with PBS buffer, is repeated 3 times, and adjusts OD values to 0.2 or so.
Take 8 μ L bacterium solutions that the (PAE/PAA/G of the silicon dioxide substrate load at 3 groups is added dropwise respectively4-GO/PAA)50Multilayer film table
Face, 3 silicon dioxide substrates when culture 1 is small in 37 DEG C of thermostatic chamber, then centrifuged with PBS cleaning, be settled to 200 μ L,
100 μ L are taken to be coated on LB solid culture plates, each sample is parallel to be surveyed 3 times, takes its average value.By titanium dioxide after each antibacterial experiment
The layer assembly film of silicon substrate load is soaked in certain time in aqueous solution, carries out antibacterial test again, investigates layer assembly film
Long-time medicament slow release and fungistatic effect.
The results show that Escherichia coli are less than 5% in fresh preparation layer assembly film surface survival rate, intermittently it is soaked in water
When total time is 72 small, bacteriostatic activity is reduced to half of initial value or so, and soaks total time when 192 is small, large intestine bar
Survival rate of the bacterium on its surface is still less than 15%.
Embodiment 2：
1st, the long-acting slow-release antibacterial film of a kind of high drug load, structure are (PO/PAA/peptide-GO/PAA)50, wherein
The PO selection polyethyleneimines (PEI), the PAA is polyacrylic acid, and peptide-GO is antibacterial peptide molecule Nap-FF-R9It is logical
Cross peptide/graphene oxide composite hybridization body structure that electrostatical binding is formed with GO.
2nd, the preparation method of the long-acting slow-release antibacterial film of the high drug load is：
(1) Nap-FF-R is prepared9Solution, concentration 4.0mmol/L, (concentration is on its self assembly concentration), uses
It is 5 that the NaOH solution of 1.0mol/L, which adjusts pH value of solution, is placed 3 days, it is nanometer corynebacterium structure to make its self assembly；
(2) compound concentration is graphene oxide (GO) solution of 0.5mg/mL, is adjusted using the NaOH solution of 1.0mol/L
PH value of solution is 7；
(3) Nap-FF-R for obtaining step (1)9The GO solution that solution is obtained with step (2) is according to volume ratio 2:1 is mixed
Close, ultrasound mixes, and ultrasonic power 100W, ultrasonic time 20min, obtains Nap-FF-R9- GO composite hybridization body structures are molten
Liquid；
(4) polyethyleneimine (PEI) solution is prepared, concentration 1.0mg/mL, pH is adjusted using the HCl solution of 1.0mol/L
For 4；
(5) polyacrylic acid (PAA) solution is prepared, concentration 1.0mg/mL, pH is adjusted using the NaOH solution of 1.0mol/L
For 9；
(6) silicon dioxide substrate is selected, silicon dioxide substrate is immersed in the PEI solution that step (4) obtains and is soaked
10min, takes out, and immerses pure water 8s, takes out nitrogen purging surface and is dried；Place into the PAA solution that step (5) obtains and soak
10min is steeped, is taken out, immerses pure water 8s, nitrogen purging surface is taken out and is dried；Then the Nap- that step (3) obtains is placed into
FF-R910min is soaked in-GO composite hybridization body structure-solutions, is taken out, immerses pure water 8s, nitrogen purging surface is taken out and is done
It is dry；Finally it is placed again into the PAA solution that step (5) obtains and soaks 10min, take out, immerse pure water 8s, takes out nitrogen purging table
Face is dried；It is so a layer group, is circulated 50 times using above-mentioned soaking step and obtain high drug load of the present invention
Long-acting slow-release antibacterial film (PEI/PAA/Nap-FF-R9-GO/PAA)50, it is referred to as layer assembly film.
(the PEI/PAA/Nap-FF-R for the high drug load that the present embodiment obtains9-GO/PAA)50Long-acting slow-release antibacterial film,
Tested by mechanical stretch, its tensile modulus of elasticity is 9~12Gpa, its vertical spring modulus is 2~4Gpa.
The long-acting slow-release antibacterial film for the high drug load that the present embodiment obtains, is measured, antibacterial activity by thermal weight loss method
Component (Nap-FF-R9) content in multilayer film is 25.7wt%；Antibacterial film long-acting slow-release 60 days in aqueous
More than.
The above is the preferred embodiment of the present invention, it is noted that is come for those skilled in the art
Say, without departing from the principles of the present invention, some improvements and modifications can also be made, these improvements and modifications also should
It is considered as protection scope of the present invention.For the technical staff of general domain, on the premise of without departing substantially from true spirit
To any obvious change that it is done, it will all form to infringement of patent right of the present invention, corresponding law duty will be undertaken
Appoint.
Claims (8)
1. the long-acting slow-release antibacterial film of a kind of high drug load, it is characterised in that the antibacterial film structure is (PO/PAA/
peptide-GO/PAA)n、(peptide-GO/PAA/PO/PAA)n、(PAA/peptide-GO/PAA/PO)nOr (PAA/PO/
PAA/peptide-GO)n；Wherein described PO is cationic polymer, and the PAA is polyacrylic acid, and the peptide-GO is
Antibacterial peptide/graphene oxide composite hybridization body structure that antibacterial peptide molecule is formed with graphene oxide by electrostatical binding, the n
For the self assembly number of plies；
The antibacterial peptide molecule is positively charged antibacterial peptide molecule；
The antibacterial peptide molecule selects G4Or Nap-FF-R9, its molecular structural formula is respectively：
(1)G4Molecular structure：
(2)Nap-FF-R9Molecular structure：
2. the long-acting slow-release antibacterial film of high drug load according to claim 1, it is characterised in that the self assembly number of plies
N chooses the integer between 10-100.
3. the long-acting slow-release antibacterial film of high drug load according to claim 1, it is characterised in that the cationic polymerization
One kind in poly- beta-amino ester, polyethyleneimine, the third alkyl dimethyl ammonium chloride of polydiene base, kayexalate of thing or
A variety of combinations, cationic polymer between layers are identical or different.
4. a kind of preparation method of the long-acting slow-release antibacterial film of high drug load, is used to prepare described in claim any one of 1-3
Long-acting slow-release antibacterial film, it is characterised in that comprise the following steps：
(1) compound concentration is the antibacterial peptide molecular solution of 2.0-15.0mmol/L, and adjusting pH value of solution is 4-6, stands, makes it from group
Fill as nanometer corynebacterium or filamentary structure；
(2) compound concentration is the graphene oxide solution of 0.1-1.0mg/mL, and adjusting pH value of solution is 7-9；
(3) the antibacterial peptide molecular solution after step (1) processing is mixed with the graphene oxide solution that step (2) obtains, mixed
In proportioning, the antibacterial peptide liquor capacity is 2-5 times of the graphene oxide solution volume；Ultrasound mix, obtain antibacterial peptide/
Graphene oxide composite hybridization body structure-solution, i.e. peptide-GO solution；
(4) cationic polymer solution is prepared, concentration 0.5-2.0mg/mL, adjusting pH value of solution is 4.0-5.0；
(5) polyacrylic acid solution is prepared, concentration 0.5-2.0mg/mL, adjusting pH value of solution is 8.5-9.5；
(6) substrate is selected, substrate is immersed in step (3), (4) or (5) either step resulting solution, soaks 5-10min, with
Take out afterwards, immerse pure water, taking-up, drying；It is then immersed in the solution that another non-first time obtained by step (3), (4) or (5) immerses
Middle 5-10min, then takes out, immerses pure water, taking-up, drying；When substrate is adsorbed in immersion solution repeatedly, cation gathers
Polymer solution and peptide-GO solution are unable to tandem immersion, it is necessary between using polyacrylic acid solution interval；
Often immerse 1 cationic polymer solution, 1 peptide-GO solution and 2 polyacrylic acid solutions and form a group layer, use
Above-mentioned immersion process moves in circles n times, that is, obtains the long-acting slow-release antibacterial film of the high drug load.
5. the preparation method of the long-acting slow-release antibacterial film of high drug load according to claim 4, it is characterised in that the step
Suddenly in (1), adjust pH after, placed 1-5 days under room temperature, the solution can self assembly be nanometer corynebacterium or filamentary structure.
6. the preparation method of the long-acting slow-release antibacterial film of high drug load according to claim 4, it is characterised in that the step
Suddenly in (3), the ultrasonic condition is：Ultrasonic power is 90-110W, ultrasonic time 10-20min.
7. the preparation method of the long-acting slow-release antibacterial film of high drug load according to claim 4, it is characterised in that the step
Suddenly in (6), the substrate selects silicon dioxide substrate.
8. the preparation method of the long-acting slow-release antibacterial film of high drug load according to claim 4, it is characterised in that the step
Suddenly in (6), using identical solution immersion order when each layer of group is soaked.
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| CN109731148B (en) * | 2019-01-24 | 2021-06-15 | 嘉兴莱普晟医疗科技有限公司 | Antibacterial heat conduction material |
| CN114904402B (en) * | 2022-06-01 | 2024-01-16 | 东华大学 | Layer-by-layer self-assembled slow-release antibacterial polymer separation membrane and preparation method and application thereof |
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