CN103585675B - A kind of bactericidal composition and use its sustained-release antibacterial film prepared and embedded material - Google Patents
A kind of bactericidal composition and use its sustained-release antibacterial film prepared and embedded material Download PDFInfo
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- CN103585675B CN103585675B CN201310594288.5A CN201310594288A CN103585675B CN 103585675 B CN103585675 B CN 103585675B CN 201310594288 A CN201310594288 A CN 201310594288A CN 103585675 B CN103585675 B CN 103585675B
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Abstract
The invention discloses a kind of bactericidal composition and the sustained-release antibacterial film using it to prepare and embedded material, described bactericidal composition includes: selected from the first kind macromolecule of polylactic acid, polycaprolactone, PLGA and polycaprolactone co-glycolic acid；Equations of The Second Kind macromolecule selected from PLEG, polycaprolactone polyethyleneglycol block copolymer, poly(ethylene oxide), polyvinyl alcohol, gelatin and hyaluronic acid；And antibacterial.The sustained-release antibacterial film using bactericidal composition of the present invention to prepare is capable of the controllable release to antibacterial.
Description
Technical field
The present invention relates to antibacterial embedded material technical field, particularly relate to a kind of bactericidal composition and use it to make
Standby sustained-release antibacterial film and embedded material.
Background technology
Surgical infection refers to need the infectious disease of operative treatment and occur in wound or postoperative infection,
In surgical field most common, account for the 1/3～1/2 of all surgical diseasess.Surgical infection be often divided into specificity and
Nonspecific infection, its pathogen constitutes complexity, once occurs, treatment difficulty.Surgical infection be usually by
Pathogenic microorganism invades caused by human body, but the resistance of human body and infection have very close relationship.
The usual purulence pathogenic bacterium causing surgical infection have staphylococcus, streptococcus, escherichia coli, bacillus pyocyaneus
And Bacillus proteus.Accept complicated major operation, instrumental examination and intubate, anti-cancer therapies, X-ray therapy, exempt from
The patient of epidemic disease inhibitor etc., owing to the chance of contact antibacterial increases or the weakening of resistance, also tends to easily send out
Raw infection.Also there are some medical workers too to rely on antibacterials, ignore sterile working or violate surgical principle,
Also some these evitable surgical infections can be caused.
It is all to give the injection of a large amount of broad ectrum antibiotic before surgery that general infection processes, and postoperative once feels
Dye, is also local douche, even systemic antibiotics treatment.At present, bacterial resistance and abuse of antibiotics relation
Greatly, general country inpatient there are about 30% use antibiotic according to statistics, and the U.S. is 20%, and China is
67%～80%, thus bring serious resistance problems, especially in big city, large hospital.According to Beijing, Shanghai,
The resistant rate of the large hospital data on the ground such as Wuhan, staphylococcus aureus and coagulase negative staphylococcus is right
Penicillin and ampicillin are up to 84%～94%, and the drug resistance of Enterobacter and acinetobacter calcoaceticus is but also much higher,
According to Wuhan latest survey, the resistant rate of ampicillin and first and second generation cephalosporin has been reached or has connect by
Nearly 100%；It is disturbing, the resistant rate of bacterial antibiotic is still in sustainable growth.
In general, cleft relapse acute sepsis phase (first 3 days) Main Pathogenic Bacteria be escherichia coli and
Other Gram-negative (G-) aerobasilus, abscess formed the phase (after 3 days) be mainly bacteroides fragilis and
Its Gram-negative (G-) anaerobic bacillus(cillus anaerobicus).And during surgical operation, often there is also the feelings such as angiorrhexis is hemorrhage
Condition, generally uses albumin glue to repair or the method hemostasis of laser burn, causes and slightly burn, increase postoperative sense
The danger of dye.Therefore, wound site, puncture site, easy damaged position or external embedded material portion in art
Position, implants containing the Absorbable membrane material of antibacterial, the embedding form of antibacterial reasonable in design or antibiotic and
Release route, could realize suiting the remedy to the case, efficiently treat.
Existing lot of research proves to utilize the high-voltage electrostatic spinning technology can be by various medicines or active substance
Being embedded in macromolecular fibre, the way of employing is from being directly blended, to emulsion blending, to multilamellar spinning head altogether
Mixed have, and the control of drug release patterns depends primarily on the active force between medicine and macromolecule, phase patibhaga-nimitta
Holding principle, general macromolecule carrier all can select water-fast system, if medicine is not readily dissolved in water, with
Between macromolecule, adhesion is relatively strong, then rate of release is slower；As soluble in water in medicine and and macromolecule between adhesion
More weak, then have the strongest prominent release, and deenergized period is the shortest.For broad ectrum antibiotic, typically all water
The little molecule of dissolubility, more weak with the adhesion of hydrophobic polymer, embedding amount is difficult to improve, and controls release
Difficulty, largely limits clinical practice.
Summary of the invention
It is an object of the invention to, it is provided that a kind of can the bactericidal composition of controllable release antibacterial and use it
The sustained-release antibacterial film of preparation and embedded material.
For realizing the purpose of the present invention, it is provided that techniques below scheme:
In first aspect, the present invention provides a kind of bactericidal composition, including:
Common selected from polylactic acid, polycaprolactone, Poly(D,L-lactide-co-glycolide and polycaprolactone-hydroxyacetic acid
The first kind macromolecule of polymers；
Selected from polylactic acid-polyethylene glycol block copolymer, polycaprolactone-polyethylene glycol block copolymer, polycyclic
The Equations of The Second Kind macromolecule of oxidative ethane, polyvinyl alcohol, gelatin and hyaluronic acid；With
Antibacterial.
In the bactericidal composition of the present invention, polylactic acid (polylactic acid, PLA), also known as polylactide, is
Being polymerized, with lactic acid, the polymer obtained for primary raw material, raw material sources fully and can regenerate, polylactic acid
Production process is pollution-free, and product can be with biodegradation, it is achieved the circulation in nature, is therefore reason
The Green Polymer Material thought.Polycaprolactone (Polycaprolactone, PCL), is at gold by 6-caprolactone
Genus organic compound (such as tetraphenyltin) does catalyst, dihydroxy or trihydroxy and does open loop under the conditions of initiator
Being polymerized, belong to aggretion type polyester, its molecular weight is different with kind and the consumption of starting material from discrimination degree
And it is different.Poly(D,L-lactide-co-glycolide (poly (lactic-co-glycolic acid), PLGA), is by two
Plant monomer lactic acid (Lactic acid, LA) and hydroxyacetic acid (glycolic acid, GA) is polymerized at random
Form, be a kind of degradable functional polymer organic compound, there is good biocompatibility, nothing
Malicious, good encystation and the performance of film forming, be widely used in pharmacy, medical engineering material and modernization
Industrial circle, at U.S. PLGA by food and drug administration (Food and Drug
Administration, FDA) certification, formally included into American Pharmacopeia as pharmaceutic adjuvant.Two kinds of monomers
Lactic acid is different with the ratio of hydroxyacetic acid can prepare different types of PLGA, such as: PLGA
75:25 represents that this polymer is made up of 75% lactic acid and 25% hydroxyacetic acid.Polycaprolactone-hydroxyacetic acid copolymerization
Thing, also known as glycolide-s-caprolactone copolymer (poly (glycolide-co-ε-caprolactone), PGCL),
It is Acetic acid, hydroxy-, bimol. cyclic ester (glycollide, GA) and the copolymer of ε-caprolactone (ε-caprolactone, CL), as
Biodegradable macromolecular material, occupies critical role in the research and development of medical macromolecular materials,
In operation suture thread, artificial skin and blood vessel, skeletal fixation and reparation, drug controlled release, organizational project
Applied in many fields.By controlling glycolide monomer and the ratio of ε-caprolactone monomer, can obtain
Acetic acid, hydroxy-, bimol. cyclic ester caprolactone copolymer to Different Weight ratio.
Polylactic acid-polyethylene glycol block copolymer, is by polylactic acid and Polyethylene Glycol (polyethylene
Glycol, PEG) copolymerization formation, it is degradable medical material, has multiple method to prepare at present, than
As Chinese invention patent publication No. CN102702535A discloses a kind of creatinine catalyzing and synthesizing polylactic acid-poly-second
The process of diol block copolymer.Polycaprolactone-polyethylene glycol block copolymer, be by polycaprolactone and
Polyethylene Glycol copolymerization formed, be degradable medical material, have multiple method to prepare at present, such as in
State invention Patent publication No CN1978492A disclose a kind of polycaprolactone-polyethylene glycol block copolymer and
Its preparation method and application.Poly(ethylene oxide) (polyethylene oxide, PEO), structure is
-[-CH2─CH2─O-]n-, it is the linear polyether of epoxyethane ring-expansion polymerization, can be used as medical ointment
Compounding ingredient, the binding agent of slugging, releasing agent and cosmetics etc..Polyvinyl alcohol (polyvinyl
Alcohol, PVA), organic compound, white plates, cotton-shaped or pulverulent solids, tasteless.Wherein, doctor
Medicine level polyvinyl alcohol is the safest a kind of macromolecule organic, to human non-toxic, has no side effect, and has good
Good biocompatibility, especially in medical treatment if its aqueous gel is at ophthalmology, wound dressing and artificial joint
Being widely used of aspect, simultaneously at polyvinyl alcohol film at medicinal film, the aspect such as artificial kidney film also makes
With.Hyaluronic acid (hyaluronic acid, HA), is by two dissacharide units D-Glucose aldehydic acid and N-
The large-scale polysaccharide of acetylglucosamine composition, different from other mucopolysaccharide, its not sulfur-bearing, its hyalomitome is divided
Son can carry the moisture of more than 500 times, for current recognized optimal moisturizing ingredient, is widely applied to protect
In the product of supporting and cosmetics.
Preferably, described antibacterial is selected from metronidazole, tinidazole, cefalexin, levofloxacin, ring third
Sha Xing, rifampicin and vancomycin.
Described antibacterial is hydrophilic broad ectrum antibiotic, and the drug release behavior that it is supported in macromolecule is with high
Molecular system swelling behavior in body fluid is in close relations, and the present invention uses composite high-molecular material system, energy
Enough improve the adhesion of Polymer Systems and medicine, and can be by controlling hydrophilic component (second therein
Family macromolecule) content realize control to drug release.
Preferably, described first kind macromolecule and the high molecular weight average molecular weight of Equations of The Second Kind are 5～500,000, example
Such as 50,000,60,000,80,000,100,000,120,000,150,000,180,000,200,000,240,000,250,000,270,000,
300000,320,000,350,000,380,000,400,000,420,000,450,000,480,000,490,000 or 500,000.
Preferably, the weight content of described antibacterial is with the high molecular gross weight of first kind macromolecule and Equations of The Second Kind
Gauge 1%-20%, such as 1%, 2%, 3%, 5%, 7%, 8%, 10%, 12%, 14%, 16%,
18% or 19%, preferably 1%-15%.
Preferably, described first kind macromolecule and the high molecular weight ratio of Equations of The Second Kind are 95:5～50:50, example
Such as 90:10,85:15,80:20,75:25,70:30,65:35,60:40,55:45 or
50:50 etc., preferably 90:10～70:30.The high molecular content of Equations of The Second Kind determines the release speed of antibacterial
Rate, content is the highest, and antibacterial release is the fastest.
Preferably, described bactericidal composition prepares by the following method: by high to first kind macromolecule and Equations of The Second Kind
Molecule is dissolved in organic solvent, and being configured to concentration is 5-50%(W/V) mixed solution, then press antibacterial
Weight content is that the amount of 1-20% in terms of the high molecular gross weight of first kind macromolecule and Equations of The Second Kind adds antibacterial
Agent, ultrasonic disperse 10-20 minute, 20-70 DEG C is stirred 2-12 hour, obtains bactericidal composition.
Preferably, described organic solvent be DMF (N, N-Dimethylformamide,
DMF) with the mixed solvent of acetone or hexafluoroisopropanol (Hexafluoroisopropanol, HFIP) solvent.
Wherein, DMF is with the mixed solvent of acetone, and DMF can be 5:1～1:2 with the volume ratio of acetone, than
Such as 5:1,4:1,3:1,2:1,1:1 or 1:2.
Preferably, in described mixed solution, first kind macromolecule and the high molecular total concentration of Equations of The Second Kind can be
6%(W/V), 8%(W/V), 10%(W/V), 12%(W/V), 15%(W/V), 18%
(W/V), 20%(W/V), 25%(W/V), 28%(W/V), 30%(W/V), 32%
(W/V), 35%(W/V), 38%(W/V), 42%(W/V), 45%(W/V) or 48%
(W/V).Wherein weight (W) is in terms of unit of gram (g), volume (V) in terms of unit milliliter (mL),
Weight/volume (W/V) is in terms of unit grams per milliliter (g/mL).
Preferably, the described ultrasonic disperse time can be 12 minutes, 14 minutes, 15 minutes, 16 minutes,
18 minutes or 19 minutes.
Preferably, temperature during described stirring can be 22 DEG C, 25 DEG C, 28 DEG C, 32 DEG C, 35 DEG C, 38 DEG C,
40 DEG C, 50 DEG C, 55 DEG C, 60 DEG C, 65 DEG C or 68 DEG C.
Preferably, described mixing time can be 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 little
Time, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 11 hours or 12 hours.
In second aspect, the present invention provides a kind of and uses bactericidal composition as described in relation to the first aspect to pass through high pressure
The sustained-release antibacterial film that electrostatic spinning prepares.
Preferably, described sustained-release antibacterial film prepares by the following method:
(1) bactericidal composition is prepared: first kind macromolecule and Equations of The Second Kind macromolecule are dissolved in organic solvent,
Being configured to concentration is 5-50%(W/V) mixed solution, then press antibacterial weight content for high with the first kind
The amount addition antibacterial of molecule and Equations of The Second Kind high molecular gross weight meter 1-20%, ultrasonic disperse 10-20 minute,
20-70 DEG C is stirred 2-12 hour, obtains bactericidal composition；
Preferably, described organic solvent is DMF and the mixed solvent of acetone or hexafluoro isopropyl
Alcoholic solvent；
(2) sustained-release antibacterial film is prepared: injected in syringe by described bactericidal composition, add stainless pin
Head, using voltage is 10-30KV high voltage power supply, and solution flow rate is 1～5mL/h, and receiving range is
5～25cm, the embedded material needing coating is coated, finally by true for embedded material room temperature complete for coating
Empty dry 24-48h, obtains being overlying on the sustained-release antibacterial film of embedded material.
Wherein, the voltage of high voltage power supply can be 12KV, 15KV, 18KV, 22KV, 25KV,
27KV or 29KV；Solution flow rate can be 1.5mL/h, 2mL/h, 2.5mL/h, 3mL/h,
3.5mL/h, 4mL/h or 4.5mL/h；Receiving range can be 6cm, 7cm, 9cm, 11cm,
13cm, 15cm, 17cm, 19cm, 21cm, 23cm or 24cm；Drying time can be 25 hours,
27 hours, 30 hours, 35 hours, 38 hours, 40 hours, 42 hours, 44 hours, 46 hours or
47 hours.
In the third aspect, the present invention provides a kind of and uses bactericidal composition as described in relation to the first aspect to pass through high pressure
Electrostatic spinning is coated the embedded material being covered with sustained-release antibacterial film obtained to the embedded material needing coating.
Preferably, the embedded material being covered with sustained-release antibacterial film described in prepares by the following method:
(1) bactericidal composition is prepared: first kind macromolecule and Equations of The Second Kind macromolecule are dissolved in organic solvent,
Being configured to concentration is 5-50%(W/V) mixed solution, then press antibacterial weight content for high with the first kind
The amount addition antibacterial of molecule and Equations of The Second Kind high molecular gross weight meter 1-20%, ultrasonic disperse 10-20 minute,
20-70 DEG C is stirred 2-12 hour, obtains bactericidal composition；
Preferably, described organic solvent is DMF and the mixed solvent of acetone or hexafluoro isopropyl
Alcoholic solvent；
(2) sustained-release antibacterial film is prepared: injected in syringe by described bactericidal composition, add stainless pin
Head, using voltage is 10-30KV high voltage power supply, and solution flow rate is 1～5mL/h, and receiving range is
5～25cm, the embedded material needing coating is coated, finally by true for embedded material room temperature complete for coating
Empty dry 24-48h, obtains being covered with the embedded material of sustained-release antibacterial film.
The invention have the benefit that antibacterial is embedded in two family macromolecule groups by the bactericidal composition of the present invention
In the composite high-molecular material system become, described antibacterial is high with the adhesion of composite high-molecular material system,
And owing to Equations of The Second Kind macromolecule has hydrophilic, its content determines the rate of release of antibacterial, content is more
Height, antibacterial release is the fastest, therefore realizes the controllable release to medicine.
It is experimentally confirmed that use the sustained-release antibacterial film that block copolymer is made as Equations of The Second Kind macromolecule,
In the phosphate buffer (PBS) of 37 DEG C, in 36 hours, the release of antibacterial is very fast, block copolymerization
During thing content about 30%, within 36 hours, burst size is 40%, maintains stable release later, and deenergized period is about
7-10 days；Use the sustained-release antibacterial film that hydrophilic high mol is made, overall maintenance as Equations of The Second Kind macromolecule
The antibacterial release of fast and stable, deenergized period is 10-15 days.
Additionally, use the sustained-release antibacterial film quality prepared of bactericidal composition of the present invention the softest, easily and
Wound surface is fitted；When antimicrobial levels is more than 5%, sustained-release antibacterial film surface bacteria cultivates 2
My god, viable bacteria can not be detected in surface.
Detailed description of the invention
Below in conjunction with embodiment, embodiment of the present invention are described in detail.Those skilled in the art will
It will be appreciated that following example are only the preferred embodiments of the present invention, in order to be more fully understood that the present invention, because of
And should not be taken as limiting the scope of the invention.For a person skilled in the art, the present invention can have respectively
Kind of change and change, all within the spirit and principles in the present invention, any amendment of being made, equivalent or
Improve, should be included within the scope of the present invention.Experimental technique in following embodiment, such as nothing
Specified otherwise, is conventional method；Experiment material used, if no special instructions, is from routine biochemistry
Chemical reagent work is purchased available.
Embodiment 1:
The present embodiment is prepared as follows sustained-release antibacterial film:
(1) bactericidal composition is prepared: added by 0.5mL levofloxacin aqueous solution (concentration is 50%)
In the mixed solvent of 8mL DMF and acetone (volume ratio of DMF/ acetone is 1/1), add poly-breast wherein
Acid-co-glycolic acid (PLGA, Mw=8 ten thousand, LA/GA=75/25) 10g and polylactic acid-polyglycol
Block copolymer (PELA, Mw=2 ten thousand, LA/EG=1/1) 2g, makes it uniform after ultrasonic 10-20 minute
Dispersion, 50 DEG C are stirred 12 hours.
(2) prepare sustained-release antibacterial film: by described mixed solution (bactericidal composition), inject 5mL syringe
In, add No. 5 rustless steel syringe needles, using voltage is the high voltage power supply of 25KV, and solution flow rate is 2mL/h,
Receiving range is 15cm；Spinning 2 hours, is coated the embedded material needing coating, finally will coating
Complete embedded material room temperature in vacuo is dried 24 hours, removes residual solvent, and protects in the drying baker of 4 DEG C
Deposit.
The sustained-release antibacterial film quality prepared according to the present embodiment is the softest, easily fits with wound surface,
Antibacterial rate of release is controlled；In antibacterial culturing experiment, viable bacteria can not be detected in 24h rear surface；This
Outward, its 36 hours interior antibacterial burst size in the phosphate buffer (PBS) of 37 DEG C is 28%,
Release every day later about 10%, about 7 days deenergized periods.The sustained-release antibacterial film of the present embodiment is capable of very
High local drug concentration, prevents the generation of postoperative infection or bacteria planting, it is possible to the formation of prevention abscess,
The present invention is simple to operate, and antibacterial effect is definite, it is possible to the effectively regeneration of suppression flora, carrier organism phase
Capacitive is good.
Embodiment 2:
The present embodiment is prepared as follows sustained-release antibacterial film:
(1) bactericidal composition is prepared: by 1g vancomycin ultrasonic disperse in 10mL hexafluoroisopropanol (HFIP)
In solution, add wherein polycaprolactone-co-glycolic acid (PGCL, Mw=20 ten thousand,
CL/GA=75/25) 3g and gelatin (Mw=8 ten thousand) 0.6g, 70 DEG C are stirred 2 hours.
(2) prepare sustained-release antibacterial film: by described mixed solution (bactericidal composition), inject 10mL injection
In device, adding No. 5 rustless steel syringe needles, using voltage is the high voltage power supply of 25KV, and solution flow rate is
2mL/h, receiving range is 15cm；Spinning 2 hours, is coated the embedded material needing coating,
After the complete material room temperature of coating is vacuum dried 24 hours, remove residual solvent, and at the drying baker of 4 DEG C
Middle preservation.
The sustained-release antibacterial film quality prepared according to the present embodiment is the softest, easily fits with wound surface,
Antibacterial rate of release is controlled；In antibacterial culturing experiment, 24h and 48h rear surface is all without detecting
Viable bacteria；Additionally, it maintains the high concentration of antibacterial to hold in the phosphate buffer (PBS) of 37 DEG C
Continuous release, release about 8% every day, about 12 days deenergized periods.The sustained-release antibacterial film of the present embodiment is capable of
The highest local drug concentration, deenergized period and release dose are steady in a long-term, and vancomycin is for there being fistulation
Mouthful, there is the clinical indication of severe abdominal infection hidden danger, it is possible to reduce the possibility that many courses of infection occur,
The present invention is simple to operate, and antibacterial effect is definite, it is possible to the effectively regeneration of suppression flora, carrier organism phase
Capacitive is good.
Embodiment 3:
The present embodiment is prepared as follows sustained-release antibacterial film:
(1) bactericidal composition is prepared: 1mL aqueous metronidazole solution (concentration is 30%) is added 10mL DMF
With (volume ratio of DMF/ acetone is 5/1) in the mixed solvent of acetone, add polylactic acid (Mw=10 wherein
Ten thousand) 10g and poly(ethylene oxide) (Mw=5 ten thousand) 2g, makes it dispersed after ultrasonic 10-20 minute, 50 DEG C
Stir 12 hours.
(2) prepare sustained-release antibacterial film: by described mixed solution (bactericidal composition), inject 5mL syringe
In, add No. 5 rustless steel syringe needles, using voltage is the high voltage power supply of 10KV, and solution flow rate is 5mL/h,
Receiving range is 15cm；Spinning 2 hours, is coated the embedded material needing coating, finally will coating
Complete embedded material room temperature in vacuo is dried 24 hours, removes residual solvent, and protects in the drying baker of 4 DEG C
Deposit.
The sustained-release antibacterial film quality prepared according to the present embodiment is the softest, easily fits with wound surface,
Antibacterial rate of release is controlled；In antibacterial culturing experiment, viable bacteria can not be detected in 24h rear surface；This
Outward, its 36 hours interior antibacterial burst size in the phosphate buffer (PBS) of 37 DEG C is 25%,
Release every day later about 11%, about 7 days deenergized periods.The sustained-release antibacterial film of the present embodiment is capable of very
High local drug concentration, prevents the generation of postoperative infection or bacteria planting, it is possible to the formation of prevention abscess,
The present invention is simple to operate, and antibacterial effect is definite, it is possible to the effectively regeneration of suppression flora, carrier organism phase
Capacitive is good.
Embodiment 4:
The present embodiment is prepared as follows sustained-release antibacterial film:
(1) bactericidal composition is prepared: 0.5mL tinidazole aqueous solution (concentration is 50%) is added 10mL
In the mixed solvent of DMF and acetone (volume ratio of DMF/ acetone is 1/2), add polycaprolactone wherein
(Mw=25 ten thousand) 10g and polyvinyl alcohol (Mw=30 ten thousand) 2g, makes it uniformly divide after ultrasonic 10-20 minute
Dissipating, 50 DEG C are stirred 12 hours.
(2) prepare sustained-release antibacterial film: by described mixed solution (bactericidal composition), inject 5mL syringe
In, add No. 5 rustless steel syringe needles, using voltage is the high voltage power supply of 30KV, and solution flow rate is 1mL/h,
Receiving range is 25cm；Spinning 2 hours, is coated the embedded material needing coating, finally will coating
Complete embedded material room temperature in vacuo is dried 48 hours, removes residual solvent, and protects in the drying baker of 4 DEG C
Deposit.
The sustained-release antibacterial film quality prepared according to the present embodiment is the softest, easily fits with wound surface,
Antibacterial rate of release is controlled；In antibacterial culturing experiment, viable bacteria can not be detected in 24h rear surface；This
Outward, its 36 hours interior antibacterial burst size in the phosphate buffer (PBS) of 37 DEG C is 30%,
Release every day later about 9%, about 7 days deenergized periods.The sustained-release antibacterial film of the present embodiment is capable of very
High local drug concentration, prevents the generation of postoperative infection or bacteria planting, it is possible to the formation of prevention abscess,
The present invention is simple to operate, and antibacterial effect is definite, it is possible to the effectively regeneration of suppression flora, carrier organism phase
Capacitive is good.
Embodiment 5:
The present embodiment is prepared as follows sustained-release antibacterial film:
(1) bactericidal composition is prepared: 0.5mL cefalexin aqueous solution (concentration is 50%) is added 10mL
In the mixed solvent of DMF and acetone (volume ratio of DMF/ acetone is 1/1), add wherein polylactic acid-
Co-glycolic acid (PLGA, Mw=50 ten thousand, LA/GA=75/25) 10g and hyaluronic acid (Mw=50
Ten thousand) 2g, makes it dispersed after ultrasonic 10-20 minute, and 50 DEG C are stirred 12 hours.
(2) prepare sustained-release antibacterial film: by described mixed solution (bactericidal composition), inject 5mL syringe
In, add No. 5 rustless steel syringe needles, using voltage is the high voltage power supply of 10KV, and solution flow rate is 2mL/h,
Receiving range is 10cm；Spinning 2 hours, is coated the embedded material needing coating, finally will coating
Complete embedded material room temperature in vacuo is dried 36 hours, removes residual solvent, and protects in the drying baker of 4 DEG C
Deposit.
The sustained-release antibacterial film quality prepared according to the present embodiment is the softest, easily fits with wound surface,
Antibacterial rate of release is controlled；In antibacterial culturing experiment, viable bacteria can not be detected in 24h rear surface；This
Outward, its 36 hours interior antibacterial burst size in the phosphate buffer (PBS) of 37 DEG C is 27%,
Release every day later about 10%, about 7 days deenergized periods.The sustained-release antibacterial film of the present embodiment is capable of very
High local drug concentration, prevents the generation of postoperative infection or bacteria planting, it is possible to the formation of prevention abscess,
The present invention is simple to operate, and antibacterial effect is definite, it is possible to the effectively regeneration of suppression flora, carrier organism phase
Capacitive is good.
Use the antibacterial release profiles of sustained-release antibacterial film prepared by the present invention by the swelling control of block copolymer,
Meet the general antibiotic administration cycle (7 days) deenergized period, in being postoperative implant due to material, it is possible to real
The highest local drug concentration, prevents the generation of postoperative infection or bacteria planting, it is possible to prevention abscess
Formed；Or release profiles is swelling by hydrophilic high mol and dissolving controls, deenergized period and release dose are long-term
Stable, for there being fistulization oral, there is the clinical indication of severe abdominal infection hidden danger, it is possible to reduce many pathogenic bacterias
Infect the possibility occurred.
The present invention is simple to operate, and antibacterial effect is definite, it is possible to effectively suppression flora regeneration, carrier is raw
The thing compatibility is good, and degradation cycle is controlled, regulation block polymer or the ratio of components of hydrophilic high mol
Example just can control the rate of release of antibiotic；The open operation exist postoperative infection have wide
General application prospect.
Applicant states, the present invention illustrates the detailed features of the present invention and the most square by above-described embodiment
Method, but the invention is not limited in above-mentioned detailed features and method detailed, i.e. do not mean that the present invention is necessary
Rely on above-mentioned detailed features and method detailed could be implemented.Person of ordinary skill in the field should be bright
, any improvement in the present invention, the present invention is selected component equivalence replace and the interpolation of auxiliary element,
Concrete way choice etc., within the scope of all falling within protection scope of the present invention and disclosure.
Claims (9)
1. a bactericidal composition, including:
Common selected from polylactic acid, polycaprolactone, Poly(D,L-lactide-co-glycolide and polycaprolactone-hydroxyacetic acid
The first kind macromolecule of polymers；
Selected from polylactic acid-polyethylene glycol block copolymer, polycaprolactone-polyethylene glycol block copolymer, polycyclic
The Equations of The Second Kind macromolecule of oxidative ethane, polyvinyl alcohol, gelatin and hyaluronic acid；With
Antibacterial；
Described bactericidal composition, it prepares by the following method: by first kind macromolecule and Equations of The Second Kind high score
Son is dissolved in organic solvent, is configured to the mixed solution that concentration is 5-50% (W/V), then presses antibacterial
Weight content is that the amount of 1-20% in terms of the high molecular gross weight of first kind macromolecule and Equations of The Second Kind adds antibacterial
Agent, ultrasonic disperse 10-20 minute, 20-70 DEG C is stirred 2-12 hour, obtains bactericidal composition；
Wherein, described first kind macromolecule and the high molecular weight ratio of Equations of The Second Kind are 95:5～50:50；Described
First kind macromolecule and the high molecular weight average molecular weight of Equations of The Second Kind are 5～500,000.
Bactericidal composition the most according to claim 1, it is characterised in that described antibacterial is selected from first
Nitre azoles, tinidazole, cefalexin, levofloxacin, ciprofloxacin, rifampicin and vancomycin.
Bactericidal composition the most according to claim 1, it is characterised in that described first kind macromolecule
Weight ratio high molecular with Equations of The Second Kind is 90:10～70:30.
Bactericidal composition the most according to claim 1, it is characterised in that described organic solvent is N, N-
The mixed solvent of dimethylformamide and acetone or hexafluoroisopropanol solvent.
5. the bactericidal composition used described in any one of claim 1-4 is prepared by high-voltage electrostatic spinning
Sustained-release antibacterial film.
Sustained-release antibacterial film the most according to claim 5, it is characterised in that described sustained-release antibacterial film is
Prepare by the following method:
(1) bactericidal composition is prepared: first kind macromolecule and Equations of The Second Kind macromolecule are dissolved in organic solvent,
It is configured to the mixed solution that concentration is 5-50% (W/V), then presses antibacterial weight content for the first kind
The amount of macromolecule and Equations of The Second Kind high molecular gross weight meter 1-20% adds antibacterial, and ultrasonic disperse 10-20 divides
Clock, 20-70 DEG C is stirred 2-12 hour, obtains bactericidal composition；
(2) sustained-release antibacterial film is prepared: injected in syringe by described bactericidal composition, add stainless pin
Head, using voltage is 10-30KV high voltage power supply, and solution flow rate is 1～5mL/h, and receiving range is
5～25cm, the embedded material needing coating is coated, finally by embedded material room temperature complete for coating
Vacuum drying 24-48h, obtains being overlying on the sustained-release antibacterial film of described embedded material.
7. the bactericidal composition used described in any one of claim 1-4 passes through high-voltage electrostatic spinning to needing
Embedded material to be coated is coated the embedded material being covered with sustained-release antibacterial film obtained.
The embedded material being covered with sustained-release antibacterial film the most according to claim 7, it is by the following method
Prepare:
(1) bactericidal composition is prepared: first kind macromolecule and Equations of The Second Kind macromolecule are dissolved in organic solvent,
It is configured to the mixed solution that concentration is 5-50% (W/V), then presses antibacterial weight content for the first kind
The amount of macromolecule and Equations of The Second Kind high molecular gross weight meter 1-20% adds antibacterial, and ultrasonic disperse 10-20 divides
Clock, 20-70 DEG C is stirred 2-12 hour, obtains bactericidal composition；
(2) sustained-release antibacterial film is prepared: injected in syringe by described bactericidal composition, add stainless pin
Head, using voltage is 10-30KV high voltage power supply, and solution flow rate is 1～5mL/h, and receiving range is
5～25cm, the embedded material needing coating is coated, finally by embedded material room temperature complete for coating
Vacuum drying 24-48h, obtains being covered with the embedded material of sustained-release antibacterial film.
The embedded material being covered with sustained-release antibacterial film the most according to claim 8, it is characterised in that described
Organic solvent is N,N-dimethylformamide and the mixed solvent of acetone or hexafluoroisopropanol solvent.
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| CN108310451A (en) * | 2018-02-07 | 2018-07-24 | 苏州元禾医疗器械有限公司 | A kind of medical dressing promoting wound healing |
| CN108452391A (en) * | 2018-02-07 | 2018-08-28 | 苏州元禾医疗器械有限公司 | A kind of preparation method of Absorbable membranes |
| CN108578788A (en) * | 2018-02-07 | 2018-09-28 | 苏州元禾医疗器械有限公司 | A kind of Absorbable membranes |
| CN109568679A (en) * | 2018-11-18 | 2019-04-05 | 西南交通大学 | A kind of biodegradable polyurethane sheath and preparation method thereof with antibacterial functions |
| CN116948281B (en) * | 2022-07-15 | 2025-11-18 | 湖北美的洗衣机有限公司 | Methods for preparing sustained-release functional units, sustained-release functional units, and household appliances |
| CN115531610A (en) * | 2022-11-09 | 2022-12-30 | 贵州医科大学附属医院 | Fiber composite membrane, its preparation method and application |
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