CN103599565A - Antibacterial composition, temperature-sensitive antibacterial film prepared by using antibacterial composition and implant material - Google Patents
Antibacterial composition, temperature-sensitive antibacterial film prepared by using antibacterial composition and implant material Download PDFInfo
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- CN103599565A CN103599565A CN201310594991.6A CN201310594991A CN103599565A CN 103599565 A CN103599565 A CN 103599565A CN 201310594991 A CN201310594991 A CN 201310594991A CN 103599565 A CN103599565 A CN 103599565A
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Abstract
The invention discloses an antibacterial composition, a temperature-sensitive antibacterial film prepared by using the antibacterial composition and an implant material. The antibacterial composition comprises an organic polymer selected from polylactic acid, polycaprolactone, a polylactic acid-glycolic acid copolymer and a polylactic acid-polyethylene glycol block copolymer, a blending colloid of polyisopropyl acrylamide and cyclodextrin or a blending colloid of polyisopropyl acrylamide and gelatin, and an antibacterial agent. The temperature-sensitive antibacterial film prepared by using the antibacterial composition through high-pressure electrostatic spinning can only release an antibacterial medicament when the temperature of a human body rises, so that the targeting property is very high.
Description
Technical field
The present invention relates to antibacterial embedded material technical field, the Thermo-sensitive antibacterial film and the embedded material that relate in particular to a kind of bactericidal composition and use it to prepare.
Background technology
When biology is subject to courses of infection, fever is a type reaction, and Homoiotherm (homeotherms), as mouse or people, can increase temperature in body and be infected to inform; And cold blooded animal (poikiotherms), as nematicide can move about to warmer environment, represents that it is infected.And in body or when ambient temperature rises, just can activation temperature the immune message bang path of the responsive sensing factor (HSF-1), this can explain that the function in HSF-1 path is for resisting alien enemy's infection simultaneously, also can explain why biology just may be had a fever by infection simultaneously.From physiological reaction, fever is that oxygen consumption increases and causes fever because leukocyte increases sharply in order to gulp down antibacterial in body, although 37 ℃ of body temperature are general normal values, and fixed value not.Under the effect of body at pyrogen or when a variety of causes causes the dysfunction of thermotaxic centre, fervescence exceeds normal range, is called heating.Everyone normal body temperature is slightly different, and is subject to the impact of many factors (time, season, environment or menstruation etc.).The reason that causes heating is a lot, and modal is to infect (comprising various infectious disease), is secondly connective tissue disease (as collagen) and malignant tumor etc.Heating is favourable also harmful to human body, and adstante febre immune function of human body obviously strengthens, the recovery from illness that this is conducive to remove pathogen and promotes disease, and also heating is also a sign of disease.The tolerable temperature that human body is the highest is 40.6～41.4 ℃ (100.4～102.0F), and rectal temperature continues to raise and surpasses 41 ℃, can cause permanent brain injury; High heat continues at more than 42 ℃ 2～4 little shock and the severe complications of often causing; Body temperature is seldom survival up to 43 ℃.
The main manifestations of postoperative infection is that the fervescence of body exceeds normal body temperature boundary, and cause of disease reason can be infective or noninfective (as inflammation, tumor or immunologic derangement).Pattern of fever can be that gap is hot in nature, after rising every day, drops to normal level again; Or stay heat for diving, after rising, do not get back to normal level.Pyrogen is the material that causes heating, has two kinds of exogenous and endogenouss.Exogenous pyrogen refers to and obtains from host, is mainly microorganism and product thereof and toxin.Studying more deep is the lipopolysaccharide (often claiming endotoxin) of gram negative bacteria and the staphylotoxin being separated to from toxic shock syndrome, TSS patient.Exogenous pyrogen often causes heating by the release of induction endogenous thermal source matter (or claiming endogenous heating cytokine), and endogenous pyrogen is the various kinds of cell by host---the polypeptide that particularly monocytes/macrophages produces.It is exogenous that postoperative infection mostly is, after bring out endogenous, the anti-infective therapy that carries out general when high heat occurs is clinical conventional way, specific aim is not strong, heavy dose of injection also easily makes microorganism or antibacterial produce drug resistance.
Therefore, this area needs only when human body temperature rises, just to discharge antibacterials, thermally sensitive antibacterial film, with specific aim pathogenic microbe killing.
Summary of the invention
The object of the invention is to, a kind of bactericidal composition is provided and uses its Thermo-sensitive antibacterial film and embedded material of preparing, this Thermo-sensitive antibacterial film only just discharges antibacterials when human body temperature rises, and therefore has very strong specific aim.
For realizing object of the present invention, provide following technical scheme:
In first aspect, the invention provides a kind of bactericidal composition, comprising:
Be selected from the organic polymer of polylactic acid, polycaprolactone, Poly(D,L-lactide-co-glycolide and polylactic acid-polyethylene glycol block copolymer;
The blend colloid of PNIPAM and cyclodextrin or the blend colloid of PNIPAM and gelatin; With
Antibacterial.
In bactericidal composition of the present invention, PNIPAM (PNIPAM) is the polymer of NIPA (N-Isopropyl acrylamide), is a kind of polymer of temperature-responsive, near about 32 ℃, can produce reversible transformation mutually.At " lower critical solution temperature " (Low Critical Solution Temperature, LCST) below, because there is the strong interaction of hydrogen bond of hydrone and NIPAM group, polymer is water miscible, and intensification can destroy hydrogen bond and contribute to hydrophobic interaction.When solution temperature arrives LCST, polymer chain can be from the ball of string state-transition of dissolving to insoluble bead state, and the difference of the MOLECULE DESIGN based on PNIPAM polymer and PNIPAM microgel structural design, can bring various new character.The length that existing research shows to promote hydrophilic segment in NIPAM can promote its LCST greatly, and its temperature sensitive temperature is controlled near 38 ℃; Or by NIPAM and the water soluble gelatine blend that possesses gelatination property, also can promote its LCST.
In bactericidal composition of the present invention, polylactic acid (polylactic acid, PLA) claim again polylactide, to take the polymer that lactic acid obtains as primary raw material polymerization, fully and can regenerate, the production process of polylactic acid is pollution-free for raw material sources, and product can biodegradation, realization, in the circulation of occurring in nature, is therefore desirable Green Polymer Material.Polycaprolactone (Polycaprolactone, PCL), at metallo-organic compound (as tetraphenyltin), to make catalyst by 6-caprolactone, dihydroxy or trihydroxy are done ring-opening polymerisation under initiator condition and are formed, belong to aggretion type polyester, its molecular weight is different and different with consumption with the kind of starting material from discrimination degree.Poly(D,L-lactide-co-glycolide (poly (lactic-co-glycolic acid), PLGA), by two kinds of monomers---lactic acid (Lactic acid, LA) and hydroxyacetic acid (glycolic acid, GA) be polymerized at random, it is a kind of degradable functional polymer organic compound, there is good biocompatibility, nontoxic, good encystation and the performance of film forming, be widely used in pharmacy, medical engineering material and modernization industry field, at U.S. PLGA, pass through (the Food and Drug Administration of food and drug administration, FDA) authentication, formally as pharmaceutic adjuvant, included into American Pharmacopeia.The ratio of two kinds of monomers---lactic acid and hydroxyacetic acid is different can prepare dissimilar PLGA, for example: PLGA75:25 represents that this polymer is comprised of 75% lactic acid and 25% hydroxyacetic acid.Polylactic acid-polyethylene glycol block copolymer, by polylactic acid and Polyethylene Glycol (polyethylene glycol, PEG) copolymerization forms, it is degradable medical material, there is at present several different methods to prepare, such as Chinese invention patent publication No. CN102702535A discloses a kind of process of creatinine catalyzing and synthesizing polylactic acid-polyethyleneglycol block copolymer.
Preferably, described antibacterial is selected from metronidazole, tinidazole, cefalexin, levofloxacin, erythromycin, vancomycin, ciprofloxacin and chloromycetin.
Preferably, described organic polymer weight average molecular weight is 5～500,000, for example 50,000,60,000,80,000,100,000,120,000,150,000,180,000,200,000,240,000,250,000,270,000,300,000,320,000,350,000,380,000,400,000,420,000,450,000,480,000,490,000 or 500,000.
Preferably, the weight content of described antibacterial is in the gross weight 1%-20% of organic polymer and blend colloid, and for example 1%, 2%, 3%, 5%, 7%, 8%, 10%, 12%, 14%, 16%, 18% or 19%, preferred 1%-15%.
As the preferred technical solution of the present invention, described bactericidal composition prepares by the following method:
(1) organic polymer solution preparation organic polymer solution: described organic polymer is dissolved in organic solvent, and stirring at room 2-5 hour, being mixed with concentration is 5-30%(W/V).
Preferably, described organic solvent can be the mixed solvent of oxolane (Tetrahydrofuran, THF) and butanone or the mixed solvent of DMF (N, N-Dimethylformamide, DMF) and acetone.Organic macromolecule concentration 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) or 30%(W/V).Wherein wt (W) is in unit gram (g), and volume (V) is in unit milliliter (mL), and weight/volume (W/V) is in unit grams per milliliter (g/mL).
(2) preparation PNIPAM colloid: by NIPA, potassium peroxydisulfate, N; N-DMAA is dissolved in the water containing cyclodextrin or gelatin; be heated to 60-90 ℃, preferably 75 ℃; then add antibacterial; continuous heating 1-5 hour under inert gas shielding, centrifugal and washing obtains PNIPAM colloid.
Preferably, the weight ratio of described NIPA, potassium peroxydisulfate, N,N-DMAA, cyclodextrin or gelatin, antibacterial and water is 1-10:0.01-1:0.1-1:0.1-5:0.1-5:50-1000; 2:0.2:0.5:1:1:200 for example, 10:1:1:4:4:500,5:0.1:0.5:2:2:300,8:0.2:0.5:3:2:800,5:1:0.4:5:0.1:900, etc.In a word, the present invention does not have too strict restriction for the content of each component in the raw material of preparation PNIPAM colloid, so long as in above-mentioned each components by weight numerical range any number than all realizing.
(3) preparation contains the mixed solution of medicine microspheres: described PNIPAM colloid is scattered in to described organic polymer solution, obtains the mixed solution containing medicine microspheres, i.e. described bactericidal composition.
In second aspect, the invention provides the Thermo-sensitive antibacterial film that the bactericidal composition of a kind of use as described in first aspect makes by high-voltage electrostatic spinning.
Preferably, described Thermo-sensitive antibacterial film makes by the following method: described bactericidal composition is injected to syringe, add rustless steel syringe needle, adopting voltage is 10-30KV high voltage power supply, solution flow rate is 1～5mL/h, and receiving range is 5～25cm, and the embedded material that needs are applied applies, finally will apply complete embedded material room temperature vacuum drying 24-48h, obtain being overlying on the Thermo-sensitive 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; Can be 25 hours, 27 hours, 30 hours, 35 hours, 38 hours, 40 hours, 42 hours, 44 hours, 46 hours or 47 hours drying time.
As the preferred technical solution of the present invention, described bactericidal composition prepares by the following method:
(1) organic polymer solution preparation organic polymer solution: described organic polymer is dissolved in organic solvent, and stirring at room 2-5 hour, being mixed with concentration is 5-30%(W/V);
Preferably, described organic solvent is the mixed solvent of oxolane and butanone or the mixed solvent of DMF and acetone;
(2) preparation PNIPAM colloid: by NIPA, potassium peroxydisulfate, N, N-DMAA is dissolved in the water containing cyclodextrin or gelatin, be heated to 60-90 ℃, preferably 75 ℃, then add antibacterial, continuous heating 1-5 hour under inert gas shielding, centrifugal and washing obtains PNIPAM colloid;
Preferably, the weight ratio of described NIPA, potassium peroxydisulfate, N,N-DMAA, cyclodextrin or gelatin, antibacterial and water is 1-10:0.01-1:0.1-1:0.1-5:0.1-5:50-1000;
(3) preparation contains the mixed solution of medicine microspheres: described PNIPAM colloid is scattered in to described organic polymer solution, obtains the mixed solution containing medicine microspheres, i.e. described bactericidal composition.
In second aspect, the invention provides the bactericidal composition of a kind of use as described in first aspect, by high-voltage electrostatic spinning, the embedded material of needs coating is applied to the embedded material that is covered with Thermo-sensitive antibacterial film obtaining.
As the preferred technical solution of the present invention, described in be covered with Thermo-sensitive antibacterial film embedded material make by the following method:
(1) organic polymer solution preparation organic polymer solution: described organic polymer is dissolved in organic solvent, and stirring at room 2-5 hour, being mixed with concentration is 5-30%(W/V);
Preferably, described organic solvent is the mixed solvent of oxolane and butanone or the mixed solvent of DMF and acetone;
(2) preparation PNIPAM colloid: by NIPA, potassium peroxydisulfate, N, N-DMAA is dissolved in the water containing cyclodextrin or gelatin, be heated to 60-90 ℃, preferably 75 ℃, then add antibacterial, continuous heating 1-5 hour under inert gas shielding, centrifugal and washing obtains PNIPAM colloid;
Preferably, the weight ratio of described NIPA, potassium peroxydisulfate, N,N-DMAA, cyclodextrin or gelatin, antibacterial and water is 1-10:0.01-1:0.1-1:0.1-5:0.1-5:50-1000;
(3) preparation contains the mixed solution of medicine microspheres: described PNIPAM colloid is scattered in to described organic polymer solution, obtains the mixed solution containing medicine microspheres, i.e. described bactericidal composition;
(4) described bactericidal composition is injected to syringe, add rustless steel syringe needle, adopting voltage is 10-30KV high voltage power supply, solution flow rate is 1～5mL/h, receiving range is 5～25cm, the embedded material that needs are applied applies, and finally will apply complete embedded material room temperature vacuum drying 24-48h, obtains being covered with the embedded material of Thermo-sensitive antibacterial film.
Beneficial effect of the present invention is: the nanometer bead that bactericidal composition of the present invention contains temperature sensitivity (containing medicine microspheres), its drug release is controlled by temperature, high when hot when infect causing, the quick delivery of antimicrobials of the little club of nanometer (being antibiotic) of temperature sensitivity; And postoperative appearance infects, nanometer bead is wrapped up metabolism by phagocyte, and antibiotic is wherein excreted together.The nanometer bead of this kind of temperature sensitivity is carried in composite high-molecular material, wound site or easy infection position after implantation, high when hot when infect causing, the little club of nanometer of temperature sensitivity discharges antibiotic fast, prevents infections in time and further worsens.In a word, the present invention, owing to adopting the nanometer bead embedding antibacterial of temperature sensitivity, changes selectivity delivery of antimicrobials according to body temperature, has both guaranteed the needs that treatment is infected, and can not bring again nothing abuse of antibiotics targetedly.
The specific embodiment
Below in conjunction with embodiment, embodiment of the present invention are described in detail.It will be understood to those of skill in the art that following examples are only the preferred embodiments of the present invention, so that understand better the present invention, thereby should not be considered as limiting scope of the present invention.For a person skilled in the art, the present invention can have various modifications and variations, within the spirit and principles in the present invention all, any modification of doing, is equal to and replaces or improvement etc., within all should being included in protection scope of the present invention.Experimental technique in following embodiment, if no special instructions, is conventional method; Experiment material used, if no special instructions, is and is purchased available from routine biochemistry chemical reagent work.
Embodiment 1:
The present embodiment is prepared as follows Thermo-sensitive antibacterial film:
(1) solution preparation PLGA macromolecular solution: by 10g PLGA(Mw=8 ten thousand, LA/GA=75/25) be dissolved in the mixed solvent (THF and acetone volume ratio are 1/1) of 40mL THF and acetone, being mixed with concentration is 25%(W/V), stirring at room 3 hours.
(2) prepare PNIPAM colloid: get 4g NIPA, 0.06g potassium peroxydisulfate and 0.16gN; N-DMAA is dissolved in 160g containing in the deionized water of 0.3g gelatin; being heated to 75 ℃ stablizes; add 2g vancomycin; under nitrogen protection, continuous heating is 2 hours; then centrifugalize goes out the PNIPAM colloid containing vancomycin, and obtains crosslinked PNIPAM colloid through three deionized water wash-centrifugalize.The PNIPAM colloidal particle size size homogeneous, the diameter that make are 50nm～500nm, and wherein after water washing, the load factor of vancomycin (with respect to consumption) is 83%.
(3) preparation contains the mixed solution of medicine microspheres: the above-mentioned PNIPAM colloid containing vancomycin is scattered in the above-mentioned PLGA macromolecular solution being mixed with, ultrasonic 3 hours, obtains the mixed solution containing medicine microspheres, i.e. described bactericidal composition.
(4) prepare Thermo-sensitive antibacterial film: by described mixed solution, inject 5mL syringe, add rustless steel syringe needle No. 5, at voltage, be 25KV, solution flow rate is 2.5mL/h, carries out electrostatic spinning under the condition that receiving range is 18cm, the embedded material that needs are applied applies, finally, by applying complete embedded material room temperature vacuum drying 24h, remove residual solvent, and preserve in 4 ℃ of drying baker.
The Thermo-sensitive antibacterial film containing antibacterial of preparing according to the present embodiment, when lower than 32 ℃, the burst size of antibacterial is 0; Between 32-37 ℃, antibacterial slowly discharges, 36h burst size <5%; In the time of 37-40 ℃, antibacterial discharges fast, and 36h burst size is about 70%; In the time of >40 ℃, antibacterial there will be sudden outburst, and in 12h, medicine discharges completely.
Embodiment 2:
The present embodiment is prepared as follows Thermo-sensitive antibacterial film:
(1) solution preparation polylactic acid macromolecular solution: 10g polylactic acid (Mw=50 ten thousand) is dissolved in to the mixed solvent (THF and acetone volume ratio are 1/1) of 40mL THF and acetone, being mixed with concentration is 30%(W/V), stirring at room 5 hours.
(2) prepare PNIPAM colloid: get 10g NIPA, 0.2g potassium peroxydisulfate and 0.3gN; N-DMAA is dissolved in 300g containing in the deionized water of 0.5g cyclodextrin; being heated to 90 ℃ stablizes; add 4g levofloxacin; under nitrogen protection, continuous heating is 2 hours; then centrifugalize goes out the PNIPAM colloid containing levofloxacin, and obtains crosslinked PNIPAM colloid through three deionized water wash-centrifugalize.The PNIPAM colloidal particle size size homogeneous, the diameter that make are 100nm～600nm, and wherein after water washing, the load factor of levofloxacin (with respect to consumption) is 75%.
(3) preparation contains the mixed solution of medicine microspheres: the above-mentioned PNIPAM colloid containing levofloxacin is scattered in the above-mentioned polylactic acid macromolecular solution being mixed with, ultrasonic 2 hours, obtains the mixed solution containing medicine microspheres, i.e. described bactericidal composition.
(4) prepare Thermo-sensitive antibacterial film: by described mixed solution, inject 5mL syringe, add rustless steel syringe needle No. 5, at voltage, be 10KV, solution flow rate is 1mL/h, carries out electrostatic spinning under the condition that receiving range is 25cm, the embedded material that needs are applied applies, finally, by applying complete embedded material room temperature vacuum drying 48h, remove residual solvent, and preserve in 4 ℃ of drying baker.
The Thermo-sensitive antibacterial film containing antibacterial of preparing according to the present embodiment, when lower than 32 ℃, the burst size of antibacterial is 0; Between 32-37 ℃, antibacterial slowly discharges, 36h burst size <10%; In the time of 37-40 ℃, antibacterial discharges fast, and 36h burst size is about 75%; In the time of >40 ℃, antibacterial there will be sudden outburst, and in 12h, medicine discharges completely.
Embodiment 3:
The present embodiment is prepared as follows Thermo-sensitive antibacterial film:
(1) solution preparation polycaprolactone macromolecular solution: 8g polycaprolactone (Mw=5 ten thousand) is dissolved in to the mixed solvent (THF and acetone volume ratio are 1/1) of 50mL THF and acetone, being mixed with concentration is 5%(W/V), stirring at room 2 hours.
(2) prepare PNIPAM colloid: get 5g NIPA, 0.1g potassium peroxydisulfate and 0.2g N; N-DMAA is dissolved in 200g containing in the deionized water of 0.4g gelatin; being heated to 60 ℃ stablizes; add 2.5g cefalexin; under nitrogen protection, continuous heating is 2 hours; then centrifugalize goes out the PNIPAM colloid containing cefalexin, and obtains crosslinked PNIPAM colloid through three deionized water wash-centrifugalize.The PNIPAM colloidal particle size size homogeneous, the diameter that make are 50nm～300nm, and wherein after water washing, the load factor of cefalexin (with respect to consumption) is 78%.
(3) preparation contains the mixed solution of medicine microspheres: the above-mentioned PNIPAM colloid containing cefalexin is scattered in the above-mentioned polycaprolactone macromolecular solution being mixed with, ultrasonic 2 hours, obtains the mixed solution containing medicine microspheres, i.e. described bactericidal composition.
(4) prepare Thermo-sensitive antibacterial film: by described mixed solution, inject 5mL syringe, add rustless steel syringe needle No. 5, at voltage, be 30KV, solution flow rate is 5mL/h, carries out electrostatic spinning under the condition that receiving range is 5cm, the embedded material that needs are applied applies, finally, by applying complete embedded material room temperature vacuum drying 36h, remove residual solvent, and preserve in 4 ℃ of drying baker.
The Thermo-sensitive antibacterial film containing antibacterial of preparing according to the present embodiment, when lower than 32 ℃, the burst size of antibacterial is 0; Between 32-37 ℃, antibacterial slowly discharges, 36h burst size <8%; In the time of 37-40 ℃, antibacterial discharges fast, and 36h burst size is about 78%; In the time of >40 ℃, antibacterial there will be sudden outburst, and in 12h, medicine discharges completely.
Embodiment 4:
The present embodiment is prepared as follows Thermo-sensitive antibacterial film:
(1) preparation polylactic acid-polyethylene glycol block copolymer macromolecular solution: the mixed solvent (THF and acetone volume ratio are 1/1) that 15g polylactic acid-polyethylene glycol block copolymer (Mw=25 ten thousand) is dissolved in to 100mL THF and acetone, being mixed with concentration is 15%(W/V) solution, stirring at room 2 hours.
(2) prepare PNIPAM colloid: get 7g NIPA, 0.3g potassium peroxydisulfate and 0.3g N; N-DMAA is dissolved in 300g containing in the deionized water of 2g gelatin; being heated to 70 ℃ stablizes; add 3g chloromycetin; under nitrogen protection, continuous heating is 2 hours; then centrifugalize goes out the PNIPAM colloid containing chloromycetin, and obtains crosslinked PNIPAM colloid through three deionized water wash-centrifugalize.The PNIPAM colloidal particle size size homogeneous, the diameter that make are 70nm～400nm, and wherein after water washing, the load factor of chloromycetin (with respect to consumption) is 82%.
(3) preparation contains the mixed solution of medicine microspheres: the above-mentioned PNIPAM colloid containing chloromycetin is scattered in the above-mentioned polylactic acid-polyethylene glycol block copolymer macromolecular solution being mixed with, ultrasonic 5 hours, obtain the mixed solution containing medicine microspheres, i.e. described bactericidal composition.
(4) prepare Thermo-sensitive antibacterial film: by described mixed solution, inject 5mL syringe, add rustless steel syringe needle No. 5, at voltage, be 20KV, solution flow rate is 3mL/h, carries out electrostatic spinning under the condition that receiving range is 18cm, the embedded material that needs are applied applies, finally, by applying complete embedded material room temperature vacuum drying 32h, remove residual solvent, and preserve in 4 ℃ of drying baker.
The Thermo-sensitive antibacterial film containing antibacterial of preparing according to the present embodiment, when lower than 32 ℃, the burst size of antibacterial is 0; Between 32-37 ℃, antibacterial slowly discharges, 36h burst size <5%; In the time of 37-40 ℃, antibacterial discharges fast, and 36h burst size is about 80%; In the time of >40 ℃, antibacterial there will be sudden outburst, and in 12h, medicine discharges completely.
The present invention is when promoting the embedding amount and embedding rate of medicine, and the control that can realize the temperature sensitivity of antibacterial discharges, technique is simple, easy operating and cost low, in surgical field, have wide practical use.
Applicant's statement, the present invention illustrates detailed features of the present invention and method detailed by above-described embodiment, but the present invention is not limited to above-mentioned detailed features and method detailed, do not mean that the present invention must rely on above-mentioned detailed features and method detailed could be implemented.Person of ordinary skill in the field should understand, any improvement in the present invention is selected the selection of the equivalence replacement of component and the interpolation of auxiliary element, concrete mode etc., within all dropping on protection scope of the present invention and open scope to the present invention.
Claims (10)
1. a bactericidal composition, comprising:
Be selected from the organic polymer of polylactic acid, polycaprolactone, Poly(D,L-lactide-co-glycolide and polylactic acid-polyethylene glycol block copolymer;
The blend colloid of PNIPAM and cyclodextrin or the blend colloid of PNIPAM and gelatin; With
Antibacterial.
2. bactericidal composition according to claim 1, is characterized in that, described antibacterial is selected from metronidazole, tinidazole, cefalexin, levofloxacin, erythromycin, vancomycin, ciprofloxacin and chloromycetin.
3. bactericidal composition according to claim 1 and 2, is characterized in that, described organic polymer weight average molecular weight is 5～500,000.
4. according to the bactericidal composition described in claim 1-3 any one, it is characterized in that, the weight content of described antibacterial is the gross weight 1%-20% in organic polymer and blend colloid, preferably 1%-15%.
5. according to the bactericidal composition described in claim 1-4 any one, it prepares by the following method:
(1) organic polymer solution preparation organic polymer solution: described organic polymer is dissolved in organic solvent, and stirring at room 2-5 hour, being mixed with concentration is 5-30%(W/V);
Preferably, described organic solvent is the mixed solvent of oxolane and butanone or the mixed solvent of DMF and acetone;
(2) preparation PNIPAM colloid: by NIPA, potassium peroxydisulfate, N, N-DMAA is dissolved in the water containing cyclodextrin or gelatin, be heated to 60-90 ℃, preferably 75 ℃, then add antibacterial, continuous heating 1-5 hour under inert gas shielding, centrifugal and washing obtains PNIPAM colloid;
Preferably, the weight ratio of described NIPA, potassium peroxydisulfate, N,N-DMAA, cyclodextrin or gelatin, antibacterial and water is 1-10:0.01-1:0.1-1:0.1-5:0.1-5:50-1000;
(3) preparation contains the mixed solution of medicine microspheres: described PNIPAM colloid is scattered in to described organic polymer solution, obtains the mixed solution containing medicine microspheres, i.e. described bactericidal composition.
6. the Thermo-sensitive antibacterial film that the bactericidal composition described in a right to use requirement 1-5 any one makes by high-voltage electrostatic spinning.
7. Thermo-sensitive antibacterial film according to claim 6, it makes by the following method: bactericidal composition is injected to syringe, add rustless steel syringe needle, adopting voltage is 10-30KV high voltage power supply, solution flow rate is 1～5mL/h, and receiving range is 5～25cm, and the embedded material that needs are applied applies, finally will apply complete embedded material room temperature vacuum drying 24-48h, obtain being overlying on the Thermo-sensitive antibacterial film of embedded material.
8. Thermo-sensitive antibacterial film according to claim 7, is characterized in that, described bactericidal composition prepares by the following method:
(1) organic polymer solution preparation organic polymer solution: described organic polymer is dissolved in organic solvent, and stirring at room 2-5 hour, being mixed with concentration is 5-30%(W/V);
Preferably, described organic solvent is the mixed solvent of oxolane and butanone or the mixed solvent of DMF and acetone;
(2) preparation PNIPAM colloid: by NIPA, potassium peroxydisulfate, N, N-DMAA is dissolved in the water containing cyclodextrin or gelatin, be heated to 60-90 ℃, preferably 75 ℃, then add antibacterial, continuous heating 1-5 hour under inert gas shielding, centrifugal and washing obtains PNIPAM colloid;
Preferably, the weight ratio of described NIPA, potassium peroxydisulfate, N,N-DMAA, cyclodextrin or gelatin, antibacterial and water is 1-10:0.01-1:0.1-1:0.1-5:0.1-5:50-1000;
(3) preparation contains the mixed solution of medicine microspheres: described PNIPAM colloid is scattered in to described organic polymer solution, obtains the mixed solution containing medicine microspheres, i.e. described bactericidal composition.
9. the embedded material that the bactericidal composition described in a right to use requirement 1-5 any one applies needs by high-voltage electrostatic spinning applies the embedded material that is covered with Thermo-sensitive antibacterial film obtaining.
10. the embedded material that is covered with Thermo-sensitive antibacterial film according to claim 9, it makes by the following method:
(1) organic polymer solution preparation organic polymer solution: described organic polymer is dissolved in organic solvent, and stirring at room 2-5 hour, being mixed with concentration is 5-30%(W/V);
Preferably, described organic solvent is the mixed solvent of oxolane and butanone or the mixed solvent of DMF and acetone;
(2) preparation PNIPAM colloid: by NIPA, potassium peroxydisulfate, N, N-DMAA is dissolved in the water containing cyclodextrin or gelatin, be heated to 60-90 ℃, preferably 75 ℃, then add antibacterial, continuous heating 1-5 hour under inert gas shielding, centrifugal and washing obtains PNIPAM colloid;
Preferably, the weight ratio of described NIPA, potassium peroxydisulfate, N,N-DMAA, cyclodextrin or gelatin, antibacterial and water is 1-10:0.01-1:0.1-1:0.1-5:0.1-5:50-1000;
(3) preparation contains the mixed solution of medicine microspheres: described PNIPAM colloid is scattered in to described organic polymer solution, obtains the mixed solution containing medicine microspheres, i.e. described bactericidal composition;
(4) described bactericidal composition is injected to syringe, add rustless steel syringe needle, adopting voltage is 10-30KV high voltage power supply, solution flow rate is 1～5mL/h, receiving range is 5～25cm, the embedded material that needs are applied applies, and finally will apply complete embedded material room temperature vacuum drying 24-48h, obtains being covered with the embedded material of Thermo-sensitive antibacterial film.
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| CN201310594991.6A CN103599565B (en) | 2013-11-21 | 2013-11-21 | Antibacterial composition, temperature-sensitive antibacterial film prepared by using antibacterial composition and implant material |
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| CN102908674A (en) * | 2012-11-09 | 2013-02-06 | 无锡中科光远生物材料有限公司 | Preparation method of stent coating with hemostasis and antibiosis functions |
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| CN1241198A (en) * | 1996-12-20 | 2000-01-12 | 香港中文大学 | Polymer gel composition and uses therefor |
| US20060198865A1 (en) * | 2005-03-07 | 2006-09-07 | Freyman Toby M | Microencapsulated compositions for endoluminal tissue engineering |
| CN101092471A (en) * | 2007-06-15 | 2007-12-26 | 北京化工大学 | Method for preparing temperature sensitive hydrogel with supramolecular structure |
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