CN104491932A - Drug-loaded nanometer anti-adhesion membrane having core/shell structure and preparation method thereof - Google Patents
Drug-loaded nanometer anti-adhesion membrane having core/shell structure and preparation method thereof Download PDFInfo
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Abstract
The invention provides a drug-loaded nanometer anti-adhesion membrane having a core/shell structure and a preparation method thereof. The drug-loaded nanometer anti-adhesion membrane having the core/shell structure is formed by connecting fibers having the inner core and outer shell structure in parallel, wherein the inner core comprises a therapeutically effective amount of active ingredients and polyvinylpyrrolidone (PVP); the outer shell is polylactic-co-glycolic acid (PLGA) and micropores are formed in the outer shell. The drug-loaded nanometer anti-adhesion membrane having the core/shell structure is simple and efficient in preparation method and inexpensive and the membrane material prepared by the drug-loaded nanometer anti-adhesion membrane has the advantages of controllable specific surface area, controllable pore size, good mechanical properties, blood permeability and controllable biodegradability, no hypersensitivity to a human body during anti-adhesion is caused and the membrane material has affinity with blood and perienchyma in the human body, bio-adhesive surface and no rejection phenomenon.
Description
Technical field
The present invention relates to a kind of Antiadhesive film and preparation method thereof.
Background technology
Postoperative intestinal adhesion is domestic and international surgical field one of still unsolved important difficult medical problem so far.Adhesion not only can cause serious complication, and bad adhesion is also the one of the main reasons that complication obviously increases when again performing the operation.The reason of Adhesion formation is caused to be many-sided, many experimental results shows, in operation process, hemorrhage and tissue injury is the main cause of Adhesion formation, in addition, the introducing of foreign body in operation process, as scrim fiber, the end of a thread, Pulvis Talci, can cause inflammatory reaction, and inflammation can cause a large amount of tissues to ooze out, the fibrin in exudate will encourage and form adhesion.Also have test to show, animal is exposed in atmosphere for a long time, makes its placenta percreta occur drying property crackle, after tissue is put back into abdominal cavity, namely occurs adhesion, illustrate that the dry factor is also a reason of Adhesion formation.Its mechanism is that drying can make Peritoneal Mesothelial Cells dead, forms thrombosis, thus causes the formation of adhesion.
Biological absorbable degraded macromolecular material is one of current comparatively ideal medical macromolecular materials.Electrostatic spinning is the technology that a kind of simple and effective prepares nanofiber.Produce injection stream by applying high electric field to polymer solution or melt, while jet is stretched, solvent volatilization forms the fiber of diameter at 2-3000nm.Biodegradable absorbing material has a lot of product, and anti-adhesion gel, anti liquid, Antiadhesive film etc., serve certain effect to preventing tissue adhesion.But antiblocking liquor liquid flowability is strong, can not play physical barriers effect well, can make wound site lowering of concentration in body with position and drain, reduce the effect of anti.And the buffer action of Antiadhesive film is better.Desirable adherence preventing material should have low irritability, suitable tissue adherence, can complete wound coverage surface and there is retention time in enough bodies, can degraded and absorbed and do not need second operation to be taken out, wound healing, has certain mechanical strength simultaneously and is convenient to implementation and operation etc.
Current existing adherence preventing material has following several: polylactic acid, modification of chitosan, carboxymethyl cellulose, hyaluronic acid.
Polylactic acid has higher molecular weight and viscosity because of it thus can be used as antitack agent, and its effect may be that it can affect the generation of agglutination to reach the effect preventing film coalescence in body.Tong Xiaochun has carried out the test of polylactic acid gel for prevention abdominal adhesions.Also find to there is some problem in polylactic acid clinical practice: in (1) clinical practice, the patient found that there is there will be non-specific aseptic inflammation, response rate is 8%, and consider that its reason may in polylactic acid degradation process, acid degradation products causes local ph to decline.The symptoms such as patient suffers from abdominal pain, heating can be caused clinically; (2) polylactic acid not easily attaches organizationally, is easy to the wound surface that slips away, and need sew up fixing.
Modification of chitosan is more common adherence preventing material, has excellent biological barrier performance and histocompatibility, is applied to and organizes wound surface, prevent postoperative tissue adhesion.Chitosan, owing to having biocompatibility and organizing the features such as degradability, can be used as desirable Post operation anti-blocking agent after making film theoretically.But it is not high enough that the chitosan used clinically at present exists purity, and poor to a lot of preventing adhesiving effect, degradation speed is difficult to think regulation and control, the degraded of chitosan is also subject to the impact of Lysozyme Levels height in human body, and assimilation effect is unpredictable.
Poly lactic-co-glycolic acid (PLGA) is typically can the polymer of synthesizing biological degradable, there is the performance of good biocompatibility, nontoxic, good encystation and film forming, be widely used in pharmacy, medical engineering material and modernization industrial circle.At U.S. PLGA by FDA certification, formally included into American Pharmacopeia as pharmaceutic adjuvant.The catabolite of PLGA is lactic acid and hydroxyacetic acid, is also simultaneously the by-product of people's metabolic pathway, and institute works as can not toxic side effect when it is applied in medical and biomaterial.By adjustment monomer ratio, and then change the degradation time of PLGA, this method has been widely used in biomedical sector, as: skin transplantation, wound suture, et al. Ke, the micro-nano grain of rice etc.At present, pure in the control PLGA synthon mol ratio control PLGA controlled degradation cycle, can't accomplish completely, mainly the low-molecular-weight polymer fragment more complicated that produces in degradation process of PLGA, is difficult to accurately carry out quantitative analysis to its degradation behavior.
Summary of the invention
The object of this invention is to provide a kind of core/shell structure medicament-carried nano Antiadhesive film and preparation method thereof, to overcome the defect that prior art exists.
Described core/shell structure medicament-carried nano Antiadhesive film, is made up of the fiber parallel connection of kernel and shell mechanism;
Wherein:
Described kernel comprises active component and the polyvinylpyrrolidone (PVP) for the treatment of effective dose;
Described shell is poly lactic-co-glycolic acid (PLGA), and described shell is provided with micropore, and aperture is 10 ~ 100 nanometers, and on the shell of every square centimeter, the quantity of micropore is 3 × 10
7~ 5 × 10
7individual;
The weight average molecular weight of described poly lactic-co-glycolic acid is 80000 ~ 100000; Polyvinylpyrrolidone weight average molecular weight is 40000 ~ 55000;
Preferably, described active component is Flurbiprofen axetil, ibuprofen, ketoprofen, indomethacin or diclofenac; Preferably, with the total weight of active component and polyvinylpyrrolidone, the weight content of Flurbiprofen axetil is 0.1 ~ 0.4%;
Preferably, the fiber number of described fiber is 0.13 ~ 0.2;
Preferably, the weight ratio of described polyvinylpyrrolidone and poly lactic-co-glycolic acid is 2:1 ~ 10:1;
The preparation method of core/shell structure medicament-carried nano Antiadhesive film of the present invention, comprises the steps:
(1) be dissolved in by poly lactic-co-glycolic acid in dichloromethane (DCM) and DMF (DMF) mixed solvent, then add nanometer dry-ice particle, mixing dispersion, as shell spinning solution;
The weight ratio of dichloromethane and DMF is 2:1 ~ 5:1;
With poly lactic-co-glycolic acid, dichloromethane, DMF and nanometer dry-ice particle total weight, the weight content of poly lactic-co-glycolic acid is 8 ~ 12%;
With poly lactic-co-glycolic acid, dichloromethane, DMF and nanometer dry-ice particle total weight, the percentage by weight of nanometer dry-ice particle is 0.1% ~ 5%, preferably 0.1% ~ 0.5%;
(2) polyvinylpyrrolidone and active medicine are dissolved in ethanol and DMF mixed solvent, stir at 20 ~ 25 DEG C, dispersion, the weight ratio of dehydrated alcohol and DMF is 1:1 ~ 3:1, obtains stratum nucleare spinning solution;
In dehydrated alcohol and DMF mixed solvent, the weight content of polyvinylpyrrolidone is 4 ~ 8%;
(3) in 3 ~ 10 minutes after the preparation of shell spinning solution, at 25 ~ 30 DEG C, by shell spinning solution and stratum nucleare spinning solution, adopt coaxial electrostatic spinning method, obtain composite drug-loaded fiber film material; Described coaxial electrostatic spinning method is method well known in the art, as Anew nanofiber fabrication technique based oncoaxial electrospinning [J] .Materials Letters such as Hong Kong University Wang Min, the method of 2012,66:257-260. bibliographical information.
(4) the composite drug-loaded fiber film material lyophilization will obtained, put into the vacuum freeze dryer being added with active carbon, by freezing-absorption-sublimed method,-45 ~-55 DEG C of lyophilizations remove dichloromethane, N in 20 ~ 24 hours, dinethylformamide solvent and moisture, obtain described long-pending core/shell structure medicament-carried nano Antiadhesive film; Preferably, also comprise sterilization steps: vacuum sterilization 4 ~ 8 hours, then along fibre orientation, fibrous membrane is cut into the Rectangular samples of 30mm × 50mm, compression molding.
The core/shell structure medicament-carried nano Antiadhesive film that the present invention obtains, can be used for anti between surgical wounds healing stage tissue, application process is as follows:
After all operations are carried out routinely, before operation terminates, complete and thoroughly stop blooding and after debridement, this Antiadhesive film evenly divided between the wound surface needing to prevent adhesion or tissue, (consumption is judged by patient depending on wound surface size, advises less wound surface 10mm × 20mm; Larger wound surface 30mm × 50mm), after adhesion solidification, (meet tissue fluid solidification in 1-2 minute) can surgical pathway be closed.
Pharmacological testing proves, health volunteer uses Flurbiprofen axetil nanofiber analgesia film 20mm × 20mm (medicament contg 50mg) 5 ~ 10min afterwards, blood drug level and peaking.When dosage is between 10 ~ 80mg, blood drug level linearly.Drug eliminated half life is 5.8h.48h after medication, urine Chinese medicine cumulative excretion amount is about to 85% of dosage.Successive administration 5 times, every minor tick 12h, after last medication, 48h urinates Chinese medicine cumulative excretion rate and reaches nearly 100%, does not find that medicine is accumulated in vivo.
The present invention with nanometer dry-ice particle for pore former, adopt coaxial electrostatic spinning method, obtain a kind of controlled superhigh specific surface area core/shell structure medicament-carried nano Antiadhesive film, preparation method is simply efficient, cheap, the membrane material of preparation has good controlled specific surface area, control pore size, mechanical property, thoroughly blood performance and controllable biodegradable performance, when anti to human body without allergy, simultaneously with the blood in human body and perienchyma, there is affinity, there is bioadhesiveness surface and without rejection phenomenon.
Accompanying drawing explanation
Fig. 1 core/shell structure medicament-carrying nano-fiber diameter Distribution cartogram;
Fig. 2 core/shell structure medicament-carrying nano-fiber surface appearance and core/shell structure scanning electron microscope (SEM) photograph;
Fig. 3 is NIH3T3 cytotoxicity testing result;
Fig. 4 is IEC-6 cytotoxicity testing result;
Fig. 5 is NIH3T3 cell adhesion rate on the different membranes;
Fig. 6 is IEC-6 cell adhesion rate on the different membranes;
Fig. 7 is the graph of a relation between drug accumulation burst size and pore former consumption.
Detailed description of the invention
Below in conjunction with accompanying drawing, the present invention is further described.
Embodiment 1
(1) poly lactic-co-glycolic acid is dissolved in dichloromethane and N, in dinethylformamide mixed solvent, at 25 DEG C after electric stirring 10 hours (rotating speed 550r/min), add the dry-ice particle electric stirring 2 hours that particle diameter is 500 nanometers, last sonic oscillation 20 minutes, obtained poly lactic-co-glycolic acid weight percent content is the spinning liquid of 10%, as shell solution;
The weight ratio of dichloromethane and DMF is 3:1;
With poly lactic-co-glycolic acid, dichloromethane, DMF and nanometer dry-ice particle total weight, the weight content of poly lactic-co-glycolic acid is 10%;
With poly lactic-co-glycolic acid, dichloromethane, DMF and nanometer dry-ice particle total weight, the percentage by weight of nanometer dry-ice particle is 0.1%;
(2) be dissolved in dehydrated alcohol and DMF mixed solvent by polyvinylpyrrolidone, Flurbiprofen axetil, stir at 25 DEG C, dispersion, the weight ratio of ethanol and DMF is 2:1, obtains stratum nucleare spinning solution;
In dehydrated alcohol and DMF mixed solvent, the weight content of polyvinylpyrrolidone is 8%;
(3) in 10 minutes after the preparation of shell spinning solution, at 25 DEG C, by shell spinning solution and stratum nucleare spinning solution, adopt coaxial electrostatic spinning method, obtain composite drug-loaded fiber film material;
Temperature 25 DEG C, relative humidity 50%, shell spinning flow velocity 0.8mm/min, stratum nucleare spinning flow velocity 0.05mm/min, spinning positive high voltage 18kV, negative high voltage 1.25kV, carry out coaxial electrostatic spinning under reel condition of acceptance.
(4) the composite drug-loaded fiber film material will obtained, put into the vacuum freeze dryer being added with active carbon, by freezing-absorption-sublimed method,-55 DEG C of lyophilizations remove dichloromethane, N in 20 hours, dinethylformamide solvent and moisture, obtain described controlled superhigh specific surface area core/shell structure medicament-carried nano Antiadhesive film; Preferably, also comprise sterilization steps: vacuum sterilization 4 hours, then along fibre orientation, fibrous membrane is cut into the Rectangular samples of 30mm × 50mm, compression molding.On shell, the aperture of micropore is 100 nanometers, and on the shell of every square centimeter, the quantity of micropore is 3 × 10
7individual;
The weight average molecular weight of polylactic-co-glycolic acid is 100000; Polyvinylpyrrolidone weight average molecular weight is 55000;
With the total weight of Flurbiprofen axetil and polyvinylpyrrolidone, the weight content of Flurbiprofen axetil is 0.4%;
The fiber number of fiber is 0.2;
The weight ratio of polyvinylpyrrolidone and poly lactic-co-glycolic acid is 2:1;
On shell, the aperture of micropore can adopt A novel method ofselecting solvents for polymerelectrospinning [J] .Polymer such as C.J.Luo, 2010, the method of 51 (7): 1654-1662. bibliographical informations detects, or adopt Preparation of porous ultrafine PGA fibers via selective dissolution ofelectrospun PGA/PLA blend fibers [J] the .Materials Letters such as Young You, 2006, the quantity that 60:757-760. method carries out detecting micropore can adopt Electrospinning and mechanical characterization of gelatinnanofibers [J] .Polymer such as Z.Huang, 2004, the method of 45 (15): 5361-5368. bibliographical informations detects, or adopt BET equation to measure,
Fig. 1 is core/shell structure medicament-carrying nano-fiber diameter Distribution cartogram; Wherein:
A figure represents poly lactic-co-glycolic acid/Flurbiprofen axetil blending nano-fiber membrane diameter Distribution, b figure represents poly lactic-co-glycolic acid/4% polyvinylpyrrolidone/Flurbiprofen axetil core/shell nano fibrous membrane diameter Distribution, c figure represents poly lactic-co-glycolic acid/6% polyvinylpyrrolidone/Flurbiprofen axetil core/shell nano fibrous membrane diameter Distribution, and d figure represents poly lactic-co-glycolic acid/6% poly lactic-co-glycolic acid/Flurbiprofen axetil core/shell nano fibrous membrane diameter Distribution.
Fig. 2 is that core/shell structure medicament-carrying nano-fiber surface appearance and core/shell structure SEM scheme.
Embodiment 2
(1) poly lactic-co-glycolic acid is dissolved in dichloromethane and N, in dinethylformamide mixed solvent, at 25 DEG C after electric stirring 10 hours (rotating speed 550r/min), add the dry-ice particle electric stirring 2 hours that particle diameter is 500 nanometers, last sonic oscillation 20 minutes, obtained poly lactic-co-glycolic acid weight percent content is the spinning liquid of 10%, as shell solution;
The weight ratio of dichloromethane and DMF is 5:1;
With poly lactic-co-glycolic acid, dichloromethane, DMF and nanometer dry-ice particle total weight, the weight content of poly lactic-co-glycolic acid is 12%;
With poly lactic-co-glycolic acid, dichloromethane, DMF and nanometer dry-ice particle total weight, the percentage by weight of nanometer dry-ice particle is 0.5%;
(2) be dissolved in dehydrated alcohol and DMF mixed solvent by polyvinylpyrrolidone, Flurbiprofen axetil, stir at 25 DEG C, dispersion, the weight ratio of dehydrated alcohol and DMF is 1:1, obtains stratum nucleare spinning solution;
In dehydrated alcohol and DMF mixed solvent, the weight content of polyvinylpyrrolidone is 4%;
(3) in 25 minutes after the preparation of shell spinning solution, at 30 DEG C, by shell spinning solution and stratum nucleare spinning solution, adopt coaxial electrostatic spinning method, obtain composite drug-loaded fiber film material;
Temperature 25 DEG C, relative humidity 50%, shell spinning flow velocity 0.8mm/min, stratum nucleare spinning flow velocity 0.05mm/min, spinning positive high voltage 18kV, negative high voltage 1.25kV, carry out coaxial electrostatic spinning under reel condition of acceptance.
(5) the composite drug-loaded fiber film material lyophilization will obtained, put into the vacuum freeze dryer being added with active carbon,-45 DEG C of lyophilizations 20 hours, remove dichloromethane/N, dinethylformamide, dehydrated alcohol/N, dinethylformamide, at room temperature vacuum drying 20 hours again, remove remaining dichloromethane/N, dinethylformamide, dehydrated alcohol/N, dinethylformamide and moisture, obtain described controlled superhigh specific surface area core/shell structure medicament-carried nano Antiadhesive film; Vacuum drying 15 hours, then along fibre orientation, is cut into the Rectangular samples of 30mm × 50mm, compression molding by fibrous membrane.
On shell, the aperture of micropore is 10 nanometers, and on the shell of every square centimeter, the quantity of micropore is 5 × 10
7individual;
The weight average molecular weight of polylactic-co-glycolic acid is 80000; Polyvinylpyrrolidone weight average molecular weight is 40000;
With the total weight of Flurbiprofen axetil and polyvinylpyrrolidone, the weight content of Flurbiprofen axetil is 0.1%;
The fiber number of fiber is 0.13;
The weight ratio of polyvinylpyrrolidone and poly lactic-co-glycolic acid is 10:1.
Embodiment 3
The cell toxicity test of medicine carrying type poly lactic-co-glycolic acid static spinning membrane
(1) be inoculated in 96 orifice plates by the cell of exponential phase, guarantee that the cell number of hatching 2 days is 6000/hole, the cell number of hatching 4 days and 7 days is respectively 4000/hole and 3000/hole;
(2) the cell inoculated in incubator adherent 6 hours, then the medicine carrying static spinning membrane of the embodiment 1 of the off-the-shelf different size similar with 96 hole sizes is put in the medium, be as the criterion in the medium to soak;
(3), after hatching 2,4,7 days respectively, take out medicine carrying type poly lactic-co-glycolic acid static spinning membrane, CCK-8 mensuration is carried out to cell;
(4) not put the hole in contrast, hole of film, data analysis is carried out.
Flurbiprofen axetil/polyvinylpyrrolidone/poly lactic-co-glycolic acid composite nano-fiber membrane and IEC-6 cell, NIH3T3 cell are carried out co-cultivation respectively, detected by CCK-8 reagent detection method, known Flurbiprofen axetil/polyvinylpyrrolidone/poly lactic-co-glycolic acid composite nano-fiber membrane does not have toxicity.
Embodiment 4
The adhesiveness test of cell on medicine carrying type poly lactic-co-glycolic acid static spinning membrane
(1) the medicine carrying type poly lactic-co-glycolic acid static spinning membrane of, 100 μm thick, 160 μm thick, 220 μm thick embodiments 1 thick by 60 μm and commercial membranes are cut into the square piece with coverslip size respectively, be taped against in 6 orifice plates, often kind of film does 6 multiple holes, 6 orifice plate lids are opened, respectively ultra-vioket radiation 30min is carried out to film; Also ultra-vioket radiation 30min is carried out to the microscope slide be placed in 6 orifice plates simultaneously, prepare inoculating cell;
(2) to every hole inoculating cell, hatch different time sections (2 days, 4 days, 7 days), the cell number of guaranteeing to hatch 2 days is 400000/hole, the cell number of hatching 4 days, 7 days is respectively 40000/hole and 4000/hole, after hatching, and sucking-off supernatant gently, then film and coverslip are forwarded on 6 new orifice plates, every hole adds MTT solution 1.5mL (5mg/mL PBS prepares, and uses front culture medium to dilute 10 times), continues to hatch 4 hours;
(3) careful suction abandons culture supernatant in hole, and every hole adds 1mL dimethyl sulfoxide, and vibration 10min, makes crystal fully melt;
(4) colorimetric: select 490nm wavelength, enzyme linked immunological monitor measures each hole absorbance value, record result;
(5) with coverslip light absorption value for contrast, calculate adhesion rate;
(6) adhesion rate computational methods: adhesion rate=(control wells light absorption value-test hole light absorption value)/control wells light absorption value × 100%.
IEC-6, NIH3T3 two kinds of cells are cultivated on the Flurbiprofen axetil/polyvinylpyrrolidone/poly lactic-co-glycolic acid composite nano-fiber membrane of different-thickness, then through relevant treatment, MTT colorimetry is utilized to detect, compared with matched group, result showed cell not easily sticks on Flurbiprofen axetil/polyvinylpyrrolidone/poly lactic-co-glycolic acid composite nano-fiber membrane.
Embodiment 5
Medicament Chinese medicine cumulative release effect experimental
Accurately take a certain amount of poly lactic-co-glycolic acid medicament-carrying nano-fiber membrane respectively in 100mL conical flask, add 50mL PBS (pH=7.4) buffer solution, sealing is placed in constant-temperature table, and set temperature is 37 DEG C, and shaking table speed is 100 rpms.Measure 10mL solution at the interval of setting to be measured, in former state, supplement the fresh PBS of 10mL, constancy of volume of keeping intact simultaneously.By the sample solution of taking-up at 246.0nm wavelength, measure absorbance A, and calculated the concentration C of sample solution Chinese medicine by standard curve A=3.95952C+0.02474, calculate its preparation further.
Drug accumulation release formula:
The concentration of C-Flurbiprofen axetil, μ g/mL;
Σ W-sampling accumulation consumes dose, μ g;
The gross weight of m-medicament-carrying nano-fiber membrane, mg;
Drug loading in R-fibrous membrane.
The medicament-carrying nano-fiber membrane envelop rate prepared by coaxial electrostatic spinning technology is all higher, close to 100%, mainly because Flurbiprofen axetil is dissolved in polyvinylpyrrolidonesolution solution by blended method, be downloaded in poly lactic-co-glycolic acid matrix by coaxial electrostatic spinning technology bag again, the loss amount of whole preparation process Chinese medicine is very little; The drug loading of poly lactic-co-glycolic acid based nano-fiber film is mainly subject to the impact of fiber surface porosity comparatively greatly, and when fiber surface porosity increases, in corresponding same time, drug accumulation release rate also can increase.Porogen in fibrous matrix, during content, affect medicament-carrying nano-fiber surface porosity factor and the most important factor of pulp freeness.Porogen consumption increases, and individual fiber surface bore dia increases, and porosity increases, and fibrous membrane specific surface area increases.But porogen consumption is unsuitable, and too much when exceeding certain consumption, place medicine can expose in fiber, and fiber does not only play controllable release to medicine, can produce on the contrary and more serious prominently releasing phenomenon; Otherwise when porogen consumption is less, shorter for the drug effect cycle, the analgesic drug (medicine as contained in this patent) that blood drug level is higher, although can reach controllable release effect, can not play good drug effect.
Claims (10)
1. core/shell structure medicament-carried nano Antiadhesive film, is characterized in that, is made up of the fiber parallel connection of kernel and shell mechanism; Wherein:
Described kernel comprises active component and the polyvinylpyrrolidone (PVP) for the treatment of effective dose;
Described shell is poly lactic-co-glycolic acid (PLGA), and described shell is provided with micropore.
2. controlled superhigh specific surface area core/shell structure medicament-carried nano Antiadhesive film according to claim 1, it is characterized in that, described micropore size is 10 ~ 100 nanometers, and on the shell of every square centimeter, the quantity of micropore is 3 × 10
7~ 5 × 10
7individual.
3. controlled superhigh specific surface area core/shell structure medicament-carried nano Antiadhesive film according to claim 1, it is characterized in that, the weight average molecular weight of described poly lactic-co-glycolic acid is 80000 ~ 100000; Polyvinylpyrrolidone weight average molecular weight is 40000 ~ 55000.
4. controlled superhigh specific surface area core/shell structure medicament-carried nano Antiadhesive film according to claim 2, it is characterized in that, the weight average molecular weight of described poly lactic-co-glycolic acid is 80000 ~ 100000; Polyvinylpyrrolidone weight average molecular weight is 40000 ~ 55000.
5. the controlled superhigh specific surface area core/shell structure medicament-carried nano Antiadhesive film according to any one of Claims 1 to 4, it is characterized in that, described active component is Flurbiprofen axetil, ibuprofen, ketoprofen, indomethacin or diclofenac.
6. controlled superhigh specific surface area core/shell structure medicament-carried nano Antiadhesive film according to claim 5, is characterized in that, with the total weight of active component and polyvinylpyrrolidone, the weight content of Flurbiprofen axetil is 0.1 ~ 0.4%.
7. the controlled superhigh specific surface area core/shell structure medicament-carried nano Antiadhesive film according to any one of Claims 1 to 4, it is characterized in that, the fiber number of described fiber is 0.13 ~ 0.2.
8. the controlled superhigh specific surface area core/shell structure medicament-carried nano Antiadhesive film according to any one of Claims 1 to 4, it is characterized in that, the weight ratio of described polyvinylpyrrolidone and poly lactic-co-glycolic acid is 2:1 ~ 10:1.
9. the preparation method of the controlled superhigh specific surface area core/shell structure medicament-carried nano Antiadhesive film according to any one of claim 1 ~ 8, is characterized in that, comprise the steps:
(1) be dissolved in by poly lactic-co-glycolic acid in dichloromethane (DCM) and DMF (DMF) mixed solvent, then add nanometer dry-ice particle, mixing dispersion, as shell spinning solution;
(2) polyvinylpyrrolidone and active medicine are dissolved in dehydrated alcohol and DMF mixed solvent, stir, dispersion, obtain stratum nucleare spinning solution;
In dehydrated alcohol and DMF mixed solvent, the weight content of polyvinylpyrrolidone is 4 ~ 8%;
(3) in 3 ~ 10 minutes after the preparation of shell spinning solution, at 25 ~ 30 DEG C, by shell spinning solution and stratum nucleare spinning solution, adopt coaxial electrostatic spinning method, obtain composite drug-loaded fiber film material;
(4) the composite drug-loaded fiber film material obtained is put into the vacuum freeze dryer being added with active carbon, by freezing-absorption-sublimed method,-45 ~-55 DEG C of lyophilizations remove dichloromethane, N in 20 hours, dinethylformamide solvent and moisture, vacuum sterilization 4 ~ 8 hours, obtains described controlled superhigh specific surface area core/shell structure medicament-carried nano Antiadhesive film.
10. method according to claim 9, is characterized in that, in step (1), the weight ratio of dichloromethane and DMF is 2:1 ~ 5:1;
With poly lactic-co-glycolic acid, dichloromethane, DMF and nanometer dry-ice particle total weight, the weight content of poly lactic-co-glycolic acid is 8 ~ 12%;
With poly lactic-co-glycolic acid, dichloromethane, DMF and nanometer dry-ice particle total weight, the percentage by weight of nanometer dry-ice particle is 0.1% ~ 5%;
In step (2), the weight ratio of dehydrated alcohol and DMF is 1:1 ~ 3:1.
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| PCT/CN2014/001166 WO2016074115A1 (en) | 2014-11-14 | 2014-12-23 | Drug loaded nano anti-adhering membrane with core/shell structure and preparation method thereof |
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