CN110292570A - A kind of blended medicament-carrying nano-fiber membrane of block polymer and its preparation and application - Google Patents
A kind of blended medicament-carrying nano-fiber membrane of block polymer and its preparation and application Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/26—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/44—Medicaments
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/21—Acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/41—Anti-inflammatory agents, e.g. NSAIDs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
Abstract
The present invention relates to a kind of blended medicament-carrying nano-fiber membrane of block polymer and its preparations and application.The tunica fibrosa is that electrostatic spinning obtains after being dissolved in organic solvent by block polymer P (DEGMA-b-OVNGal), Poly L-lactide-caprolactone PLCL and drug.The preparation method includes: that block polymer P (DEGMA-b-OVNGal) and Poly L-lactide-caprolactone PLCL are dissolved in organic solvent, drug is added, then electrostatic spinning.The nano fibrous membrane can be widely applied for the case where oral cavity dressing, Wound dressing etc. need rapid delivery of pharmaceuticals.
Description
Technical field
The invention belongs to medicament-carrying nano-fiber and its preparation and application field, in particular to a kind of blended load of block polymer
Medicine nano fibrous membrane and its preparation and application.
Background technique
Sugar plays very important role in biosystem, it is related to the identification of various biomolecules.Sugar is introduced
Into polymer, the sugar-containing polymer of various different structures and function can be manually obtained.These have good containing sugar copolymer
Hydrophily and biocompatibility, can be widely applied to field of biomedicine.
Reversible addion-fragmentation chain transfer free radical polymerization (RAFT) method is Rizzardo in the 37th international macromolecule conference
The upper concept for having made to be put forward for the first time in the report of " Tailored polymers by free radical processes ".It will
RAFT method is applied in the synthesis of sugar-containing polymer, can obtain compound with regular structure, the small high polymer of molecular weight dispersion width, can be with
Improve the application performance containing sugar copolymer.
Electrospun nano-fibers mainly overcome surface tension by the electrostatic force of polymer solution, this to charge
Polymer drop forms taylor cone in the showerhead with jet spinning fiber, (concentration of polymer, blended by a series of conditions
Proportion, the size of spinning flow velocity, the size of voltage) optimization, spin the smooth medicament-carrying nano-fiber in controlled diameter, surface, can
Such material is applied to biological medicine (wound dressing) field.
Ketoprofen (Ketoprofen, KET) is the non-steroidal anti-inflammatory drug with benzenpropanoic acid structure, has good town
Bitterly, antipyretic, anti-inflammatory effect has a wide range of applications on clinical treatment.But Ketoprofen has digestive tract side effects, for a long time
Take to stomach stimulate it is larger, the adverse reactions such as ulcer, bleeding can be caused.Therefore, by the method knot of Ketoprofen and electrostatic spinning
It closes, using the controlled release and sustained release of drug, reduces side effect.
Responsive to temperature type controlled drug delivery systems are to make drug specific using responsive to temperature type polymer material as carrier
With certain speed slow release under the conditions of temperature, reach a kind of means more effectively treated to privileged site disease.Utilize drug
Controlled release fertilizer system, can control drug in specific time and privileged site slow release, drug concentration maintain one it is constant
Value, for the big drug of toxicity, can slow down the toxic side effect of drug.For example, one kind of Liu Kailin et al. preparation
The sensitive medicament-carried sustained release nano fiber film of temperature, preparation method include: to be dissolved in N- caprolactam and azodiisobutyronitrile
Poly-N-vinylcaprolactam is obtained in dimethylformamide, it is then that poly-N-vinylcaprolactam and ethyl cellulose EC is molten
Solution in a solvent, is added drug, obtains spinning solution, the tunica fibrosa that spinning solution progress electrostatic spinning is obtained, then is dried, and obtains
To the sensitive medicament-carried sustained release nano fiber film of temperature.The sensitive medicament-carried sustained release nano fiber film of temperature prepared by the invention is used for temperature
Sensitive medicaments control release and slow release system.
Summary of the invention
Technical problem to be solved by the invention is to provide a kind of blended medicament-carrying nano-fiber membrane of block polymer and its systems
Standby and application, with overcome the defect singly spun in the prior art (if only it is single spin block saccharide-based polymer if, it is unfavorable at silk,
When 10% low concentration, hydrophily is strong, not at silk；It when 20% high concentration, does not form a film on aluminium foil receiver).
The present invention provides a kind of blended medicament-carrying nano-fiber membrane of block polymer, the nano fibrous membrane is gathered by block
Electrostatic spinning obtains after conjunction object P (DEGMA-b-OVNGal), Poly L-lactide-caprolactone PLCL and drug are dissolved in organic solvent
It arrives.
The drug is Ketoprofen；Organic solvent are as follows: volume ratio is the methylene chloride and acetone of 1.8-2.1:1.
The present invention also provides a kind of preparation methods of the blended medicament-carrying nano-fiber membrane of block polymer, comprising:
It (1) is 0.9- with mass ratio by block polymer P (DEGMA-b-OVNGal) and Poly L-lactide-caprolactone PLCL
1.2:0.9-1.2 is dissolved in organic solvent, and drug is added, and is stirred to being completely dissolved, is obtained spinning solution, wherein P (DEGMA-
It b-OVNGal is) 0.2-0.5:0.1-0.2 with drug quality ratio, the matter of P (DEGMA-b-OVNGal) and PLCL in spinning solution
Amount concentration is 10%-30%；
(2) spinning solution in step (1) is subjected to electrostatic spinning, optimizes spinning parameter, to obtain that surface is smooth, pattern
It is blended to obtain block polymer after removing the organic solvent on nano fibrous membrane for uniform medicament-carrying nano-fiber membrane, vacuum drying
Medicament-carrying nano-fiber membrane.
Organic solvent in the step (1) are as follows: volume ratio is the methylene chloride and acetone of 1.8-2.1:1；Drug is ketone Lip river
It is fragrant.
Mixing time is 20-30h in the step (1).
The technological parameter of electrostatic spinning in the step (2) are as follows: voltage 12-18KV, flow velocity 0.15-0.25mL/h,
Receiving distance is 10-20cm, and local environment temperature is 25 DEG C, humidity 55-75%, and the spinning time is 5-10h.
Vacuum drying time is for 24 hours in the step (2).
The present invention also provides a kind of application of nano fibrous membrane in biological medicine.Such as it is controlled for temperature sensitive drug
In delivery systme.
Beneficial effect
(1) method that the present invention uses electrostatic spinning, is prepared for the sensitive medicament-carried sustained release nano fiber film of temperature, preparation method
Operate that easy, experiment condition is mild.
(2) nano fibrous membrane for preparing in the present invention, by be loaded into Ketoprofen drug can be widely applied for oral cavity dressing,
The case where Wound dressing etc. needs rapid delivery of pharmaceuticals.
Detailed description of the invention
Fig. 1 is that block polymer P (DEGMA-b-OVNGal)/blended medicament-carrying nano-fiber membrane of PLCL is swept in embodiment 3
Retouch electron microscope and diameter distribution profile.
Fig. 2 is the synthetic route chart of P (DEGMA-b-OVNGal) in embodiment 1.
Fig. 3 is the FT-IR figure of the P (DEGMA-b-OVNGal) and raw material that prepare in embodiment 1.
Fig. 4 is the P (DEGMA-b-OVNGal) prepared in embodiment 1 and raw material1H NMR spectra.
Fig. 5 is block polymer P (DEGMA-b-OVNGal)/PLCL blended nano fibrous membrane scanning electricity in embodiment 2
Mirror figure (b) is 15% blended spinning solution, is (c) 20% blended spinning solution, (d) is wherein (a) is 10% blended spinning solution
30% blended spinning solution.
Fig. 6 is block polymer P (DEGMA-b-OVNGal)/PLCL blended nano fibrous membrane diameter point in embodiment 2
Butut (b) is 15% blended spinning solution, is (c) 20% blended spinning solution, (d) is wherein (a) is 10% blended spinning solution
30% blended spinning solution.
Fig. 7 is block polymer P (DEGMA-b-OVNGal)/blended nano fibrous membrane of PLCL in embodiment 2 at 37 DEG C
Contact angle test analysis chart (b) be 15% blended spinning solution, (c) be 20% blended wherein (a) is 10% blended spinning solution
Spinning solution (d) is 30% blended spinning solution.
Fig. 8 be embodiment 3 in block polymer P (DEGMA-b-OVNGal)/blended medicament-carrying nano-fiber membrane of PLCL and
Block polymer P (DEGMA-b-OVNGal)/PLCL blended nano fibrous membrane FT-IR figure.
Fig. 9 is block polymer P (DEGMA-b-OVNGal)/blended medicament-carrying nano-fiber membrane of PLCL in embodiment 3 37
Contact angle test analysis chart at DEG C.
Figure 10 is block polymer P (DEGMA-b-OVNGal)/PLCL blended medicament-carrying nano-fiber membrane medicine in embodiment 4
Object release figure.
Figure 11 is the drug release profiles of the sensitive medicament-carried sustained release nano fiber film of temperature in comparative example 1.
Specific embodiment
Present invention will be further explained below with reference to specific examples.It should be understood that these embodiments are merely to illustrate the present invention
Rather than it limits the scope of the invention.In addition, it should also be understood that, after reading the content taught by the present invention, those skilled in the art
Member can make various changes or modifications the present invention, and such equivalent forms equally fall within the application the appended claims and limited
Range.
Vinyl acetate, mercuric acetate, copper acetate, bacillus subtilis property protease, pyridine, adipic acid, the concentrated sulfuric acid are anhydrous
Sodium acetate, petroleum ether, ethyl acetate, n-hexane are purchased from Sinopharm Chemical Reagent Co., Ltd.；Con A, RCA120, cow's serum
Albumen (BSA), S- dodecyl-S'- (2- carboxyl-isopropyl) three thioesters (DDATC), 2- methyl -2- acrylic acid -2- (2- first
Oxygroup ethyoxyl) ethyl ester (DEGMA), it is purchased from Sigma-Aldrich, the U.S.；N,N-Dimethylformamide (DMF), grape
Sugar is purchased from Aladdin biochemical technology Co., Ltd (Chinese Shanghai).
Embodiment 1
By vinyl adipic acid gala sugar ester (OVNGal) and (the preparation side poly- diethylene glycol dimethacrylate (PDEGMA)
Method: monomer DEGMA (1.8 × 10 is weighed-2Mol, 3.39g), chain-transferring agent CMPCD (1.8 × 10-4Mol, 40.2mg), initiator
AIBN(3.6×10-5Mol, 6.3mg) it is dissolved completely in the DMF of 6mL, it is put into magnetic stir bar, seals reaction dress with sealed membrane
It sets, is removed to vacuumize after air in reaction unit with frozen-thawed and pour nitrogen again, in 70 DEG C of perseverances after repeating aforesaid operations three times
1h is reacted in warm oil bath pan, terminates reaction with ice water is cooling after reaction.By reaction solution with n-hexane precipitate three times, to just oneself
After alkane volatilization completely, drying in vacuum oven is put it into, products therefrom is that faint yellow colloid substance is macromolecular RAFT
Reagent PDEGMA) it is in molar ratio 50:1, i.e., the N that OVNGal 0.1535g and PDEGMA 0.3017g are dissolved in 1mL is weighed respectively,
In dinethylformamide (DMF), under temperature 70 C, initiator azodiisobutyronitrile AIBN 0.35mg is added, is protected in nitrogen
It is stirred to react 48h under shield, obtains P (DEGMA-b-OVNGal).The preparation flow figure of block is as shown in Figure 2.
Fig. 3 and Fig. 4 shows that P (DEGMA-b-OVNGal) is successfully prepared.(PDEGMA-TfOH is macromolecular RAFT in Fig. 3
Reagent PDEGMA, when synthesizing RAFT reagent, the purpose that trimethyl sulfonic acid is added is in order to allow CMPCD to protonate, to improve
The yield of PDEGMA)
Embodiment 2
The configuration of (1) 10% blended spinning solution:
Weigh respectively above-mentioned P (DEGMA-b-OVNGal) 0.4140g and PLCL0.4140g (P (DEGMA-b-OVNGal):
PLCL=1:1, g/g), it makes it completely dissolved in the organic solvent of 8.28mL, solvent is methylene chloride: acetone (2:1, mL/
ML), it is made into the spinning solution of mass concentration 10%.Ultrasonic 15min, subsequent degassifying processing.
The configuration of 15% blended spinning solution:
Above-mentioned P (DEGMA-b-OVNGal) 0.15g and PLCL 0.15g (P (DEGMA-b-OVNGal): PLCL is weighed respectively
=1:1, g/g), make it completely dissolved in the organic solvent of 2mL, solvent is methylene chloride: acetone (2:1, mL/mL) is made into
The spinning solution of mass concentration 15%.
The configuration of 20% blended spinning solution:
Weigh respectively above-mentioned P (DEGMA-b-OVNGal) 0.222g and PLCL0.222g (P (DEGMA-b-OVNGal):
PLCL=1:1, g/g), it makes it completely dissolved in the organic solvent of 2.2mL, solvent is methylene chloride: acetone (2:1, mL/
ML), it is made into the spinning solution of mass concentration 20%.
The configuration of 30% blended spinning solution:
Above-mentioned P (DEGMA-b-OVNGal) 0.3g and PLCL0.3g (P (DEGMA-b-OVNGal): PLCL=is weighed respectively
1:1, g/g), make it completely dissolved in the organic solvent of 2.0mL, solvent is methylene chloride: acetone (2:1, mL/mL) is made into
The spinning solution of mass concentration 30%.
(2) spinning solution of configured 4 kinds of concentration is respectively pivoted in electrostatic spinning apparatus, reconciles spinning parameter and carries out electricity
It spins, ejection flow velocity is 0.2mL/h, electrostatic pressure 15KV, and receiving distance is 15cm, and local environment temperature is 25 DEG C, and humidity exists
65% or so, the spinning time is 5h；The tunica fibrosa being collected into is put into vacuum oven air drying for 24 hours, obtains 4 kinds of various concentrations
Block polymer P (DEGMA-b-OVNGal)/blended nano fibrous membrane of PLCL.
Block polymer P (DEGMA-b-OVNGal)/PLCL blended nano fibrous membrane scanning electron microscope (SEM) photograph in the present embodiment
As shown in figure 5, it can be observed that fiber is in net distribution, the phenomenon that without obvious adhesion, illustrate to be added nanometer after drug Ketoprofen
The diameter of spinning fibre obviously attenuates.
Fig. 6 is the scanning electron microscope (SEM) photograph by medicament-carrying nano-fiber membrane, counts fiber diameter distribution profile with Image J, from
It can be observed that normal distribution is presented in the distribution map in figure, illustrate that the diameter of preparation-obtained nano fibrous membrane is relatively stable,
But plucked is smaller, by comparison, selects 10% block polymer P (DEGMA-b-OVNGal)/PLCL blended, goes forward side by side
Row carries medicine electrospinning.
From Fig. 7 it is observed that gradually rising with concentration of dope, the hydrophobicity of tunica fibrosa can enhance accordingly.
Embodiment 3
(1) 0.1360g Ketoprofen is added into 10% blended solution of above-mentioned configuration and makes it completely dissolved, is stirred with magnetic force
Device stirring is mixed for 24 hours, until being uniformly mixed.
(2) configured spinning solution 8.28mL is attached in electrostatic spinning apparatus, reconciles spinning parameter and carry out electrospinning, sprays
Flow velocity is 0.2mL/h, electrostatic pressure 15KV, and receiving distance is 15cm, and local environment temperature is 25 DEG C, humidity 65% or so,
The spinning time is 5h；The tunica fibrosa being collected into is put into vacuum oven air drying for 24 hours, obtains block polymer P (DEGMA-b-
OVNGal the blended medicament-carrying nano-fiber membrane of)/PLCL.
Block polymer P (DEGMA-b-OVNGal)/PLCL blended medicament-carrying nano-fiber membrane scanning electricity in the present embodiment
Mirror figure SEM and diameter distribution profile the phenomenon that without obvious adhesion, illustrates to add as shown in Figure 1, it can be observed that fiber is in net distribution
Enter after drug Ketoprofen and P (DEGMA-b-OVNGal)/PLCL is still spinnable.Pass through the scanning electricity of medicament-carrying nano-fiber membrane
Mirror figure counts fiber diameter distribution profile with Image J, and normal distribution, explanation is presented in the distribution map as can be observed from Figure
The diameter of preparation-obtained nano fibrous membrane is relatively stable, but plucked is smaller, and its average diameter is 3.338 μm.
Block polymer P (DEGMA-b-OVNGal)/PLCL blended medicament-carrying nano-fiber membrane infrared light in the present embodiment
Spectrogram as shown in figure 8,1 × 1cm of clip tunica fibrosa, carry out Fourier transform infrared spectroscopy test.As can be observed from Figure
There is a peak at 1660cm-1 in nanofiber after carrying medicine, is determined that this is C=in the R-CO- (C6H5) for leading position to replace
Thus the peak that O stretching vibration generates proves that Ketoprofen is already loaded into fiber.
Block polymer P (DEGMA-b-OVNGal)/blended medicament-carrying nano-fiber membrane of PLCL is at 37 DEG C in the present embodiment
Contact angle test analysis chart it is as shown in Figure 9.Contact angle is 95.85 ° after carrying medicine as can be observed from Figure, it is known that nanofiber
Hydrophily reduces after phase transition.
Embodiment 4
The PBS buffer solution for taking medicament-carrying nano-fiber membrane immersion 10mL in 0.5g embodiment 3, is placed in SHZ-82 gas bath constant temperature and shakes
In bed, parameter is respectively set to 37 DEG C and 25 DEG C, and speed is 100 times/min.1mL dissolution medium is taken out at regular intervals, together
When fill into the PBS buffer solution of same volume.Using UV-1800 ultraviolet-uisible spectrophotometer measurement dissolution medium in 254nm
Absorbance and calculate drug Cumulative release amount.Drug release patterns are as shown in Figure 10, as can be observed from Figure in difference
Temperature under the conditions of, the release rate of Ketoprofen is very different, when temperature is 25 DEG C, the rate of release of drug compared with
Fastly, 12 hours when preparation reach 83.29% or so, and when temperature is 37 DEG C, the rate of release of drug is slower,
Preparation only has 64.96% at 12 hours, this is because the performance that temperature sensitive monomer is presented under condition of different temperatures is different,
Drug is caused to discharge difference from material.
Comparative example 1
The N- caprolactam monomer of 1.01g and 1mg azodiisobutyronitrile will be dissolved in the dimethylformamide of 1mL
In, it is precipitated after reacting 8h in the lower 70 DEG C of oil baths of nitrogen environment with anhydrous ether, obtains poly-N-vinylcaprolactam.Then day is used
The EC solid powder of the flat poly-N-vinylcaprolactam for weighing 0.499g and 0.501g, makes it completely dissolved in the anhydrous second of 4mL
In alcohol, 0.05g Ketoprofen is added and makes it completely dissolved, obtains spinning until being uniformly mixed with magnetic stirrer 48h
Configured spinning solution 4mL is attached in electrostatic spinning apparatus by liquid, is adjusted spinning parameter and is carried out electrospinning, is sprayed flow velocity and is
0.3mL/h, electrostatic pressure 13kV, receiving distance is 15cm, and local environment temperature is 25 DEG C, humidity 40-50%, the spinning time
For 5h；The tunica fibrosa being collected into is put into air drying in vacuum oven and for 24 hours, obtains the sensitive medicament-carried sustained release nano fiber of temperature
Film.The sensitive medicament-carried sustained release nano fiber film of prepared temperature is for temperature sensitive drug control release and slow release system.
Shown in the data such as 11 that release the drug are lower.
Medicament-carrying nano-fiber membrane system compares in Figure 11 and Figure 10: block polymer of the present invention with caprolactone is blended carries again
Ketoprofen drug, obtained medicament-carrying nano-fiber membrane, drug has discharged substantially when 12h or so to be terminated.And this is right
Poly-N-vinylcaprolactam and ethyl cellulose EC dissolve obtained medicament-carrying nano-fiber membrane in a solvent in ratio, from figure
In it can be observed that under the conditions of different temperature, the release rate of Ketoprofen is very different, when temperature is 25 DEG C,
The rate of release of drug is very fast, and preparation reaches 55% or so at 60 hours, and when temperature is 37 DEG C, drug
Rate of release is slower, and preparation only has 20% at 60 hours, this is because poly-N-vinylcaprolactam is in different temperatures
Under the conditions of the performance that presents it is different, cause drug different from the release in material.
Claims (7)
1. a kind of blended medicament-carrying nano-fiber membrane of block polymer, which is characterized in that the nano fibrous membrane is by block polymerization
Electrostatic spinning obtains after object P (DEGMA-b-OVNGal), Poly L-lactide-caprolactone PLCL and drug are dissolved in organic solvent.
2. nano fibrous membrane according to claim 1, which is characterized in that the drug is Ketoprofen；Organic solvent are as follows: volume
Than the methylene chloride and acetone for 1.8-2.1:1.
3. a kind of preparation method of the blended medicament-carrying nano-fiber membrane of block polymer, comprising:
(1) it is 0.9-1.2 with mass ratio by block polymer P (DEGMA-b-OVNGal) and Poly L-lactide-caprolactone PLCL:
0.9-1.2 is dissolved in organic solvent, and drug is added, and is stirred to being completely dissolved, is obtained spinning solution, wherein P (DEGMA-b-
It OVNGal is) 0.2-0.5:0.1-0.2 with the mass ratio of drug, the matter of P (DEGMA-b-OVNGal) and PLCL in spinning solution
Amount concentration is 10%-30%；
(2) spinning solution in step (1) is subjected to electrostatic spinning, it is fine to obtain the blended medicament-carried nano of block polymer for vacuum drying
Tie up film.
4. method according to claim 3, which is characterized in that organic solvent in the step (1) are as follows: volume ratio 1.8-
The methylene chloride and acetone of 2.1:1；Drug is Ketoprofen.
5. method according to claim 3, which is characterized in that mixing time is 20-30h in the step (1).
6. method according to claim 3, which is characterized in that the technological parameter of electrostatic spinning in the step (2) are as follows: voltage
For 12-18KV, flow velocity 0.15-0.25mL/h, receiving distance is 10-20cm, and local environment temperature is 25 DEG C, humidity 55-
75%, the spinning time is 5-10h.
7. a kind of application of nano fibrous membrane as described in claim 1 in biological medicine.
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| CN201910540396.1A Active CN110292570B (en) | 2019-06-21 | 2019-06-21 | Block polymer blended drug-loaded nanofiber membrane and preparation and application thereof |
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| US20030147954A1 (en) * | 2002-02-01 | 2003-08-07 | Pacific Corporation | Cyclosporin-containing sustained release pharmaceutical composition |
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| US20030147954A1 (en) * | 2002-02-01 | 2003-08-07 | Pacific Corporation | Cyclosporin-containing sustained release pharmaceutical composition |
| CN104761694A (en) * | 2015-04-15 | 2015-07-08 | 东华大学 | Method for synthesizing galactose block copolymer employing RAFT (reversible addition fragmentation chain transfer) method |
| CN107773528A (en) * | 2016-08-24 | 2018-03-09 | 南京星银药业集团有限公司 | A kind of acetic acid Ac-D-2Nal-D-4Cpa-D-3Pal-Ser-4Aph(Hor)-D-4Aph(Cbm)-Leu-Lys(iPr)-Pro-D-Ala-NH2 injection-type sustained-release implant |
| CN107536827A (en) * | 2017-08-03 | 2018-01-05 | 东华大学 | A kind of sensitive medicament-carried sustained release nano fiber film of temperature and its preparation method and application |
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| YONGLI ZHENG ET AL.: ""AuNSs@Glycopolymer-ConA hybrid nanoplatform for photothermal therapy of hepatoma cells"", 《CHEMICAL ENGINEERING JOURNAL》 * |
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