CN103599090A - Multi-layer drug sustain-release nano fiber membrane and preparation method thereof - Google Patents
Multi-layer drug sustain-release nano fiber membrane and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a multi-layer drug sustain-release nano fiber membrane and a preparation method thereof. The inner layer and outer layer of the multi-layer membrane are both composed of a polymer A nano fiber with a good biological compatibility, and the middle layer is a drug-carrying nano fiber which is prepared by blending curcumin (CM) and a polymer B with a good biological compatibility. The preparation method comprises the following steps: dissolving the polymer A into a solvent, subjecting the polymer A to an electrostatic spinning process so as to prepare the inner layer, then subjecting a mixed solution of the polymer B and CM to an electrostatic spinning process, continuously depositing the mixed solution on the inner layer so as to obtain the middle layer, finally subjecting the polymer A to an electrostatic spinning process for a second time, and continuously depositing the polymer A on the middle layer so as to obtain the outer layer. The membrane preparation method is simple, can effectively relieve the burst release phenomenon in the early release stage, and can control the drug release by changing the thickness of the polymer A. Taking polymer A-polylactic acid (PLA), and polymer B-cellulose acetate (CA) as an example, the in vitro drug release test results have shown that the drug release rate of the multi-layer drug-carrying membrane is both less than that of a single layer drug loaded membrane no matter after 1 hour or after 240 hours.
Description
Technical field
The present invention relates to medical release membranes and preparation method thereof, be specifically related to support a kind of multilayer medicine sustained release nano fiber film of antibacterial, anticoagulation medicine curcumin (CM) and preparation method thereof.
Background technology
Adopt electrostatic spinning technique to prepare medicament-carrying nano-fiber, device is simple, cost is lower, prepared nanofiber diameter is little, porosity is high, specific surface area is large, can greatly improve the bioavailability of medicine, meanwhile, the pharmaceutical dosage form of fiber shape, also has good physical strength and processing characteristics.Polymer is dissolved together with medicine and make homogeneous solution in the same way; in spinning process, make medicine be dispersed in nanofiber; can protect medicine by gastric acid and enzyme, not corroded degraded in entering human body process; thereby effectively avoided the degeneration of active constituents of medicine to lose efficacy; improved the stability of medicine; and action time that can prolong drug, improve bioavailability.Multilayer medicine sustained release nano fiber, can prolong drug diffusion length, can effectively improve the drug release initial stage and prominently release phenomenon, and expand the research range of drug delivery system.
CM is a kind of beta-diketon polyphenol compound extracting from zingiberaceous plant Rhizoma Curcumae Longae.CM is used as flavorant always to be used, and it is also one of important medical material of ayurvedic medicine simultaneously, and it can be antibacterial, antiplatelet aggregation, antitumor etc., because CM toxic and side effects is little, obtain easily, cheap, taking convenience, so have broad application prospects in clinical practice, yet the research of many pharmacokinetics shows, the oral bioavailability of CM is very low, after oral, with original shape, with feces, excrete approximately 89%, with urine, excrete on a small quantity.Cause the reason of low bioavailability affected by the water insoluble and labile character of CM.Therefore,, although the effect of CM is very wide, its clinical practice is seriously limited by its lower bioavailability, has hindered greatly its development prospect.
At present, to carrying the research of the preparation method of CM nano controlled-release system, almost do not carry out both at home and abroad, rarely seen have foreign patent that CM is made to slow release aerosol for anti-inflammatory therapy, use degradable polymer to wrap up for therapeutic field of tumor CM with domestic patent, about the preparation method of CM multilayer medicine sustained release nano fiber film, have not yet to see report.
Summary of the invention
The object of the invention is to propose a kind of preparation method of the multilayer medicine sustained release nano fiber film based on electrostatic spinning.For the water insoluble and labile defect of CM, by being wrapped in, CM in intermediate layer polymer, makes medicament-carrying nano-fiber, thereby improve the hydrophobic property of CM, extend the action time of CM, improve the bioavailability of CM, multiple structure has extended the diffusion length of medicine, has improved the prominent phenomenon of releasing of drug release initial stage and also can control slow releasing pharmaceutical by changing ectonexine polymer thickness.
For achieving the above object, technical scheme of the present invention is a kind of multilayer medicine sustained release nano fiber film, the inside and outside layer of described multilayer film is polymer A nanofiber, the intermediate layer of described multilayer film is the medicament-carrying nano-fiber that CM and polymer B form, and the structure of described multilayer film is followed successively by internal layer, intermediate layer, skin from inside to outside.
For the ease of preparing described multilayer medicine sustained release nano fiber film, further preferred technical scheme is that described nanofiber layer is to make with electrostatic spinning mode layering successive sedimentation.
In order to improve preferably prominent phenomenon the effective control slow releasing pharmaceutical released of drug release initial stage, further preferred technical scheme also has, and described polymer A and polymer B are the mixture of one or more materials of polylactic acid, cellulose acetate, fibroin, chitosan, gelatin, hyaluronic acid, sodium alginate.
For achieving the above object, another technical scheme of the present invention is the preparation method of a kind of multilayer medicine sustained release nano fiber film of design, and described preparation method comprises the following steps:
Step 1, polymer A is dissolved in solvent, prepares inside and outside layer spinning liquid, CM and polymer B are dissolved in solvent, preparation intermediate layer medicine carrying spinning liquid;
Step 2, by internal layer spinning liquid electrostatic spinning, make internal layer nanofiber, then by medicine carrying spinning liquid electrostatic spinning, successive sedimentation makes intermediate layer nanofiber on internal layer, finally, then by outer spinning liquid electrostatic spinning, successive sedimentation makes outer nanofiber on intermediate layer.
For the ease of preparing described multilayer medicine sustained release nano fiber film, preferred technical scheme is, polymer A described in step 1 is polylactic acid (PLA), and polymer B is cellulose acetate (CA), and described solvent is acetone, dichloromethane, dimethyl acetylamide, dimethyl formamide.
In order to realize better the sustained release performance of multilayer film, further preferably technical scheme is, described CM concentration is 10%～30% (w/w), and described PLA layer nanofiber diameter is 500～700nm, and described medicament-carrying nano-fiber diameter is 500～600nm.
Medicament-carrying nano-fiber prepared by the present invention is shaped good, even thickness, and smooth surface, does not have beading, and fiber is evenly distributed and is non-weaving cloth shape in all directions, can be used as slow-release fiber.Tablets in vitro experiment shows, multilayer medicine sustained release nano fiber film sustained release 10d in phosphate buffer that the present invention is prepared, the release rate of 1h is up to 2.7%, after 240h, drug release rate is up to 55.9%, and single layer structure medicine carrying membrane 1h release rate is 9.4%, after 240h, drug release rate is 58.8%.This preparation method is simple and practical, and introduced a kind of newtype drug transmission system (DDS), multilayer medicine sustained release nano fiber film can effectively improve the prominent phenomenon of releasing of drug release initial stage, and can significantly extend action time of curcumin, thereby greatly improve the bioavailability of curcumin, can control slow releasing pharmaceutical by changing PLA layer thickness.Meanwhile, adopt the preparation method of curcumin multilayer medicine sustained release nano fiber of the present invention, widened the research range of drug delivery system (DDS).
Accompanying drawing explanation
The compound schematic diagram of Fig. 1 curcumin multilayer medicine sustained release nano fiber film.
Fig. 2 CA supports CM medicament-carrying nano-fiber scanning electron microscope (SEM) photograph (* 10000).
The specific embodiment
Below in conjunction with accompanying drawing and embodiment, the specific embodiment of the present invention is further described.Following examples are only for technical scheme of the present invention is more clearly described, and can not limit the scope of the invention with this.
Embodiment 1
(1) load weighted CA, CM are dissolved in the mixed solvent of acetone and dimethyl acetylamide (volume ratio 3: 2), being mixed with CA concentration is 13%, CM concentration is the medicine carrying spinning liquid of 10%～30% (w/w), load weighted PLA is dissolved in the mixed solvent of dichloromethane and dimethyl formamide (volume ratio 7: 3), is mixed with PLA concentration and is 8% spinning liquid.
(2) PLA spinning liquid is injected in the syringe of electrostatic spinning apparatus, is fixed on micro-injection pump, adopt dull and stereotyped collecting method, setting time of reception is 2h, technological parameter is, voltage 18kV, flow velocity 1.0ml/h, apart from 17cm, obtain ground floor PLA nanofiber, i.e. orlop in Fig. 1.
(3), after having spun ground floor, according to the method for (2), in like manner then medicine carrying spinning liquid is proceeded to electrostatic spinning, setting time of reception is 18h, and technological parameter is 18kV, flow velocity 0.5ml/h, distance is 16cm, obtains second layer medicament-carrying nano-fiber, i.e. intermediate layer in Fig. 1.
(4) after having spun the second layer, repeat (2), obtain the 3rd layer of PLA nanofiber ，Ji Tu1Zhong the superiors.
Result shows, by SEM, scheme to observe, Photoshop CS4 software measurement, PLA nanofiber diameter is 500～700nm, CA medicament-carrying nano-fiber is shaped good, even thickness, smooth surface, does not have beading, and fiber is evenly distributed and is non-weaving cloth shape in all directions, can be used as slow-release fiber, fibre diameter is 500～600nm.Tablets in vitro experiment shows, multilayer medicine sustained release nano fiber film sustained release 10d in phosphate buffer, and the release rate of 1h is 2.7%, after 240h, drug release rate is 55.9%, and single layer structure medicine carrying membrane 1h release rate is 9.4%, after 240h, drug release rate is 58.8%.
Embodiment 2
(1) load weighted CA, CM are dissolved in the mixed solvent of acetone and dimethyl acetylamide (volume ratio 3: 2), being mixed with CA concentration is 13%, CM concentration is the medicine carrying spinning liquid of 10%～30% (w/w), load weighted PLA is dissolved in the mixed solvent of dichloromethane and dimethyl formamide (volume ratio 7: 3), is mixed with PLA concentration and is 8% spinning liquid.
(2) PLA spinning liquid is injected in the syringe of electrostatic spinning apparatus, is fixed on micro-injection pump, adopt dull and stereotyped collecting method, setting time of reception is 5h, and technological parameter is, voltage 18kV, flow velocity 1.0ml/h, apart from 17cm, obtains ground floor PLA nanofiber.
(3) after having spun ground floor, according to the method for (2), in like manner then medicine carrying spinning liquid is proceeded to electrostatic spinning, setting time of reception is 18h, and technological parameter is 18kV, flow velocity 0.5ml/h, and distance is 16cm, obtains second layer medicament-carrying nano-fiber.
(4) after having spun the second layer, repeat (2), obtain the 3rd layer of PLA nanofiber.
Result shows, by SEM, scheme to observe, Photoshop CS4 software measurement, PLA nanofiber diameter is 500～700nm, CA medicament-carrying nano-fiber is shaped good, even thickness, smooth surface, does not have beading, and fiber is evenly distributed and is non-weaving cloth shape in all directions, can be used as slow-release fiber, fibre diameter is 500～600nm.Tablets in vitro experiment shows, multilayer medicine sustained release nano fiber film sustained release 10d in phosphate buffer, and the release rate of 1h is 2.4%, after 240h, drug release rate is 53.1%, and single layer structure medicine carrying membrane 1h release rate is 9.4%, after 240h, drug release rate is 58.8%.
Embodiment 3
(1) load weighted CA, CM are dissolved in the mixed solvent of acetone and dimethyl acetylamide (volume ratio 3: 2), being mixed with CA concentration is 13%, CM concentration is the medicine carrying spinning liquid of 10%～30% (w/w), load weighted PLA is dissolved in the mixed solvent of dichloromethane and dimethyl formamide (volume ratio 7: 3), is mixed with PLA concentration and is 8% spinning liquid.
(2) PLA spinning liquid is injected in the syringe of electrostatic spinning apparatus, is fixed on micro-injection pump, adopt dull and stereotyped collecting method, setting time of reception is 7h, and technological parameter is, voltage 18kV, flow velocity 1.0ml/h, apart from 17cm, obtains ground floor PLA nanofiber.
(3) after having spun ground floor, according to the method for (2), in like manner then medicine carrying spinning liquid is proceeded to electrostatic spinning, setting time of reception is 18h, and technological parameter is 18kV, flow velocity 0.5ml/h, and distance is 16cm, obtains second layer medicament-carrying nano-fiber.
(4) after having spun the second layer, repeat (2), obtain the 3rd layer of PLA nanofiber.
Result shows, by SEM, scheme to observe, Photoshop CS4 software measurement, PLA nanofiber diameter is 500～700nm, CA medicament-carrying nano-fiber is shaped good, even thickness, smooth surface, does not have beading, and fiber is evenly distributed and is non-weaving cloth shape in all directions, can be used as slow-release fiber, fibre diameter is 500～600nm.Tablets in vitro experiment shows, multilayer medicine sustained release nano fiber film sustained release 10d in phosphate buffer, and the release rate of 1h is 2.2%, after 240h, drug release rate is 50.8%, and single layer structure medicine carrying membrane 1h release rate is 9.4%, after 240h, drug release rate is 58.8%.
The above is only the preferred embodiment of the present invention; it should be pointed out that for those skilled in the art, do not departing under the prerequisite of the technology of the present invention principle; can also make some improvements and modifications, these improvements and modifications also should be considered as protection scope of the present invention.
Claims (7)
1. a multilayer medicine sustained release nano fiber film, it is characterized in that, the inside and outside layer of described multilayer film is polymer A nanofiber, the intermediate layer of described multilayer film is the medicament-carrying nano-fiber that medicine curcumin (CM) and polymer B form, this multilayer film is followed successively by polymer A nanofiber from inside to outside, medicament-carrying nano-fiber, polymer A nanofiber.
2. multilayer medicine sustained release nano fiber film as claimed in claim 1, is characterized in that, described ectonexine is the polymer nanofiber that biocompatibility is good, and described intermediate layer is the good polymer drug-carried nanofiber of biocompatibility that has supported CM.
3. multilayer medicine sustained release nano fiber film as claimed in claim 2, is characterized in that, described multilayer film is that nanofiber is made with electrostatic spinning mode layering successive sedimentation.
4. multilayer medicine sustained release nano fiber film as claimed in claim 3, is characterized in that, described polymer A and polymer B are the mixture of one or more materials of polylactic acid, cellulose acetate, fibroin, chitosan, gelatin, hyaluronic acid, sodium alginate.
5. a method of preparing multilayer medicine sustained release nano fiber film as claimed in claim 1, is characterized in that, this preparation method comprises the following steps:
Step 1, polymer A is dissolved in solvent, prepares inside and outside layer spinning liquid, medicine and polymer B are dissolved in solvent, preparation intermediate layer medicine carrying spinning liquid;
Step 2, by internal layer spinning liquid electrostatic spinning, make internal layer nanofiber, then by medicine carrying spinning liquid electrostatic spinning, successive sedimentation makes intermediate layer nanofiber on internal layer, finally, then by outer spinning liquid electrostatic spinning, successive sedimentation makes outer nanofiber on intermediate layer.
6. the method for preparing multilayer medicine sustained release nano fiber film as claimed in claim 5, it is characterized in that, polymer A described in step 1 is polylactic acid (PLA), polymer B is cellulose acetate (CA), and described solvent is acetone, dichloromethane, dimethyl acetylamide, dimethyl formamide.
7. the method for preparing multilayer medicine sustained release nano fiber film as claimed in claim 5, it is characterized in that, described CM concentration is 10%～30% (w/w), and described PLA layer nanofiber diameter is 500～700nm, and described medicament-carrying nano-fiber diameter is 500～600nm.
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| CN104029443A (en) * | 2014-05-28 | 2014-09-10 | 中原工学院 | Method for preparing polylactic acid multilayer fiber membrane for PM2.5 protecting mask |
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| CN105040137A (en) * | 2015-06-08 | 2015-11-11 | 浪莎针织有限公司 | Method for preparing curcumin-loaded polyacrylonitrile fiber by dope dyeing method |
| CN105908363A (en) * | 2016-05-12 | 2016-08-31 | 华南农业大学 | Static spraying composite film and preparation method and application thereof |
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| CN114376795A (en) * | 2021-12-17 | 2022-04-22 | 淮阴工学院 | Heterostructure composite double-layer porous dressing with electro-drug release characteristic and preparation method thereof |
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