CN102475920A - Preparation method and application of sustained-release system of anti-inflammatory medicament and growth factor - Google Patents
Preparation method and application of sustained-release system of anti-inflammatory medicament and growth factor Download PDFInfo
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- CN102475920A CN102475920A CN2010105527427A CN201010552742A CN102475920A CN 102475920 A CN102475920 A CN 102475920A CN 2010105527427 A CN2010105527427 A CN 2010105527427A CN 201010552742 A CN201010552742 A CN 201010552742A CN 102475920 A CN102475920 A CN 102475920A
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Abstract
The invention belongs to the technical field of biomedical materials, and particularly relates to a preparation method and an application of a sustained-release system of anti-inflammatory medicaments and growth factors; a nanofiber drug loaded film prepared by the method is applicable to postoperative adhesion prevention and inflammation resistance, and skin tissue engineering stents. As a postoperative adhesion preventing film, the product has biodegradability and good biocompatibility, and can prevent postoperative inflammatory response through the controlled release of anti-inflammatory medicaments; meanwhile, through the combination of the medicaments with growth factors, the product can be used in skin tissue engineering, not only prevents inflammatory response at affected sites, but also releases growth factors to promote the regeneration and healing of skin cells. The nanofiber drug loaded film preparation method has a simple process and good controllability, and has wide application prospects in the fields of postoperative adhesion prevention and inflammation resistance, as well as skin tissue engineering.
Description
Technical field
The invention belongs to technical field of biomedical materials, be specifically related to a kind of medicine and growth factor slow-release system that is used for post-operation adhesion preventing or skin tissue recovering.
Background technology
The extensive use in the medical science in modern times of macromolecular material and complex thereof, and the polymer that biodegradable absorbs is one of present comparatively ideal biological medical polymer material.But the electricity spinning is the new technique of a kind of simple and effective ground preparation nanofiber, and it is through applying high electric field generation injection stream to polymer solution or solution, and solvent evaporates when jet is stretched forms the fiber of diameter at 3-5000nm.Electricity spinning fibre has particularly been obtained plurality of applications in the bio-medical field in field of functional materials, applies section, operation isolating membrane etc. like tissue engineering bracket, wound.And in the medicament slow release field, electric spining technology also has potential application prospect.
Tissue adhesion is that one of unsolved important topic has still been arranged since the history of operation both at home and abroad, and there are nearly various types of operation cases of ten million in the whole nation every year, and nearly all operation all relates to anti and local anti-inflammatory problem between the tissue.The transparent fat acid that uses is clinically at present received and is existed purity not high with chitin glue, and preventing adhesiving effect is poor, no local anti-inflammatory disease effect etc., and application surface is very narrow.Past only limits to abdominal operation adhesion inhibiting properties intestinal obstruction in the research of prevention of postoperative adhesion, once used the built-in silicone oil in abdominal cavity, methods such as medium molecular dextran and streptokinase, but all do not have positive effect.Simultaneously, because post-operation inflammatory can cause multiple complications, therefore the generation of prevention of inflammation reaction also is an important technology index of anti in anti.
The human skin tissue reparation need have highly upgrades regenerated ability, and having active non-mature cell in the surrounding health tissue can form new tissue along support, adds the regeneration that somatomedin can promote new skin histology greatly.Existing report shows that (basic fibroblast growth factor bFGF) has extremely strong BA to basic fibroblast growth factor; Can promote the wound surface angiogenesis; The nutritional status of microcirculation improvement and tissue can stimulate fibroblast and myoblastic division and propagation simultaneously effectively, improves the anti-infection ability of wound surface; To repair skin trauma have obvious facilitation [10 ］, in tissue engineering technique, shown great using value.When Park etc. add tobramycin and basic fibroblast growth factor (bFGF) or platelet derived growth factor (PDGF) in double-layer collagen one hyaluronic acid artificial skin substitute, can obviously strengthen wound healing ［ 11 ］.But since somatomedin generally have water to exist and room temperature environment under be easy to lose biological activity, regular meeting is owing to intravital environment and inactivation does not reach desired biological effect when therefore directly using somatomedin.Therefore, how under physical environment, keeping and to prolong as far as possible the biological activity of somatomedin, is to make the somatomedin ability real in the clinical key that plays a role.
Shakespare 12] and point out that using-system engineering skin does not have much meanings on the wound surface of some process expectant treatments ability spontaneous recoverys, emphasis should more be the reaction that causes inflammation and be used for these wound surface at present in the treatment of holostrome skin injury.For solving infection problems, existing at present scientific research group adds antibiotic and uses slow release method in organization engineering skin.As Matsuda [13] etc. in the layer of silica gel of similar Integra artificial skin with containing antibiotic polylactic acid microcapsule, make it can discharge antibiotic constantly.
Therefore introduce somatomedin and anti-inflammatory medicaments in the skin tissue engineering scaffold simultaneously; Utilize biodegradable polymer material load anti-inflammatory medicaments and somatomedin; Decrease the position in disease and continue to discharge medicine and somatomedin, in local anti-inflammatory disease, the inducing cell differentiation.
Domestic patent of invention " a kind of method for preparing that is used for tissue repair growth factor slow-release system " (publication number: CN1584143A) disclose a kind of method for preparing Biodegradable high-molecular slow release somatomedin system with method of electrostatic spinning; Domestic patent of invention " a kind of synthetic using of post-operative adhesion-preventing material used " (publication number: CN 1436801A) disclose a kind of method for preparing of preparing PDLGA copolymer post-operation adhesion preventing film through solution polymerization process.CHU BENJAMIN provides in (W002092339) method of electrostatic spinning to prepare the method for operation antiadhesion barrier and postoperative medical releasing film in patent " Biodegradable and/or bioabsorbable fibrous articles and methods for using the articles for medical applications ".
The present invention is through the method for electrostatic spinning; Anti-inflammatory medicaments, somatomedin and degradable high polymer material is compound, nano-fiber film is constantly degraded, with drug release; Prevent the inflammatory reaction of wound site, and induce disease to decrease position cell regeneration through growth factors released.
Summary of the invention
The purpose of this invention is to provide a kind of nanometer fiber slow-releasing system that is loaded with anti-inflammatory medicaments and somatomedin.This method technology is simple, easy to operate; Utilize this method; Not only can be made into the post-operation adhesion preventing film that is loaded with anti-inflammatory medicaments; Implant and prevent that tissue adhesion from leading to complications; More can in organization engineering skin, add antibiotic and use slow release method, make the tissue engineering bracket functionalization directly as medicine and growth factor slow-release sex organization engineering rack.
The present invention proposes is loaded with anti-inflammatory medicaments and growth factor nano fiber slow-releasing system, is a kind of film product, and the diameter of nanofiber is 50-800nm, is evenly distributed, and its composition is following by the quality proportioning:
100 parts of biodegradable polymer
Anti-inflammatory medicaments 0.01-10 part
Somatomedin 0-1 part, preferred 0.001-1 part.
Method of electrostatic spinning is adopted in the preparation of above-mentioned nanometer fiber slow-releasing system, and concrete steps are following:
(1) the preparation spinning solution by above-mentioned quality proportioning, is dissolved in degradable polymer, anti-inflammatory medicaments and somatomedin in the coordinative solvent, obtains spinning solution, and wherein, the solution concentration of biodegradable polymer is 0.05-0.3g/mL;
(2) electrostatic spinning, the flow velocity of control spinning solution is 1～15ml/h, voltage is 10-30KV, obtains being loaded with the nano-fiber film of anti-inflammatory medicaments and somatomedin.
Among the present invention, described biodegradable polymer material comprises: polylactide (PLA), gather Acetic acid, hydroxy-, bimol. cyclic ester (PGA), polycaprolactone (PCL), the copolymer of Acetic acid, hydroxy-, bimol. cyclic ester and lactide (PLGA), the copolymer of lactide and Polyethylene Glycol (PLA-PEG); Poly butyric ester gathers hydroxyl valerate and gathers hydroxycaproic ester; Collagen, gelatin; Polyvinyl alcohol; Chitosan and derivant thereof; The degradable polyurethane class; Merlon; Or the blend of several kinds of above-mentioned materials.
Among the present invention, employed medicine is various anti-inflammatory medicaments, like Cefoxitin, amphiphilic enzyme element, neomycin, mupirocin or polymyxin B, perhaps is antifungal agent (nystatin is like norfloxacin or ciprofloxacin etc.).
Among the present invention, employed somatomedin mainly is epidermal growth factor (EGF), blood vessel endothelial cell growth factor VEGF), basic fibroblast growth factor (bFGF) etc. a kind of.
Among the present invention, employed solvent is: the mixture of dichloromethane, chloroform, oxolane (THF), dimethyl formamide (DMF), acetone a kind of or several kinds.
Nano-fiber film provided by the invention can be used as the post-operation adhesion preventing film, implants to prevent that postoperative intestinal adhesion from leading to complications, and has the effect of anti-inflammatory response simultaneously:
This nano-fiber film also can be used for skin tissue engineering, for example directly as tissue engineering bracket, makes the tissue engineering bracket functionalization.In process of tissue reparation, growth factors released in the time of anti-inflammatory, the differentiation of induced tissue cell.
Method provided by the present invention compared with prior art; Have the following salience effect that a bit reaches: this method is simple to operate; Operation is easy, can make nano-fiber film when preventing tissue adhesion, play the effect of anti-inflammatory, because medicine joins and carries out the nanofiber that electric spinning obtains in the degradable polymer solution and have high-specific surface area; The adjustable scope of drug loading and rate of release is big; And along with the degraded of polymeric material, the hole of fiber surface increases, and rate of releasing drug can be improved.
As skin tissue engineering scaffold, medicine and somatomedin are combined in addition, can prevent the inflammatory reaction of damaged part on the one hand through medicine, the histiocytic breeding of growth factor-induced and the differentiation of release capable of using simultaneously.
Description of drawings
Fig. 1: the SEM figure of nanofiber medicament slow release thin film.
Fig. 2: the drug release curve of various polymerization thing nano-fiber film.
The specific embodiment
(1) biodegradable polymer that mass ratio is certain and medicine and (or) somatomedin is dissolved in the appropriate solvent, is made into certain density electric spinning solution;
(2) the electric spinning solution of joining is carried out electrostatic spinning, obtain the nano-fiber film product;
(3) nano-fiber film that obtains is used for postoperative and organizes Antiadhesive film or skin tissue engineering scaffold.
Can further specify and explain the present invention through embodiment below.
Embodiment 1:
1) be that PLGA and the Cefoxitin of 100:l is dissolved in the mixed solvent of DMF/THF (1/1) with mass ratio, be made into electric spinning solution, the concentration of PLGA is O.lg/mL;
2) the electric spinning solution of joining is carried out electrostatic spinning, control voltage is 15KV, and the spinning solution flow velocity is Sml/h, and obtaining fibre diameter is the nano-fiber film product of 80-800nm;
3) nano-fiber film that obtains is used for postoperative and organizes anti, can prevent inflammation and complication that the local organization adhesion causes.
Embodiment 2:
1) be that PLLA and the Cefoxitin of 100:l is dissolved in the mixed solvent of DMF/=chloromethanes (1/1.5) with mass ratio, be made into electric spinning solution, wherein the concentration of PLLA is 0.1 g/mL;
2) the electric spinning solution of joining is carried out electrostatic spinning, control voltage is 30KV, and the spinning solution flow velocity is 15ml/h, and obtaining diameter is the nano-fiber film product of 100-lOOOnm;
3) nano-fiber film that obtains is used for postoperative and organizes anti, can prevent inflammation and complication that the local organization adhesion causes.
Embodiment 3:
1) be that PLA-PEG and the Cefoxitin of 50:1 is dissolved in the acetone soln with mass ratio, be made into electric spinning solution, wherein the concentration of PLA-PEG is 0.2g/mL.
2) the electric spinning solution of joining is carried out electrostatic spinning, control voltage is 10KV, and the spinning solution flow velocity is Iml/h, and obtaining diameter is the nano-fiber film product of 100-800nm;
3) nano-fiber film that obtains is used for postoperative and organizes anti, with inflammation and the complication that prevents that the local organization adhesion from causing.
Embodiment 4:
1) be that PLA-PEG and the Cefoxitin of 50:1 is dissolved in the acetone soln with mass ratio, be made into electric spinning solution, wherein, PLA-PEG concentration is 0.2g/mL.
2) give above-mentioned solution 1) the middle epidermal growth factor (EGF) that adds, the concentration of epidermal growth factor is O.Olg/mL:
3) the electric spinning solution of joining is carried out electrostatic spinning, control voltage is 20KV, and the spinning solution flow velocity is lOml/h, and obtaining diameter is the nano-fiber film product of 100-800nm;
4) nano-fiber film that obtains can be used for skin tissue engineering scaffold.
Embodiment 5:
1) be that PLLA and the Cefoxitin of 100:1 is dissolved in the mixed solvent of DMF/=chloromethanes (1/1.5) with mass ratio, be made into electric spinning solution, wherein the concentration of PLLA is O.lg/mL;
2) give above-mentioned solution 1) the middle epidermal growth factor (EGF) that adds; The concentration of epidermal growth factor is 0.02g/mL;
3) the electric spinning solution of joining is carried out electrostatic spinning, control voltage is 20KV, and the spinning solution flow velocity is 12ml/h, and obtaining diameter is the nano-fiber film product of 90-800nm:
4) nano-fiber film that obtains can be used for skin tissue engineering scaffold;
Embodiment 6:
1) be that PLGA and the Cefoxitin of 100:1 is dissolved in the mixed solvent of DMF/THF (1/1) with mass ratio, be made into electric spinning solution, wherein the concentration of PLGA is O.lg/mL.
2) give above-mentioned solution 1) the middle epidermal growth factor (EGF) that adds, the concentration of epidermal growth factor is O.Olg/mL;
3) the electric spinning solution of joining is carried out electrostatic spinning, control voltage is 30KV, and the spinning solution flow velocity is lOml/h, and obtaining diameter is the nano-fiber film product of 80-500nm;
4) nano-fiber film that obtains can be used for skin tissue engineering scaffold.
Embodiment 8:
1) be that collagen and the nystatin of 100:1 is dissolved in the mixed solvent of DMF/THF (1/1) with mass ratio, be made into electric spinning solution, wherein the concentration of collagen is O.lg/mL.
2) give above-mentioned solution 1) in add the epidermal growth factor (EGF) of 0.002g/mL respectively, vascular endothelial cell growth factor (VEGF), basic fibroblast growth factor (bFGF), the concentration of EGF, VEGF, bFGF is respectively 0.002g/mL;
3) the electric spinning solution of joining is carried out electrostatic spinning, control voltage is 10KV, and the spinning solution flow velocity is lOml/h, and obtaining diameter is the nano-fiber film product of 80-500nm;
4) nano-fiber film that obtains can be used for skin tissue engineering scaffold:
Embodiment 9:
1) be that chitosan and the polymyxin B of 100:l is dissolved in the mixed solvent of DMF/THF (1/1) with mass ratio, be made into electric spinning solution, the concentration of chitosan and polymyxin B is O.lg/mL;
2) give above-mentioned solution 1) in add the epidermal growth factor (EGF) of 0.002g/mL respectively, vascular endothelial cell growth factor (VEGF), basic fibroblast growth factor (bFGF), the concentration of EGF, VEGF, bFGF is respectively 0.002g/mL;
3) the electric spinning solution of joining is carried out electrostatic spinning, control voltage is 30KV, and the spinning solution flow velocity is 15ml/h, and obtaining diameter is the nano-fiber film product of 80-500nm:
4) nano-fiber film that obtains can be used for skin tissue engineering scaffold.
Claims (3)
1. anti-inflammatory medicaments and growth factor slow-release body are thin film, it is characterized in that the diameter of nanofiber is 50-800nm, are evenly distributed, and its composition is following by the quality proportioning:
100 parts of biodegradable polymer
Anti-inflammatory medicaments 0.01-10 part
Somatomedin 0-1 part.
2. the method for preparing like described a kind of anti-inflammatory medicaments of claim l and growth factor slow-release body is characterized in that adopting quiet spin processes, and concrete steps are following:
(1) the preparation spinning solution by said quality proportioning, is dissolved in biodegradable polymer, anti-inflammatory medicaments and somatomedin in the coordinative solvent, obtains spinning solution, and wherein, the solution concentration of biodegradable polymer is 0.05-0.3g/mL;
(2) electrostatic spinning, the flow velocity of control spinning solution is 1～15ml/h, voltage is 10-30KV, obtains being loaded with the nano-fiber film of anti-inflammatory medicaments and somatomedin.
3. according to described a kind of anti-inflammatory medicaments of claim l and growth factor slow-release body; It is characterized in that described biodegradable polymer material comprises: polylactide; Gather Acetic acid, hydroxy-, bimol. cyclic ester, polycaprolactone, the copolymer of Acetic acid, hydroxy-, bimol. cyclic ester and lactide; The copolymer of lactide and Polyethylene Glycol: poly butyric ester, gather hydroxyl valerate and gather hydroxycaproic ester; Collagen, gelatin; Polyvinyl alcohol; Chitosan and derivant thereof; The degradable polyurethane class; Merlon; Or the blend of several kinds of above-mentioned materials.It is characterized in that described anti-inflammatory medicaments is Cefoxitin, amphiphilic enzyme element, neomycin, mupirocin or polymyxin B.It is characterized in that said solvent is the mixture of a kind of of dichloromethane, chloroform, oxolane, dimethyl formamide, acetone or several kinds.
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Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102965838A (en) * | 2012-12-11 | 2013-03-13 | 青岛大学 | Method for preparing micro-nano fiber film by electrostatic spinning method |
| CN103100116A (en) * | 2012-12-31 | 2013-05-15 | 范存义 | Tissue adhesion prevention material, medicine-carrying material and preparation method thereof |
| CN103768662A (en) * | 2014-02-26 | 2014-05-07 | 中国科学院长春应用化学研究所 | Preparation method of biodegradable medical surgical anti-adhesion membrane |
| CN104947305A (en) * | 2014-03-31 | 2015-09-30 | 上海微创医疗器械（集团）有限公司 | Hernia repair mesh and preparation method thereof |
| CN105040280A (en) * | 2015-06-26 | 2015-11-11 | 中国人民解放军南京军区南京总医院 | Polypropylene mesh/electro-spinning nano-fiber membrane as well as preparation method and application thereof |
| CN105903089A (en) * | 2016-05-06 | 2016-08-31 | 上海交通大学医学院附属上海儿童医学中心 | Application of gelatin/polycaprolactone nanofiber material in surgical postoperative adhesion prevention |
| CN105999431A (en) * | 2016-07-06 | 2016-10-12 | 张波 | Neurosurgical postoperative anti-adhesion membrane and preparation method thereof |
| CN110478521A (en) * | 2018-05-14 | 2019-11-22 | 桂林医学院 | Medicament-carrying nano-fiber and its preparation method and application |
| CN110548018A (en) * | 2018-05-14 | 2019-12-10 | 桂林医学院 | Drug-loaded nanofiber and preparation method and application thereof |
| WO2021120302A1 (en) * | 2019-12-16 | 2021-06-24 | 深圳市光远生物材料有限责任公司 | Soft tissue repair fiber film material, preparation method therefor and application thereof |
| CN114259608A (en) * | 2021-12-14 | 2022-04-01 | 无锡中科光远生物材料有限公司 | Bilateral hemostatic anti-adhesion material and preparation method thereof |
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2010
- 2010-11-22 CN CN2010105527427A patent/CN102475920A/en active Pending
Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102965838A (en) * | 2012-12-11 | 2013-03-13 | 青岛大学 | Method for preparing micro-nano fiber film by electrostatic spinning method |
| CN103100116A (en) * | 2012-12-31 | 2013-05-15 | 范存义 | Tissue adhesion prevention material, medicine-carrying material and preparation method thereof |
| CN103768662A (en) * | 2014-02-26 | 2014-05-07 | 中国科学院长春应用化学研究所 | Preparation method of biodegradable medical surgical anti-adhesion membrane |
| CN103768662B (en) * | 2014-02-26 | 2016-06-01 | 中国科学院长春应用化学研究所 | The preparation method of a kind of biodegradable medical surgery anti-adhesion membrane |
| CN104947305A (en) * | 2014-03-31 | 2015-09-30 | 上海微创医疗器械（集团）有限公司 | Hernia repair mesh and preparation method thereof |
| CN105040280B (en) * | 2015-06-26 | 2017-06-20 | 中国人民解放军南京军区南京总医院 | Polypropylene mesh/Electrospun nano-fibers film and its preparation method and application |
| CN105040280A (en) * | 2015-06-26 | 2015-11-11 | 中国人民解放军南京军区南京总医院 | Polypropylene mesh/electro-spinning nano-fiber membrane as well as preparation method and application thereof |
| CN105903089A (en) * | 2016-05-06 | 2016-08-31 | 上海交通大学医学院附属上海儿童医学中心 | Application of gelatin/polycaprolactone nanofiber material in surgical postoperative adhesion prevention |
| CN105999431A (en) * | 2016-07-06 | 2016-10-12 | 张波 | Neurosurgical postoperative anti-adhesion membrane and preparation method thereof |
| CN110478521A (en) * | 2018-05-14 | 2019-11-22 | 桂林医学院 | Medicament-carrying nano-fiber and its preparation method and application |
| CN110548018A (en) * | 2018-05-14 | 2019-12-10 | 桂林医学院 | Drug-loaded nanofiber and preparation method and application thereof |
| CN110478521B (en) * | 2018-05-14 | 2021-10-29 | 桂林医学院 | Drug-loaded nanofiber and preparation method and application thereof |
| CN110548018B (en) * | 2018-05-14 | 2023-01-24 | 桂林医学院 | Drug-loaded nanofiber and preparation method and application thereof |
| WO2021120302A1 (en) * | 2019-12-16 | 2021-06-24 | 深圳市光远生物材料有限责任公司 | Soft tissue repair fiber film material, preparation method therefor and application thereof |
| CN114259608A (en) * | 2021-12-14 | 2022-04-01 | 无锡中科光远生物材料有限公司 | Bilateral hemostatic anti-adhesion material and preparation method thereof |
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Application publication date: 20120530 |