CN102133428A - Protein-loading tissue engineering fiber bracket - Google Patents
Protein-loading tissue engineering fiber bracket Download PDFInfo
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- CN102133428A CN102133428A CN2011100688041A CN201110068804A CN102133428A CN 102133428 A CN102133428 A CN 102133428A CN 2011100688041 A CN2011100688041 A CN 2011100688041A CN 201110068804 A CN201110068804 A CN 201110068804A CN 102133428 A CN102133428 A CN 102133428A
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Abstract
The invention provides a tissue engineering fiber bracket prepared by electrostatic spinning of an emulsion method, belonging to the technical field of medicaments. The tissue engineering fiber bracket comprises the following components in percentage by weight: 0.5-20% of protein, 0.5-20% of high molecular polysaccharide, 0-15% of suspending agent and 60-99% of slow-release polymer. In the invention, the fiber has strong plasticity and can be made into fiber brackets in various shapes as required. The invention can enhance the stability of protein in preparation, storage and in-vivo treatment processes of the tissue engineering fiber bracket, can improve the release curve of protein or polypeptide medicaments, and can increase the protein load of the fiber.
Description
Technical field
What the present invention relates to is a kind of organizational project fibrous framework of technical field of pharmaceuticals, and what be specifically related to is a kind of proteic organizational project fibrous framework that supports.
Background technology
Relevant at present supporting in the research of proteic organizational project fibrous framework ignored the protection problem to protein active and conformation usually, has prominent phenomenon and the low encapsulation efficiency released of proteic initial stage simultaneously.
Find through literature search prior art, Li Xiaoqiang etc. are at Colloids and Surfaces B:Biointerfaces2010 the 75th phase 418-424 page or leaf, article autograph " Encapsulation of proteins in poly (1-lactide-co-caprolactone) fibers by emulsion electrospinning " (preparation of emulsion method electrostatic spinning supports proteic polylactic acid-caprolactone copolymer fiber), propose to adopt bovine serum albumin (BSA, 7.69%, w/w) and polylactic acid-caprolactone copolymer (PLACL, 92.31%, w/w) preparation slow-release fiber.There is the comparatively serious prominent phenomenon of releasing in the outer release profiles of resulting corpus fibrosum, and discharges 27% in first day, does not reach ideal slow release effect, does not also mention proteic conformation protection result.
Summary of the invention
The objective of the invention is at the deficiencies in the prior art, a kind of proteic organizational project fibrous framework that supports is provided.The present invention's effective conformation of stabilize proteins in the preparation of organizational project fibrous framework, storage, interior therapeutic process is improved the release profiles of protein drug simultaneously, improves drug loading.
The present invention is achieved by the following technical solutions:
Component of the present invention and percentage by weight are: albumen 0.5-20%, macromolecule polysaccharide 0.5-20%, suspending agent 0-15%, slow release macromolecule 60-99%.
Described albumen comprises erythropoietin (EPO), recombinant human granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimutaing factor (GM-CSF), interferon (INF), growth hormone (GH), insulin (Insulin), epidermal growth factor (EGF), fibroblast growth factor (FGF), transforming growth factor (TGF-β), insulin like growth factor (IGF), vascular endothelial cell growth factor (VEGF), PDGF (PDGF), endothelial cell growth factor (ECGF) (ECGF), nerve growth factor (NGF), bone-derived growth factor (BDGF), bone morphogenetic protein(BMP) (BMP), tissue polypeptide antigen (TPA), antibody (antibody), blood coagulation factor VIII (VIII) etc. is used for the albumen of tissue regeneration treatment.
Described macromolecule polysaccharide is the one or any mixing in glucosan, soluble cellulose derivant, hyaluronic acid, the alginate.
Described suspending agent is micromolecule suspending agents such as glycerol, syrup and sorbitol, or arabic gum, tragakanta, natural polymer suspending agents such as sodium alginate, or cellulose family, polyvinyl alcohol etc. are semi-synthetic or the synthetic high polymer suspending agent.
Described slow release macromolecule refers to the polyamino acid of polyester, poly-anhydride or skeleton non-peptide bond, comprising: polylactic acid, polylactic acid-polyglycolic acid and combination thereof, poly-Acetic acid, hydroxy-, bimol. cyclic ester, polycaprolactone, polybutylcyanoacrylate, poly phosphazene, poly phosphate etc.
The present invention can prepare by common electrospinning process or coaxial cospinning method.
The present invention is substrate with the degradable high polymer material; The macromolecule polysaccharide aqueous solution is as " interior aqueous favoring ", add macromolecule polysaccharide at interior aqueous phase and can regulate proteic rate of release jointly with the slow release macromolecule, add the mobility of macromolecule polysaccharide according to treatment needs sustained release speed at interior aqueous phase, reduce the generation of clustering phenomena by increased viscosity reduction protein molecular; Macromolecule polysaccharide and albumen have good biocompatibility, can reduce owing to albumen and slow release are high molecular directly to contact the protein adsorption that causes, can improve the stability of albumen in the preparation of organizational project fibrous framework, storage, interior therapeutic process.
The fiber that the present invention makes is the conformation of stabilize proteins effectively, improves the stability of albumen in support preparation, storage, dispose procedure, improves proteic release profiles in the general organizational project fiber, can increase proteic loading in the fiber in addition.Can keep albumen and continue discharge two weeks to three month and first Tiantu and release and be not more than 15% of albumen loading, total burst size near or be not less than 85% of albumen loading.
Description of drawings
Fig. 1 embodiment of the invention fiber membrane stereoscan photograph (amplification: 2,740);
Fibre morphology surface sweeping electromicroscopic photograph (amplification: 3,000) in Fig. 2 embodiment of the invention fiber dispose procedure.
The specific embodiment
Below in conjunction with accompanying drawing the proteic organizational project fibrous framework and preparation and extracorporeal releasing experiment thereof of supporting of the present invention implemented to elaborate: following examples are being to implement under the prerequisite with the technical solution of the present invention; provided detailed embodiment and process, but protection scope of the present invention is not limited to following embodiment.Among the following embodiment, the experimental technique of unreceipted actual conditions, usually according to normal condition, or the condition of advising according to manufacturer.
Embodiment 1
A) (0.5%, (0.5%, w/w) aqueous solution 0.5ml is as interior water w/w) to be dissolved in macromolecule polysaccharide with BSA;
B) with the polylactic-co-glycolic acid copolymer (99%, w/w) be dissolved in N, among dinethylformamide and the chloroform equal-volume mixed organic solvents 2.5ml as outer oil phase;
C) interior water dropwise adds in the outer oil phase, adopts magnetic agitation 1000rpm, 30 minutes, forms the W/O emulsion.
D) above-mentioned W/O emulsion is added in the syringe, the static that adds high pressure uses micro-injection pump and receptor, is woven into fiber membrane at room temperature static;
E) fiber membrane is at room temperature left standstill dry, obtain emulsion method electrostatic spinning organizational project fiber.Fiber plasticity is strong, can fashion into the fibrous framework of different shape according to needs.
Precision weighing 10mg fiber (stereoscan photograph is seen Fig. 1), add 1mlPBS solution, in 37 ℃, the cultivation of 60rpm gas bath shaking table, regularly take out supernatant and add buffer medium, the content of BSA in the method test supernatant of employing microbca, deduct the reading of blank fiber, calculate the fiber release.Fibre morphology surface sweeping electromicroscopic photograph is seen Fig. 2 in the dispose procedure.
Experimental result shows: the steady slow release of organizational project fiber, first Tiantu are released and are not more than 10% of medicine carrying capacity, and total burst size is approaching or be not less than 85% of medicine carrying capacity, do not have prominent releasing and incomplete release phenomenon.
Embodiment 2
A) (20%, (20%, w/w) aqueous solution 0.5ml is as interior water w/w) to be dissolved in macromolecule polysaccharide with BSA;
B) with the polylactic-co-glycolic acid copolymer (60%, w/w) be dissolved in N, among dinethylformamide and the chloroform equal-volume mixed organic solvents 2.5ml as outer oil phase;
C) interior water dropwise adds in the outer oil phase, adopts magnetic agitation 1000rpm, 30 minutes, forms the W/O emulsion.
D) above-mentioned W/O emulsion is added in the syringe, the static that adds high pressure uses micro-injection pump and receptor, is woven into fiber membrane at room temperature static;
E) fiber membrane is at room temperature left standstill dry, obtain emulsion method electrostatic spinning organizational project fiber.Fiber plasticity is strong, can fashion into the fibrous framework of different shape according to needs.
Precision weighing 10mg fiber adds 1mlPBS solution, in 37 ℃, the cultivation of 60rpm gas bath shaking table, regularly take out supernatant and add buffer medium, the method of employing microbca is tested the content of BSA in the supernatant, deducts the reading of blank fiber, calculates the fiber release.
Experimental result shows: the steady slow release of organizational project fiber, first Tiantu are released and are not more than 10% of medicine carrying capacity, and total burst size is approaching or be not less than 85% of medicine carrying capacity, do not have prominent releasing and incomplete release phenomenon.
A) (10.25%, (10.25%, w/w) aqueous solution 0.5ml is as interior water w/w) to be dissolved in macromolecule polysaccharide with BSA;
B) with the polylactic-co-glycolic acid copolymer (72%, w/w) be dissolved in N, among dinethylformamide and the chloroform equal-volume mixed organic solvents 2.5ml, add class of suspending agent department 80 (7.5%, w/w) the outer oil phase of conduct;
C) interior water dropwise adds in the outer oil phase, adopts magnetic agitation 1000rpm, 30 minutes, forms the W/O emulsion.
D) above-mentioned W/O emulsion is added in the syringe, the static that adds high pressure uses micro-injection pump and receptor, is woven into fiber membrane at room temperature static;
E) fiber membrane is at room temperature left standstill dry, obtain emulsion method electrostatic spinning organizational project fiber.Fiber plasticity is strong, can fashion into the fibrous framework of different shape according to needs.
Precision weighing 10mg fiber adds 1mlPBS solution, in 37 ℃, the cultivation of 60rpm gas bath shaking table, regularly take out supernatant and add buffer medium, the method of employing microbca is tested the content of BSA in the supernatant, deducts the reading of blank fiber, calculates the fiber release.
Experimental result shows: the steady slow release of organizational project fiber, first Tiantu are released and are not more than 10% of medicine carrying capacity, and total burst size is approaching or be not less than 85% of medicine carrying capacity, do not have prominent releasing and incomplete release phenomenon.
Embodiment 4
A) (0.5%, (0.5%, w/w) aqueous solution 0.5ml is as interior water w/w) to be dissolved in macromolecule polysaccharide with BSA;
B) with the polylactic-co-glycolic acid copolymer (84%, w/w) be dissolved in N, among dinethylformamide and the chloroform equal-volume mixed organic solvents 2.5ml, add class of suspending agent department 80 (15%, w/w) the outer oil phase of conduct;
C) water in above-mentioned and outer oil phase are placed the capillary tube of coaxial cospinning respectively, the static that adds high pressure simultaneously, use micro-injection pump and receptor are woven into fiber membrane at room temperature static;
E) fiber membrane is at room temperature left standstill dry, obtain emulsion method electrostatic spinning organizational project fiber.Fiber plasticity is strong, can fashion into the fibrous framework of different shape according to needs.
Precision weighing 10mg fiber adds 1mlPBS solution, in 37 ℃, the cultivation of 60rpm gas bath shaking table, regularly take out supernatant and add buffer medium, the method of employing microbca is tested the content of BSA in the supernatant, deducts the reading of blank fiber, calculates the fiber release.
Experimental result shows: the steady slow release of organizational project fiber, first Tiantu are released and are not more than 10% of medicine carrying capacity, and total burst size is approaching or be not less than 85% of medicine carrying capacity, do not have prominent releasing and incomplete release phenomenon.
Embodiment 5
A) (1%, (12%, w/w) aqueous solution 0.5ml is as interior water w/w) to be dissolved in macromolecule polysaccharide with BSA;
B) with the polylactic-co-glycolic acid copolymer (79.5%, w/w) be dissolved in N, among dinethylformamide and the chloroform equal-volume mixed organic solvents 2.5ml, add class of suspending agent department 80 (7.5%, w/w) the outer oil phase of conduct;
C) interior water dropwise adds in the outer oil phase, adopts magnetic agitation 1000rpm, 30 minutes, forms the W/O emulsion.
D) above-mentioned W/O emulsion is added in the syringe, the static that adds high pressure uses micro-injection pump and receptor, is woven into fiber membrane at room temperature static;
E) fiber membrane is at room temperature left standstill dry, obtain emulsion method electrostatic spinning organizational project fiber.Fiber plasticity is strong, can fashion into the fibrous framework of different shape according to needs.
Precision weighing 10mg fiber adds 1mlPBS solution, in 37 ℃, the cultivation of 60rpm gas bath shaking table, regularly take out supernatant and add buffer medium, the method of employing microbca is tested the content of BSA in the supernatant, deducts the reading of blank fiber, calculates the fiber release.
Experimental result shows: the steady slow release of organizational project fiber, first Tiantu are released and are not more than 10% of medicine carrying capacity, and total burst size is approaching or be not less than 85% of medicine carrying capacity, do not have prominent releasing and incomplete release phenomenon.
Claims (9)
1. one kind supports proteic organizational project fibrous framework, it is characterized in that its component and percentage by weight are: albumen 0.5-20%, macromolecule polysaccharide 0.5-20%, suspending agent 0-15%, slow release macromolecule 60-99%.
2. according to claim 1ly support proteic organizational project fibrous framework, it is characterized in that described albumen comprises erythropoietin, recombinant human granulocyte colony stimulating factor, granulocyte-macrophage colony stimutaing factor, interferon, growth hormone, insulin, epidermal growth factor, fibroblast growth factor, transforming growth factor, insulin like growth factor, vascular endothelial cell growth factor, PDGF, endothelial cell growth factor (ECGF), nerve growth factor, bone-derived growth factor, bone morphogenetic protein(BMP), tissue polypeptide antigen, antibody, blood coagulation factor VIII.
3. according to claim 1ly support proteic organizational project fibrous framework, it is characterized in that described macromolecule polysaccharide is the one or any mixing in glucosan, soluble cellulose derivant, hyaluronic acid, the alginate.
4. according to claim 1ly support proteic organizational project fibrous framework, it is characterized in that described suspending agent is the micromolecule suspending agent, or the natural polymer suspending agent, or semi-synthetic or synthetic high polymer suspending agent.
5. according to claim 4ly support proteic organizational project fibrous framework, it is characterized in that described micromolecule suspending agent is glycerol, syrup and sorbitol.
6. according to claim 4ly support proteic organizational project fibrous framework, it is characterized in that described natural polymer suspending agent is arabic gum, tragakanta, sodium alginate.
7. according to claim 4ly support proteic organizational project fibrous framework, it is characterized in that, described semi-synthetic or synthetic high polymer suspending agent is a cellulose family, polyvinyl alcohol is semi-synthetic or the synthetic high polymer suspending agent.
8. according to claim 1ly support proteic organizational project fibrous framework, it is characterized in that described slow release macromolecule refers to the polyamino acid of polyester, poly-anhydride or skeleton non-peptide bond.
9. describedly support proteic organizational project fibrous framework according to claim 1 or 8, it is characterized in that described slow release macromolecule comprises: polylactic acid, polylactic acid-polyglycolic acid and combination thereof, poly-Acetic acid, hydroxy-, bimol. cyclic ester, polycaprolactone, polybutylcyanoacrylate, poly phosphazene, poly phosphate.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102188755A (en) * | 2011-04-29 | 2011-09-21 | 上海交通大学 | Method for preparing protein-loaded tissue engineering fiber support |
| CN103205863A (en) * | 2013-04-17 | 2013-07-17 | 钟春燕 | Method for manufacturing bacterial cellulose slow-release dressing |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1903939A (en) * | 2006-07-20 | 2007-01-31 | 上海交通大学 | Polysaccharide polymer having protein large molecule and its preparation method |
| CN101509154A (en) * | 2009-03-23 | 2009-08-19 | 东华大学 | Method for producing shell-core structure medicament nano-fibre with emulsion electrostatic spinning technology |
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- 2011-03-22 CN CN2011100688041A patent/CN102133428A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1903939A (en) * | 2006-07-20 | 2007-01-31 | 上海交通大学 | Polysaccharide polymer having protein large molecule and its preparation method |
| CN101509154A (en) * | 2009-03-23 | 2009-08-19 | 东华大学 | Method for producing shell-core structure medicament nano-fibre with emulsion electrostatic spinning technology |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102188755A (en) * | 2011-04-29 | 2011-09-21 | 上海交通大学 | Method for preparing protein-loaded tissue engineering fiber support |
| CN103205863A (en) * | 2013-04-17 | 2013-07-17 | 钟春燕 | Method for manufacturing bacterial cellulose slow-release dressing |
| CN103205863B (en) * | 2013-04-17 | 2016-02-10 | 钟春燕 | A kind of preparation method of bacterial cellulose slow-release dressing |
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Application publication date: 20110727 |