CN104109254A - I-type collagen-sodium alginate-polyvinyl alcohol composite film and preparation method thereof - Google Patents
I-type collagen-sodium alginate-polyvinyl alcohol composite film and preparation method thereof Download PDFInfo
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- CN104109254A CN104109254A CN201410325153.3A CN201410325153A CN104109254A CN 104109254 A CN104109254 A CN 104109254A CN 201410325153 A CN201410325153 A CN 201410325153A CN 104109254 A CN104109254 A CN 104109254A
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Abstract
The invention provides an I-type collagen-sodium alginate-polyvinyl alcohol composite film which comprises the following components by weight percent: 20% to 60% of I-type collagen, 20% to 60% of sodium alginate and 20% to 60% of polyvinyl alcohol. A preparation method of the composite film comprises the following steps: firstly, respectively dissolving the I-type collagen, the sodium alginate and the polyvinyl alcohol in different reaction kettles and regulating the pH of the I-type collagen to be within 5 to 8; then, successively adding a sodium alginate liquid and a polyvinyl alcohol liquid in proportion into an I-type collagen liquid and stirring for 4 to 10 hours; adding a defoaming agent to a mixed liquid and stirring for 20 to 60 minutes; then, pumping the mixed liquid into a storage tank and standing for defoaming; after the defoaming is checked to reach a requirement, pumping the mixed liquid into a film casting machine so as to obtain a film in a casting manner, drying and soaking the film in a cross-linking agent liquid or standing under a cross-linking condition for cross-linking for 4 to 24 hours, cleaning and drying; finally, shaping the film, packaging and irradiating, thereby obtaining the I-type collagen-sodium alginate-polyvinyl alcohol composite film. The composite film material is good in mechanical property, hydrophilcity and biocompatibility, moderate in degradation velocity and simple in preparation process. Thus, the composite film material can be widely applied to wound dressing, hemostatic materials, tissue engineering scaffold materials and the like.
Description
Technical field
The present invention relates to type i collagen-sodium alginate-polyvinyl alcohol composite membrane and preparation method thereof, belong to biomedical materials field.
Background technology
The special construction that 3 polypeptide chains of type i collagen form triple helical has determined its some specified propertys, its tensile strength is very high, there is outstanding one-tenth fibre property, can promote cell proliferation, growth, the multiple good characteristics such as self-association of degradable, histocompatibility, hemostatic and collagen, so type i collagen is widely used in field of tissue engineering technology.Sodium alginate, due to good biological degradability and biocompatibility, has been widely used in the fields such as chemistry, biology, medicine, food, and with its good film-forming properties, is widely used in multi-purpose mould material preparation.PVA has good solvent resistance and good film-forming properties, and can form the film of smooth surface, very powerful, resistance to solvent, anti tear, and owing to thering is good biodegradability, human body be had no side effect, be also a kind of good bio-medical material.
At present, that in mould material preparation, conventionally select is chitosan, sodium alginate, polyvinyl alcohol, collagen protein, PLA, PLGA etc., and for example patent CN102978740A has reported that use vinylon high-strength and high-modulus technique produces a kind of protein conjugated fibre by collagen protein and polyvinyl alcohol mixing spinning; Patent 200510020902.2 adopts metal ion-modified collagen-polyvinyl alcohol composite fiber to improve the stability of spinning solution and the intensity of conjugated fibre; For simulation collagen and the ratio of elastin in natural blood vessel, there is investigator to select 45% collagen and 15% elastin, add respectively 40% biodegradable polymers PLGA, PLA, PCL, PLLA or poly(lactic acid)-caprolactone electrospinning and prepare compound rest (Heydarkhan-Hagvall S, Schenke-Layland K, Dhanasopon AP
et al. Three-dimensional electrospun ECM-based hybrid scaffolds for cardiovascular tissue engineering[J].
biomaterials, 2008,29 (19): 2907-2914.); The people such as Jiang Jianming have prepared collagen-alginate-hydroxyapatite timbering material (Jiang Jianming by plural gel approach, Wang Xiaoliang, Wang Xiaomin, Deng. plural gel approach is prepared collagen-alginate-hydroxyapatite timbering material [J]. chemical research and application, 2007,19 (6): 695-697.).In aforesaid method, have the following disadvantages: (1) most of collagen starting material (collagen protein) are the hydrolysates of collagen distinctive biological activity while having lost collagen maintenance triple helix; (2) the artificial macromolecular material compound tense such as collagen and PLA, PLGA need be used organic solvent dissolution, such as the stronger solvent of the toxicity such as hexafluoroisopropanol or tetrahydrofuran (THF), after dissolving, make the structure and function of collagen be affected, and residual organic solvent will directly affect the biocompatibility of material; (3) mould material of collagen and sodium alginate is not having under crosslinked condition, bad mechanical property, and structure is easily caved in, and is not suitable as timbering material.
Summary of the invention
The object of the invention is provides a kind of type i collagen-sodium alginate-polyvinyl alcohol composite membrane with suitable wetting ability, permeable gas, good mechanical properties, good biocompatibility and preparation method thereof for field of biomedical materials.
The object of the invention is to be realized by following technical measures, wherein said raw material per-cent, except special instruction, is all weight percentage:
(1) type i collagen is dissolved in the reactor containing mineral acid or organic acid soln, at 4～10 ℃, stirs and make it to dissolve completely, be mixed with massfraction and be 0.5%～1% type i collagen solution;
(2) sodium alginate powder is dissolved in and in the reactor containing distilled water, is heated to 40～60 ℃ of stirrings and makes it to dissolve completely, be mixed with massfraction and be 1%～5% sodium alginate soln, be cooled to room temperature stand-by;
(3) polyvinyl alcohol is dissolved in and in the reactor containing distilled water, is heated to 50～90 ℃ and makes it to dissolve completely, be mixed with massfraction and be 4%～10% polyvinyl alcohol solution, be cooled to room temperature stand-by;
(4) gained type i collagen in step (1) being neutralized to pH with the sodium hydroxide of 0.2～0.5mol/L is 5～8, then according to the shared mass percent of each raw material: type i collagen 20%～60%, sodium alginate 20%～60%, polyvinyl alcohol 20%～60%, three kinds of solution more than mixing in reactor stir 4～10 hours at 4～10 ℃;
(5) in step (4) gained mixing solutions, add defoamer, stir 20-60 minute, then blended liquid is pumped into hold-up vessel, standing froth breaking;
(6) check that froth breaking reaches after requirement, blended liquid is pumped into flow-casting film forming machine, casting film-forming, then drying and forming-film;
(7) dried film immersed in cross-linking agent solution or be placed under crosslinked condition after crosslinked 4～24 hours, cleaning, drier;
(8), after forming process, packing, irradiation, obtain type i collagen-sodium alginate-polyvinyl alcohol composite membrane.
Type i collagen-sodium alginate-polyvinyl alcohol the composite film material being prepared by aforesaid method, be white in color or micro-yellow membranaceous, smooth, without the visible impurity of naked eyes; Porosity: 70%～85%; Tensile strength: 30～45MPa; Elongation at break: 30%～40%; Water-intake rate: 1500g/g～2000g/g; Water retention: 300g/g～400g/g; Permeability to water vapour: 37 ℃ time, be 2000 ~ 3000g/ (m under dry state condition
224h).
The present invention has the following advantages:
1. the present invention's type i collagen used extracts through acid-enzyme hydrolysis method, it is advantageous that mild condition, environmentally friendly, extraction yield is high, can keep preferably the triple helix structure of collagen and reduce the antigenicity of collagen, retain its biological activity, can improve the biocompatibility of material;
2. the present invention utilizes polyvinyl alcohol good physical mechanical property and histocompatibility, and the good advantages such as wetting ability, biological degradability and film-forming properties of sodium alginate, overcomes collagen bad mechanical property, the shortcoming such as resistance to enzymolysis not;
In preparation process of the present invention not with an organic solvent, can the good biocompatibility of reserved materials itself;
4. preparation technology's simple and stable of the present invention, low, the gentle environmental protection of cost, be easy to realize suitability for industrialized production, and possess the specific function of medical material, has the potentiality of applying, and market outlook are wide.
Embodiment
Below by enforcement, the present invention is specifically described; be necessary to be pointed out that at this present embodiment is only used to further illustrate the present invention; and can not be interpreted as limiting the scope of the invention, the person skilled in the art in this field can make some nonessential improvement and adjustment according to the content of foregoing invention.
embodiment 1
(1) type i collagen is dissolved in the reactor containing acetum, at 4 ℃, stirs and make it to dissolve completely, be mixed with massfraction and be 0.5% type i collagen solution;
(2) sodium alginate powder is dissolved in and in the reactor containing distilled water, is heated to 45 ℃ of stirrings and makes it to dissolve completely, be mixed with massfraction and be 2% sodium alginate soln, be cooled to room temperature stand-by;
(3) polyvinyl alcohol is dissolved in and in the reactor containing distilled water, is heated to 80 ℃ and makes it to dissolve completely, be mixed with massfraction and be 4%～10% polyvinyl alcohol solution, be cooled to room temperature stand-by;
(4) gained type i collagen in step (1) being neutralized to pH with the sodium hydroxide of 0.2mol/L is 7, then according to the shared mass percent of each raw material: type i collagen 20%, sodium alginate 60%, polyvinyl alcohol 20%, three kinds of solution more than mixing in reactor stir 4 hours at 4 ℃;
(5) in step (4) gained mixing solutions, add defoamer, stir 30 minutes, then blended liquid is pumped into hold-up vessel, standing froth breaking;
(6) check that froth breaking reaches after requirement, blended liquid is pumped into flow-casting film forming machine, casting film-forming, then dry;
(7) dried composite membrane immersed in cross-linking agent solution or be placed under crosslinked condition after crosslinked 12 hours, cleaning, drier;
(8), after forming process, packing, irradiation, obtain type i collagen-sodium alginate-polyvinyl alcohol composite membrane.
embodiment 2
(1) type i collagen is dissolved in the reactor containing acetum, at 4 ℃, stirs and make it to dissolve completely, be mixed with massfraction and be 0.8% type i collagen solution;
(2) sodium alginate powder is dissolved in and in the reactor containing distilled water, is heated to 40 ℃ of stirrings and makes it to dissolve completely, be mixed with massfraction and be 2% sodium alginate soln, be cooled to room temperature stand-by;
(3) polyvinyl alcohol is dissolved in and in the reactor containing distilled water, is heated to 80 ℃ and makes it to dissolve completely, be mixed with massfraction and be 8% polyvinyl alcohol solution, be cooled to room temperature stand-by;
(4) gained type i collagen in step (1) being neutralized to pH with the sodium hydroxide of 0.3mol/L is 6.5, then according to the shared mass percent of each raw material: type i collagen 20%, sodium alginate 20%, polyvinyl alcohol 60%, three kinds of solution more than mixing in reactor stir 6 hours at 4 ℃;
(5) in step (4) gained mixing solutions, add defoamer, stir 30 minutes, then blended liquid is pumped into hold-up vessel, standing froth breaking;
(6) check that froth breaking reaches after requirement, blended liquid is pumped into flow-casting film forming machine, casting film-forming, then dry;
(7) dried composite membrane immersed in cross-linking agent solution or be placed under crosslinked condition after crosslinked 12 hours, cleaning, drier;
(8), after forming process, packing, irradiation, obtain type i collagen-sodium alginate-polyvinyl alcohol composite membrane.
embodiment 3
(1) type i collagen is dissolved in the reactor of hydrochloric solution, at 10 ℃, stirs and make it to dissolve completely, be mixed with massfraction and be 0.8% type i collagen solution;
(2) sodium alginate powder is dissolved in and in the reactor containing distilled water, is heated to 45 ℃ of stirrings and makes it to dissolve completely, be mixed with massfraction and be 2% sodium alginate soln, be cooled to room temperature stand-by;
(3) polyvinyl alcohol is dissolved in and in the reactor containing distilled water, is heated to 60 ℃ and makes it to dissolve completely, be mixed with massfraction and be 8% polyvinyl alcohol solution, be cooled to room temperature stand-by;
(4) gained type i collagen in step (1) being neutralized to pH with the sodium hydroxide of 0.5mol/L is 6.5, then according to the shared mass percent of each raw material: type i collagen 33.3%, sodium alginate 33.3%, polyvinyl alcohol 33.3%, three kinds of solution more than mixing in reactor stir 4 hours at 4 ℃;
(5) in step (4) gained mixing solutions, add defoamer, stir 60 minutes, then blended liquid is pumped into hold-up vessel, standing froth breaking;
(6) check that froth breaking reaches after requirement, blended liquid is pumped into flow-casting film forming machine, casting film-forming, then dry;
(7) dried composite membrane immersed in cross-linking agent solution or be placed under crosslinked condition after crosslinked 12 hours, cleaning, drier;
(8), after forming process, packing, irradiation, obtain type i collagen-sodium alginate-polyvinyl alcohol composite membrane.
Claims (7)
1.I Collagen Type VI-sodium alginate-polyvinyl alcohol composite film material, is characterized in that the Key Performance Indicator of this mould material is as follows:
(1) outward appearance: mould material be white in color or micro-yellow membranaceous, smooth, without the visible impurity of naked eyes;
(2) porosity: 70%～85%;
(3) tensile strength: 30～45MPa;
(4) elongation at break: 30%～40%;
(5) water-intake rate: 1500g/g～2000g/g;
(6) water retention: 300g/g～400g/g;
(7) permeability to water vapour: 37 ℃ time, be 2000 ~ 3000g/ (m under dry state condition
224h);
(8) cell compatibility: cytotoxicity should be not more than 1 grade;
(9) sterility test: aseptic;
(10) thermal source: without thermal source;
(11) sensitization test: without delayed hypersensitivity.
2. according to the preparation method of the composite film material described in claim 1, it is characterized in that:
(1) type i collagen is dissolved in the reactor containing mineral acid or organic acid soln, at 4～10 ℃, stirs and make it to dissolve completely, be mixed with massfraction and be 0.5%～1% type i collagen solution;
(2) sodium alginate powder is dissolved in and in the reactor containing distilled water, is heated to 40～60 ℃ of stirrings and makes it to dissolve completely, be mixed with massfraction and be 1%～5% sodium alginate soln, be cooled to room temperature stand-by;
(3) polyvinyl alcohol is dissolved in and in the reactor containing distilled water, is heated to 50～90 ℃ and makes it to dissolve completely, be mixed with massfraction and be 4%～10% polyvinyl alcohol solution, be cooled to room temperature stand-by;
(4) gained type i collagen in step (1) being neutralized to pH with the sodium hydroxide of 0.2～0.5mol/L is 5～8, then according to the shared mass percent of each raw material: type i collagen 20%～60%, sodium alginate 20%～60%, polyvinyl alcohol 20%～60%, three kinds of solution more than mixing in reactor stir 4～10 hours at 4～10 ℃;
(5) in step (4) gained mixing solutions, add defoamer, stir 20-60 minute, then blended liquid is pumped into hold-up vessel, standing froth breaking;
(6) check that froth breaking reaches after requirement, blended liquid is pumped into flow-casting film forming machine, casting film-forming, then drying and forming-film;
(7) dried film immersed in cross-linking agent solution or be placed under crosslinked condition after crosslinked 4～24 hours, cleaning, drier;
(8), after forming process, packing, irradiation, obtain type i collagen-sodium alginate-polyvinyl alcohol composite membrane.
3. composite film material according to claim 2, it is characterized in that: more than described type i collagen molecular weight 300,000 dalton, there is complete triple helix structure, derive from pigskin, ox-hide, pig tendon or beef tendon, while dissolving type i collagen, acid solution used is a kind of of acetic acid (analytical pure) solution, sulfuric acid (analytical pure) solution or hydrochloric acid (analytical pure) solution.
4. composite film material according to claim 2, is characterized in that: described sodium alginate is analytical pure; The polymerization degree of polyvinyl alcohol is 1500～2600, analytical pure.
5. composite film material according to claim 2, is characterized in that: described defoamer is any one in ethylene glycol, glycerine, ethanol.
6. composite film material according to claim 2, is characterized in that: described linking agent or crosslinked condition are any one or two kinds of in UV-crosslinked, heat cross-linking, 1-ethyl-3-(3-dimethyl amine propyl group)-carbodiimide, diglycidyl ether of ethylene glycol, propanetriol-diglycidyl-ether, genipin, pycnogenols, gallic acid.
7. composite film material according to claim 2, is characterized in that: drying mode is air-dry, lyophilize or microwave low-temperature drying.
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Cited By (6)
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| CN104974384A (en) * | 2015-06-25 | 2015-10-14 | 山东洁晶集团股份有限公司 | Sodium alginate film and preparation method thereof |
| CN108310451A (en) * | 2018-02-07 | 2018-07-24 | 苏州元禾医疗器械有限公司 | A kind of medical dressing promoting wound healing |
| CN108530651A (en) * | 2018-01-25 | 2018-09-14 | 四川大学 | PH is sensitive, can self-healing, can cell adhesion medical aquogel and preparation method thereof |
| CN108578760A (en) * | 2018-02-07 | 2018-09-28 | 苏州元禾医疗器械有限公司 | A kind of preparation method of the medical dressing of promotion wound healing |
| CN109251352A (en) * | 2018-08-30 | 2019-01-22 | 太原理工大学 | A kind of polyvinyl alcohol/sodium alginate of structure-controllable/hydroxyapatite porous support preparation method |
| CN111607114A (en) * | 2020-06-16 | 2020-09-01 | 陕西科技大学 | Preparation method of green degradable multifunctional collagen-based nano composite membrane |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104974384A (en) * | 2015-06-25 | 2015-10-14 | 山东洁晶集团股份有限公司 | Sodium alginate film and preparation method thereof |
| CN108530651A (en) * | 2018-01-25 | 2018-09-14 | 四川大学 | PH is sensitive, can self-healing, can cell adhesion medical aquogel and preparation method thereof |
| CN108310451A (en) * | 2018-02-07 | 2018-07-24 | 苏州元禾医疗器械有限公司 | A kind of medical dressing promoting wound healing |
| CN108578760A (en) * | 2018-02-07 | 2018-09-28 | 苏州元禾医疗器械有限公司 | A kind of preparation method of the medical dressing of promotion wound healing |
| CN109251352A (en) * | 2018-08-30 | 2019-01-22 | 太原理工大学 | A kind of polyvinyl alcohol/sodium alginate of structure-controllable/hydroxyapatite porous support preparation method |
| CN111607114A (en) * | 2020-06-16 | 2020-09-01 | 陕西科技大学 | Preparation method of green degradable multifunctional collagen-based nano composite membrane |
| CN111607114B (en) * | 2020-06-16 | 2022-09-27 | 陕西科技大学 | Preparation method of green degradable multifunctional collagen-based nano composite membrane |
| US11613616B2 (en) | 2020-06-16 | 2023-03-28 | Shaanxi University Of Science & Technology | Preparation method of green, biodegradable, and multifunctional collagen-based nanocomposite film |
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