CN105288734A - Composite crosslinked type I collagen membrane and preparation method thereof - Google Patents
Composite crosslinked type I collagen membrane and preparation method thereof Download PDFInfo
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- CN105288734A CN105288734A CN201510813849.5A CN201510813849A CN105288734A CN 105288734 A CN105288734 A CN 105288734A CN 201510813849 A CN201510813849 A CN 201510813849A CN 105288734 A CN105288734 A CN 105288734A
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Abstract
The invention discloses a preparation method of a composite crosslinked type I collagen membrane. The method includes the steps of: firstly subjecting type I collagen to dissolution stirring in an acid solution in a reaction kettle for 12-24h, then adding a defoaming agent into the solution, conducting stirring for 20-60min, then pumping the solution into a storage tank, and conducting static defoaming; conducting inspection to ensure that defoaming reaches the requirement, then pumping the solution into a film casting machine, carrying out film casting, then performing drying, dipping the film into a first cross-linking agent solution or placing the film under cross-linking conditions for 12-24h, and conducting cleaning, then dipping the film into a second cross-linking agent solution or placing the film under cross-linking conditions for 12-24h, and then performing cleaning and drying; and finally, conducting forming processing, packaging and irradiation, thus obtaining the composite crosslinked type I collagen membrane. The membrane material has good mechanical properties, hydrophilicity, antimicrobial activity and biological compatibility, the degradation rate is controllable and can reach long degradation time, also the preparation process is simple, the equipment is simple, the raw materials are cheap and easily available, and the composite crosslinked type I collagen membrane can be widely used as medical wound dressings, tissue engineering scaffold materials and the like in the medical field.
Description
Technical field
The present invention relates to a kind of composite crosslinking type i collagen film and preparation method thereof, belong to biomedical materials field.
Background technology
Collagen is a kind of natural protein, and its wide material sources, are mainly present in animal skin, bone, heel string, ligament and blood vessel, is structural protein important in connective tissue and cartilaginous tissue.The mainly type i collagen of current most study.Type i collagen, compared with other albumen, has good biological activity, can promote the propagation of cell, growth, differentiation and migration, biodegradable and have good histocompatibility.But mechanical property and the resistance to enzymolysis ability of collagen-based materials are all limited, because which limit its application in biomedical materials field.The modification of collagen-based materials obviously can improve its shortcoming existed with crosslinked.Procyanidin is a kind of plant polyphenol, has stronger antibacterial, antioxidation and capability of resistance to radiation, can form hydrogen bond thus produce crosslinked with collagen, and its safety non-toxic.Oxidizing biomass class cross-linking agent, as oxidized sodium alginate, oxidated carboxymethyl cellulose, oxidized cellulose, oxidation chitosan, Oxytarch class, can be used as biomaterial to use, after oxidation, introduce aldehyde radical, correctability is containing amino material, and it has been proved to be nontoxic under study for action, is a kind of good hydrophilic modifier.
At present, being cross-linked of collagen-based materials, mainly uses the modifier of chemosynthesis class, as formaldehyde, glutaraldehyde, carbodiimides, genipin etc.Such as, patent CN102416195B discloses a kind of preparation method of collagen protein sponge, utilizes the cross-linked collagen sponges such as formaldehyde, glutaraldehyde and carbodiimides to improve its toughness and to reduce degradation rate respectively.Patent CN104399120A discloses a kind of preparation method of collagem membrane, and collagen solution is adjusted pH to 6 ~ 8, then by collagen protein collosol and gel, then is shaken under cross-linking agent EDC effect by blob of viscose and is cross-linked and press mold after cleaning, obtain collagem membrane.
In said method, have the following disadvantages: (1) most of collagen raw material (collagen protein) is the hydrolyzate of collagen, lost collagen keep triple helix time distinctive biological activity, partial properties lose; (2) cross-linking agent self toxicity is comparatively large, and easily remains, and directly affects the biocompatibility of material; (3) crosslink material degree is not high, and mechanical property and resistance to enzymolysis performance can not get larger lifting; (4) cross-linking agent self does not possess useful function, can not give collagen membrane material with new more excellent performance while modification.
Summary of the invention
The object of the invention is for field of biomedical materials provide a kind of mechanical property, biocompatibility, hydrophilic good, there is biocidal property, degradation rate is controlled and composite crosslinking type i collagen film of longer degradation time and preparation method thereof can be reached.
The object of the invention is to be realized by following technical measures:
(1) type i collagen is dissolved in the reactor containing mineral acid or organic acid soln, stirs at 4 ~ 10 DEG C and within 12 ~ 24 hours, make it to dissolve completely, be mixed with the type i collagen solution that mass fraction is 0.5% ~ 1%;
(2) in type i collagen solution, add defoamer, stir 20-60 minute, then solution is pumped into holding vessel, leave standstill froth breaking;
(3), after checking that froth breaking reaches requirement, solution pump is entered flow-casting film forming machine, casting film-forming, then dry;
(4) gained type i collagen film in step (3) is immersed in the first cross-linking agent solution or under being placed in cross linking conditions after crosslinked 12 ~ 24 hours, cleaning;
(5) step (4) gained cross linking membrane is immersed in the second cross-linking agent solution or crosslinked after 12 ~ 24 hours under being placed in cross linking conditions, cleaning, dry;
(6) after processing and forming, packaging, irradiation, namely obtain composite crosslinking type i collagen film.
More than described type i collagen molecular weight 300,000 dalton, there is complete triple helix structure, derive from Corii Sus domestica, Corii Bovis seu Bubali, pig tendon or beef tendon, during dissolving type i collagen, acid solution used is the one of acetum, sulfuric acid solution or hydrochloric acid solution, and above reagent is analytical pure.
Described defoamer is any one in ethylene glycol, glycerol, ethanol.
Described drying mode is air-dry, lyophilization or microwave low-temperature drying.
The first cross-linking agent described is any one or two kinds of in procyanidin, catechin, and cross-linking agent mass concentration is in aqueous 1 ~ 10mg/mL.
Described the second cross-linking agent is any one or two kinds of in oxidized sodium alginate, oxidated carboxymethyl cellulose, oxidized cellulose, oxidation chitosan, Oxytarch, and cross-linking agent mass concentration is in aqueous 0.1 ~ 5mg/mL.
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 ratio is high, and can keep the triple helix structure of collagen preferably and reduce the antigenicity of collagen, retain its biological activity, biocompatibility is good.
2. the first cross-linking agent that the present invention uses is plant extract, and wide material sources, safety non-toxic, both had bacteriostasis, can be used as again effective cross-linking agent of collagen.
3. the second cross-linking agent that the present invention uses is aldehyde crosslinking agent, and biological material has aldehyde radical, crosslinkable collagen after oxidation, and the premium properties simultaneously had because of biological material self also improves the combination property of collagen membrane material.
4. the composite crosslinking method that the present invention uses is cross-linked type i collagen film, and not only increase its mechanical property, impart its biocidal property, and be comparatively used alone the performance that a kind of cross-linking agent further increases its resistance to enzymolysis, biocompatibility is good.
5. preparation technology's simple and stable of the present invention, cost is low, process conditions are gentle, process environmental protection, be easy to realize suitability for industrialized production, and possess the specific function of medical material, there are the potentiality applied, wide market.
Detailed description of the invention
Below by enforcement, the present invention is specifically described; what be necessary to herein means out is that the present embodiment is only used to further illustrate the present invention; and limiting the scope of the invention can not be interpreted as, 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, stirs at 4 DEG C and within 24 hours, make it to dissolve completely, be mixed with the type i collagen solution that mass fraction is 0.5%;
(2) in type i collagen solution, add defoamer glycerol, stir 20 minutes, then solution is pumped into holding vessel, leave standstill froth breaking;
(3), after checking that froth breaking reaches requirement, solution pump is entered flow-casting film forming machine, casting film-forming, then dry;
(4) gained type i collagen film in step (3) is immersed in 2mg/mL procyanidin solution after crosslinked 20 hours, cleaning;
(5) again step (4) gained cross linking membrane is immersed in 0.8mg/mL oxidized fibre cellulose solution after crosslinked 20 hours, cleaning, dry;
(6) again after processing and forming, packaging, irradiation, namely obtain composite crosslinking type i collagen film.
embodiment 2:
(1) type i collagen is dissolved in the reactor containing acetum, stirs at 4 DEG C and within 24 hours, make it to dissolve completely, be mixed with the type i collagen solution that mass fraction is 0.7%;
(2) in type i collagen solution, add defoamer ethanol, stir 20 minutes, then solution is pumped into holding vessel, leave standstill froth breaking;
(3), after checking that froth breaking reaches requirement, solution pump is entered flow-casting film forming machine, casting film-forming, then dry;
(4) gained type i collagen film in step (3) is immersed in 3mg/mL procyanidin solution after crosslinked 24 hours, cleaning;
(5) again step (4) gained cross linking membrane is immersed in 0.5mg/mL oxidized sodium alginate solution after crosslinked 24 hours, cleaning, dry;
(6) again after processing and forming, packaging, irradiation, namely obtain composite crosslinking type i collagen film.
embodiment 3:
(1) type i collagen is dissolved in the reactor containing acetum, stirs at 4 DEG C and within 24 hours, make it to dissolve completely, be mixed with the type i collagen solution that mass fraction is 0.7%;
(2) in type i collagen solution, add defoamer ethanol, stir 20 minutes, then solution is pumped into holding vessel, leave standstill froth breaking;
(3), after checking that froth breaking reaches requirement, solution pump is entered flow-casting film forming machine, casting film-forming, then dry;
(4) gained type i collagen film in step (3) is immersed in 5mg/mL catechin solution after crosslinked 24 hours, cleaning;
(5) step (4) gained cross linking membrane being immersed 2mg/mL is oxidized in chitosan solution after crosslinked 24 hours again, and cleaning is dry;
(6) again after processing and forming, packaging, irradiation, namely obtain composite crosslinking type i collagen film.
Claims (7)
1. a composite crosslinking type i collagen membrane material, is characterized in that the Key Performance Indicator of this membrane material is as follows:
(1) outward appearance: it is membranaceous that membrane material is micro-yellow, smooth, without naked eyes visible foreign;
(2) tensile strength: 40 ~ 60MPa;
(3) elongation at break: 30% ~ 60%;
(4) the degraded by collagenase time: 1 month ~ 12 months;
(5) cell compatibility: cytotoxicity 0 grade or 1 grade;
(6) sterility test: aseptic;
(7) thermal source: without thermal source;
(8) sensitization test: without delayed hypersensitivity.
2., according to the preparation method of the composite crosslinking type i collagen membrane 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, stirs at 4 ~ 10 DEG C and within 12 ~ 24 hours, make it to dissolve completely, be mixed with the type i collagen solution that mass fraction is 0.5% ~ 1%;
(2) in type i collagen solution, add defoamer, stir 20-60 minute, then solution is pumped into holding vessel, leave standstill froth breaking;
(3), after checking that froth breaking reaches requirement, solution pump is entered flow-casting film forming machine, casting film-forming, then dry;
(4) gained type i collagen film in step (3) is immersed in the first cross-linking agent solution or under being placed in cross linking conditions after crosslinked 12 ~ 24 hours, cleaning; Again step (4) gained cross linking membrane is immersed in the second cross-linking agent solution or crosslinked after 12 ~ 24 hours under being placed in cross linking conditions, cleaning, dry; After processing and forming, packaging, irradiation, namely obtain composite crosslinking type i collagen film.
3. composite crosslinking type i collagen film 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 Corii Sus domestica, Corii Bovis seu Bubali, pig tendon or beef tendon, during dissolving type i collagen, acid solution used is the one of acetum, sulfuric acid solution or hydrochloric acid solution, and above reagent is analytical pure.
4. composite crosslinking type i collagen film according to claim 2, is characterized in that: described defoamer is any one in ethylene glycol, glycerol, ethanol.
5. composite crosslinking type i collagen film according to claim 2, is characterized in that: drying mode is air-dry, lyophilization or microwave low-temperature drying.
6. composite crosslinking type i collagen film according to claim 2, is characterized in that: the first cross-linking agent described is any one or two kinds of in procyanidin, catechin, and cross-linking agent mass concentration is in aqueous 1 ~ 10mg/mL.
7. composite crosslinking type i collagen film according to claim 2, it is characterized in that: described the second cross-linking agent is any one or any two kinds in oxidized sodium alginate, oxidated carboxymethyl cellulose, oxidized cellulose, oxidation chitosan, Oxytarch, and cross-linking agent mass concentration is in aqueous 0.1 ~ 5mg/mL.
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Cited By (7)
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| CN106496620A (en) * | 2016-11-22 | 2017-03-15 | 四川大学 | A kind of modified collagen and preparation method thereof |
| CN106821772A (en) * | 2017-03-06 | 2017-06-13 | 广东石油化工学院 | A kind of preparation method of network interpenetrating face mask substrate material |
| CN107513173A (en) * | 2017-08-23 | 2017-12-26 | 四川大学 | A kind of preparation method of organic-silicon-modified collagem membrane |
| CN107551963A (en) * | 2017-10-10 | 2018-01-09 | 吴迪 | A kind of preparation method of industry silicasol |
| CN107602883A (en) * | 2017-08-23 | 2018-01-19 | 四川大学 | A kind of edible collagem membrane of controllable color and preparation method thereof |
| CN111714694A (en) * | 2019-05-30 | 2020-09-29 | 四川大学 | Collagen-based cell scaffold with angiogenesis promoting performance and preparation method thereof |
| CN112920468A (en) * | 2021-01-26 | 2021-06-08 | 江南大学 | Anthocyanin-based freshness indication label and preparation method thereof |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106496620A (en) * | 2016-11-22 | 2017-03-15 | 四川大学 | A kind of modified collagen and preparation method thereof |
| CN106821772A (en) * | 2017-03-06 | 2017-06-13 | 广东石油化工学院 | A kind of preparation method of network interpenetrating face mask substrate material |
| CN107513173A (en) * | 2017-08-23 | 2017-12-26 | 四川大学 | A kind of preparation method of organic-silicon-modified collagem membrane |
| CN107602883A (en) * | 2017-08-23 | 2018-01-19 | 四川大学 | A kind of edible collagem membrane of controllable color and preparation method thereof |
| CN107602883B (en) * | 2017-08-23 | 2020-04-28 | 四川大学 | Edible collagen membrane capable of regulating and controlling color and preparation method thereof |
| CN107551963A (en) * | 2017-10-10 | 2018-01-09 | 吴迪 | A kind of preparation method of industry silicasol |
| CN111714694A (en) * | 2019-05-30 | 2020-09-29 | 四川大学 | Collagen-based cell scaffold with angiogenesis promoting performance and preparation method thereof |
| CN111714694B (en) * | 2019-05-30 | 2021-04-06 | 四川大学 | Collagen-based cell scaffold with angiogenesis promoting performance and preparation method thereof |
| CN112920468A (en) * | 2021-01-26 | 2021-06-08 | 江南大学 | Anthocyanin-based freshness indication label and preparation method thereof |
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