CN1316465A - Flexible silk fibroin membrane and its preparing process - Google Patents
Flexible silk fibroin membrane and its preparing process Download PDFInfo
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- CN1316465A CN1316465A CN 01108134 CN01108134A CN1316465A CN 1316465 A CN1316465 A CN 1316465A CN 01108134 CN01108134 CN 01108134 CN 01108134 A CN01108134 A CN 01108134A CN 1316465 A CN1316465 A CN 1316465A
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- silk fibroin
- epoxy
- silk
- fibroin
- glycidyl ether
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Abstract
A flexible and tough fibroin membrane used as artificial material to replace human organs such as skin, blood vessal, etc is prepared from silk through degumming, dissolving, dialysis, purifying, mixing with epoxy resin as cross-linking agent and catalyst, and drying. Its advantages include no toxin and harm, high biological compatibility and flexibility, non-crystal structure, and difficult dissolving in water.
Description
The present invention relates to a kind of flexible film that is processed into natural high molecular substance and preparation method thereof, particularly a kind of is flexible silk fibroin membrane of being processed into of main raw material and preparation method thereof with silk.
In the prior art, though multiple synthetic and natural polymer film is arranged, for example polyvinyl alcohol, polyethylene, Mierocrystalline cellulose, urethane, tetrafluoroethylene, chitosan, collagen film etc., but the raw material sources that during used as biomedical material, the biocompatibility that has is bad, have are not enough or cost an arm and a leg.Therefore people seek the medical and biomembrane material of ideal constantly.Silk is made up of about 75% fibroin and about 25% silk gum, is quite pure natural protein fiber, and the amino acid of fibroin is formed with human collagen albumen certain similarity, nontoxicity, has no stimulation, and has excellent biological compatibility.Therefore silk is the more satisfactory raw material of making biomedical mould material.But because regenerated silk protein is water miscible, and snappiness is relatively poor, so fibroin membrane is greatly limited in the range of application of biomedical sector.Before the present invention makes, openly reported a kind of method that makes fibroin membrane be insoluble in water on the magazine of " J.Appl.Polym.Sci.Appl.Polym.Symp " 1985,41,187, fibroin membrane be impregnated in methyl alcohol or the ethanolic soln exactly; Equally, on " Suzhou Silk Polytechnic College journal " 1993,13 (1), 40, also openly reported a kind ofly, made fibroin that the βization transformation take place, thereby reach the method that fibroin membrane is insoluble in the purpose of water with the nascent fibroin membrane of steam treatment.But the fibroin membrane that makes of above-mentioned open report is insoluble in the method for water, because fibroin generation crystallization in the film, relies between the fibroin macromole that a large amount of H keys is combined closely, proper alignment, limited macromolecular displacement, so, hard and crisp in dry state, snappiness is relatively poor, is difficult to be actually utilized.At present, can provide a kind of water that both had been insoluble in, have good flexible fibroin membrane and film-forming method thereof again, not appear in the newspapers as yet.
Purpose of the present invention is exactly the deficiency at prior art, and a kind of water that both had been insoluble in is provided, and has better flexibility and elastic flexible silk fibroin membrane and preparation method thereof again.
For realizing the described flexible silk fibroin membrane of the object of the invention, the technical scheme that adopts is: with domestic silkworm silk or its goods (cocoon layer, silk, raw silk, silk mill's lower temple, silk mill real silk fabric scrap stock etc.) is main raw material, Resins, epoxy is film forming linking agent, make fibroin protein film, silk fibroin content is 50～98% in the film, the structure of fibroin is a non-crystalline state, thus make this film reach in water dissolve-loss ratio less than 1.5%, Young's modulus is less than 200N/mm
2, tensile break strength is greater than 500N/cm
2, elongation at break greater than 45%, the specified elongation elasticity response rate is greater than 60% index.
The preparation method of flexible silk fibroin membrane of the present invention is earlier silk to be obtained pure silk fibroin solution after coming unstuck, dissolve, dialyse, purifying, and carries out the processing of following steps again:
1. be to add linking agent Resins, epoxy in 3～30% the silk fibroin solution at solid content, the addition of Resins, epoxy accounts for and contains 1～50% of solid total amount in the silk fibroin solution;
2. drying and forming-film under 20～80 ℃ temperature condition.
In the above-mentioned flexible silk fibroin membrane preparation, described film forming crosslinking agent is one or more in the following Resins, epoxy:
1.A type glycidyl ether:
In the formula, R is:
2. phenol F type glycidyl ether:
In the formula, R is:
3. aliphatic glycidyl ether:
4. aliphatic epoxy compound:
5. polyether-type glycidyl ether:
6. polyene alcohols glycidyl ether:
7. polyacrylate(s) epoxy compounds:
In the formula, R is: H, CH
3, C
2H
5, C
2H
4OH, C
3H
7, or C
4H
9
Among the above-mentioned preparation method, behind the interpolation linking agent Resins, epoxy, add the catalyzer that accounts for weight epoxy 0～2% again in silk fibroin solution, catalyzer is NaF, NaNO
3, Na
2SO
4, KBr, KI, NaSCN, KSCN, Na
2S
2O
3In a kind of.
Flexible silk fibroin membrane of the present invention owing to being main raw material with the silk fibroin, adopts avirulent Resins, epoxy as linking agent, therefore, has excellent biological compatibility.In addition, owing to contain two or more epoxy group(ing) in the Resins, epoxy molecule, the radical reaction that can have active H with the phenolic hydroxyl group of the alcoholic extract hydroxyl group of Serine in the fibroin macromole, tyrosine, lysine amino, the imidazolyl of Histidine, carboxyl of aspartic acid etc., thereby with crosslinked between the fibroin macromole, compared with prior art, have following advantage:
1. epoxy compounds forms interlinkage between the fibroin macromole, makes to produce the proteic three-dimensional net structure of elastic-like in the fibroin membrane, improves the elasticity of fibroin membrane;
2. the soft segment in the epoxy compounds has higher elasticity, and the elasticity that improves fibroin membrane is had bigger contribution;
3. the gentle chain in the epoxy compounds can will suitably be isolated between the fibroin macromole, prevent to produce between the fibroin macromole a large amount of hydrogen bonded, prevent the fibroin crystallization, be subjected to external force with convenient film and do the time spent, the fibroin macromolecular chain is intersegmental in the three-dimensional network is easy to generate displacement, and this displacement is recoverable, has so both improved the flexibility of fibroin membrane, has improved the elasticity of fibroin membrane again.
Flexible silk fibroin membrane of the present invention and preparation method thereof is further illustrated in conjunction with following embodiment.
Embodiment one:
1. 1 kilogram of cocoon layer is put into 20 liters of concentration and be 0.5% neutral soap solution, handled 2 hours down, take off the silk gum of most silk periphery, obtain pure silk element (being silk fibroin) behind the thorough washing in 98～100 ℃ temperature condition;
2. the pure silk element after will drying with the lithium-bromide solution of 28 liter of 8.5 mol, stirs under 60 ± 2 ℃ temperature, is dissolved into the silk fibroin mixing solutions;
3. be the dialysis material with cellulose membrane, the silk fibroin mixing solutions water of gained is dialysed,, filter with absorbent cotton again, obtain pure silk fibroin protein solution with impurity such as removal lithiumbromides;
4. add aliphatic glycidyl ether type Resins, epoxy in silk fibroin solution, molecular weight is 460～560, and the addition of Resins, epoxy is 37.4% of a solution solid content, fully stirs;
5. add catalyzer KSCN in above-mentioned solution, the addition of catalyzer is 1% of a weight epoxy, fully stirs;
6. above-mentioned solution is injected in the casting film mould of polystyrene system about 5 hours of 50 ℃ of dryings;
7. after moisture equilibrium in 4 hours, in the casting film mould, strip out pliable and tough fibroin membrane, be cut into 10 * 10cm
2Specification is packed and is sealed with the double-layer plastic bag, with the gammairradiation sterilization, gets product then.Its primary structure, performance index are as shown in table 1.
Embodiment two:
1. 0.5 kilogram of leftover bits and pieces raw silk (byproduct behind silk mill's silk cocoon filature) is put into 10 liters of concentration and be 0.05% aqueous sodium carbonate, boiled 0.5 hour, the silk gum of most silk periphery is taken off in re-treatment three times, obtains pure silk element (being silk fibroin);
2. the pure silk element after will drying is 45: 30: 25 nitrocalcite, water, an ethanolic soln with 3 liter weight ratio, stirs under 80 ± 2 ℃ temperature, is dissolved into the fibroin mixing solutions;
3. be the dialysis material with cellulose membrane, the silk fibroin mixing solutions water of gained is dialysed,, filter with the multilayer absorbent gauze again, obtain pure silk fibroin protein solution to remove impurity such as nitrocalcite, ethanol;
4. add the polyether-type tetraglycidel ether epoxy resin in silk fibroin solution, molecular weight is 922～1022, and the addition of Resins, epoxy is 23.3% of a solution solid content, fully stirs;
5. in above-mentioned solution, add catalyst n a
2S
2O
3, the addition of catalyzer is 0.01% of a weight epoxy, fully stirs;
6. above-mentioned solution is injected in the casting film mould of tetrafluoroethylene system, drying is about 3 hours under 60 ℃ temperature;
7. after moisture equilibrium in 8 hours, in the casting film mould, strip out pliable and tough fibroin membrane, be cut into 20 * 20cm
2Specification is packed and is sealed with the double-layer plastic bag, with the gammairradiation sterilization, gets product then.Its primary structure, performance index are as shown in table 2.
Embodiment three:
1. after 1 kilogram of real silk gloss silk fabric (scrap stock of silk mill, concise processing) being cleaned, dried, be 1: 8: 2 calcium chloride, water, ethanolic soln with 20 liters of mol ratios, heating for dissolving under 78 ± 2 ℃ temperature is made the silk fibroin mixing solutions;
2. be the dialysis material with cellulose membrane, the silk fibroin mixing solutions water of gained dialysed that to remove calcium chloride, impurity such as ethanol filter with the multilayer absorbent gauze again, obtain pure silk fibroin protein solution;
3. add the aliphatic epoxy compound in silk fibroin solution, molecular weight is 2627～2737, and the addition of Resins, epoxy is 30.0% of a solution solid content, fully stirs;
4. add catalyzer KI in above-mentioned solution, the addition of catalyzer is 1% of a weight epoxy, fully stirs;
5. above-mentioned solution injects in the casting film mould of polyethylene system, and drying is about 8 hours under about 45 ℃ of temperature;
6. after moisture equilibrium in 6 hours, in the casting film mould, strip out pliable and tough fibroin membrane, be cut into 10 * 10cm
2Specification is packed and is sealed with the double-layer plastic bag, with the gammairradiation sterilization, gets product then.Its primary structure, performance index are as shown in table 3.
Flexible silk fibroin membrane provided by the present invention, it is main raw material with silk, and silk is a kind of quite pure natural protein, and the amino acid of silk fibroin contains a large amount of glycocoll and L-Ala in forming, with the proteic amino acid composition of formation human collagen certain similarity is arranged, therefore the flexible silk fibroin membrane made from it has good consistency, aseptic nontoxic with human body, with low cost, but normal temperature standing storage down; Simultaneously since with Resins, epoxy as linking agent, can make fibroin membrane be insoluble in water, prevented the crystallization of fibroin in the film again, make fibroin membrane possess snappiness preferably.Can be used as surgical repair materials such as endocranium, esophagus, heart valve, blood vessel, ligament, tendon, reach surface of a wound covering, artificial skin material, slow releasing carrier of medication etc.
Table 1
| Thickness (μ m) | Fibroin structure in the film | Dissolve-loss ratio in the water (%) | Breaking tenacity (N/cm 2) | Elongation at break (%) | Elasticity of elongation rate (%) | Young's modulus (N/mm 2) |
| ????50 | Non-crystalline state | ????0.9 | ????520 | ????130.6 | ????69.0 | ??103.5 |
Table 2
| Thickness (μ m) | Fibroin structure in the film | Dissolve-loss ratio in the water (%) | Breaking tenacity (N/cm 2) | Elongation at break (%) | Elasticity of elongation rate (%) | Young's modulus (N/mm 2) |
| ????20 | Non-crystalline state | ????0.5 | ????933.0 | ????101.1 | ????82.0 | ????81.1 |
Table 3
| Thickness (μ m) | Fibroin structure in the film | Dissolve-loss ratio in the water (%) | Breaking tenacity (N/cm 2) | Elongation at break (%) | Elasticity of elongation rate (%) | Young's modulus (N/mm 2) |
| ??110 | Non-crystalline state | ????1.3 | ????1262.0 | ????57.2 | ????98.1 | ????52.3 |
Claims (4)
1. flexible silk fibroin membrane, it is that main raw material processes with domestic silkworm silk or its goods, it is characterized in that: the film forming linking agent of silk fibroin is a Resins, epoxy, silk fibroin content is 50～98% in the film, the structure of fibroin is a non-crystalline state, dissolve-loss ratio is less than 1.5% in the water, and Young's modulus is less than 200N/mm
2, tensile break strength is greater than 500N/cm
2, elongation at break is greater than 45%, and the specified elongation elasticity response rate is greater than 60%.
2. the preparation method as claims 1 described flexible silk fibroin membrane obtains pure silk fibroin solution with silk earlier after coming unstuck, dissolve, dialyse, purifying, and it is characterized in that carrying out the processing of following steps again:
A. add linking agent Resins, epoxy in total solid content is 3～30% silk fibroin solution, the addition of Resins, epoxy accounts for and contains 1～50% of solid total amount in the silk fibroin solution;
B. drying and forming-film under 20～80 ℃ temperature condition.
3. a kind of flexible silk fibroin membrane according to claim 1 is characterized in that: described film forming crosslinking agent is one or more in the following Resins, epoxy:
A. bisphenol A-type glycidyl ether:
In the formula, R is:
B. Bisphenol F type glycidyl ether:
In the formula, R is:
C. aliphatic glycidyl ether:
D. aliphatic epoxy compound:
E. polyether-type glycidyl ether:
F. polyene alcohols glycidyl ether:
In the formula, R is: H, CH
3, C
2H
5, C
2H
4OH, C
3H
7, or C
4H
9
G. polyacrylate(s) epoxy compounds:
In the formula, R is: H, CH
3, C
2H
5, C
2H
4OH, C
3H
7, or C
4H
9
4. the preparation method of a kind of flexible silk fibroin membrane according to claim 2 is characterized in that: behind step a, add the catalyzer that accounts for weight epoxy 0～2% again, described catalyzer is: NaF, NaNO
3, Na
2SO
4, KBr, KI, NaSCN, KSCN, Na
2S
2O
3In a kind of.
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|---|---|---|---|
| CNB011081341A CN1157443C (en) | 2001-03-13 | 2001-03-13 | Flexible silk fibroin membrane and its preparing process |
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| CN1316465A true CN1316465A (en) | 2001-10-10 |
| CN1157443C CN1157443C (en) | 2004-07-14 |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1895266B (en) * | 2006-06-09 | 2010-05-12 | 甘肃省畜牧兽医研究所 | Compound slow-releasing immune enhancer for cock |
| CN101397756B (en) * | 2008-11-03 | 2010-09-08 | 浙江理工大学 | Preparation and application of fibroin strengthening protecting agent |
| CN101053670B (en) * | 2007-04-03 | 2011-02-02 | 浙江理工大学 | Silk fibroin and polymeric lactic acid compound film and its preparation method |
| CN102847198A (en) * | 2012-09-17 | 2013-01-02 | 浙江星月生物科技股份有限公司 | Silk fibroin film insoluble in water, and preparation and application of silk fibroin film |
| CN105968384A (en) * | 2016-05-19 | 2016-09-28 | 苏州大学 | Amorphous silk fibroin nanofiber solution and preparation method thereof |
| CN106456832A (en) * | 2014-06-13 | 2017-02-22 | 大韩民国（农村振兴厅长） | Artificial biomembrane using cocoon and method for manufacturing same |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100395284C (en) * | 2006-04-19 | 2008-06-18 | 东华大学 | Preparation process of SF/SiO2 Nano composite membrane |
| CN101760027B (en) * | 2008-12-26 | 2012-01-04 | 复旦大学 | Regenerated silk fibroin film and preparation method thereof |
-
2001
- 2001-03-13 CN CNB011081341A patent/CN1157443C/en not_active Expired - Fee Related
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1895266B (en) * | 2006-06-09 | 2010-05-12 | 甘肃省畜牧兽医研究所 | Compound slow-releasing immune enhancer for cock |
| CN101053670B (en) * | 2007-04-03 | 2011-02-02 | 浙江理工大学 | Silk fibroin and polymeric lactic acid compound film and its preparation method |
| CN101397756B (en) * | 2008-11-03 | 2010-09-08 | 浙江理工大学 | Preparation and application of fibroin strengthening protecting agent |
| CN102847198A (en) * | 2012-09-17 | 2013-01-02 | 浙江星月生物科技股份有限公司 | Silk fibroin film insoluble in water, and preparation and application of silk fibroin film |
| CN106456832A (en) * | 2014-06-13 | 2017-02-22 | 大韩民国（农村振兴厅长） | Artificial biomembrane using cocoon and method for manufacturing same |
| CN105968384A (en) * | 2016-05-19 | 2016-09-28 | 苏州大学 | Amorphous silk fibroin nanofiber solution and preparation method thereof |
| CN105968384B (en) * | 2016-05-19 | 2018-03-27 | 苏州大学 | A kind of amorphous silk fibroin nano-fiber solution and preparation method thereof |
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|---|---|
| CN1157443C (en) | 2004-07-14 |
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