CN1260363A - Porous fibroin membrane and its preparation method - Google Patents
Porous fibroin membrane and its preparation method Download PDFInfo
- Publication number
- CN1260363A CN1260363A CN 00102103 CN00102103A CN1260363A CN 1260363 A CN1260363 A CN 1260363A CN 00102103 CN00102103 CN 00102103 CN 00102103 A CN00102103 A CN 00102103A CN 1260363 A CN1260363 A CN 1260363A
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Abstract
The present invention uses natural silk as main raw material, and adopts the processes of degumming, dissolving, dialyzing, concentrating and freeze-drying to obtain whole porous silk-extract membrane which possesses excellent biocompatibility, and can be used as wound surface covering and artificial skin material, drug control releasing material and anticoagulant material. Its mean pore size is 1-500 micrometers, its internal pores are communicated each other, its pore structure parameters can be controlled, and its finished product also can be undergone the processes of packaging and disinfection, etc..
Description
The present invention relates to a kind of porous-film that is processed into natural high molecular substance and preparation method thereof, particularly a kind of is main raw material with silk, porous fibroin protein film that is processed into and preparation method thereof.
In the prior art, though kinds of artificial and natural porous polymer film are arranged, for example polystyrene, polyvinyl alcohol, polyethylene, Mierocrystalline cellulose, collagen protein etc., but during used as biomedical material, the biocompatibility that has is bad, the raw material sources that have are not enough or cost an arm and a leg, and therefore, people seek the bio-medical porous material of ideal constantly.Studies have shown that, silk is made up of about 75% fibroin and about 25% silk gum, it is quite pure natural protein fiber, the amino acid of fibroin is formed with human collagen albumen certain similarity, its nontoxicity, nonirritant, have excellent biological compatibility, so silk is the more satisfactory raw material of making biomedical material.Before the present invention makes, Japanese fiber association will 44 (11), 535-540 (1988) has openly reported a kind ofly dries film forming sneak into polyoxyethylene glycol in the fibroin aqueous solution after, and water makes molten the going of polyoxyethylene glycol in the film method of porous fibroin membrane again.But because the aperture very little (＜1 μ m) of the porous-film of making in this way, and be difficult to mutual perforation between the hole in the film, can't satisfy when being used for some biomedical material desired aperture greater than 1 μ m, connect mutually between the internal holes, can control every pore structure parameter, the requirement of whole rather than blocky porous fibroin membrane.
Purpose of the present invention is exactly the deficiency at prior art, and a kind of porous fibroin membrane that can satisfy the biomedical material requirement and preparation method thereof is provided.
Porous fibroin membrane of the present invention, it is that main raw material processes with silk, it is characterized in that: in the described porous fibroin membrane, silk fibroin content is 80%～90%, and all the other are additive; Its outward appearance is a white, does not ftracture, and is soft; Mean pore size is 1～500 μ m; Hole density is 1～3000/mm
2Connect mutually between internal holes and the hole; Dissolve-loss ratio is less than 2% in the water; Rate of perviousness is greater than 100g/m
2H.
The method for preparing porous fibroin membrane of the present invention obtains pure silk fibroin solution with silk earlier after coming unstuck, dissolve, dialyse, purifying, it is characterized in that carrying out the processing of following steps again:
A. under normal temperature～50 ℃,, make its solid content reach 3～30% with the silk fibroin solution evaporation concentration;
B. prepare additive, wherein contain 10～60% R (OH) n, 10～60% RCH (NH
2) COOH, all the other are linking agent;
C. adding concentration and be 0～10% additive in metal die, is freezing 10min～24h under-4～-85 ℃ a certain temperature in temperature;
D. adding additive in spissated silk fibroin solution, inject in the above-mentioned metal die, is freezing 10min～24h in-4～-85 ℃ in temperature;
E. above-mentioned Frozen Body is carried out vacuum-drying, vacuum drying preceding 5～24h, temperature is set in-4～-40 ℃ a certain temperature, in the process of vacuum drying thereafter, per hour heats up 1～10 ℃ until room temperature, makes porous fibroin membrane again after moisture equilibrium.
Described additive, wherein R (OH) n is CH
3CH
2CH
2OH, CH
3CH
2CH
2CH
2OH, CH
3CH
2OH, C
6H
14O
4, CH
2CH (OH) CH
2OH, HOCH
2CH
2OH, HOCH
2CH
2(OH) CH
2OH, HOCH
2(CHOH)
nCH
2OH, HOCH
2CH
2(OCH
2CH
2) nCH
2CH
2Among the OH 1～2 kind; RCH (NH wherein
2) COOH is: CH
3CH (NH
2) COOH, CH
2(NH
2) COOH, H
2NC (NH
2) NH (CH
2)
3CH (NH) COOH, HOOCCH
2CH
2CH (NH
2) COOH, CH
3CH
2(OH) CH (NH
2) COOH, HO-C
6H
4-CH
2CH (NH
2) COOH, H
2N (CH
2)
4CH (NH
2) COOH, HOOCCH
2CH (NH
2) among the COOH 1～2 kind; Wherein linking agent is: a kind of in BTCA, epoxy compounds, the citric acid.
Porous fibroin membrane of the present invention owing to being main raw material with silk, therefore, has excellent biological compatibility; In preparation process, owing to used additive, so can make whole, indehiscent porous fibroin membrane; Simultaneously owing to adopted concentrated-freezing-freezing again-vacuum drying preparation technology, so can control the every pore structure parameter and the physicochemical property of porous fibroin membrane, and make perforation mutually between porous fibroin protein film internal holes and the hole, thereby satisfied the requirement of biomedical material.
Porous-film of the present invention and preparation method thereof is further illustrated by following examples.
Embodiment one:
1. 1 kilogram of silk 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 1: 8: 2 calcium chloride, water, an ethanolic soln with 10 liters of mol ratios, becomes the silk fibroin mixing solutions 78 ± 2 ℃ of following heating for dissolving;
3. 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;
4. the pure silk cellulose solution maintains under 35 ℃, carries out evaporation concentration while stirring, makes the solution solid content reach 16.7%;
5. implantation concentration is 5% additive in aluminum alloy mould, and additive contains 10～60% CH
2CH (OH) CH
2OH, 10～60% CH
3CH
2(OH) CH (NH
2) COOH, all the other were citric acid ,-80 ℃ of following pre-freezes 2 hours;
6. after in spissated silk fibroin solution, adding the additive identical, inject in the above-mentioned aluminum alloy mould, descended freezing 2 hours at-80 ℃ with step 5;
With above-mentioned Frozen Body together with mould, place vacuum-drying in the freeze drier, preceding 24 hours of drying process, homo(io)thermism per hour heats up thereafter 2 ℃, until room temperature in-20 ℃;
8. after moisture equilibrium in 4 hours, in aluminum alloy mould, strip out porous fibroin membrane, be cut into 10 centimetres of specifications of 10 cm x, pack and seal, with the gammairradiation sterilization, get product then with the double-layer plastic bag.Its primary structure, performance index such as table one.
Embodiment two:
1. 0.5 kilogram of leftover bits and pieces silk 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 1: 8: 2 calcium chloride, water, an ethanolic soln with 5 liters of mol ratios, becomes the fibroin mixing solutions 78 ± 2 ℃ of following heating for dissolving;
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 calcium chloride, ethanol;
4. the pure silk cellulose solution maintains under 40 ℃, carries out evaporation concentration while stirring, makes the solution solid content reach 7.4%;
5. implantation concentration is 10% additive in stainless steel mould, and additive contains 10～60% HOCH
2(CHOH)
4CH
2OH, 10～60% H
2N (CH
2)
4CH (NH
2) COOH, all the other were epoxy compounds ,-16 ℃ of following pre-freezes 6 hours;
6. after in spissated silk fibroin solution, adding the additive identical, inject in the above-mentioned stainless steel mould, descended freezing 6 hours at-16 ℃ with step 5;
With above-mentioned Frozen Body together with stainless steel mould, place vacuum-drying in the freeze drier, preceding 18 hours of drying process, homo(io)thermism per hour heats up thereafter 2 ℃, until room temperature in-16 ℃;
8. after moisture equilibrium in 12 hours, in mould, strip out porous fibroin membrane, be cut into 20 centimetres of specifications of 10 cm x, pack and seal, with the gammairradiation sterilization, get product its primary structure, performance index such as table two then with the double-layer plastic bag.
Porous 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 porous fibroin membrane made from it has good tissue consistency, aseptic nontoxic with human body, and has high ventilation, water vapour permeability; The silk raw material is very abundant in China, so cost is lower; Simultaneously because this porous fibroin membrane drying, but normal temperature prolonged preservation down can not go mouldy, so store, transportation and use be all more convenient.It can be used as that the surface of a wound covers and artificial skin material, drug controlled release material, anticoagulant material etc.
Table one:
| Mean pore size (μ m) | Hole density is (individual/mm 2) | Dissolve-loss ratio in the water (%) | Breaking tenacity (N/cm 2) | Elongation at break (%) | Rate of perviousness (g/m 2h) | Rate of compression (%) | Compression work elastic recovery rate (%) |
| ????13.1 | ????1912 | ????0.4 | ????34.3 | ????69.7 | ????267.0 | ????8.8 | ????58.5 |
Table two:
| Mean pore size (μ m) | Hole density is (individual/mm 2) | Dissolve-loss ratio in the water (%) | Breaking tenacity (N/cm 2) | Elongation at break (%) | Rate of perviousness (g/m 2h) | Rate of compression (%) | Compression work elastic recovery rate (%) |
| ????175.1 | ????15.8 | ????1.3 | ????21.7 | ????15.8 | ????290.5 | ????64.3 | ????21.5 |
Claims (3)
1. porous fibroin membrane, it is that main raw material processes with silk, it is characterized in that: in the described porous fibroin membrane, silk fibroin content is 80%～90%, and all the other are additive; Its outward appearance is a white, does not ftracture, and is soft; Mean pore size is 1～500 μ m; Hole density is 1～3000/mm
2Connect mutually between internal holes and the hole; Dissolve-loss ratio is less than 2% in the water; Rate of perviousness is greater than 100g/m
2H.
2. the preparation method of a porous 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. under normal temperature-50 ℃,, make its solid content reach 3～30% with the silk fibroin solution evaporation concentration;
B. prepare additive, wherein contain 10～60% R (OH) n, 10～60% RCH (NH
2) COOH,
All the other are linking agent;
C. adding concentration and be 0～10% additive in metal die, is-4～-85 ℃ in temperature
A certain temperature under freezing 10min～24h;
D. in spissated silk fibroin solution, add additive, inject in the above-mentioned metal die, in temperature
Be freezing 10min～24h in-4～-85 ℃;
E. above-mentioned Frozen Body is carried out vacuum-drying, vacuum drying preceding 5～24h, temperature is set in
-4～-40 ℃ a certain temperature, in the process of vacuum drying thereafter, per hour heat up 1～
10 ℃ until room temperature, makes porous fibroin membrane again after moisture equilibrium.
3. the preparation method of porous fibroin membrane according to claim 2 is characterized in that described additive, and wherein R (OH) n is CH
3CH
2CH
2OH, CH
3CH
2CH
2CH
2OH, CH
3CH
2OH, C
6H
14O
4, CH
2CH (OH) CH
2OH, HOCH
2CH
2OH, HOCH
2CH
2(OH) CH
2OH, HOCH
2(CHOH) nCH
2OH, HOCH
2CH
2(OCH
2CH
2) nCH
2CH
2Among the OH 1～2 kind; RCH (NH wherein
2) COOH is: CH
3CH (NH
2) COOH, CH
2(NH
2) COOH, H
2NC (NH
2) NH (CH
2)
3CH (NH) COOH, HOOCCH
2CH
2CH (NH
2) COOH, CH
3CH
2(OH) CH (NH
2) COOH, HO-C
6H
4-CH
2CH (NH
2) COOH, H
2N (CH
2)
4CH (NH
2) COOH, HOOCCH
2CH (NH
2) among the COOH 1～2 kind; Wherein linking agent is: a kind of in BTCA, epoxy compounds, the citric acid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN00102103A CN1118518C (en) | 2000-02-11 | 2000-02-11 | Porous fibroin membrane and its preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN00102103A CN1118518C (en) | 2000-02-11 | 2000-02-11 | Porous fibroin membrane and its preparation method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1260363A true CN1260363A (en) | 2000-07-19 |
| CN1118518C CN1118518C (en) | 2003-08-20 |
Family
ID=4576269
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN00102103A Expired - Fee Related CN1118518C (en) | 2000-02-11 | 2000-02-11 | Porous fibroin membrane and its preparation method |
Country Status (1)
| Country | Link |
|---|---|
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Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100342924C (en) * | 2004-10-13 | 2007-10-17 | 苏州苏豪生物材料科技有限公司 | Skin substitute and its preparation method |
| CN101857729A (en) * | 2010-06-02 | 2010-10-13 | 苏州大学 | Water-insoluble silk fibroin porous material and preparation method thereof |
| CN101864177A (en) * | 2010-05-28 | 2010-10-20 | 苏州大学 | Preparation method of porous silk fibroin material |
| 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 |
| CN102102278A (en) * | 2011-02-21 | 2011-06-22 | 浙江理工大学 | Preparation method of silk fibroin-poly(hydroxybutyrate-hydroxyvalerate) composite fiber membrane |
| CN101502669B (en) * | 2009-03-05 | 2013-04-17 | 苏州大学 | Silk fibroin porous three-dimensional material and preparation method thereof |
| CN103223193A (en) * | 2013-04-10 | 2013-07-31 | 浙江大学 | High strength silk fibroin bone repair scaffold material preparation method |
| CN103289107A (en) * | 2013-05-28 | 2013-09-11 | 苏州丝美特生物技术有限公司 | Preparation method and application of injectable silk fibroin in-situ gel |
| CN104383598A (en) * | 2014-12-04 | 2015-03-04 | 湖北赛罗生物材料有限责任公司 | Bioactive material as well as preparation method and application thereof |
| WO2016022834A1 (en) * | 2014-08-07 | 2016-02-11 | Tufts University | Microphysiologic methods and compositions |
| CN106189269A (en) * | 2016-08-02 | 2016-12-07 | 安徽美翔塑业有限公司 | A kind of silkworm silk glass fibre is blended antifungal inflight meal bag and preparation method thereof |
| CN111635565A (en) * | 2020-06-03 | 2020-09-08 | 杭州电子科技大学 | Fibroin functional layer for improving mask allergy and preparation method thereof |
| WO2021183056A1 (en) * | 2020-03-11 | 2021-09-16 | Nanyang Technological University | A skin test platform formed from a composite material |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2422308A1 (en) * | 1974-03-07 | 1975-09-18 | Ici Australia Ltd | Polymer film wound dressing - contg. protein, pref. casein (salt), and moisture-retainer, and opt. formed in situ. |
| CN1059129C (en) * | 1995-07-25 | 2000-12-06 | 苏州大学 | Wound surface protection film and its preparation method |
-
2000
- 2000-02-11 CN CN00102103A patent/CN1118518C/en not_active Expired - Fee Related
Cited By (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100342924C (en) * | 2004-10-13 | 2007-10-17 | 苏州苏豪生物材料科技有限公司 | Skin substitute and its preparation method |
| 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 |
| CN101502669B (en) * | 2009-03-05 | 2013-04-17 | 苏州大学 | Silk fibroin porous three-dimensional material and preparation method thereof |
| CN101864177A (en) * | 2010-05-28 | 2010-10-20 | 苏州大学 | Preparation method of porous silk fibroin material |
| CN101857729A (en) * | 2010-06-02 | 2010-10-13 | 苏州大学 | Water-insoluble silk fibroin porous material and preparation method thereof |
| CN101857729B (en) * | 2010-06-02 | 2011-09-14 | 苏州大学 | Water-insoluble silk fibroin porous material and preparation method thereof |
| CN102102278A (en) * | 2011-02-21 | 2011-06-22 | 浙江理工大学 | Preparation method of silk fibroin-poly(hydroxybutyrate-hydroxyvalerate) composite fiber membrane |
| CN103223193A (en) * | 2013-04-10 | 2013-07-31 | 浙江大学 | High strength silk fibroin bone repair scaffold material preparation method |
| CN103289107A (en) * | 2013-05-28 | 2013-09-11 | 苏州丝美特生物技术有限公司 | Preparation method and application of injectable silk fibroin in-situ gel |
| CN103289107B (en) * | 2013-05-28 | 2015-02-04 | 苏州丝美特生物技术有限公司 | Preparation method and application of injectable silk fibroin in-situ gel |
| WO2016022834A1 (en) * | 2014-08-07 | 2016-02-11 | Tufts University | Microphysiologic methods and compositions |
| US11802270B2 (en) | 2014-08-07 | 2023-10-31 | Tufts University | Microphysiologic methods and compositions |
| CN104383598A (en) * | 2014-12-04 | 2015-03-04 | 湖北赛罗生物材料有限责任公司 | Bioactive material as well as preparation method and application thereof |
| CN106189269A (en) * | 2016-08-02 | 2016-12-07 | 安徽美翔塑业有限公司 | A kind of silkworm silk glass fibre is blended antifungal inflight meal bag and preparation method thereof |
| WO2021183056A1 (en) * | 2020-03-11 | 2021-09-16 | Nanyang Technological University | A skin test platform formed from a composite material |
| CN115087706A (en) * | 2020-03-11 | 2022-09-20 | 南洋理工大学 | Skin test platform formed from composite materials |
| CN111635565A (en) * | 2020-06-03 | 2020-09-08 | 杭州电子科技大学 | Fibroin functional layer for improving mask allergy and preparation method thereof |
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| CN1118518C (en) | 2003-08-20 |
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