CN106399416A - Synthesis method of maillard product modified polycaprolactone in ionic liquid - Google Patents
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Abstract
The invention discloses a synthesis method of maillard product modified polycaprolactone in ionic liquid and belongs to the technical field of modification of polycaprolactone. The synthesis method includes: mixing a solution of small-molecular reducing sugar containing primary hydroxyl groups with a collagen buffer solution, performing freezing and drying to obtain the mixture, and dispersing the mixture in ionic liquid for reaction under the temperature of 60-150DEG C; after reaction is completed, decreasing the temperature to below 100DEG C, adding caprolactone monomers and lipase, taking the maillard product as an initiating agent, and performing ring-opening polymerization under catalysis of lipase to obtain the maillard product modified polycaprolactone. The synthesis method has the advantages that the maillard product is synthesized in the ionic liquid and the modified polycaprolactone is catalyzed and synthesized by adopting the lipase, and moderate reaction condition, no metal residues and the like are achieved.
Description
Technical field
The present invention relates to a kind of synthetic method in ionic liquid for Mei Lade product modification polycaprolactone, belong to poly- own interior
Ester modified technical field.
Background technology
Polycaprolactone is a kind of important medical bio degradation material, and it is widely used as suturess, medicament slow release
Material and Medical rack material.But as medical material, there is the too strong defect of hydrophobicity in polycaprolactone, and this can lead to gather
Caprolactone and cell culture medium are difficult to infiltrate, and the adhesion growth on its surface for the cell is relatively difficult, and foreign body occurs in the course of time
The reaction of the bio-incompatibilities such as reaction, causes aseptic inflammation.Therefore, in order to improve the cell compatibility of polycaprolactone, having must
It is modified.
There are reports, using the groups such as chitin, shitosan, hydroxyethyl cellulose and starch in Digestive Enzyme or
Be incorporated into polycaprolactone end under the catalysis of other inorganic metal catalyst it is achieved that polycaprolactone function modified.With common
Polysaccharose substance compare, albumen is a kind of macro-molecular protein of generally existing in animal body, its cell compatibility more preferably, because
This, if albumen can be introduced in polycaprolactone organization material, more favourable to its cellular affinity of raising and biocompatibility.But
Nobody can be using the modified polycaprolactone of lipase-catalyzed method synthetic proteinses class, this is because albumen itself lacks enough
Lipase-catalyzed site, therefore cannot be directly realized by its functionalization and modification using enzyme law catalysis, if urged using metal ion
Change, then because its hot conditions limits, albumen can occur degeneration in catalytic process, lose modified meaning.
U.S. rad product is one kind that the amino on reducing sugar terminal carbonyl and protein is formed under simple heating condition
Protein-sugar covalent complex.Due to introducing sugar chain in protein molecule, so after Maillard reaction, protein
Property, such as：Dissolubility, emulsibility, foaming characteristic, heat stability etc., all more modified before be greatly improved.Currently for U.S.
The research of Maillard reaction is mainly used in field of food, this is because Maillard reaction occurs mainly in the course of processing of food
In, Maillard reaction all has a major impact to food flavor, color and luster, the dissolving/emulsifying of albumen and the fresh-keeping of food.Additionally,
Recent studies on display Mei Lade product also has special antioxygenic property and anti-microbial property, is therefore used as Mei Lade product anti-
The research of oxidant and other additives is also gradually paid attention to, and has the Maillard reaction in research display body recently to people
Body health also has a major impact, but is applied to Polycaprolactone modified not yet someone's research at present.
In terms of Mei Lade Product formation, existing method is broadly divided into wet method and dry method, wherein wet method be suitable only for sugar and
Albumen is all dissolved in the situation of water, and its response speed is slower, generally requires more than tens hours；Dry method mainly adopts powder thing
Heated after matter mixing, the reaction of this method is very fast, course of reaction acutely, substantially cannot effective control, product property is poor.
Recently, researcher is had to disclose a kind of shitosan-xylan maillard reaction product and its preparation method and application
(CN103304682A) in the invention, researcher make use of ionic liquid to carry out Maillard reaction as solvent, but this
The method of kind is still belonging to the category of wet method, can only be for the thing being dissolved in chloro 1- butyl -3- Methylimidazole. ionic liquid
Matter is useful, and this ionic liquid is limited to the dissolution degree of protein matter, so this application is limited.
In existing Polycaprolactone modified method, using biosynthesis technology, natural polymer is carried out with polycaprolactone
Nzymatic synthesis grafting copolymerization is than a kind of attractive green method of modifying.In the process, enzyme must be in water-less environment
It is catalyzed, but traditional non-aqueous system, how based on toxic solvent, is had negative effect to enzyme activity and stability, very
The application of the method is limited on big degree.In recent years, with the development of this novel green solvent of ionic liquid, this problem has
Prestige is resolved.A lot of research displays, ionic liquid is the perfect medium of lipase-catalyzed synthesis.Most of Digestive Enzyme is in ion
Stability in liquid and selectivity have increase, and the conversion ratio of product is also quite attractive.
In existing ionic liquid, the study on the modification of polycaprolactone focuses primarily upon the strong solvability using ionic liquid
After the natural products such as starch, cellulose or shitosan are dissolved, obtain homogeneous graft, then recycle traditional nothing
Machine metal ion catalyst does initiator to realize the ring-opening polymerisation of caprolactone, finally realizes polycaprolactone end-functionalization and changes
Property.For example：Liu Jiyan using 1- butyl -3- Methylimidazole. bromide ion liquid as the cosolvent of starch and caprolactone, in isooctyl acid
Synthesize biodegradable starch/polycaprolactone graft copolymer under the catalysis of stannous, but this molecular weight of product is relatively low, because
This can be dissolved in water.Huang Qing adopts ionic liquid at room temperature chloro 1- butyl -3- Methylimidazole. as the solvent of Rhizoma amorphophalli glucomannan,
Using stannous octoate as catalyst success in Rhizoma amorphophalli glucomannan surface grafting polycaprolactone long-chain；Zhaodong Wang exists
In 1- ethyl-3-methylimidazole acetate ionic liquid, shitosan/polycaprolactone grafting is catalyzed and synthesized using stannous iso caprylate
Copolymer.These researchs remain traditional inorganic metal catalyzed ring opening polymerization in itself, and ionic liquid is only played the part of wherein
The role of solvent.
Content of the invention
In order to solve the above problems, it is collagen-modified that the present invention proposes direct enzymatic clarification one kind in ionic liquid
The method of polycaprolactone, by introducing cell recognition preferable collagen protein macromole in polycaprolactone material, improves poly-
The cellular affinity of caprolactone material and feature.It is suitable to lipase-catalyzed primary hydroxyl position due to lacking in collagen molecules
Point is it is impossible to directly carry out enzyme process ring-opening polymerisation as initiator to caprolactone using it.For this reason, the present invention will by Maillard reaction
Small molecule reducing sugar containing primary hydroxyl is grafted on collagen protein, the primary hydroxyl number on lifting albumen, obtains being suitable to fat
Enzymatic U.S. rad product, then as initiator, carry out ring-opening polymerization by means of lipase-catalyzed caprolactone monomer,
Finally give Mei Lade product modification polycaprolactone.When this method avoids conventional metals catalyst ring-opening polymerisation, high temperature is to protein
Destruction and its metal ion residue problem, and the Mei Lade product introducing is a kind of glycoprotein, its biocompatibility more preferably,
This product is favorably improved the biocompatibility of polycaprolactone.The inventive method also have efficiently, selectivity is good, action condition temperature
With and the features such as environmental friendliness.
The method synthesizing Mei Lade product modification polycaprolactone in ionic liquid of the present invention, methods described is to contain
The solution of small molecule reducing sugar of primary hydroxyl and the mixing of collagen protein buffer solution, lyophilization obtains mixture, then will mix
Compound is scattered in ionic liquid, reacts at 60～150 DEG C；After completion of the reaction, it is cooled to less than 100 DEG C, add caprolactone
Monomer and Digestive Enzyme, carry out ring-opening polymerization under the catalysis of Digestive Enzyme, obtain Mei Lade product modification polycaprolactone.
In one embodiment of the invention, the described small molecule reducing sugar containing primary hydroxyl be glucose, galactose,
In Lactose etc. any one or multiple.
In one embodiment of the invention, the mass ratio of described sugar and collagen protein is 1:1～1:3.
In one embodiment of the invention, described dispersion be by mixture according to mass fraction 0.1%～5% ratio
Example is scattered in ionic liquid.
In one embodiment of the invention, described ionic liquid be 1- butyl -3- Methylimidazole. hexafluorophosphate or
Person's 1- butyl -3- methyl imidazolium tetrafluoroborate ionic liquid.
In one embodiment of the invention, the mass ratio between described ionic liquid and caprolactone monomer is 0.1
～10.
In one embodiment of the invention, the time of reaction is 5～240 minutes at described 60～150 DEG C.
In one embodiment of the invention, described cooling is to be cooled to less than 60～100 DEG C.
In one embodiment of the invention, described Digestive Enzyme is candida antarctica lipase B or Pancreas Sus domestica fat
Enzyme.
In one embodiment of the invention, described Digestive Enzyme addition be caprolactone monomer quality 0.1%～
10%.
In one embodiment of the invention, the enzyme activity of described Digestive Enzyme is 3000U/g.
In one embodiment of the invention, described ring-opening polymerization is that vibration is anti-at temperature is 60～100 DEG C
Answer 1～144 hour.
In one embodiment of the invention, described preparation method also includes, to anti-after ring-opening polymerization finishes
Answer addition dichloromethane in mixture, so that target product is completely dissolved, filter, then add -20 DEG C of proper volume in filtrate
～-4 DEG C of cold methanols, in -20 DEG C～-4 DEG C environment, standing a period of time, refilters, obtains crude product；Taken out with acetone for solvent
Put on and state crude product, obtain Mei Lade product modification polycaprolactone.
In one embodiment of the invention, the method for the present invention is specifically：
(1) lactose solution and the collagen protein phosphate buffer (pH=7.8) of 1% mass fraction are prepared respectively, according to
Volume ratio 1:3 ratio mix homogeneously, after -20 DEG C of lyophilizations 48 hours, by this mixture according to mass fraction 0.1%～5%
Ratio be scattered in ionic liquid, afterwards ionic liquid temperature is risen to 60～150 DEG C, react 5～240 minutes；
(2) after completion of the reaction, above-mentioned ionic liquid temperature is down to 60 DEG C, is separately added into 6-caprolactone monomer and fat
Enzyme, being placed on temperature after logical nitrogen-sealed is to react 1～144 hour in 60～100 DEG C of constant temperature oscillation reactors；
(3) add the dichloromethane of 2 times of bulk product in above-mentioned product, fall Digestive Enzyme with filter paper filtering afterwards, then to
- 20 DEG C of cold methanols of 10 times of filtrate volumes are added, standing filtered after 24 hours in -20 DEG C of environment, obtained crude product in filtrate；
(4) for solvent, above-mentioned crude product is extracted 24 hours with acetone, obtain Mei Lade product modification polycaprolactone.
Second object of the present invention is to provide the Mei Lade product modification polycaprolactone obtaining according to the method described above.
Third object of the present invention is to provide the application of described Mei Lade product modification polycaprolactone.
In one embodiment of the invention, described application is used as medical material.
In one embodiment of the invention, described application specifically be used as suturess, Thermosensitive Material Used for Controlled Releasing of Medicine or
Medical rack material.
Beneficial effects of the present invention：
(1) the Mei Lade product modification polycaprolactone synthetic method of the present invention, modifying process is environment friendly and pollution-free, by ion
Maillard reaction in liquid introduces the reducing sugar small molecule containing primary hydroxyl on collagen protein, is successfully realized using fat
Catalyzing and synthesizing Mei Lade product modification polycaprolactone, its reaction condition is gentle for enzyme, and non-metallic ion remains.
(2), in the present invention, selected two kinds of ionic liquids not only can be as the disperse medium of Maillard reaction but also permissible
Catalytic reaction medium as Digestive Enzyme.On the one hand ionic liquid to be carried out dry process reaction as heating medium, using so
Method, not only contribute to dispersion and its mixing of reaction substrate, and condition be relatively mild and controlled, the Mei Lade that obtains produces
Physical performance is good；On the other hand：Such ionic liquid is substantially harmless to Digestive Enzyme, and some researchs also show ionic liquid to Digestive Enzyme
Catalytic polymerization also has facilitation, therefore need not remove the open loop that ionic liquid can carry out next step after Maillard reaction
Polyreaction.
(3) product cell affinity is more preferable.The Mei Lade product addressed using the present invention, to Polycaprolactone modified, can obtain
Obtain more preferable cellular affinity, collagen protein and the maillard reaction product of Lactose, have amphipathic, using this material to poly- own
Lactone-modified can lift its cellular affinity, and it is more multi-functional to give it.
Specific embodiments
Wettability method of testing：
Drip method test is carried out using JC2000D4 contact angle measurement.Modified polycaprolactone is pressed using tablet machine
Piece, makes the thin slice of thick about 2mm.During test, smooth for sample is fixed on instrument platform.Dripping at sample 10mm
Deionized water drop, measures the contact angle that water droplet is formed with sample room after 60 seconds, each sample is surveyed 5 times, averaged.
MTT detection is cytotoxic assay (non-direct contact)：
Sample soaks 36h with DMEM after the sterilization of 24h ultraviolet disinfection, is removed by filter (0.22 μm of pore size)
Sample obtains impregnating culture medium, stand-by.NIH/3T3 cell suspending liquid (the 5* of 100 μ L is added in the Tissue Culture Plate in 96 holes
104Individual/mL), it is placed in 37 DEG C, 5%CO2, saturated humidity incubator in cultivate 24h, make cell completely adherent after remove culture plate
In culture medium, add dipping culture medium continue culture 24h, be eventually adding MTT (tetramethyl azo azoles salt) solution of 10 μ L extremely
In every hole, put into and in incubator, continue incubation 4h, the absorbance at 450nm, each sample test are measured by ELISA microplate reader
It is repeated 5 times.
Cytotoxic assay result is expressed as：
Cell survival percentage ratio (%)=A1/A0*100
Wherein, A1, A0 are respectively the absorbance of sample and blank
Grafting efficiency:
Calculated using weight method, grafting efficiency=[graft monomer quality/(graft monomer quality+homopolymerization material
Amount)] * 100%
Hereinafter the preferred embodiments of the present invention are illustrated it will be appreciated that preferred embodiment described herein is only used
In the description and interpretation present invention, it is not intended to limit the present invention.
Embodiment 1：
(1) lactose solution and the collagen protein phosphate buffer (pH=7.8) of 1% mass fraction are prepared respectively, according to
Volume ratio 1:3 ratio mix homogeneously, after -20 DEG C of lyophilizations 48 hours, by this mixture according to mass fraction 0.1% ratio
It is scattered in 1- butyl -3- Methylimidazole. hexafluorophosphoric acid ionic liquid, afterwards ionic liquid temperature is risen to 150 DEG C, react 5
Minute；
(2) after completion of the reaction, above-mentioned ionic liquid temperature is down to 60 DEG C, is separately added into 6-caprolactone monomer and the South Pole is false
Silk Yeast-lipase B, being placed on temperature after logical nitrogen-sealed is to react 1 hour in 100 DEG C of constant temperature oscillation reactors；
(3) add the dichloromethane of 2 times of bulk product in above-mentioned product, fall Digestive Enzyme with filter paper filtering afterwards, then to
- 20 DEG C of cold methanols of 10 times of filtrate volumes are added, standing filtered after 24 hours in -20 DEG C of environment, obtained crude product in filtrate；
(4) for solvent, above-mentioned crude product is extracted 24 hours with acetone, obtain Mei Lade product modification polycaprolactone.
Obtain Mei Lade product modification polycaprolactone through said method, be computed its grafting efficiency and be about 70%, it is pressed
Carry out contact angle test after piece, show that its water droplet wetting contact angle is 45 °, mtt assay detection shows cell survival rate more than 95%.
Embodiment 2：
(1) lactose solution and the collagen protein phosphate buffer (pH=7.8) of 1% mass fraction are prepared respectively, according to
Volume ratio 1:3 ratio mix homogeneously, after -20 DEG C of lyophilizations 48 hours, by this mixture according to mass fraction 0.1% ratio
It is scattered in 1- butyl -3- Methylimidazole. hexafluorophosphoric acid ionic liquid, afterwards ionic liquid temperature is risen to 60 DEG C, reaction
240 minutes；
(2) after completion of the reaction, above-mentioned ionic liquid temperature is down to 60 DEG C, is separately added into 6-caprolactone monomer and Pancreas Sus domestica fat
Fat enzyme, being placed on temperature after logical nitrogen-sealed is to react 144 hours in 60 DEG C of constant temperature oscillation reactors；
(3) add the dichloromethane of 2 times of bulk product in above-mentioned product, fall Digestive Enzyme with filter paper filtering afterwards, then to
- 20 DEG C of cold methanols of 10 times of filtrate volumes are added, standing filtered after 24 hours in -20 DEG C of environment, obtained crude product in filtrate；
(4) for solvent, above-mentioned crude product is extracted 24 hours with acetone, obtain Mei Lade product modification polycaprolactone.
Obtain Mei Lade product modification polycaprolactone through said method, be computed its grafting efficiency and be about 60%, it is pressed
Carry out contact angle test after piece, show that its water droplet wetting contact angle is 50 °, mtt assay detection shows cell survival rate more than 90%.
Embodiment 3：
(1) lactose solution and the collagen protein phosphate buffer (pH=7.8) of 1% mass fraction are prepared respectively, according to
Volume ratio 1:3 ratio mix homogeneously, after -20 DEG C of lyophilizations 48 hours, by this mixture according to mass fraction 0.1% ratio
It is scattered in 1- butyl -3- methyl imidazolium tetrafluoroborate ionic liquid, afterwards ionic liquid temperature is risen to 150 DEG C, react 5
Minute；
(2) after completion of the reaction, above-mentioned ionic liquid temperature is down to 60 DEG C, is separately added into 6-caprolactone monomer and Pancreas Sus domestica fat
Fat enzyme, being placed on temperature after logical nitrogen-sealed is to react 1 hour in 100 DEG C of constant temperature oscillation reactors；
(3) add the dichloromethane of 2 times of bulk product in above-mentioned product, fall porcine pancreatic lipase with filter paper filtering afterwards,
Add -20 DEG C of cold methanols of 10 times of filtrate volumes again in filtrate, standing filtered after 24 hours in -20 DEG C of environment, obtain thick
Product；
(4) for solvent, above-mentioned crude product is extracted 24 hours with acetone, obtain Mei Lade product modification polycaprolactone.
Obtain Mei Lade product modification polycaprolactone through said method, be computed its grafting efficiency and be about 63%, it is pressed
Carry out contact angle test after piece, show that its water droplet wetting contact angle is 50 °, mtt assay detection shows cell survival rate more than 90%.
Embodiment 4：
(1) lactose solution and the collagen protein phosphate buffer (pH=7.8) of 1% mass fraction are prepared respectively, according to
Volume ratio 1:3 ratio mix homogeneously, after -20 DEG C of lyophilizations 48 hours, by this mixture according to mass fraction 0.1% ratio
It is scattered in 1- butyl -3- methyl imidazolium tetrafluoroborate ionic liquid, afterwards ionic liquid temperature is risen to 60 DEG C, reaction
240 minutes；
(2) after completion of the reaction, above-mentioned ionic liquid temperature is down to 60 DEG C, is separately added into 6-caprolactone monomer and the South Pole is false
Silk Yeast-lipase B, being placed on temperature after logical nitrogen-sealed is to react 144 hours in 60 DEG C of constant temperature oscillation reactors；
(3) add the dichloromethane of 2 times of bulk product in above-mentioned product, fall antarctic candida with filter paper filtering afterwards
Lipase B, then add -20 DEG C of cold methanols of 10 times of filtrate volumes in filtrate, standing mistake after 24 hours in -20 DEG C of environment
Filter, obtains crude product；
(4) for solvent, above-mentioned crude product is extracted 24 hours with acetone, obtain Mei Lade product modification polycaprolactone.
Obtain Mei Lade product modification polycaprolactone through said method, be computed its grafting efficiency and be about 72%, it is pressed
Carry out contact angle test after piece, show that its water droplet wetting contact angle is 58 °, mtt assay detection shows cell survival rate more than 85%.
Comparative examples 1：
The ionic liquid of the step (1) of embodiment 1 is substituted with aqueous solution, reaction obtains Mei Lade product, then again will
Product is scattered in ionic liquid, and other steps are consistent with embodiment 1 with parameter.Result shows：This method obtains Mei Lade product
Color is shallower, and this explanation reducing sugar is relatively low to collagen protein grafting degree, reacts, using this product, the modification obtaining further and gathers
Caprolactone, is computed its grafting efficiency and is about 58%, carries out Contact-angle measurement to after its tabletting, and result shows its wetting contact angle
For 70 °, the cell survival rate that mtt assay measures is 75% about, all poly- own not as good as obtaining Mei Lade product modification in ionic liquid
Lactone is good.More than the result shows more efficient during in ionic liquid, Maillard reaction is than aqueous solution, the product obtaining
Wettability and cellular affinity can be also more preferable.
Comparative examples 2：
The step (1) of embodiment 1 is omitted, directly by lactose dispersion in 1- butyl -3- Methylimidazole. hexafluorophosphate from
In sub- liquid, other steps are consistent with embodiment 1 with parameter.Result shows：The lactose modification polycaprolactone that this method obtains, it connects
Branch efficiency is about 47%, and the wetting contact angle that pressed disc method measures is 60 °, and the cell survival rate that mtt assay measures is 70% about, all
Good not as good as Mei Lade product modification polycaprolactone.More than the result shows the wettability of Mei Lade product and cellular affinity energy
Also more preferable.
Comparative examples 3：
The step (1) of embodiment 1 is omitted, directly collagen protein is scattered in 1- butyl -3- Methylimidazole. hexafluorophosphoric acid
In ionic liquid, other steps are consistent with embodiment 1 with parameter.Result shows：This method obtains collagen-modified poly- own interior
Ester products amount is less, is computed its grafting efficiency and is about 4%, the wetting contact angle that pressed disc method measures is 74 °, mtt assay measures
Cell survival rate is 70% about, all good not as good as Mei Lade product modification polycaprolactone.If this explanation is on collagen molecules
Do not introduce the small molecule reducing sugar containing primary hydroxyl, Digestive Enzyme cannot complete the catalysis to polycaprolactone with collagen protein for substrate
Ring-opening polymerization, most of caprolactone monomer is catalyzed into as polycaprolactone homopolymer.
Although the present invention is open as above with preferred embodiment, it is not limited to the present invention, any is familiar with this skill
The people of art, without departing from the spirit and scope of the present invention, can do various changes and modification, therefore the protection model of the present invention
Enclosing should be by being defined that claims are defined.
Claims (10)
1. a kind of method of modification polycaprolactone is it is characterised in that methods described is by the small molecule reducing sugar containing primary hydroxyl
Solution and the mixing of collagen protein buffer solution, lyophilization obtains mixture, then mixture is scattered in ionic liquid,
At 60～150 DEG C, reaction obtains Mei Lade product；After completion of the reaction, it is cooled to less than 100 DEG C, add caprolactone monomer and fat
Fat enzyme, carries out ring-opening polymerization under the catalysis of Digestive Enzyme, obtains Mei Lade product modification polycaprolactone.
2. method according to claim 1 is it is characterised in that the described small molecule reducing sugar containing primary hydroxyl is following
Any one or multiple：Glucose, galactose, Lactose.
3. method according to claim 1 is it is characterised in that described ionic liquid is 1- butyl -3- Methylimidazole. hexafluoro
Phosphate or 1- butyl -3- methyl imidazolium tetrafluoroborate ionic liquid.
4. method according to claim 1 is it is characterised in that described dispersion is according to mass fraction 0.1% by mixture
～5% ratio is scattered in ionic liquid；Mass ratio between described ionic liquid and caprolactone monomer is 0.1～10.
5. method according to claim 1 it is characterised in that described Digestive Enzyme be candida antarctica lipase B or
Porcine pancreatic lipase.
6. method according to claim 1 is it is characterised in that described ring-opening polymerization is to be 60～100 DEG C in temperature
Lower oscillating reactionss 1～144 hour.
7. method according to claim 1 is it is characterised in that described Digestive Enzyme addition is caprolactone monomer quality
0.1%～10%.
8. method according to claim 1 is it is characterised in that described preparation method also includes, complete in ring-opening polymerization
Add dichloromethane in Bi Houxiang reactant mixture, so that target product is completely dissolved, filter, then add proper volume in filtrate
- 20 DEG C～-4 DEG C cold methanols, in -20 DEG C～-4 DEG C environment standing a period of time, refilter, obtain crude product；With acetone
For the above-mentioned crude product of solvent extraction, obtain the collagen-modified polycaprolactone of glycosylation.
9. the Mei Lade product modification polycaprolactone obtaining according to the arbitrary methods described of claim 1～8.
10. the application of the Mei Lade product modification polycaprolactone described in claim 9.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103059280A (en) * | 2013-02-04 | 2013-04-24 | 武汉理工大学 | Natural polysaccharide-grafted polycaprolactone in ionic liquid as well as preparation method and application thereof |
| CN103642006A (en) * | 2013-11-29 | 2014-03-19 | 华南理工大学 | Method for grafting polycaprolactone onto hemicellulose in ionic liquid |
| CN105061733A (en) * | 2015-07-30 | 2015-11-18 | 南京林业大学 | Synthesis method of cellulose grafted polycaprolactone |
| CN105541998A (en) * | 2015-12-10 | 2016-05-04 | 中国海洋大学 | Glycosylation method for improving emulsification stability of collagen |
-
2016
- 2016-10-26 CN CN201610943833.0A patent/CN106399416B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103059280A (en) * | 2013-02-04 | 2013-04-24 | 武汉理工大学 | Natural polysaccharide-grafted polycaprolactone in ionic liquid as well as preparation method and application thereof |
| CN103642006A (en) * | 2013-11-29 | 2014-03-19 | 华南理工大学 | Method for grafting polycaprolactone onto hemicellulose in ionic liquid |
| CN105061733A (en) * | 2015-07-30 | 2015-11-18 | 南京林业大学 | Synthesis method of cellulose grafted polycaprolactone |
| CN105541998A (en) * | 2015-12-10 | 2016-05-04 | 中国海洋大学 | Glycosylation method for improving emulsification stability of collagen |
Non-Patent Citations (6)
| Title |
|---|
| INES SOUSA ET AL.: "Collagen surface modified poly(ε-caprolactone) scaffolds with improved hydrophilicity and cell adhesion properties", 《MATERIALS LETTERS》 * |
| LAURENCE ROUXHET ET AL.: "Adsorption of albumin collagen and fibronectin on the surface of poly hydroxybutyrate hydroxyvalerate PHB HV and of poly caprolactone PCL films modified by an alkaline hydrolysis and of poly(ethylene terephtalate)(PET) track-etched membranes", 《JNOURNAL OF BIOMATERIALS SCIENCE，POLYMER EDITION》 * |
| 刘建垒等: "牛血清白蛋白与不同糖美拉德反应体系的荧光光谱学研究", 《食品安全质量检测学报》 * |
| 张敏等: "胶原膜糖基化产物的制备及表征", 《皮革科学与工程》 * |
| 戴亚平等: "端基含乳糖的改性聚己内酯的酶法合成", 《化工新型材料》 * |
| 许宁: "生物可降解性聚酯的亲水修饰及功能化", 《道客巴巴》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108752938A (en) * | 2018-06-21 | 2018-11-06 | 宁波沸柴机器人科技有限公司 | A kind of food package film and its preparation and application |
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