CN103524759B - The preparation method of animal ceratin based high molecular hydrogel and the application as pharmaceutical carrier - Google Patents
The preparation method of animal ceratin based high molecular hydrogel and the application as pharmaceutical carrier Download PDFInfo
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Abstract
The invention provides a kind of preparation method of animal ceratin based high molecular hydrogel, after animal ceratin is scattered in urea or sodium hydroxide solution, with dithiothreitol (DTT) or mercaptoethanol for reductive agent reduces, then with N, N '-methylene-bisacrylamide is linking agent, makes animal ceratin and methacrylic acid carry out being polymerized and obtain.Experiment shows, animal ceratin based high molecular hydrogel prepared by the present invention has good swelling and deswelling performance, and has pH susceptibility, has slow release effect well to small molecule model medicine, therefore can be used as the production of pharmaceutical carrier for pharmaceutical preparation.
Description
Technical field
The invention belongs to technical field of macromolecules, relate to a kind of preparation method of macromolecule hydrogel, particularly relate to a kind of preparation method of animal ceratin based high molecular hydrogel.The present invention also relates to the application of this animal ceratin based high molecular hydrogel as pharmaceutical carrier simultaneously.
Background technology
Keratin sulfate is the one of protein, very abundant at occurring in nature, and China produces hundreds of thousands of ton per year, is extensively present in the epidermis of humans and animals, hair, hoof, shell, pawl and pin etc., is a kind of renewable resources, but is usually abandoned by as waste.Keratin sulfate is the structural protein of ectoderm cell, is extensively present in the skin of animal and the derivative of skin, as hair, hoof, shell, pawl, angle, scale etc.Keratin sulfate can be divided into
α-Keratin sulfate and
β-Keratin sulfate two class.Keratic compositing characteristic is: Gelucystine and Polar Amides acid content higher, demonstrate special soundness because there is a large amount of-S-S-key in its structure.Discarded keratin resource mainly refers to hair, coffin, the toenail of animal, and poultry feather etc.Keratin sulfate is also the class non-food protein enriched the most, and therefore, exploitation keratin resource can not cause the food shortages crisis of similar starch.
Pig feather keratin is a kind of structural protein, has high cystine and a large amount of hydroxy-amino-acids, especially containing a large amount of Serines (15%).Keratin sulfate contains a certain amount of non-covalent interaction (electrostatic force, hydrogen bond and hydrophobic interaction) and covalent linkage interacts (disulfide linkage).The feather keratin based biomaterial of pig (film, cavernous body, support and fiber) has carried out the research of several years.
Natural keratin as a kind of natural macromolecular material, not only abundance, cheap, and there are degradable, physiologically acceptable, some premium propertiess such as thermally-stabilised, can be widely used, there is good economic benefit and development prospect, therefore, need to explore further, develop.Along with the theoretical investigation of keratin and carrying out of applied research, Keratin sulfate has been widely used in feed and textile industry, and has a lot of people both at home and abroad just at the exploitation of research and utilization Keratin sulfate tensio-active agent, flocculation agent, amino acid products, series health-care products and makeup etc.
Although, the Keratin sulfate of high molecular has very high physical strength, excellent processing characteristics, degradability, good biocompatibility, the advantage such as nontoxic and cheap, wound dressings can be used as, play the effect of opposing bacterial activity and accelerating wound healing, thus there is very large recycling and be worth.But Keratin sulfate macromolecular material is little in the application achievements of biomedical sector.Keratin sulfate (CN101372503A) that is simple from feather, pig hair, high efficiency extraction is base material, prepare keratin membrane material (the Fang-Ying Li that can be used for pharmaceutical carrier, Rong-Min Wang, Yu-Feng He etc., Journal of Controlled Release, 2011,152, e92-93).These achievements belong to primary research achievement.
Summary of the invention
The object of the invention is for problems of the prior art, a kind of preparation method of animal ceratin based high molecular hydrogel is provided;
Another object of the present invention is to provide the application of this animal ceratin based high molecular hydrogel a kind of as pharmaceutical carrier.
(1) preparation of animal ceratin based high molecular hydrogel
The preparation of animal ceratin based high molecular hydrogel of the present invention, after animal ceratin is scattered in urea or sodium hydroxide solution, reduce using dithiothreitol (DTT) or mercaptoethanol as reductive agent, then with N, N '-methylene-bisacrylamide is linking agent, make animal ceratin and methacrylic acid carry out being polymerized and obtain, concrete preparation technology is:
Animal ceratin powder is scattered in dispersion liquid, under nitrogen protection, adds reductive agent, stirring reaction 1 ~ 6 hour at 20 ~ 100 DEG C; Add initiator again, stirring reaction 10 ~ 120 minutes at 30 ~ 85 DEG C; Then monomer methacrylic acid and linking agent is added, polyreaction 5 ~ 50 minutes at 30 ~ 85 DEG C; Add sodium bicarbonate to stir, after the bubble collapse in gel, be placed in 20 ~ 80 DEG C of water-baths and continue reaction 0.5 ~ 4 hour formation hydrogel; Finally by hydrogel respectively at 50 ~ 95% aqueous ethanolic solution, soak 12 ~ 24 hours in distilled water, obtain keratin based macromolecule hydrogel.
Described animal ceratin powder is feather keratin powder, pig feather keratin powder.Its concrete preparation technology is see CN101372503A;
Described dispersion liquid is urea soln or the sodium hydroxide solution of concentration 2 ~ 20 mol/L.In order to make animal ceratin powder fully disperse, in 20 ~ 80 DEG C of dispersed with stirring 1 ~ 6 hour;
Described reductive agent is dithiothreitol (DTT) solution or mercaptoethanol; The consumption of reductive agent is 1 ~ 10% of animal ceratin opaque amount;
Described initiator is Potassium Persulphate or ammonium persulphate; The consumption of initiator is 0.1 ~ 1% of animal ceratin opaque amount;
The degree of neutralization of described methacrylic acid is 10 ~ 60%, and its consumption is 3 ~ 10 times of animal ceratin opaque amount;
Described linking agent is N, N '-methylene-bisacrylamide, its consumption is 0.1 ~ 1% of methacrylic acid or animal ceratin opaque amount;
The consumption of described sodium bicarbonate is 5 ~ 10% of animal ceratin opaque amount.
(2) structural characterization of animal ceratin based high molecular hydrogel
1, Infrared spectroscopy
Fig. 1 is the infrared spectrogram (in figure, curve 1 is feather keratin, and curve is feather keratin polymethacrylic acid hydrogel, and curve 3 is polymethyl acrylic acid) of feather keratin based high molecular hydrogel of the present invention.As can be seen from the figure, 1700 and 1180 cm
-1there is the charateristic avsorption band (these peaks are caused by stretch vibrations and flexible vibrations of C-O of C=O) of polymethyl acrylic acid in place.At 1643 cm
-1, 1527 cm
-1with 1237 cm
-1absorption peak be attributed to the amide I band of peptide bond (-CONH-) in feather keratin respectively, acid amides II is with and acid amides III band charateristic avsorption band, and the location tables of above charateristic avsorption band understands the conformation of protein material.582 cm
-1the absorption peak at place is the stretching vibration absorption peak of disulfide linkage S-S in feather keratin, 990cm
-1absorption peak be the charateristic avsorption band of cystine residue C-S key in feather keratin, 3290 cm
-1near be associate-NH ,-OH charateristic avsorption band.Fig. 2 is that (in figure, curve 1 is pig feather keratin for the infrared spectrogram of the feather keratin based macromolecule hydrogel of pig of the present invention; Curve 2 is Keratin sulfate polymethacrylic acid hydrogel, and curve 3 is polymethyl acrylic acid).Can find out, 1702 cm
-1and 1181cm
-1there is the charateristic avsorption band of polymethyl acrylic acid in place.At 1640 cm
-1, 1526cm
-1and 1235cm
-1absorption peak be attributed to the amide I band of peptide bond (-CONH-) in Keratin sulfate respectively, acid amides II is with and acid amides III band charateristic avsorption band, and the location tables of above charateristic avsorption band understands the conformation of protein material.585 cm
-1the absorption peak at place is the stretching vibration absorption peak of disulfide linkage S-S in Keratin sulfate, 991cm
-1absorption peak be the charateristic avsorption band of cystine residue C-S key in Keratin sulfate, 3292cm
-1near be associate-NH ,-OH charateristic avsorption band.Fig. 1,2 result describe methacrylic acid successful graft polymerization in Keratin sulfate.
2, scanning electron microscope analysis
Different amplification is adopted to carry out scanning electron microscope analysis to protein-based macromolecule hydrogel after lyophilize, Fig. 3 is the scanning electron microscope (SEM) photograph (in figure, a is electromicroscopic photograph under feather keratin based high molecular hydrogel high power, and b is electromicroscopic photograph under the feather keratin based macromolecule hydrogel low power of pig) of dry rear protein-based macromolecule hydrogel.Can find out, from low power lens, (b) can see that keratin based macromolecule hydrogel has vesicular structure, and its Powdered Keratin sulfate raw material is without this pass structure.Under high power, can be clearly seen that Keratin sulfate powder is all in networked pore structures; Keratin based hydrogel has hole not of uniform size, and pore distribution is more.This is conducive to load and the release of medicine.
(3) performance analysis of animal ceratin based high molecular hydrogel
1, thermogravimetric analysis
For pig feather keratin, after lyophilize, thermogravimetric analysis is carried out to animal ceratin based high molecular hydrogel of the present invention.Result as shown in Figure 4, can be found out, keratic initial decomposition temperature is respectively 140 DEG C, and extension starting temperature is 210 DEG C, and extension final temperature is 450 DEG C, and weightless slope maximum point temperature is 290 DEG C.The initial decomposition temperature adding the keratin based macromolecule hydrogel that methacrylic polymeric obtains is respectively 220 DEG C, and extension starting temperature is 280 DEG C, and extension final temperature is at 420 DEG C, and weightless slope maximum point temperature is 300 DEG C.Show that the thermostability of keratin based macromolecule hydrogel prepared by the present invention is compared with the keratic good stability of raw material.
2, swelling behavior
Method for testing swelling properties: first, three kinds of common simulated solutions such as difference preparing normal saline, D/W, synthetic urine solution.Secondly, 0.1g animal ceratin based high molecular hydrogel is positioned over respectively the solution of the above-mentioned different physiological condition of 10 mL, leaves standstill hypsokinesis in 3 days and go out solution, take out gel, drain away the water, weigh.Fig. 5 is the swelling ratio of the keratin based macromolecule hydrogel of gained of the present invention in intermediate water, physiological saline, D-Glucose solution, synthetic urine solution (1 is pig feather keratin hydrogel, and 2 is feather keratin hydrogel).Result shows, the swelling ratio of animal ceratin based high molecular hydrogel in intermediate water, D-Glucose is higher, and feather keratin hydrogel swelling ratio at 25 DEG C can reach 190(g/g), pig feather keratin can reach 180(g/g), there is superabsorbent water hydrogel performance.And it is lower at physiological saline, synthetic urine solution swelling ratio.
3, vitro drug release performance
Using rhodamine B as small molecule model medicine, the release performance of the keratin based macromolecule hydrogel of test animal.The keratin based macromolecule hydrogel lyophilize of synthesis is placed on swelling absorption in the rhodamine B aqueous solution, after swelling equilibrium, hydrogel surface after medicine carrying is rinsed and is placed on 37 DEG C, the PBS buffered soln of different pH value discharges, adopt ultraviolet-visible spectrum to detect release behavior to rhodamine B.
Fig. 6 is feather keratin based high molecular hydrogel at 37 DEG C of In-vitro release curves to rhodamine B.Result shows, feather keratin based high molecular hydrogel of the present invention has slow release effect to small molecules (rhodamine B) model drug, and when pH=7.4, drug release has cumulative maximum release rate, and feather keratin based high molecular hydrogel can reach 97% at 24 hours.
Fig. 7 is the feather keratin based macromolecule hydrogel of pig of the present invention 37 DEG C of In-vitro release curves to rhodamine B.Result shows, the feather keratin based macromolecule hydrogel of pig of the present invention has slow release effect to small molecules (rhodamine B) model drug.Wherein, when pH=8.4, drug release has cumulative maximum release rate, and the feather keratin based macromolecule hydrogel of pig can reach 93% at 24 hours.
In sum, animal ceratin based high molecular hydrogel prepared by the present invention has good swelling and deswelling performance, and has pH susceptibility.Experiment shows, keratin based macromolecule hydrogel has slow release effect to small molecule model medicine, therefore, can be used as pharmaceutical carrier for the production of pharmaceutical preparation.
Accompanying drawing explanation
Fig. 1 is the infrared spectrogram of feather keratin based high molecular hydrogel of the present invention;
Fig. 2 is the infrared spectrogram of the feather keratin based macromolecule hydrogel of pig of the present invention;
Fig. 3 is the scanning electron microscope (SEM) photograph of feather keratin based high molecular hydrogel of the present invention;
Fig. 4 is the thermogravimetric curve of the keratin based macromolecule hydrogel of the present invention;
Fig. 5 is keratin based macromolecule hydrogel swelling ratio under various circumstances;
Fig. 6 is that feather keratin based high molecular hydrogel of the present invention is at various ph values to the release profiles of rhodamine B;
Fig. 7 is that the feather keratin based macromolecule hydrogel of pig of the present invention is at various ph values to the release profiles of rhodamine B.
Embodiment
Below by the preparation further instruction of specific embodiment to animal ceratin based high molecular hydrogel of the present invention.
embodiment 1
Take 0.25 g feather keratin powder, be placed in 100mL three-necked bottle, add the urea soln of 25mL 8mol/L, dispersed with stirring 1 hour at 45 DEG C; Logical nitrogen, adds dithiothreitol (DTT) 0.005g, stirs after 1 hour, add ammonium persulphate 0.05g, react 40 minutes; Drip the methacrylic acid (degree of neutralization 50%) that 2mL neutralizes with sodium hydroxide, then the N of 0.25g is added, N '-methylene-bisacrylamide reacts 10 minutes, add 0.25g sodium bicarbonate to stir, in solution to be mixed after bubble collapse, pour in 10mL vial, be placed in 60 DEG C of water-baths and continue reaction 2 hours, form hydrogel; Finally hydrogel is soaked in ethanol 24 hours (within every 2 hours, changing an ethanol), then be placed in water immersion 24 hours (changing a water in every 2 hours), obtain feather keratin based high molecular hydrogel.The swelling ratio of this hydrogel in physiological saline, D/W is respectively 50,190(g/g).
embodiment 2
Take 0.25 g feather keratin powder and be placed in 100mL three-necked bottle, add the urea soln of 25mL 8mol/L, dispersed with stirring 1 hour at 55 DEG C; Logical nitrogen, adds dithiothreitol (DTT) 0.005g, stirs 1 hour, add Potassium Persulphate 0.05g, react after 40 minutes; Drip the methacrylic acid (degree of neutralization 50%) that 2mL neutralizes with sodium hydroxide, then the N of 0.25g is added, N '-methylene-bisacrylamide reacts 10 minutes, add 0.25g sodium bicarbonate to stir, pour in 10mL vial after bubble collapse in solution to be mixed, be placed in 55 DEG C of water-baths to continue reaction and form hydrogel after 2 hours, finally hydrogel is soaked in ethanol 24 hours (within every 2 hours, changing an ethanol), be placed in water again and soak 24 hours (changing a water in every 2 hours), obtain feather keratin based high molecular hydrogel.The swelling ratio of this hydrogel in physiological saline, D/W is respectively 58.4,176(g/g).
embodiment 3
Take 0.25 g feather keratin powder and be placed in 100mL three-necked bottle, add the urea soln of 25mL 8mol/L, dispersed with stirring 1 hour at 65 DEG C; Logical nitrogen, adds dithiothreitol (DTT) 0.005g, stirs 1 hour, add Potassium Persulphate 0.05g, react 40 minutes; Drip the methacrylic acid (degree of neutralization 50%) that 2mL neutralizes with sodium hydroxide, the N of 0.25g is added after dripping, N '-methylene-bisacrylamide reacts 10 minutes, add 0.5g sodium bicarbonate, solution stirring to be mixed evenly, pour in 10ml vial after bubble collapse, is put into 70 DEG C of water-baths and is continued reaction and form hydrogel after 2 hours; Finally hydrogel is soaked in ethanol 24 hours (within every 2 hours, changing an ethanol), then be placed in water immersion 24 hours (changing a water in every 2 hours), obtain feather keratin based high molecular hydrogel.The swelling ratio of this hydrogel in physiological saline, D/W is respectively 30,172(g/g).
embodiment 4
Take 0.25 g feather keratin powder and be placed in 100mL three-necked bottle, add the sodium hydroxide solution of 25mL 1mol/L, dispersed with stirring 1 hour at 65 DEG C; Logical nitrogen, adds dithiothreitol (DTT) 0.001g, stirs 1 hour, add Potassium Persulphate 0.05g, react 40 minutes; Drip the methacrylic acid (degree of neutralization 50%) that 2mL neutralizes with sodium hydroxide, add the N of 0.25g, N '-methylene-bisacrylamide reacts 10 minutes; Add 0.25g sodium bicarbonate, solution stirring to be mixed evenly, pour in 10mL vial after bubble collapse, is placed in 60 DEG C of water-baths and continues reaction and form hydrogel after 2 hours; Finally hydrogel is soaked in ethanol 24 hours (within every 2 hours, changing an ethanol), then be placed in water immersion 24 hours (changing a water in every 2 hours), obtain feather keratin based high molecular hydrogel.The swelling ratio of this hydrogel in physiological saline, D/W is respectively 56.3,167(g/g).
embodiment 5
Take 0.25 g feather keratin powder and be placed in 100mL three-necked bottle, add the urea soln of 25mL 8mol/L, dispersed with stirring 1 hour at 65 DEG C; Logical nitrogen, adds mercaptoethanol 1.0mL, stirs 1 hour, add Potassium Persulphate 0.05g, react 40 minutes; Drip the methacrylic acid (degree of neutralization 50%) that 2mL neutralizes with sodium hydroxide, add the N of 0.25g after dripping, N '-methylene-bisacrylamide reacts 10 minutes; Add 0.25g sodium bicarbonate, solution stirring to be mixed evenly, pour in 10mL vial after bubble collapse, is placed in 55 DEG C of water-baths and continues reaction and form hydrogel after 2 hours; Finally hydrogel is soaked in ethanol 24 hours (within every 2 hours, changing an ethanol), then be placed in water immersion 24 hours (changing a water in every 2 hours), obtain feather keratin based high molecular hydrogel.The swelling ratio of this hydrogel in physiological saline, D/W is respectively 37,178(g/g).
embodiment 6
Take 0.25 g feather keratin powder and be placed in 100mL three-necked bottle, add the urea soln of 25mL 8mol/L, dispersed with stirring 1 hour at 65 DEG C; Logical nitrogen, adds mercaptoethanol 1.0mL, stirs 1 hour, add Potassium Persulphate 0.05g, react 40 minutes; Drip the methacrylic acid (degree of neutralization 50%) that 2mL neutralizes with sodium hydroxide, add the N of 0.25g, N ,-methylene-bisacrylamide reacts 10 minutes; Add 0.25g sodium bicarbonate, solution stirring to be mixed evenly, pour in 10mL vial after bubble collapse, is placed in 65 DEG C of water-baths and continues reaction and form hydrogel after 2 hours; Finally hydrogel is soaked in ethanol 24 hours (within every 2 hours, changing an ethanol), then be placed in water immersion 24 hours (changing a water in every 2 hours), obtain feather keratin based high molecular hydrogel.The swelling ratio of this hydrogel in physiological saline, D/W is respectively 78,190(g/g).
embodiment 7
Take 0.25 g feather keratin powder and be placed in 100mL three-necked bottle, add the urea soln of 25mL 8mol/L, dispersed with stirring 1 hour at 65 DEG C; Logical nitrogen, adds mercaptoethanol 1.0mL, stirs 1 hour, add Potassium Persulphate 0.01g, react 40 minutes; Drip the methacrylic acid (degree of neutralization 50%) that 2mL neutralizes with sodium hydroxide, add the N of 0.25g, N '-methylene-bisacrylamide reacts 1 minute; Add 0.25g sodium bicarbonate, solution stirring to be mixed evenly, pour in 10mL vial after bubble collapse, is placed in 55 DEG C of water-baths and continues reaction and form hydrogel after 2 hours; Finally hydrogel is soaked in ethanol 24 hours (within every 2 hours, changing an ethanol), then be placed in water immersion 24 hours (changing a water in every 2 hours), obtain feather keratin based high molecular hydrogel.The swelling ratio of this hydrogel in physiological saline, D/W is respectively 65,167(g/g).
embodiment 8
Take 0.25 g feather keratin powder and be placed in 100mL three-necked bottle, add the sodium hydroxide solution of 1mol/L, logical nitrogen, dispersed with stirring 1 hour at 65 DEG C; Add dithiothreitol (DTT) 0.005g, stir 1 hour, add Potassium Persulphate 0.03g, react 40 minutes; Drip the methacrylic acid (degree of neutralization 50%) that 2mL neutralizes with sodium hydroxide, add the N of 0.25g, N '-methylene-bisacrylamide reacts 10 minutes; Add 0.25g sodium bicarbonate, solution stirring to be mixed evenly, pour in 10mL vial after bubble collapse, is placed in 55 DEG C of water-baths and continues reaction and form hydrogel after 2 hours, obtain feather keratin based high molecular hydrogel.The swelling ratio of this hydrogel in physiological saline, D/W is respectively 45,159(g/g).
embodiment 9
Take 0.25 g feather keratin powder and be placed in 100mL three-necked bottle, add the urea soln of 25mL 8mol/L, dispersed with stirring 1 hour at 65 DEG C; Logical nitrogen, adds dithiothreitol (DTT) 0.005g, stirs 1 hour, add ammonium persulphate 0.05g, react 40 minutes; Drip the methacrylic acid (degree of neutralization 50%) that 2mL neutralizes with sodium hydroxide, add the N of 0.5g after dripping, N '-methylene-bisacrylamide reacts 10 minutes; Add 0.25g sodium bicarbonate, solution stirring to be mixed evenly, pour in 10mL vial after bubble collapse, is placed in 68 DEG C of water-baths and continues reaction and form hydrogel after 2 hours; Finally hydrogel is soaked in ethanol 24 hours (within every 2 hours, changing an ethanol), then be placed in water immersion 24 hours (changing a water in every 2 hours), obtain feather keratin based high molecular hydrogel.The swelling ratio of this hydrogel in physiological saline, D/W is respectively 47,171(g/g).
embodiment 10
Take 0.25 g feather keratin powder and be placed in 100mL three-necked bottle, add the urea soln of 25mL 8mol/L, dispersed with stirring 1 hour at 65 DEG C; Logical nitrogen, adds dithiothreitol (DTT) 0.005g, stirs 1 hour, add ammonium persulphate 0.05g, react 40 minutes; Drip the methacrylic acid (degree of neutralization 50%) that 2mL neutralizes with sodium hydroxide, then add the N of 0.4g, N '-methylene-bisacrylamide reacts 10 minutes; Add 0.25g sodium bicarbonate, solution stirring to be mixed evenly, pour in 10mL vial after bubble collapse, is placed in 60 DEG C of water-baths and continues reaction and form hydrogel after 2 hours; Finally hydrogel is soaked in ethanol 24 hours (within every 2 hours, changing an ethanol), then be placed in water immersion 24 hours (changing a water in every 2 hours), obtain feather keratin based high molecular hydrogel.The swelling ratio of this hydrogel in physiological saline, D/W is respectively 39,178(g/g).
embodiment 11
Take 0.25 g pig feather keratin powder and be placed in 100mL three-necked bottle, add the sodium hydroxide solution of 1mol/L, dispersed with stirring 1 hour at 45 DEG C; Logical nitrogen, adds dithiothreitol (DTT) 0.005g, stirs 1 hour, add ammonium persulphate 0.05g, react 40 minutes; Drip the methacrylic acid (degree of neutralization 50%) that 2mL neutralizes with sodium hydroxide; Add the N of 0.25g, N '-methylene-bisacrylamide reacts 10 minutes; Add 0.25g sodium bicarbonate, solution stirring to be mixed evenly, pour in 10mL vial after bubble collapse, be placed in 55 DEG C of water-baths to continue reaction and form hydrogel after 2 hours, finally hydrogel is soaked in ethanol 24 hours (within every 2 hours, changing an ethanol), be placed in water again and soak 24 hours (changing a water in every 2 hours), obtain the feather keratin based macromolecule hydrogel of pig.The swelling ratio of this hydrogel in physiological saline, D/W is respectively 48,189(g/g).
embodiment 12
Take 0.25 g pig feather keratin powder and be placed in 100mL three-necked bottle, add the urea soln of 25mL 8mol/L, dispersed with stirring 1 hour at 55 DEG C; Logical nitrogen, adds dithiothreitol (DTT) 0.005g, stirs 1 hour, add ammonium persulphate 0.05g, react 40 minutes; Drip the methacrylic acid (degree of neutralization 50%) that 2mL neutralizes with sodium hydroxide, add the N of 0.25g after dripping, N '-methylene-bisacrylamide reacts 10 minutes; Add 0.25g sodium bicarbonate, solution stirring to be mixed evenly, pour in 10mL vial after bubble collapse, then be placed in 50 DEG C of water-baths to continue reaction and form hydrogel after 2 hours, finally hydrogel is soaked in ethanol 24 hours (within every 2 hours, changing an ethanol), be placed in water again and soak 24 hours (changing a water in every 2 hours), obtain the feather keratin based macromolecule hydrogel of pig.The swelling ratio of this hydrogel in physiological saline, D/W is respectively 34,182(g/g).
embodiment 13
Take 0.25 g pig feather keratin powder and be placed in 100mL three-necked bottle, add the urea soln of 25mL 8mol/L, dispersed with stirring 1 hour at 65 DEG C; Logical nitrogen, adds dithiothreitol (DTT) 0.005g, stirs 1 hour, add ammonium persulphate 0.05g, react 40 minutes; Drip the methacrylic acid (degree of neutralization 50%) that 2mL neutralizes with sodium hydroxide, add the N of 0.25g after dripping, N '-methylene-bisacrylamide reacts 10 minutes; Add 0.5g sodium bicarbonate, solution stirring to be mixed evenly, pour in 10mL vial after bubble collapse, be placed in 70 DEG C of water-baths to continue reaction and form hydrogel after 2 hours, finally hydrogel is soaked in ethanol 24 hours (within every 2 hours, changing an ethanol), be placed in water again and soak 24 hours (changing a water in every 2 hours), obtain the feather keratin based macromolecule hydrogel of pig.The swelling ratio of this hydrogel in physiological saline, D/W is respectively 78,179(g/g).
embodiment 14
Take 0.25 g pig feather keratin powder and be placed in 100mL three-necked bottle, add the urea soln of 25mL 8mol/L, dispersed with stirring 1 hour at 65 DEG C; Logical nitrogen, adds dithiothreitol (DTT) 0.001g, stirs 1 hour, add ammonium persulphate 0.05g, react 40 minutes; Drip the methacrylic acid (degree of neutralization 50%) that 2mL neutralizes with sodium hydroxide, add the N of 0.25g after dripping, N '-methylene-bisacrylamide reacts 10 minutes; Add 0.25g sodium bicarbonate, solution stirring to be mixed evenly, pour in 10mL vial after bubble collapse, be placed in 70 DEG C of water-baths to continue reaction and form hydrogel after 2 hours, finally hydrogel is soaked in ethanol 24 hours (within every 2 hours, changing an ethanol), be placed in water again and soak 24 hours (changing a water in every 2 hours), obtain the feather keratin based macromolecule hydrogel of pig and coagulate.The swelling ratio of this hydrogel in physiological saline, D/W is respectively 48,190(g/g).
embodiment 15
Take 0.25 g pig feather keratin powder and be placed in 100mL three-necked bottle, add the urea soln of 25mL 8mol/L, dispersed with stirring 1 hour at 65 DEG C; Logical nitrogen, adds mercaptoethanol 0.003g, stirs 1 hour; Add ammonium persulphate 0.05g, react 40 minutes; Drip the methacrylic acid (degree of neutralization 50%) that 2mL neutralizes with sodium hydroxide, add the N of 0.25g after dripping, N '-methylene-bisacrylamide reacts 10 minutes; Add 0.25g sodium bicarbonate, solution stirring to be mixed evenly, pour in 10mL vial after bubble collapse, be placed in 70 DEG C of water-baths to continue reaction and form hydrogel after 2 hours, finally hydrogel is soaked in ethanol 24 hours (within every 2 hours, changing an ethanol), be placed in water again and soak 24 hours (changing a water in every 2 hours), obtain the feather keratin based macromolecule hydrogel of pig.This hydrogel is respectively 56 at the swelling ratio of physiological saline, D/W, 188(g/g).
embodiment 16
Take 0.25 g pig feather keratin powder and be placed in 100mL three-necked bottle, add the urea soln of 25mL 8mol/L, dispersed with stirring 1 hour at 65 DEG C; Logical nitrogen, adds dithiothreitol (DTT) 0.005g, stirs 1 hour; Add ammonium persulphate 0.05g, react 40 minutes; Drip the methacrylic acid (degree of neutralization 50%) that 2mL neutralizes with sodium hydroxide, add the N of 0.25g after dripping, N '-methylene-bisacrylamide reacts 10 minutes; Add 0.25g sodium bicarbonate, solution stirring to be mixed evenly, pour in 10mL vial after bubble collapse, be placed in 80 DEG C of water-baths to continue reaction and form hydrogel after 2 hours, finally hydrogel is soaked in ethanol 24 hours (within every 2 hours, changing an ethanol), be placed in water again and soak 24 hours (changing a water in every 2 hours), obtain the feather keratin based macromolecule hydrogel of pig.The swelling ratio of this hydrogel in physiological saline, D/W is respectively 41,163(g/g).
embodiment 17
Take 0.25 g pig feather keratin powder and be placed in 100mL three-necked bottle, add the urea soln of 25mL 8mol/L, dispersed with stirring 1 hour at 65 DEG C; Logical nitrogen, adds mercaptoethanol 0.005g, stirs 1 hour; Add ammonium persulphate 0.01g, react 40 minutes; Drip the methacrylic acid (degree of neutralization 50%) that 2mL neutralizes with sodium hydroxide, the N of 0.25g is added after dripping, N '-methylene-bisacrylamide reacts 10 minutes, add 0.25g sodium bicarbonate, solution stirring to be mixed evenly, pour in 10mL vial after bubble collapse, be placed in 80 DEG C of water-baths to continue reaction and form hydrogel after 2 hours, finally hydrogel is soaked in ethanol 24 hours (within every 2 hours, changing an ethanol), be placed in water again and soak 24 hours (changing a water in every 2 hours), obtain the feather keratin based macromolecule hydrogel of pig.The swelling ratio of this hydrogel in physiological saline, D/W is respectively 59,177(g/g).
embodiment 18
Take 0.25 g pig feather keratin powder and be placed in 100mL three-necked bottle, add the urea soln of 25mL 8mol/L, dispersed with stirring 1 hour at 65 DEG C; Logical nitrogen, adds dithiothreitol (DTT) 0.005g, stirs 1 hour, add ammonium persulphate 0.03g, react 40 minutes; Drip the methacrylic acid (degree of neutralization 50%) that 2mL neutralizes with sodium hydroxide, add the N of 0.25g after dripping, N '-methylene-bisacrylamide reacts 10 minutes; Add 0.25g sodium bicarbonate, solution stirring to be mixed evenly, pour in 10mL vial after bubble collapse, be placed in 80 DEG C of water-baths to continue reaction and form hydrogel after 2 hours, finally hydrogel is soaked in ethanol 24 hours (within every 2 hours, changing an ethanol), be placed in water again and soak 24 hours (changing a water in every 2 hours), obtain the feather keratin based macromolecule hydrogel of pig.The swelling ratio of this hydrogel in physiological saline, D/W is respectively 57,175(g/g).
embodiment 19
Take 0.25 g pig feather keratin powder and be placed in 100mL three-necked bottle, add the urea soln of 25mL 8mol/L, dispersed with stirring 1 hour at 65 DEG C; Logical nitrogen, adds dithiothreitol (DTT) 0.005g, stirs 3 hours, add ammonium persulphate 0.05g, react 40 minutes; Drip the methacrylic acid (degree of neutralization 50%) that 2mL neutralizes with sodium hydroxide, add the N of 0.5g after dripping, N '-methylene-bisacrylamide reacts 10 minutes; Add 0.25g sodium bicarbonate, solution stirring to be mixed evenly, pour in 10mL vial after bubble collapse, be placed in 80 DEG C of water-baths to continue reaction and form hydrogel after 2 hours, finally hydrogel is soaked in ethanol 24 hours (within every 2 hours, changing an ethanol), be placed in water again and soak 24 hours (changing a water in every 2 hours), obtain the feather keratin based macromolecule hydrogel of pig.The swelling ratio of this hydrogel in physiological saline, D/W is respectively 89,145(g/g).
embodiment 20
Take 0.25 g pig feather keratin powder and be placed in 100mL three-necked bottle, add the urea soln of 25mL 8mol/L, dispersed with stirring 2 hours at 65 DEG C; Logical nitrogen, adds dithiothreitol (DTT) 0.005g, stirs 1 hour; Add ammonium persulphate 0.05g, react 40 minutes; Drip the methacrylic acid (degree of neutralization 50%) that 2mL neutralizes with sodium hydroxide, add the N of 0.4g after dripping, N '-methylene-bisacrylamide reacts 10 minutes; Add 0.25g sodium bicarbonate, solution stirring to be mixed evenly, pour in 10mL vial by solution after bubble collapse, be placed in 80 DEG C of water-baths to continue reaction and form hydrogel after 4 hours, finally hydrogel is soaked in ethanol 24 hours (within every 2 hours, changing an ethanol), be placed in water again and soak 24 hours (changing a water in every 2 hours), obtain the feather keratin based macromolecule hydrogel of pig.The swelling ratio of this hydrogel in physiological saline, D/W is respectively 67,187(g/g).
Claims (6)
1. the preparation method of animal ceratin based high molecular hydrogel, is scattered in dispersion liquid by animal ceratin powder, under nitrogen protection, adds reductive agent, stirring reaction 1 ~ 6 hour at 20 ~ 100 DEG C; Add initiator again, stirring reaction 10 ~ 120 minutes at 30 ~ 85 DEG C; Then add monomer methacrylic acid and linking agent, at 30 ~ 85 DEG C, polyreaction obtains gel in 5 ~ 50 minutes; Add sodium bicarbonate to stir, after the bubble collapse in gel, be placed in 20 ~ 80 DEG C of water-baths and continue reaction 0.5 ~ 4 hour formation hydrogel; Finally by hydrogel respectively at 50 ~ 95% aqueous ethanolic solution, soak 12 ~ 24 hours in distilled water, obtain keratin based macromolecule hydrogel;
Described animal ceratin powder is feather keratin powder, pig feather keratin powder;
Described dispersion liquid is urea soln or the sodium hydroxide solution of concentration 2 ~ 20 mol/L;
Described reductive agent is dithiothreitol (DTT) solution or mercaptoethanol; The consumption of reductive agent is 1 ~ 10% of animal ceratin opaque amount;
The degree of neutralization of described monomer methacrylic acid is 10 ~ 60%, and the consumption of methacrylic acid is 3 ~ 10 times of animal ceratin opaque amount.
2. the preparation method of animal ceratin based high molecular hydrogel as claimed in claim 1, is characterized in that: the dispersion of described animal ceratin powder is dispersed with stirring 1 ~ 6 hour at 20 ~ 80 DEG C.
3. the preparation method of animal ceratin based high molecular hydrogel as claimed in claim 1 or 2, is characterized in that: described initiator is Potassium Persulphate or ammonium persulphate; The consumption of initiator is 0.1 ~ 1% of animal ceratin opaque amount.
4. the preparation method of animal ceratin based high molecular hydrogel as claimed in claim 1 or 2, is characterized in that: described linking agent is N, N '-methylene-bisacrylamide, its consumption is 100 ~ 150% of animal ceratin opaque amount.
5. the preparation method of animal ceratin based high molecular hydrogel as claimed in claim 1 or 2, is characterized in that: the consumption of sodium bicarbonate is 5 ~ 10% of animal ceratin opaque amount.
6. as claimed in claim 1 the animal ceratin based high molecular hydrogel prepared of method as the application of pharmaceutical carrier.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107158752A (en) * | 2017-05-25 | 2017-09-15 | 中原工学院 | A kind of responsive to temperature type keratin base inhales the preparation method for releasing light wood material |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104892864B (en) * | 2015-06-03 | 2017-09-22 | 西北师范大学 | The preparation and the application as pharmaceutical carrier of a kind of composite microporous gel of keratin sodium alginate |
| CN104861179B (en) * | 2015-06-03 | 2017-09-12 | 西北师范大学 | The preparation and the application as pharmaceutical carrier of a kind of feather keratin sodium alginate composite high-molecular sensitive hydrogel |
| CN105017495B (en) * | 2015-06-29 | 2017-11-10 | 西北师范大学 | A kind of preparation of soybean protein base dual-sensitivity high molecule micropore gel and the application as pharmaceutical carrier |
| CN105218835B (en) * | 2015-09-25 | 2017-12-12 | 西北师范大学 | A kind of preparation of keratin base sensitive high-molecular gel and the application as pharmaceutical carrier |
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| CN110483705A (en) * | 2019-08-14 | 2019-11-22 | 西安工业大学 | A kind of hemostasis hydrogel and preparation method thereof based on keratin |
| CN111848291A (en) * | 2020-07-09 | 2020-10-30 | 陕西科技大学 | Environment-friendly coated slow-release organic fertilizer and preparation method thereof |
| CN114618010A (en) * | 2020-12-09 | 2022-06-14 | 四川大学 | Multifunctional keratin-based hydrogel and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101798458A (en) * | 2010-03-24 | 2010-08-11 | 中国科学院长春应用化学研究所 | Poly (L-glutamic acid)/polyacrylic acid hydrogel and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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Non-Patent Citations (2)
| Title |
|---|
| "改性羽毛蛋白接枝丙烯酸高吸水性树脂的制备与吸水性能";尹国强等;《化工进展》;20080705;第27卷(第7期);第1100-1105页 * |
| "羊毛角蛋白降解行为机理";徐博等;《北京纺织》;20040430(第4期);第54-56页 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107158752A (en) * | 2017-05-25 | 2017-09-15 | 中原工学院 | A kind of responsive to temperature type keratin base inhales the preparation method for releasing light wood material |
| CN107158752B (en) * | 2017-05-25 | 2019-04-12 | 中原工学院 | The preparation method of light wood material is released in a kind of responsive to temperature type keratin base suction |
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