CN101230135B - Hydrogel materials based on ethylenediaminetetraacetic dianhydride and its uses - Google Patents
Hydrogel materials based on ethylenediaminetetraacetic dianhydride and its uses Download PDFInfo
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Abstract
The invention discloses ethylenediamine tetraacetic anhydride (EDTAh)-based hydrogel material. Firstly, ethylenediamine tetraacetic anhydride EDTAh reacts with diamine DA through amidation reaction to generate an EDTAh-DA linear chain copolymer, namely, pEDTAh-DA, then intramolecular dehydration is performed to pEDTAh-DA in a heated condition to generate copolymer containing poly-imide, namely, EDTAh-DA-Imide, and finally, EDTAh-DA-Imide reacts with a crosslinking agent to generate a cross linking product with pH sensibility. The hydrogel has good biological compatibility, biodegradability and pH sensibility, and is expected to become novel intelligent hydrogel medicine release material.
Description
Technical field
The present invention relates to a class based on Wholly-degradable progress in Intelligent Hydrogel of ethylene diamine tetra-acetic anhydride and preparation method thereof, this hydrogel material is a kind of good drug release material.
Background technology
The drug release material has become the hot subject of biomaterial scholar research both at home and abroad at present.The drug release material of research mainly comprises polyester, polyamino acid, poly phosphate, poly-acid anhydrides, polyacrylic ester, polyacrylamide and hydrogel etc. at present.Under the physiological environment condition, can degrade and to be divided into degraded type and non-degradable type drug release material to the drug release material according to material; To environmental stimulus, have or not response can be divided into intelligent drug release material and common drug releasable material again according to material as temperature, pH value, ionic strength etc.At present the degradable medicaments releasable material of broad research such as poly(lactic acid) (PLA), poly-glycollide (PGA) and multipolymer (PLGA), poly-acid anhydrides etc. directly do not respond the stimulation of environment itself with regard to material, and intellectual drug releasable material such as polyacrylamide and derivative thereof have temperature sensitive characteristic, polyacrylic acid and derivative thereof and have pH susceptibility.Study degradable intelligent drug release material and be an important topic in the current drug release material field.
Hydrogel is meant can be by water swollen semi-solid state crosslinking polymer network.Aquagel state has usually: wetting ability that (1) is extremely good and water-absorbent; (2) thus because of having after the suction and body tissue plesiomorphism, softness, the lubricated environment that the surface provides and the body tissue surface is affine, have excellent biological compatibility; (3) expand character (the Ratner BD that formation gel barrier has the stripping of control medicine because of meeting water or Digestive system, Hoffman AS.Synthetichydrogels for biomedical applications (bio-medical synthetic water gel) .Washington, DC:AmericanChemical Society.1976; 1-36).The ideal hydrogel should have a large amount of hydrophilic radicals and controlled crosslinking degree, thereby forms hydrophilic network.The hydrogel of research such as polyacrylamide, polyacrylic, polyvinyl alcohol etc. mainly are that the free radical reaction formation that relies on two keys is connected to main cross-linked network with C-C at present, and this cross-linked network that connects with C-C all is nondegradable usually.
Based on the present Research of above-mentioned relevant drug release material, study and develop a kind of degradable progress in Intelligent Hydrogel, be the important directions and the breach of present hydrogel researchdevelopment.Yao Kangde etc. once will gather (L-L-glutamic acid-γ-benzyl ester) ammonia and separate the back and generate poly-(L-glutamic acid N-hydroxypropyl ester) hydrogel polypeptide films, and studied this polypeptide films the stimuli responsive function (see Yao Kangde. " intelligent material ". Tianjin: the .1996 of press of University Of Tianjin; 269).Giammona etc. are once in J Controlled Release (sustained release magazine), 1996; 41 (3): utilize glutaraldehyde to α among the 195-203, β-poly-aspartoyl hydrazine carries out crosslinked, has made α, β-poly-aspartoyl hydrazine hydrogel, and be drug target with the cytosine(Cyt), studied the Release Performance of this gel.Kunioka etc. are once in J Environ Polym Degrad (environment polymer degradation magazine), 1996; 4 (2): utilize gamma-radiation irradiation poly-(gamma-glutamic acid) and poly-(ε-Methionin) among the 12-129, made polyglutamic acid/polylysine hydrogel.J PolymScience such as Denis, and Part A:Polym Chemistry (the polymer science magazine, A collects: polymer chemistry), 1996; 34 (10): it is crosslinked that 2019-2027 also utilizes biosynthetic poly-(gamma-glutamic acid) to carry out with saturated dihalide, obtains poly-(gamma-glutamic acid) hydrogel.People such as Liu Zhenhua then make a search for institutes such as above people and are analyzed and improve, thereby with the DL-aspartic acid is monomer, gather-the DL-succimide by the condensation polymerization reaction is synthetic, thanomin and butanediamine with different ratios carries out open loop and crosslinked then, obtain α, β-poly--DL-asparagine derivative hydrogel is though this hydrogel has degradability, but because of its can only depend merely in the hydramine to be introduced-OH regulates pH susceptibility, so its pH susceptibility is not satisfactory.IranPolymer Institute such as Mehdi (Iranian polymkeric substance research institute), 2000; Organic PolymerChemistry Research Laboratory (organic polymer chemical research laboratory) such as 13 January and Shadpour, 2003; 5 September were raw material with diamines and aromatic dicarboxylic cyclic acid anhydride once, had made a kind of carboxylic straight chain prepolymer, and the single step reaction of going forward side by side has obtained a kind of straight chain polymer polymkeric substance that contains binary cyclic imide base.It is linking agent that this high molecular polymer that contains binary cyclic imide base can utilize diamine or hydramine etc., makes the degradable intelligent aqueous gel capable that contains a large amount of amino, hydroxyl or carboxyl.But as the drug release material that uses in the human body, it must satisfy have good blood compatibility and histocompatibility when contacting with biological tissue, developments such as Mehdi etc. and Shadpour remain further checking based on the blood compatibility of the pH sensitive aquagel of aromatic dicarboxylic anhydride and histocompatibility.
Based on above-mentioned analysis, design and develop and a kind ofly collect good biocompatibility, biodegradable, intelligently have great importance for the process that promotes drug release material research for hydrogel drug release material all over the body.
Summary of the invention
The objective of the invention is to design and a kind of hydrogel material of preparation, and set up the preparation method of this hydrogel of cover preparation based on ethylene diamine tetra-acetic anhydride (EDTAD).This hydrogel has good biocompatibility, biodegradable and pH susceptibility, is expected to become a kind of novel hydrogel drug release material.
It is raw material synthetic biodegradable pH sensitive hydrogel drug release material with ethylene diamine tetra-acetic anhydride (EDTAD) that the present invention has designed a kind of, and its preparation process is:
1. ethylene diamine tetra-acetic anhydride (EDTAD) generates EDTAD-DA straight copolymer (pEDTAD-DA) with diamines (DA) by amidate action, and reaction scheme is:
Wherein: R is an alkyl or aryl; N is the polymerization degree, n 〉=2.EDTAh-DA straight-chain polymer (pEDTAh-DA)
2. the pEDTAD-DA that is 1. made by step issues living intramolecular dehydration at heating condition and generates and contain polynary imido multipolymer (EDTAD-DA-Imide).
Wherein: R is an alkyl or aryl.
(EDTAh-DA-Imide)
N is the polymerization degree, n 〉=2.
3. by step make in 2. contain polynary imido multipolymer EDTAD-DA-Imide and the linking agent reaction generates the cross-linking products with pH susceptibility, purpose product promptly of the present invention---based on the hydrogel material of ethylene diamine tetra-acetic anhydride.
EDTA is that a kind of the proof at present can be widely used in human body Ao and close toxin expelling by the complete excretory material of human body.In the present invention, (under physiological pH condition, amine exists with the form of ammonium salt the amido linkage of EDTAD and diamines formation at scission of link generation EDTA and ammonium salt under the effect of enzyme or water.)。The general formula of used diamines (DA) is H
2N-R-NH
2, wherein R is an alkyl or aryl, comprises quadrol (EDA), propylene diamine (PDA), butanediamine (BDA) or hexanediamine aliphatie diamine and aromatic diamines such as Ursol D, mphenylenediamine such as (HAD).EDTAD and DA reaction, reaction system is a solution reaction system, requires used solvent can dissolve EDTAD and DA simultaneously.Such solvent comprises dimethyl sulfoxide (DMSO) (DMSO), N, dinethylformamide (DMF), dioxane etc.According to the difference of diamines, temperature of reaction is 25 ℃-100 ℃, and the reaction times is 3 hours-24 hours.Obtain EDTAD-DA straight copolymer (pEDTAD-DA) after the reaction product of EDTAD and DA is purified.
PEDTAD-DA is the straight-chain polymer of a kind of side chain band-COOH, in the side chain-the molecule dehydration can take place, generate stable six-ring imide in COOH with acid amides on the main chain-CONH-base.In theory, the imido reaction of this generation six-ring is as long as can finish under heating condition.Step of the present invention 2. in, pEDTAD-DA issues living intramolecular dehydration at heating condition and generates and contain polynary imido multipolymer (EDTAD-DA-Imide), its realization approach has following several:
(1) direct heating pEDTAD-DA makes its dehydration form the multipolymer (EDTAD-DA-Imide) that contains polynary imide structure, and temperature is 100 ℃-200 ℃, and the time is 5 hours-15 hours;
(2) heat pEDTAD-DA under the effect of catalyzer, make its dehydration form the multipolymer (EDTAD-DA-Imide) that contains polynary imide structure, temperature is 80 ℃-180 ℃, and the time is 3 hours-10 hours; Used catalyzer comprises phosphoric acid, tetra-sodium, and polyphosphoric acid or p-methyl benzenesulfonic acid etc., catalyst consumption is 0.001%～10% of a pEDTAD-DA quality.
In approach (1) and (2), the pEDTAD-DA thermal dehydration can be body fusion dehydration, also can be in the organic solvent medium that does not contain proton hydrogen thermal dehydration.The organic solvent medium that does not contain proton hydrogen comprises N, dinethylformamide, dimethyl sulfoxide (DMSO), benzene, toluene, dimethylbenzene etc.
Similar to anhydride group, imide is the very high group of a kind of reactive behavior, and as easy as rolling off a log and the group that contains reactive hydrogen are as-NH
2React with-OH, the imide scission of link generates the structure that contains two acid amides respectively and contains the structure of an acid amides and an ester.The polynary imide that contains high reaction activity among the multipolymer EDTAD-DA-Imide that 2. step produces, therefore, imide can partially or completely react with the material that contains reactive hydrogen among the multipolymer EDTAD-DA-Imide, generates the cross-linking copolymer that contains different side-chain radicals.These materials that contain reactive hydrogen comprise diamine, polyamine, hydramine, dibasic alcohol, polyvalent alcohol etc.Step specific implementation process 3. can be divided into following a few class:
(1) is linking agent with diamines or polyamine, generates side chain with EDTA-DA-Imide reaction to contain-the cross-linking agent Amine-crosslinked-pEDTA-DA of NH2.The structural representation of cross-linking agent DA-crosslinked-pEDTA-DA that with the diamines is the linking agent preparation is as follows:
(2) be linking agent with dibasic alcohol or polyvalent alcohol or hydramine, generate side chain with the EDTAD-DA-Imide reaction to contain-the cross-linking agent Alcohol-crosslinked-pEDTA-DA of OH.Wherein, be the cross-linking agent Diol-crosslinked-EDTAD-DA of linking agent preparation with the dibasic alcohol and be that the structural representation of cross-linking agent Alcoholamine-crosslinked-EDTAD-DA of linking agent preparation is as follows with the hydramine:
Wherein: R, R ' are alkyl or aryl.
(Diol-crosslinked-EDTAh-DA) or (Alcoholamine-crosslinked-EDTAh-DA)
(3) be linking agent with diamines+glycol, diamines+polyvalent alcohol, diamines+hydramine, polyamine+glycol, polyamine+polyvalent alcohol or polyamine+hydramine, generate side chain with the EDTA-DA-Imide reaction and contain simultaneously-NH
2Cross-linking agent Aminehydroxyl-crosslinked-pEDTA-DA with-OH.
In step each implementation process described in 3., according to the difference of linking agent, temperature of reaction is controlled at-10 ℃-80 ℃, and the time is 5 hours-48 hours.The used in amounts of linking agent is determined according to the polymerization degree n of EDTAD-DA-Imide, the cross-linked dosage that requires to add is enough to open imide rings all among the EDTAD-DA-Imide and two EDTAD-DA-Imide molecules can be coupled at the crosslinked network structure of formation, also free-NH must be arranged simultaneously
2Or-OH holds existence, to provide cross-linking agent suitable pH susceptibility.Therefore, the consumption of linking agent should be n～2n times of EDTAD-DA-Imide mole dosage, and n is the polymerization degree, n 〉=2.
In the present invention, have following characteristic according to 1., the 2. and 3. made a series of hydrogel materials of step based on ethylene diamine tetra-acetic anhydride (EDTAD):
(1) monomer in all multipolymers all is to connect by amido linkage or ester bond, therefore can be degraded into small molecules fully, and all degraded products all can be had good biological capacitive and security by body metabolism or drainage;
(2) side chain be rich in-COOH or-NH
2Or-OH, have extremely strong wetting ability and water-retaining capacity, what is more important, by adjusting-COOH ,-NH
2With the content adjustable material of-OH susceptibility to different pH values.This from the infrared spectrogram of Fig. 1 pEDTAD-BDA as can be seen, among the figure: 1677.55cm
-1Be the C-O stretching vibration peak of carbonyl in the amido linkage, 1541.65cm
-1Be the flexural vibration peak of N-H in the amido linkage, 1734.65cm
-1Be the stretching vibration peak of carbonyl C-O in the carboxyl, and 3395.77cm
-1Wide and the strong peak that occurs then is-O-H stretching vibration among the COOH and-CONH-in the common result of N-H stretching vibration.These results show, the anhydride bond among the EDTAD with BDA in-NH
2The N-acylation reaction has taken place, and has generated pEDTAD-BDA.Simultaneously, from the infrared spectrogram of Fig. 2 BDA-crosslinked-EDTAD-BDA also as can be seen, among the figure: 1636.26cm
-1Be the C-O stretching vibration peak of carbonyl in the amido linkage, pEDTA-BDA is at 1720cm
-1Carbonyl C-O stretching vibration peak almost completely disappears in place's carboxyl.At 3430.34cm
-1Wide and the strong absorption peak at place is side chain-NH among the BDA-crosslinked-EDTAD-BDA
2The N-H stretching vibration peak and the N-H stretching vibration peak of amido linkage.These results show: among the pEDTAD-BDA-intramolecular dehydration taken place and generated the EDTAD-BDA-Imide that contains imide structure in COOH fully, and the imide among the EDTAD-BDA-Imide fully and BDA taken place crosslinkedly, generated BDA-crosslinked-EDTAD-BDA.
(3) in the cross-linking agent formation of cross-linked network by can hydrolysis or the amido linkage or the ester bond of enzymolysis realize.Therefore, cross-linked network can be degraded, and unlike the cross-linked network non-degradable that connects with the C-C key.
Based on above 3 points, this collection good biocompatibility, biodegradable, intelligent for hydrogel all over the body may have some unique hydrogel character and mechanisms for drug release, being expected has unique application in drug release and other medical field.
Description of drawings
The infrared spectrogram of Fig. 1 pEDTAD-BDA.(KBr pressed disc method, instrument: PE GX type infrared spectrometer)
The infrared spectrogram of Fig. 2 BDA-crosslinked-EDTAD-BDA.(KBr pressed disc method, instrument: PE GX type infrared spectrometer)
Embodiment
In the there-necked flask that thermometer, mechanical stirrer and prolong are housed, add 1.5mol EDTAD and 15ml methyl-sulphoxide (DMSO).Under nitrogen protection, slowly be warming up to 80 ℃, stir the DMSO solution that drips the butanediamine of 16ml 0.1mol/ml down, add in the 90min.React after 6 hours, reaction product is slowly splashed in tetrahydrofuran (THF) (THF) solution filtering precipitate.Adopt the separation and purification of THF-DMSO system to get EDTAD-BDA straight copolymer (pEDTAD-BDA) three times throw out.Ninhydrin is measured the number-average molecular weight of pEDTA-BDA
Polymerization degree n=25.
Embodiment 2 is that feedstock production contains imido multipolymer: EDTAD-BDA-Imide with embodiment 1 product pEDTAD-BDA.0.8 gram phosphoric acid and 100 gram pEDTAD-BDA are put into the twoport flask, and oil bath slowly is warming up to 160 ℃ under the nitrogen protection.React and use DMSO-THF co-precipitation system purification reaction product 3 times after 5 hours, get purified EDTAD-BDA-Imide.
Embodiment 3 is a raw material with embodiment 2 product EDTAD-BDA-Imide, and butanediamine is that linking agent prepares cross-linking agent BDA-crosslinked-pEDTAD-BDA:
After (about 2.53mmol) be dissolved in the 50ml methyl-sulphoxide with 20 gram EDTAD-BDA-Imide, slowly drip the DMSO solution of 8ml0.01mol/ml butanediamine (80mmol), 25 ℃ of temperature of reaction.Dropwise, 25 ℃ were reacted 10 hours down.In reaction solution suspension impouring 300ml distilled water, left standstill 14 days, obtain a large amount of swelling things.Change distilled water, continue to soak the swelling thing 8 hours, repeat this operation 2 times, vacuum-drying gets the crosslinked cross-linking products BDA-crosslinked-pEDTAD-BDA of BDA under the room temperature.
Embodiment 4 is a raw material with embodiment 2 product EDTAD-BDA-Imide, and butyleneglycol (BDO) is a linking agent, preparation cross-linking agent BDO-crosslinked-pEDTAD-BDA:,
10 gram EDTAD-BDA-Imide (about 1.26mmol) are dissolved in the 30ml methyl-sulphoxide.The DMSO solution of slow Dropwise 5 ml 0.01mol/ml butyleneglycol (50mmol), 60 ℃ of temperature of reaction.Dropwise, 60 ℃ were reacted 36 hours down.In reaction solution suspension impouring 300ml distilled water, left standstill 14 days, obtain a large amount of swelling things.Change distilled water, continue to soak the swelling thing 8 hours, repeat this operation 2 times, vacuum-drying gets the crosslinked cross-linking products BDO-crosslinked-pEDTAD-BDA of butyleneglycol under the room temperature.
Embodiment 5 is a raw material with embodiment 2 product EDTAD-BDA-Imide, and thanomin (EOA) is a linking agent, preparation cross-linking agent EOA-crosslinked-pEDTAD-BDA:
10 gram EDTAD-BDA-Imide (about 1.26mmol) are dissolved in the 30ml methyl-sulphoxide.Slowly drip the DMSO solution of 4ml 0.01mol/ml thanomin (40mmol), 40 ℃ of temperature of reaction.Dropwise, 40 ℃ were reacted 48 hours down.In reaction solution suspension impouring 300ml distilled water, left standstill 14 days, obtain a large amount of swelling things.Change distilled water, continue to soak the swelling thing 8 hours, repeat this operation 2 times, vacuum-drying gets the crosslinked cross-linking products EOA-crosslinked-pEDTAD-BDA of thanomin under the room temperature.
Embodiment 6 is a raw material with embodiment 2 product EDTAD-BDA-Imide, and butanediamine (BDA) and butyleneglycol (BDO) are linking agent, preparation cross-linking agent BDABDO-crosslinked-pEDTAD-BDA:
20 gram EDTAD-BDA-Imide (about 2.53mmol) are dissolved in the 60ml methyl-sulphoxide.Drip the DMSO solution of 4ml0.01mol/ml butyleneglycol (40mmol), 60 ℃ of following reactions were cooled to 25 ℃ after 36 hours.Drip the DMSO solution of 4ml 0.01mol/ml butanediamine (40mmol) again, 25 ℃ are incubated 36 hours.In reaction suspension impouring 300ml distilled water, left standstill 14 days, obtain a large amount of swelling things.Change distilled water, continue to soak the swelling thing 8 hours, repeat this operation 2 times, vacuum-drying gets BDA and the crosslinked cross-linking products BDABDO-crosslinked-pEDTAD-BDA of BDO under the room temperature.
Embodiment 7 ethylene diamine tetra-acetic anhydrides (EDTAD) and hexanediamine (HDA) prepared in reaction EDTAD-HDA straight copolymer (pEDTAD-HDA):
In the there-necked flask that thermometer, mechanical stirrer and prolong are housed, add 1.5mol EDTAD and 15ml methyl-sulphoxide (DMSO).Under nitrogen protection, slowly be warming up to 80 ℃, stir the DMSO solution that drips the hexanediamine of 16ml 0.1mol/ml down, drip off in the 90min.React after 15 hours, reaction product is slowly splashed in tetrahydrofuran (THF) (THF) solution filtering precipitate.Adopt the separation and purification of THF-DMSO system to get EDTAD-HDA straight copolymer (pEDTAD-HDA) three times throw out.Number-average molecular weight
Polymerization degree n=133.
Embodiment 8 is that feedstock production contains imido multipolymer EDTAD-HDA-Imide with embodiment 7 product pEDTAD-HDA:
Add 50 gram pEDTAD-HAD and 120ml DMSO in the three-necked bottle that thermometer, agitator and return line are housed, oil bath slowly is warming up to 110 ℃ under the nitrogen protection.Stirring reaction is used DMSO-THF co-precipitation system purification reaction product 3 times after 15 hours, get purified EDTAD-HDA-Imide.
Embodiment 9 is a raw material with embodiment 8 product EDTAD-HDA-Imide, and butanediamine is that linking agent prepares cross-linking agent BDA-crosslinked-pEDTAD-HAD:
After (about 0.222mmol) be dissolved in the 30ml methyl-sulphoxide with 10 gram EDTAD-HDA-Imide, the DMSO solution of slow Dropwise 5 ml0.01mol/ml butanediamine (50mmol), temperature of reaction-5 ℃.Dropwise ,-5 ℃ are warming up to 25 ℃ of reactions 24 hours after the reaction 10 down.In reaction solution suspension impouring 300ml distilled water, left standstill 14 days, obtain a large amount of swelling things.Change distilled water, continue to soak the swelling thing 8 hours, repeat this operation 2 times, vacuum-drying gets the crosslinked cross-linking products BDA-crosslinked-pEDTAD-HDA of BDA under the room temperature.
Claims (10)
1. hydrogel material based on ethylene diamine tetra-acetic anhydride, its preparation process is:
1. ethylene diamine tetra-acetic anhydride EDTAD and diamines DA generate EDTAD-DA straight copolymer pEDTAD-DA by amidate action, and its constitutional features is as follows:
Wherein R is an alkyl or aryl, and n is the polymerization degree, n 〉=2;
2. the pEDTAD-DA that 1. makes of step issues living intramolecular dehydration at heating condition and generates and contain polynary imido multipolymer EDTAD-DA-Imide, and its constitutional features is as follows:
Wherein: R is an alkyl or aryl, and n is the polymerization degree, n 〉=2;
3. by step make in 2. contain polynary imido multipolymer EDTAD-DA-Imide and the linking agent reaction generates the cross-linking products with tool pH susceptibility, promptly based on the hydrogel material of ethylene diamine tetra-acetic anhydride EDTAD.
2. the hydrogel material based on ethylene diamine tetra-acetic anhydride according to claim 1 is characterized in that: described diamines is selected from aliphatie diamine and derivative thereof, or aromatic diamine and derivative thereof, and its constitutional features is H
2N-R-NH
2, wherein R is an alkyl or aryl.
3. the hydrogel material based on ethylene diamine tetra-acetic anhydride according to claim 1, it is characterized in that: describedly generate EDTAD-DA straight copolymer pEDTAD-DA by amidate action by ethylene diamine tetra-acetic anhydride EDTAD and diamines DA, its temperature of reaction is 25 ℃-100 ℃, and the reaction times is 3 hours-24 hours; Its reaction system is a solution reaction, and used solvent can dissolve EDTAD and DA simultaneously.
4. the hydrogel material based on ethylene diamine tetra-acetic anhydride according to claim 3 is characterized in that: solvent for use is dimethyl sulfoxide (DMSO), dimethyl formamide or dioxane.
5. the hydrogel material based on ethylene diamine tetra-acetic anhydride according to claim 1, it is characterized in that: described pEDTAD-DA issues living intramolecular dehydration generation at heating condition and contains polynary imido multipolymer EDTAD-DA-Imide, wherein heating is direct heating pEDTAD-DA, make its dehydration form EDTAD-DA-Imide, temperature is 100 ℃-200 ℃, and the time is 5 hours-15 hours; Or under the effect of catalyzer, heat pEDTAD-DA, and make its dehydration form EDTAD-DA-Imide, temperature is 80 ℃-180 ℃, the time is 3 hours-10 hours; Used catalyzer comprises phosphoric acid, tetra-sodium, polyphosphoric acid or p-methyl benzenesulfonic acid, and consumption is 0.001%～10% of a pEDTAD-DA quality.
6. the hydrogel material based on ethylene diamine tetra-acetic anhydride according to claim 5, it is characterized in that: described pEDTAD-DA issues living intramolecular dehydration generation at heating condition and contains polynary imido multipolymer EDTAD-DA-Imide, wherein dehydration is body fusion dehydration, or in the organic solvent medium that does not contain proton hydrogen thermal dehydration.
7. the hydrogel material based on ethylene diamine tetra-acetic anhydride according to claim 6 is characterized in that: the described organic solvent medium that does not contain proton hydrogen is dimethyl formamide, methyl-sulphoxide, benzene, toluene or dimethylbenzene.
8. the hydrogel material based on ethylene diamine tetra-acetic anhydride according to claim 1, it is characterized in that: described linking agent is diamines, polyamine, glycol, polyvalent alcohol, hydramine, diamines+glycol, diamines+polyvalent alcohol, diamines+hydramine, polyamine+glycol, polyamine+polyvalent alcohol or polyamine+hydramine, its consumption determines according to the polymerization degree n of polymkeric substance EDTAD-DA-Imide, for the n～2n of EDTAD-DA-Imide mole number doubly.
9. the hydrogel material based on ethylene diamine tetra-acetic anhydride according to claim 8 is characterized in that: when linking agent is diamines or polyamine, and the cross-linking products that described EDTAD-DA-Imide and linking agent reaction generate, its side chain has-NH
2When linking agent is glycol or polyvalent alcohol or hydramine, the cross-linking products that described EDTAD-DA-Imide and linking agent reaction generate, its side chain has-OH; When diamines+glycol, diamines+polyvalent alcohol, diamines+hydramine, polyamine+glycol, polyamine+polyvalent alcohol or polyamine+hydramine during as linking agent, the cross-linking products that described EDTAD-DA-Imide and linking agent reaction generate, its side chain has-NH simultaneously
2With-OH; Temperature of reaction is controlled at-10 ℃-80 ℃, and the time is 5 hours-48 hours.
10. any described hydrogel material based on ethylene diamine tetra-acetic anhydride with claim 1-9 is used as drug release material and the biomaterial that is applied to medical field.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1156411A (en) * | 1994-08-10 | 1997-08-06 | 因捷尔拂勒小夫涅德列娜契斯卡耶公司 | B. I. Parlyls (UA) |
-
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1156411A (en) * | 1994-08-10 | 1997-08-06 | 因捷尔拂勒小夫涅德列娜契斯卡耶公司 | B. I. Parlyls (UA) |
Non-Patent Citations (5)
| Title |
|---|
| Functional Polymers29 1.1996,29(1),29-39. * |
| Véronique Montembault et al..Synthesis of chelating molecules as agents for magneticresonance imaging, 31. Polycondensationof diethylenetriaminepentaacetic acid bisanhydride with diolsand diamines.Reactive & Functional Polymers29 1.1996,29(1),29-39. |
| Véronique Montembault et al..Synthesis of chelating molecules as agents for magneticresonance imaging, 31. Polycondensationof diethylenetriaminepentaacetic acid bisanhydride with diolsand diamines.Reactive & * |
| 罗彦凤等.二胺改性聚乳酸的合成与表征.高分子材料科学与工程21 2.2005,21(2),139-142,146. |
| 罗彦凤等.二胺改性聚乳酸的合成与表征.高分子材料科学与工程21 2.2005,21(2),139-142,146. * |
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