CN1613890A - Biological degradable PES graft polyphosphonitrile copolymer and its preparation - Google Patents
Biological degradable PES graft polyphosphonitrile copolymer and its preparation Download PDFInfo
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- CN1613890A CN1613890A CNA2003101032586A CN200310103258A CN1613890A CN 1613890 A CN1613890 A CN 1613890A CN A2003101032586 A CNA2003101032586 A CN A2003101032586A CN 200310103258 A CN200310103258 A CN 200310103258A CN 1613890 A CN1613890 A CN 1613890A
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Abstract
A biotic degradation polyester graft polyphosphazene interpolymer and its preparation method are disclosed. The biotic degradation polyester graft polyphosphazene interpolymer can be prepared by open loop polymerizing of lactonic monomer initiated by linear polyphosphazene containing side group that replaced the hydroxy. The adjustment of the hydrophilia, degradation, biotic compatible and the cellular affinity can be done to satisfy the different medical purpose through choosing different kinds of the second or the third replacing group and controlling their substituted ratio. Its advantages include: excellent biotic degradation, biotic compatible and non-toxicity.
Description
Technical field:
The present invention relates to a kind of biodegradability polyester grafting polyphosphonitrile multipolymer and preparation method thereof.
Background technology:
Biodegradable polymer is to be hydrolyzed, or is promoted degraded by enzyme, microorganism, thereby causes molecular weight and molecular weight, lose intensity, so that eventual degradation becomes small molecules, monomer, or becomes the polymer of carbonic acid gas and water.After utilizing biodegradable polymer as suture, nail or other medical repair materials, because material degradation in vivo and metabolism voluntarily, final or be excreted or absorbed by body, after repairing, organ needs trouble that their are taken out again thereby can exempt; Can also adopt such material as pharmaceutical carrier, realize the long-term control of medicine is discharged and constant release, and the activity of biologically active substance is kept or the like.Therefore, biodegradable polymer has crucial status and effect at medical field.Especially in recent years, developing rapidly of Tissue Engineering Study proposed requirement more, that upgrade to the various types of cells timbering material, more promoted the exploitation of new bio degradable macromolecule.
Polyphosphonitrile is the polymer that a class has inorganic main chain, its main chain is to replace banded nitrogen, phosphorus atom formation with single, double key, all be connected with two side groups on each phosphorus atom, side group can be the different various groups of performance such as alkyl, alkoxyl group, fragrant oxygen base, heterocycle, inorganic or organo-metallic unit, thereby obtain the very wide various macromolecular materials of physico-chemical property variation range, as have the polymer of different performances such as good light, thermostability, oxidation-resistance, water-soluble, biocompatibility and biodegradability.Therefore, obtain paying close attention to about the research of polyphosphonitrile functional materials, range of application relates to bio-medical material, fire retardant material, specialty elastomer material and photoelectric material etc.
Have the polyphosphonitrile polymer of function side group, its synthetic route can be divided into two classes substantially: the one, and first polymerization obtains the high molecular weight reactive intermediate, carries out substitution reaction with it with functional nucleophilic reagent again; The 2nd, first anamorphic zone has the monomer of functional group, and repolymerization obtains the target polymer.What usually adopt at present, is article one approach that is proposed by Allcock etc.
Degradability polyphosphonitrile the earliest is at synthetic in 1977 by people such as Allcock, they adopt triethylamine catalysis polydichlorophosphazenes and glycine ethyl ester, L-LEU methyl esters, alanine methyl ester or phenylalanine methyl ester reaction, obtained having the polyphosphonitrile [Macromolecules of different aminoacids ester side group, 1977,10:824-830], and employing mixes the method that replaces with first ammonia, made the product with different aminoacids ester substitution value.The polyphosphonitrile that this amino acid ester replaces is owing to having excellent biological compatibility and biodegradability receives much concern.But the research of the medical use of polyphosphonitrile at that time mainly concentrates on medicine sustained release aspect.Having prepared side group as the Goedermoed group of Holland is that the polyphosphonitrile of 50% glycine ethyl ester and 50% ethyl glutamate is the Melphalan medicine of carrier, is used for the treatment of cancer; The Moon of Korea S and Park group with identical preparing carriers the Haloxone medicine that is used to quit drug abuse; And gondola Caliceti etc. has synthesized polyphosphonitrile macromolecule anticancer drug etc.
Laurencin once was used for osteanagenesis in the polyphosphonitrile with glycine ethyl ester and methylphenoxy mixing replacement in 1993, and tested several cells biocompatibility thereon, think that the polyphosphonitrile material can be used for tissue regeneration research [J Biomed Mater Res, 1993,27:963-973]; Langone etc. also once will gather (alanine ethyl ester-co-imidazoles) phosphonitrile and be prepared into the nerve-inducing pipe and be used for neurotization [Biomaterials, 1995,16:347-353].But, so far about the polyphosphonitrile polymer is applied in the Tissue Engineering Study relevant report but still seldom, this mainly is because the controllability of the mechanical property of prior biological degradable poly phosphonitrile material and biodegradability is limited.
It is the polyphosphonitrile [Macromolecules of ethyl glycolate or lactate that people such as Allcock in 1994 have synthesized side chain, 1994,27:1-4], the degraded product of this class material is ethanol, oxyacetic acid or lactic acid, and phosphoric acid salt and ammonia, be easy to by human body metabolism, be considered to the promising bio-medical material of a class.But, because the solubleness of sodium alkoxide in organic solvent of ethyl glycolate or lactate is lower, limited the replacement rate of product, cause the synthetic difficult of this type of polyphosphonitrile.
Kumar (Polymer Preprints, 2003,44:924) report a kind of polyphosphonitrile that replaces with aminomethyl phenyl under the butyllithium effect, caused valerolactone or caprolactone anionic ring-opening polymerization, obtained a kind of poly-valerolactone or caprolactone grafted polyphosphonitrile polymkeric substance.Yet because the strong-hydrophobicity of polycaprolactone and slow degradation speed, and the nondegradation of methyl and phenyl, the degradation speed of above-mentioned graft copolymer is extremely slow, thereby and is not suitable as tissue engineering cell scaffold material or medicine sustained release solid support material.
Summary of the invention:
The objective of the invention is to overcome the shortcoming of prior art, provide a kind of and be easy to synthesize, good biocompatibility, the regulatable aliphatic polyester grafting of degradation speed polyphosphonitrile multipolymer and preparation method thereof.
A kind of biodegradability polyester grafting polyphosphonitrile multipolymer, its chemical structural formula is as follows:
Wherein x+y=2 and y can not be 0, n=10-5000;
R is any in amino acid ester, first ammonia, imidazoles, alkoxyl group, the methoxy poly (ethylene glycol) ether or their combination;
R ' is
M=0～15 wherein.
R " be aliphatic polyester, and preferably have following constitutional features:
Wherein, a, b, c are the molar fraction of each structural unit in multipolymer, and the scope of a, b, c is 0～1.0, and a+b+c=1, but a and c can not be 0 simultaneously.Its total structural unit scope of counting is 1～150, and optimum range is 5～50.
The preparation method of biodegradability polyester grafting polyphosphonitrile multipolymer of the present invention, the line style polyphosphonitrile that adopts the hydroxyl side group to replace directly causes the method for internal ester monomer ring-opening polymerization, concrete reaction conditions is: after line style polyphosphonitrile that the hydroxyl side group is replaced and internal ester monomer mix, in the presence of catalyst Ti acid butyl ester or stannous iso caprylate, carry out ring opening copolymer under the vacuum condition of 15Pa being lower than, polymeric reaction temperature is 110～190 ℃, reaction times is 3～120 hours, catalyst consumption is 0.001～2% of a reaction mass gross weight, is preferably 0.005～1.0%.
The line style polyphosphonitrile that the hydroxyl side group replaces in the above-mentioned preparation process and the material proportion of internal ester monomer can calculate according to the substitution value and the side chain lengths of hydroxyl in the subject polymer.Usually (PNR
xR '
y)
nThe molar ratio range of structural unit and internal ester monomer is 1: 0.1～100.
Internal ester monomer can be a kind of in rac-Lactide, glycollide or the caprolactone or their combination, and rac-Lactide is L-rac-Lactide or D preferably, the L-rac-Lactide.
The pendant hydroxyl groups of the line style polyphosphonitrile that intermediate product hydroxyl side group of the present invention replaces can be single replacement or mix ethylene glycol or the polyoxyethylene glycol that replaces.
Synthesizing of the line style polyphosphonitrile that the hydroxyl side group replaces, can adopt Iodotrimethylsilane that the polyphosphonitrile of methyl cellosolve or the replacement of methoxy poly (ethylene glycol) ether is carried out the method preparation of end group displacement, hydrolysis then [referring to Macromolecules, 1992,25:5573-5577].The solvent of end group replacement(metathesis)reaction is non-ether type polar solvents such as trichloromethane, methylene dichloride, and the solvent of one-step hydrolysis reaction then is the tetrahydrofuran (THF) that can dissolve each other with water or dioxane etc., and temperature of reaction is 30～35 ℃, and the reaction times is 1～7 day.The line style polyphosphonitrile that the hydroxyl side group for preparing through this method replaces, the content of its pendant hydroxyl groups can be by the consumption control of Iodotrimethylsilane, and the consumption of Iodotrimethylsilane is directly proportional with the content of pendant hydroxyl groups.
Synthesizing of the line style polyphosphonitrile that line style polyphosphonitrile desired raw material methyl cellosolve that preparation hydroxyl side group replaces or methoxy poly (ethylene glycol) ether replace, can adopt methyl cellosolve an alkali metal salt or methoxy poly (ethylene glycol) an alkali metal salt and linear poly-dichlorides phosphorus nitrile in tetrahydrofuran (THF), dioxane, benzene or toluene, to carry out substitution reaction and prepare [referring to Macromolecules, 1995,28:2500-2505], temperature of reaction is 40-100 ℃, and the reaction times is 12～84 hours.
Be a simple signal of whole process of preparation below:
R
1Group can come from one or more in amino acid ester, first ammonia, imidazoles, alkoxyl group, the methoxy poly (ethylene glycol) ether;
R
2Group is:
R
3Group is:
Studies show that [Biomaterials, 1993,14:491-496; Macromolecules, 1994,27:1071-1075; J Controlled Release, 1993,24:167-180] polyphosphonitrile that replaces of amino acid ester finally all degradable be amino acid (ester), phosphoric acid salt, ammonia, ethanol or methyl alcohol and first ammonia etc., and reach a conclusion by the product variation that detects in the degradation process: the mechanism of degradation of polyphosphonitrile is by the side group triggered degradation, be side group earlier from the main chain hydrolysis come off, the hydrolysis and the hydrolysis of phosphorus nitrogen main chain of amino acid ester take place again.Therefore, parent/the hydrophobicity of side group and degradability have determined the degradation speed of polyphosphonitrile, the group (as imidazolyl etc.) that promptly increases the hydrolysis sensitivity can be accelerated hydrolysis rate, or introduces hydrophobic group (as phenoxy group etc.) and can reduce degradation speed to prolong the work-ing life of material.
The aliphatic poly lactone, as polylactide (PLA), poly-glycollide (PGA), polycaprolactone (PCL) and their multipolymer, owing to have excellent biological compatibility, adjustable physicochemical property and degradation speed, be the tissue engineering cell scaffold material that a class has been widely studied.Because the degraded product of polyester be acid, so poly-faster (lactic acid-co-oxyacetic acid) multipolymer of degradation speed, as (PLGA50/50) etc., when being applied in the body, regular meeting is owing to the accumulation of acid degradation product causes aseptic inflammation.
And the acid product that said hydrolyzed produces can promote the degraded of polyphosphonitrile; The alkaline bleach liquor degradation product of the polyphosphonitrile acid degraded product that can neutralize effectively again keeps the neutrality of system.Therefore, such polyester/polyphosphonitrile composite body system is applied to human body, can avoids because the aseptic inflammation that the accumulation of acid degradation product is caused.
The invention effect:
Polyester grafting polyphosphonitrile multipolymer of the present invention since the alkaline bleach liquor degradation product of polyphosphonitrile can be to a certain extent in and the acid degradation product of polyester, make degraded product have self-neutralization, the aseptic inflammation that can alleviate or avoid the accumulation by polyester acid degradation product to cause.
The present invention can select the different types of second or the 3rd to be total to substituted radical, and by their substitution value of control, wetting ability, degradation property, biocompatibility and cellular affinity to polyester graft copolymer are regulated, the performance of multipolymer can be changed, to satisfy the requirement of different medical usages in very wide scope.
Aliphatic polyester grafting polyphosphonitrile multipolymer of the present invention has excellent biodegradability, biocompatibility and nontoxicity, improves and regulated the wetting ability and the biodegradation rate of aliphatic polyester; The degraded product of polyester grafting polyphosphonitrile multipolymer has self-neutralization because the alkaline bleach liquor degradation product of polyphosphonitrile can be to a certain extent in and the acid degradation product of polyester, can alleviate the aseptic inflammation that the accumulation by polyester acid degradation product may cause.Be the novel biodegradable polymer of a class, have wide biomedical applications.
Preparation method of the present invention because use nontoxicity, commercialization and having gone through the butyl (tetra) titanate or the stannous iso caprylate that can be used for medical material is catalyzer, therefore both be beneficial to and carried out scale operation, and also be beneficial to method synthetic multipolymer thus is applied to prepare medical product.
Embodiment:
Embodiment 1
Will by the ring-opening polymerization of hexachloro-phosphonitrile ring tripolymer to linear poly-dichlorides phosphorus nitrile 0.58g (polymerization degree is about 450, molecular weight is 5～60,000), be dissolved in the 10ml dry tetrahydrofuran, to wherein slowly dripping the tetrahydrofuran solution 50ml that contains methoxy poly (ethylene glycol) sodium 7.0g (is 350 to be example with the molecular weight of polyethers), refluxed 24 hours then in 60 ℃.Remove by filter the sodium-chlor of generation, then above-mentioned tetrahydrofuran solution is adopted normal hexane precipitate polyphosphonitrile (PMEP-1) elastomerics that replaces of methoxy poly (ethylene glycol).
Above-mentioned elastomerics 7.45g is dissolved in trichloromethane 50ml,, is warming up to 30～35 ℃ of reactions after 3 days, remove solvent under reduced pressure to dry then to wherein adding Iodotrimethylsilane 2.0g.And then gains are dissolved in tetrahydrofuran (THF), to wherein adding 5: 1 (tetrahydrofuran (THF)/water, v/v) water, room temperature hydrolysis 1 hour, remove desolvate and water after, terminal be that the polyoxyethylene glycol 50% of hydroxyl replaces, the polyphosphonitrile (PEP-1) of methoxy poly (ethylene glycol) 50% replacement.
With PEP-1 (3.65g) and L-rac-Lactide 3.60g, in inert atmosphere (argon gas or nitrogen) protection down, add stannous iso caprylate 0.008g, reacted 24 hours in 130 ℃ under under vacuum condition, (being lower than 15Pa) then, must gather (L-rac-Lactide) grafting polyphosphonitrile.The percentage of grafting of poly-(L-rac-Lactide) is 50%, and average chain length is 10 lactic acid units.
Embodiment 2
Will by the ring-opening polymerization of hexachloro-phosphonitrile ring tripolymer to linear poly-dichlorides phosphorus nitrile 1.16g (polymerization degree is about 1000, molecular weight is about 100,000), be dissolved in the 20ml dry tetrahydrofuran, to wherein slowly dripping the tetrahydrofuran solution 50ml that contains methyl cellosolve sodium 4.0g, refluxed 24 hours then in 60 ℃.Remove by filter the sodium-chlor of generation, then above-mentioned tetrahydrofuran solution is adopted normal hexane precipitate polyphosphonitrile (PMEP-2) elastomerics that replaces of methoxy ethoxy.
Above-mentioned elastomerics 3.90g is dissolved in methylene dichloride 40ml,, is warming up to 30～35 ℃ of reactions after 3 days, remove solvent under reduced pressure to dry then to wherein adding Iodotrimethylsilane 4.0g.And then gains are dissolved in dioxane, to wherein adding 3: 1 (tetrahydrofuran (THF)/water, v/v) water, room temperature hydrolysis 1 hour, remove desolvate and water after, terminal be that the ethylene glycol 50% of hydroxyl replaces, the polyphosphonitrile (PEP-2) of methoxy ethoxy 50% replacement.
With PEP-2 (1.81g) and L-rac-Lactide 7.20g, in inert atmosphere (argon gas or nitrogen) protection down, add stannous iso caprylate 0.009g, reacted 24 hours in 130 ℃ under under vacuum condition, (being lower than 15Pa) then, must gather (L-rac-Lactide) grafting polyphosphonitrile.The percentage of grafting of poly-(L-rac-Lactide) is 50%, and average chain length is 10 lactic acid units.
Embodiment 3
To be dissolved in trichloromethane 40ml by the PMEP-2 (3.90g) of embodiment 2 preparations,, be warming up to 30～35 ℃ of reactions after 2 days, remove solvent under reduced pressure to dry then to wherein adding Iodotrimethylsilane 2.40g.And then gains are dissolved in tetrahydrofuran (THF), to wherein adding 5: 1 (tetrahydrofuran (THF)/water, v/v) water, room temperature hydrolysis 1 hour, remove desolvate and water after, terminal be that the ethylene glycol 30% of hydroxyl replaces, the polyphosphonitrile (PEP-3) of methoxy ethoxy 70% replacement.
With PEP-3 (1.87g) and D, L-rac-Lactide 4.33g is under inert atmosphere (argon gas or nitrogen) protection; add stannous iso caprylate 0.006g; in 140 ℃ of reactions 12 hours, must gather (D, L-rac-Lactide) grafting polyphosphonitrile under under vacuum condition, (being lower than 15Pa) then.The percentage of grafting of poly-(D, L-rac-Lactide) is 30%, and average chain length is 10 lactic acid units.
Embodiment 4
To be dissolved in trichloromethane 40ml by the PMEP-2 (3.90g) of embodiment 2 preparations,, be warming up to 30～35 ℃ of reactions after 5 days, remove solvent under reduced pressure to dry then to wherein adding Iodotrimethylsilane 5.60g.And then gains are dissolved in tetrahydrofuran (THF), to wherein adding 2: 1 (tetrahydrofuran (THF)/water, v/v) water, room temperature hydrolysis 3 hours, remove desolvate and water after, terminal be that the ethylene glycol 70% of hydroxyl replaces, the polyphosphonitrile (PEP-4) of methoxy ethoxy 30% replacement.
With PEP-4 (1.75g) and L-rac-Lactide 10.08g, in inert atmosphere (argon gas or nitrogen) protection down, add stannous iso caprylate 0.024g, reacted 24 hours in 130 ℃ under under vacuum condition, (being lower than 15Pa) then, must gather (L-rac-Lactide) grafting polyphosphonitrile.The percentage of grafting of poly-(L-rac-Lactide) is 70%, and average chain length is 10 lactic acid units.
Embodiment 5
To be dissolved in trichloromethane 40ml by the PMEP-2 (3.90g) of embodiment 2 preparations,, be warming up to 30～35 ℃ of reactions after 1 day, remove solvent under reduced pressure to dry then to wherein adding Iodotrimethylsilane 0.40g.And then gains are dissolved in tetrahydrofuran (THF), to wherein adding 5: 1 (tetrahydrofuran (THF)/water, v/v) water, room temperature hydrolysis 3 hours, remove desolvate and water after, terminal be that the ethylene glycol 5% of hydroxyl replaces, the polyphosphonitrile (PEP-5) of methoxy ethoxy 95% replacement.
With PEP-5 (1.94g) and L-rac-Lactide 5.04g, in inert atmosphere (argon gas or nitrogen) protection down, add stannous iso caprylate 0.001g, reacted 24 hours in 130 ℃ under under vacuum condition, (being lower than 15Pa) then, must gather (L-rac-Lactide) grafting polyphosphonitrile.The percentage of grafting of poly-(L-rac-Lactide) is 5%, and average chain length is 70 lactic acid units.
Embodiment 6
Will be by embodiment 2 synthetic PEP-2 (1.81g), glycollide 2.90g and L-rac-Lactide 3.60g; under inert atmosphere (argon gas or nitrogen) protection; add stannous iso caprylate 0.008g; in 180 ℃ of reactions 18 hours, must gather (L-rac-Lactide-co-glycollide) grafting polyphosphonitrile under under vacuum condition, (being lower than 15Pa) then.Wherein the unitary mol ratio of lactic acid units and oxyacetic acid is 1: 1, and poly-(L-rac-Lactide-co-glycollide) percentage of grafting is 50%.
Embodiment 7
Will be by embodiment 2 synthetic PEP-2 (1.81g), glycollide 2.61g, L-rac-Lactide 3.24g and caprolactone 1.14g; under inert atmosphere (argon gas or nitrogen) protection; add stannous iso caprylate 0.009g; in 160 ℃ of reactions 48 hours, must gather (glycollide-co-L-rac-Lactide-co-caprolactone) grafting polyphosphonitrile under under vacuum condition, (being lower than 15Pa) then.Wherein the mol ratio of oxyacetic acid unit, lactic acid units and caprolactone units is 45: 45: 10, and poly-(glycollide-co-L-rac-Lactide-co-caprolactone) percentage of grafting is 50%.
Embodiment 8
Will by the ring-opening polymerization of hexachloro-phosphonitrile ring tripolymer to linear poly-dichlorides phosphorus nitrile 1.16g (polymerization degree is about 1000, molecular weight is about 100,000), be dissolved in the 20ml dry benzene, then to wherein slowly dripping the benzole soln 20ml that contains glycine ethyl ester 1.45g and triethylamine 1.42g, in 0 ℃ of reaction after 6 hours, continue room temperature reaction 10 hours.Remove by filter the triethylamine hydrochloride of generation, then above-mentioned benzole soln is adopted the normal hexane precipitation.After the drying, above-mentioned product is dissolved in the 30ml tetrahydrofuran (THF), to wherein slowly dripping the tetrahydrofuran solution 10ml that contains methyl cellosolve sodium 1.2g, refluxed 24 hours then in 60 ℃.Remove by filter the sodium-chlor of generation, then above-mentioned tetrahydrofuran solution is adopted normal hexane precipitate polyphosphonitrile (PGMEP) elastomerics that glycine ethyl ester 70% replaces, methoxy ethoxy 30% replaces.
Above-mentioned elastomerics 2.33g is dissolved in trichloromethane 20ml,, is warming up to 30～35 ℃ of reactions after 3 days, remove solvent under reduced pressure to dry then to wherein adding Iodotrimethylsilane 1.2g.And then gains are dissolved in tetrahydrofuran (THF), to wherein add 5: 1 (tetrahydrofuran (THF)/water, water v/v), room temperature hydrolysis 1 hour, remove desolvate and water after, terminal be that the ethylene glycol 30% of hydroxyl replaces, the polyphosphonitrile (PGEP) of glycine ethyl ester 70% replacement.
With PGEP (2.27g) and L-rac-Lactide 4.32g, in inert atmosphere (argon gas or nitrogen) protection down, add stannous iso caprylate 0.005g, reacted 24 hours in 130 ℃ under under vacuum condition, (being lower than 15Pa) then, must gather (L-rac-Lactide) grafting polyphosphonitrile.The percentage of grafting of poly-(L-rac-Lactide) is 30%, and average chain length is 10 lactic acid units.
Embodiment 9
Will be by embodiment 2 synthetic PEP-2 (1.95g) and L-rac-Lactide 7.20g; under inert atmosphere (argon gas or nitrogen) protection; add butyl (tetra) titanate 0.05g, under vacuum condition, (be lower than 15Pa) then under in 130 ℃ of reactions 24 hours, must gather (L-rac-Lactide) grafting polyphosphonitrile.The percentage of grafting of poly-(L-rac-Lactide) is 50%, and average chain length is 10 lactic acid units.
Claims (8)
1. biodegradability polyester grafting polyphosphonitrile multipolymer, its form and chemical structural formula as follows:
X+y=2 and y can not be 0 in the formula, n=10～5000;
R is any in amino acid ester, first ammonia, imidazoles, alkoxyl group, the methoxy poly (ethylene glycol) ether or their combination;
R ' is
R wherein " be aliphatic polyester, m=0～15.
2. according to the multipolymer of claim 1, it is characterized in that: aliphatic polyester R " have a following constitutional features:
Wherein, a, b, c are the molar fraction of each structural unit in multipolymer, and the scope of a, b, c is 0～1.0, and a+b+c=1, but a and c can not be 0 simultaneously; Its total structural unit scope of counting is 1～150.
3. according to the multipolymer of claim 2, it is characterized in that: constitute aliphatic polyester R " total structural unit scope of counting be 5～50.
4. the preparation method of a biodegradability polyester grafting polyphosphonitrile multipolymer, the line style polyphosphonitrile that adopts the hydroxyl side group to replace directly causes the method for internal ester monomer ring-opening polymerization, concrete reaction conditions is: after line style polyphosphonitrile that the hydroxyl side group is replaced and internal ester monomer mix, in the presence of catalyst Ti acid butyl ester or stannous iso caprylate, be lower than under the vacuum condition of 15Pa and carry out ring opening copolymer, 110～190 ℃ of polymeric reaction temperatures, 3～120 hours reaction times, catalyst consumption is 0.001～2% of a reaction mass gross weight, and said internal ester monomer is a rac-Lactide, a kind of in glycollide or the caprolactone or their combination.
5. according to the preparation method of claim 4, it is characterized in that: temperature of reaction is 130～170 ℃, and in 20～80 hours reaction times, catalyst consumption is 0.005～1.0% of a reaction mass gross weight, and lactide monomer is L-rac-Lactide or D, the L-rac-Lactide.
6. according to the preparation method of claim 4 or 5, it is characterized in that: the pendant hydroxyl groups of the line style polyphosphonitrile that the hydroxyl side group replaces is single replacement or mixes ethylene glycol or the polyoxyethylene glycol that replaces that the hydroxyl degree of its side group is 1～100%.
7. according to the preparation method of claim 6, it is characterized in that: the line style polyphosphonitrile that the hydroxyl side group replaces adopts Iodotrimethylsilane the line style polyphosphonitrile of methyl cellosolve or the replacement of methoxy poly (ethylene glycol) ether to be carried out the method preparation of end group displacement, hydrolysis then; The solvent of end group replacement(metathesis)reaction is non-ether type polar solvent, tetrahydrofuran (THF) or the dioxane of the solvent of one-step hydrolysis reaction then for dissolving each other with water, and temperature of reaction is 30～35 ℃, the reaction times is 1～7 day.
8. according to the preparation method of claim 7, it is characterized in that: the line style polyphosphonitrile that methyl cellosolve or methoxy poly (ethylene glycol) ether replace adopts methyl cellosolve an alkali metal salt or methoxy poly (ethylene glycol) an alkali metal salt and linear poly-dichlorides phosphorus nitrile to carry out substitution reaction in tetrahydrofuran (THF), dioxane, benzene or toluene and prepares, temperature of reaction is 40-100 ℃, and the reaction times is 12～84 hours.
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| CN101450996B (en) * | 2007-12-07 | 2011-02-16 | 北京化工大学 | Glucose responding type polyphosphazene hydrogel |
| CN101759855A (en) * | 2010-03-04 | 2010-06-30 | 浙江大学 | pH response type amphiphilic grafted polyphosphazene and synthesis method thereof |
| CN101785865A (en) * | 2010-03-04 | 2010-07-28 | 浙江大学 | pH response type amphipathic stem-grafting polyphosphazenes feeding micelle and preparation method thereof |
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| CN103421167A (en) * | 2013-07-08 | 2013-12-04 | 常州大学 | One-step synthetic method of degradable branched polyester |
| CN103421167B (en) * | 2013-07-08 | 2016-02-24 | 常州大学 | A kind of one-step synthesis method method of degradable branched polyester |
| CN114746511A (en) * | 2019-11-29 | 2022-07-12 | 韩国科学技术研究院 | Thermosensitive hydrogel composition with modified reversible sol-gel transition properties and use thereof |
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