CN101585919B - Hyperbranched polyphosphate with biocompatibility and method for synthesizing the same - Google Patents
Hyperbranched polyphosphate with biocompatibility and method for synthesizing the same Download PDFInfo
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- CN101585919B CN101585919B CN2009100537519A CN200910053751A CN101585919B CN 101585919 B CN101585919 B CN 101585919B CN 2009100537519 A CN2009100537519 A CN 2009100537519A CN 200910053751 A CN200910053751 A CN 200910053751A CN 101585919 B CN101585919 B CN 101585919B
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- branched polyphosphate
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Abstract
The invention, which belongs to the field of polymer material technique, provides a hyperbranched polyphosphate with biocompatibility and a preparation method thereof, including: placing AB type annular phosphate monomer at 20-60 DEG C. for bulk polymerization reaction and then dissolving in water, methanol, ethanol, N, N-dimethylformamide or dimethyl sulphoxide; executing washing sediment and vacuum drying processes in sequence for the solution with acetone, obtaining hyperbranched polyphosphate using repeated phosphate structure as framework and hydroxyl as terminal, with biocompatibility and biodegradability. Compared with the line-shaped polyphosphate, the hyperbranched polyphosphate prepared by the invention has the advantages of low viscosity, high rheology behavior, considerable terminal functional group, as well as simple preparation method, high product purity, large scale preparation without catalyst, and plentiful terminal hydroxyls with can be further modified. Therefore, the hyperbranched polyphosphate has utility values in the fields of controlled release medicament, gene transfection, tissue engineering, etc.
Description
Technical field
What the present invention relates to is material of a kind of technical field of polymer materials and preparation method thereof, specifically is a kind of hyper branched polyphosphate ester and synthetic method thereof with biocompatibility.
Background technology
Poly phosphate is the novel biomaterial of a class, has caused that people pay close attention to widely.Because its similar is in natural phosphorous polymers such as biological nucleic acid in vivo and techoic acids, biocompatibility and biological degradability are good, have the stronger cell parent's drink ability and the penetrating ability of cytolemma, and its structurally variable is big, aspects such as bio-medical field, particularly genetically engineered and nerve trachea reparation have been applied to.A lot of useful exploration work have been done by Leong group in this field, discover and in polymkeric substance, introduce the physical and mechanical properties that poly phosphate can effectively improve material, improve the wetting ability and the degradation property of polymkeric substance, and can make gene avoid the degraded of nuclease, slowly discharged, improved expression of gene efficient and (seen " Journal of PolymerScience Part A:Polymer Chemistry ", 1996, V34, P621; " Journal of AmericanChemical Society ", 2001, V123, P9480).As seen poly phosphate will be the very promising biological medical polymer material of a class.
Up to now, the synthetic method of poly phosphate mainly comprises several types such as polycondensation, open loop and enzymic catalytic reaction.Because polycondensation not only need be removed in the reaction process micromolecular compound that constantly produces, and to monomeric charge than strict, thereby the polymkeric substance that utilizes polycondensation method synthetic macromolecule amount difficulty comparatively.Enzymic catalytic reaction requires harsh to reaction conditions, the minor amount of water branch in the system has an immense impact on to polyreaction, is difficult to obtain the high-molecular weight polymer of controllable structure.Ring-opening polymerization can be avoided these unfavorable factors effectively, can conveniently obtain the high-molecular weight poly phosphate, and by regulating initiator and monomeric feed ratio, can obtain the controlled polymkeric substance of structure and molecular weight.People such as Wang and Iwasaki utilize respectively ring-opening polymerization synthesized a series of novel poly phosphates (see " Biomacromolecules ", 2006, V7, P1433; " Macromolecules ", 2007, V40, P8136; " Macromolecules ", 2006, V39, P473; " Biomacromolecules ", 2009, V10, P66).But in a single day the metal catalyst that remains in the ring-opening polymerization in the polymkeric substance can not eliminate fully, and its potential toxicity also can limit the application of this polymkeric substance in the bio-medical field.
In recent years, have biocompatibility and biodegradable hyperbranched polymer and caused that people pay close attention to widely.Hyperbranched polymer has unexistent constructional feature of conventional linear polymkeric substance and advantage, as has the quasi-spherical molecule structure, contains a large amount of functional end-groups and inner cavity, has characteristics such as low viscosity and high rheological, and synthetic simple relatively.Therefore, utilize hyperbranched polymer development functionality material to have broad prospects.In addition,, its Application Areas be can expand greatly, drug conveying and target sustained release, gene therapy and transfection and bioengineered tissue etc. for example are used for by the structural unit of functional groups introducing hyperbranched polymer.Find that by existing literature search the synthetic method of utilizing the annular phosphate ring-opening polymerization that has from initiating group to prepare hyper branched polyphosphate ester yet there are no report.Equally, carrying out the annular phosphate ring-opening polymerization under the situation of catalyst-free does not appear in the newspapers as yet yet.
Summary of the invention
The present invention is directed to the prior art above shortcomings, a kind of hyper branched polyphosphate ester and synthetic method thereof with biocompatibility is provided, utilize AB type annular phosphate monomer, warp is from the condensation ring-opening polymerization, and a step makes the terminal wetting ability hyper branched polyphosphate ester of hydroxyl that is.The hyper branched polyphosphate ester that the present invention relates to is synthetic easy, need not any catalyzer, and products therefrom is pure, is a kind of synthetic method of green; The hyper branched polyphosphate ester that polyreaction obtains has biocompatibility, and biodegradable, and its a large amount of terminal hydroxyl can supply further modification.
The present invention is achieved by the following technical solutions:
The chemical formula that the present invention relates to have the biocompatibility hyper branched polyphosphate ester is as follows:
Wherein: R=-CH
2CH
2-,-CH
2CH
2CH
2CH
2-or-CH
2CH
2OCH
2CH
2-.
Described hyper branched polyphosphate ester with biocompatibility is the faint yellow xanchromatic thick liquid that arrives, and molecular weight is 2200～5000, and molecular weight distributing index is 2.50～4.10, its second-order transition temperature T
gWith heat decomposition temperature T
dBe respectively-38.2 ℃～-38.6 ℃ and 318 ℃～322 ℃.
The preparation method who the present invention relates to have the hyper branched polyphosphate ester of biocompatibility comprises:
The first step, AB type annular phosphate monomer placed under 20 ℃～60 ℃ temperature carry out being dissolved in water, methyl alcohol, ethanol, N behind the bulk polymerization, in dinethylformamide or the dimethyl sulfoxide (DMSO);
Described AB type annular phosphate monomer is meant: 2-hydroxyl-oxethyl-2-oxygen-1,3,2-dioxaphospholane, 4-hydroxyl butoxy-2-oxygen-13,2-dioxaphospholane or 2-(2-hydroxyl-oxethyl) oxyethyl group-2-oxygen-1,3, a kind of in the 2-dioxaphospholane.
Second step, with acetone above-mentioned solution is carried out washing of precipitate and vacuum drying treatment successively, obtain the skeleton rephosphorization acrylate structure of attaching most importance to, terminal have biocompatibility and a biodegradable hyper branched polyphosphate ester for hydroxyl.
The hyper branched polyphosphate ester that the present invention relates to is a kind of hyperbranched polymer with biocompatibility and biodegradable.Compare with linear poly phosphate, this hyper branched polyphosphate ester has the advantage of low viscosity, high rheological and a large amount of functional end-groups, and the preparation method is simple and easy, need not catalyzer, product purity height, but mass preparation, a large amount of terminal hydroxyls also can be for further modifying.Therefore, such branched polymer material is at medicine controlled releasing, and fields such as gene transfection and organizational project have practical value.
Description of drawings
Fig. 1 is embodiment 1 a preparation gained hyper branched polyphosphate ester macromolecular structure synoptic diagram;
Fig. 2 is embodiment 1 a preparation gained hyper branched polyphosphate ester
1H NMR spectrogram;
Fig. 3 is embodiment 1 a preparation gained hyper branched polyphosphate ester
31P NMR spectrogram;
Fig. 4 is embodiment 2 preparation gained hyper branched polyphosphate ester macromolecular structure synoptic diagram;
Fig. 5 is the hyper branched polyphosphate ester macromolecular structure synoptic diagram of embodiment 3 preparation gained.
Embodiment
Below embodiments of the invention are elaborated, present embodiment is being to implement under the prerequisite with the technical solution of the present invention, provided detailed embodiment and concrete operating process, but protection scope of the present invention is not limited to following embodiment.
The first step, with 3.0g (17.8mmol) 2-hydroxyl-oxethyl-2-oxygen-1,3, the 2-dioxaphospholane places behind the reaction flask 60 ℃ oil bath magnetic agitation reaction 60 hours;
Second step, in reaction flask, add 10 milliliters of ethanol, treat to dissolve fully the back and in acetone, precipitate, with the acetone repetitive scrubbing repeatedly after vacuum-drying again, obtain the aqueous hyper branched polyphosphate ester of flaxen thickness, productive rate 90.6%.
As shown in Figure 1, be the polymer architecture synoptic diagram that present embodiment makes, the chemical formula of gained hyper branched polyphosphate ester is:
Wherein: R=CH
2CH
2-.
Molecular weight adopts gel to see through chromatogram (GPC) and measures, and is eluent with water (containing the 0.01mol/L SODIUMNITRATE), and measured molecular weight is 2900, and molecular weight distributing index is 4.10.
As shown in Figures 2 and 3, for making polymkeric substance in the present embodiment
1H NMR and
31P NMR spectrogram is with d
6-DMSO is a solvent, and wherein the ownership at each peak is indicated in collection of illustrative plates respectively.
The first step, with 3.0g (14.2mmol) 4-hydroxyl butoxy-2-oxygen-1,3, the 2-dioxaphospholane places behind the reaction flask 60 ℃ oil bath magnetic agitation reaction 60 hours;
Second step, in reaction flask, add 10 milliliters of ethanol, treat to dissolve fully the back and in acetone, precipitate, with the acetone repetitive scrubbing repeatedly after vacuum-drying again, obtain the aqueous hyper branched polyphosphate ester of yellow thickness, productive rate 88.0%.
As shown in Figure 5, be resulting polymers structural representation in the present embodiment, the chemical formula of gained hyper branched polyphosphate ester is:
Wherein: R=-CH
2CH
2CH
2CH
2-.
Molecular weight adopts gel to see through chromatogram (GPC) and measures, and is eluent with water (containing the 0.01mol/L SODIUMNITRATE), and measured molecular weight is 2200, and molecular weight distributing index is 2.50.
Embodiment 3
The first step, with 3.0g (15.3mmol) 2-(2-hydroxyl-oxethyl) oxyethyl group-2-oxygen-1,3, the 2-dioxaphospholane places behind the reaction flask 60 ℃ oil bath magnetic agitation reaction 60 hours;
Second step, in reaction flask, add 10 milliliters of ethanol, treat to dissolve fully the back and in acetone, precipitate, with the acetone repetitive scrubbing repeatedly after vacuum-drying again, obtain the aqueous hyper branched polyphosphate ester of yellow thickness, productive rate 92.5%.
As shown in Figure 6, be the structural representation of resulting polymers in the present embodiment, the chemical formula of gained hyper branched polyphosphate ester is:
Wherein: R=-CH
2CH
2OCH
2CH
2-.
Molecular weight adopts gel to see through chromatogram (GPC) and measures, and is eluent with water (containing the 0.01mol/L SODIUMNITRATE), and measured molecular weight is 5000, and molecular weight distributing index is 3.48.
With the foregoing description 1, it is 0.001 that the hyper branched polyphosphate ester of embodiment 2 and embodiment 3 preparations is mixed with concentration with cell culture fluid respectively, 0.01,0.1,1.0,3.0,10.0mg/mL solution, respectively culturing cell adopted conventional MTT method to carry out the cytoactive test after 24 hours then, the result shows that cell activity illustrates that still near 100% this polymkeric substance has good biocompatibility when hyper branched polyphosphate ester concentration reaches 10mg/mL.Therefore, such branched polymer material is at medicine controlled releasing, and fields such as gene transfection and organizational project have practical value.
Claims (4)
1. one kind has the biocompatibility hyper branched polyphosphate ester, it is characterized in that, its chemical formula is:
Wherein: R=-CH
2CH
2-,-CH
2CH
2CH
2CH
2-or-CH
2CH
2OCH
2CH
2-.
2. according to claim 1 have a biocompatibility hyper branched polyphosphate ester, it is characterized in that, described hyper branched polyphosphate ester with biocompatibility is the faint yellow xanchromatic thick liquid that arrives, and molecular weight is 2200～5000, and molecular weight distributing index is 2.50～4.10.
3. according to claim 1 have a biocompatibility hyper branched polyphosphate ester, it is characterized in that described second-order transition temperature T with hyper branched polyphosphate ester of biocompatibility
gWith heat decomposition temperature T
dBe respectively-38.2 ℃～-38.6 ℃ and 318 ℃～322 ℃.
4. the preparation method with biocompatibility hyper branched polyphosphate ester according to claim 1 is characterized in that, may further comprise the steps:
The first step, AB type annular phosphate monomer placed carry out under 20 ℃～60 ℃ being dissolved in water, methyl alcohol, ethanol, N behind the bulk polymerization, in dinethylformamide or the dimethyl sulfoxide (DMSO);
Second step, with acetone above-mentioned solution is carried out washing of precipitate and vacuum drying treatment successively, obtain the skeleton rephosphorization acrylate structure of attaching most importance to, terminal have biocompatibility and a biodegradable hyper branched polyphosphate ester for hydroxyl;
Described AB type annular phosphate monomer is meant: 2-hydroxyl-oxethyl-2-oxygen-1,3,2-dioxaphospholane, 4-hydroxyl butoxy-2-oxygen-1,3,2-dioxaphospholane or 2-(2-hydroxyl-oxethyl) oxyethyl group-2-oxygen-1,3, a kind of in the 2-dioxaphospholane.
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| CN108832175B (en) * | 2017-11-07 | 2020-08-21 | 江汉大学 | Preparation method of polymer electrolyte |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002092667A1 (en) * | 2001-05-14 | 2002-11-21 | Johns Hopkins Singapore Pte Ltd. | Biodegradable polyphosphates for controlled release of bioactive substances |
| CN101205302A (en) * | 2007-11-09 | 2008-06-25 | 中国科学技术大学 | Polyphosphate ester-polycaprolactone tri-block copolymer and uses thereof |
| CN101402736A (en) * | 2008-11-12 | 2009-04-08 | 华中科技大学 | Biodegradable unsaturated polyphosphate, preparation and use method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002092667A1 (en) * | 2001-05-14 | 2002-11-21 | Johns Hopkins Singapore Pte Ltd. | Biodegradable polyphosphates for controlled release of bioactive substances |
| CN101205302A (en) * | 2007-11-09 | 2008-06-25 | 中国科学技术大学 | Polyphosphate ester-polycaprolactone tri-block copolymer and uses thereof |
| CN101402736A (en) * | 2008-11-12 | 2009-04-08 | 华中科技大学 | Biodegradable unsaturated polyphosphate, preparation and use method thereof |
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| Title |
|---|
| JP特开2009-51928A1 2009.03.12 |
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