CN110078880A - Isocyanate-crosslinked polyethylene glycol decanedioic acid glyceride bioelastomer and its preparation method and application - Google Patents
Isocyanate-crosslinked polyethylene glycol decanedioic acid glyceride bioelastomer and its preparation method and application Download PDFInfo
- Publication number
- CN110078880A CN110078880A CN201810077797.3A CN201810077797A CN110078880A CN 110078880 A CN110078880 A CN 110078880A CN 201810077797 A CN201810077797 A CN 201810077797A CN 110078880 A CN110078880 A CN 110078880A
- Authority
- CN
- China
- Prior art keywords
- bioelastomer
- preparation
- polyethylene glycol
- solution
- decanedioic acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/40—High-molecular-weight compounds
- C08G18/42—Polycondensates having carboxylic or carbonic ester groups in the main chain
- C08G18/4236—Polycondensates having carboxylic or carbonic ester groups in the main chain containing only aliphatic groups
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/40—High-molecular-weight compounds
- C08G18/42—Polycondensates having carboxylic or carbonic ester groups in the main chain
- C08G18/4244—Polycondensates having carboxylic or carbonic ester groups in the main chain containing oxygen in the form of ether groups
- C08G18/4247—Polycondensates having carboxylic or carbonic ester groups in the main chain containing oxygen in the form of ether groups derived from polyols containing at least one ether group and polycarboxylic acids
- C08G18/4252—Polycondensates having carboxylic or carbonic ester groups in the main chain containing oxygen in the form of ether groups derived from polyols containing at least one ether group and polycarboxylic acids derived from polyols containing polyether groups and polycarboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/02—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds
- C08G63/12—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds derived from polycarboxylic acids and polyhydroxy compounds
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/66—Polyesters containing oxygen in the form of ether groups
- C08G63/668—Polyesters containing oxygen in the form of ether groups derived from polycarboxylic acids and polyhydroxy compounds
Abstract
The invention discloses a kind of isocyanate-crosslinked polyethylene glycol decanedioic acid glyceride bioelastomers and its preparation method and application.Bioelastomer structure of the invention is shown in formula I, the integer that wherein n is 10~80；M is the integer of 2-14.Bioelastomer of the invention, mechanical strength, hydrophilic and hydrophobic, degradation behavior, cell behavior and biocompatibility can be regulated and controled and be optimized by the content of isocyanates and polyethylene glycol, be a kind of soft tissue repair material of great potential applicability in clinical practice.
Description
Technical field
The present invention relates to a kind of isocyanate-crosslinked polyethylene glycol decanedioic acid glyceride bioelastomer and its preparations
Methods and applications.
Background technique
With the progress of tissue engineering technique, requirement of the people for repair materials is higher and higher.Bioelastomer material
The characteristics such as viscoplasticity, mechanical property as similar in its excellent flexibility and surrounding tissue, cause on bio-medical
Very big concern.It is such as medical since in the 1950s, applied the bioelastomer of polyurethanes in medicine and hygiene fields
Conduit, film article etc. are to use and study most commonly used bioelastomer material except silicone elastomer is external at present.But
In long-term use process, some problems are exposed, wherein most importantly poor biocompatibility.
Poly- decanedioic acid glyceride (PGS) is a kind of with good mechanical strength, biocompatibility and biological degradability
Macromolecule has the function of promoting vascularization, therefore is widely used in soft tissue engineering in recent years.However, due to the poly- last of the ten Heavenly stems two
Acid glyceride crosslinking condition is complicated, and hydrophily is poor after molding, limited in the service performance of soft tissue, and cannot be used for albumen
Or drug etc. has the load of the factor of bioactivity.
Therefore, there is an urgent need in the art to develop, low-temperature curable, condition of molding are simple, biocompatibility is excellent, can
Bioelastomer material for active factors load.
Summary of the invention
The purpose of the present invention is to provide a kind of low-temperature curable, condition of molding is simple, biocompatibility is excellent, can
Bioelastomer material for active factors load.
The first aspect of the present invention provides a kind of bioelastomer, and it includes following structural units are as follows:
The integer that n is 10~80；
The integer that m is 2~14.
In another preferred example, in the bioelastomer, the molar ratio of decanedioic acid and glycerol and polyethylene glycol is
0.65~2.8.
In another preferred example, in the bioelastomer, decanedioic acid is 1- with the molar ratio of glycerol and polyethylene glycol
1.8, preferably 1.3 or 1.4.
In another preferred example, in the bioelastomer, molar ratio≤4 of polyethylene glycol and glycerol；Hexa-methylene
The molar ratio of diisocyanate and glycerol is 0.2~1.5.
In another preferred example, the molar ratio of polyethylene glycol and glycerol is 0.1-4.
In another preferred example, the molar ratio of polyethylene glycol and glycerol be 0.2-4, preferably 0.25,0.67,1.5 or
4。
In another preferred example, n be 15~70 integer, 20~60 integer or 30~50 integer.
In another preferred example, the integer of m 3-12,4-10,5-8.
In another preferred example, the bioelastomer has following one or more features:
(1) hydrophilic angle can be at 20~89 °；
(2) 0.5-18.0MPa of Young's modulus；
(3) 0.1-12.0MPa of tensile strength；
(4) elongation at break 23.0-400.0%；
External degradation is 10~99% within (5) 30 days.
Bioelastomer of the present invention is Biodegradable cross-linked polymer.
This bioelastomer can prepare the three-dimensional structure elastomer of arbitrary shape by distinct methods, and power good enough
Its shape can also be maintained by learning performance.
The second aspect of the present invention provides the preparation method of bioelastomer described in first aspect, including following step
It is rapid:
Polyethylene glycol decanedioic acid glyceride performed polymer is reacted to obtain with hexamethylene diisocyanate in a solvent
The bioelastomer,
Wherein, the solvent is benzene,toluene,xylene, pentane, hexane, octane, hexamethylene, cyclohexanone, toluene hexamethylene
Ketone, chlorobenzene, dichloro-benzenes, methylene chloride, methanol, ethyl alcohol, isopropanol, ether, propylene oxide, methyl acetate, ethyl acetate, vinegar
Propyl propionate, acetone, espeleton, methylisobutylketone, glycol monoethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, acetonitrile,
Pyridine, phenol, N, N- dimethylformamide, tetrahydrofuran or two or more mixed solvents.
Preferably, the number-average molecular weight of the prepolymer is 4000-9000, coefficient of dispersion 1.2-3.0.
In another preferred example, the preparation method further includes the steps that catalyst, the catalyst are added in a solvent
It is selected from: stannous octoate, dibutyltin dilaurate, two (dodecyl sulphur) dibutyl tins, dibutyltin diacetate, the new last of the ten Heavenly stems
Sour bismuth, zinc Isoocatanoate etc..
In another preferred example, the solvent adding amount is the 0 of polyethylene glycol decanedioic acid glyceride prepolymer mass
~100 times.
In another preferred example, when the solvent adding amount is not 0 times, the preparation of bioelastomer is comprised the steps of
(a) under the atmosphere of argon gas, dried polyethylene glycol decanedioic acid glyceride performed polymer is dissolved in anhydrous N, N-
In dimethylformamide, solution concentration is 0.01~∞ g/ml；
(b) under the atmosphere of argon gas, mass volume ratio is dissolved in the solution of step a) lower than 0.01% stannous octoate；
(c) under the atmosphere of argon gas, the solution of step b) is transferred in reaction unit, and connects Xi Laike operating system,
10~20min is heated at 20~65 DEG C；
(d) under argon atmosphere, the hexamethylene diisocyanate of corresponding mole is added in the device of step 3),
It is slowly dropped in solution；
(e) under argon atmosphere, the reaction was continued 5~12 hours in 20~65 DEG C for solution in step d), and taking-up is transferred to four
In fluorine mold, it is stored at room temperature 2 days, is dried in vacuo 48 hours at room temperature, obtains bioelastomer.
Preferably, the number-average molecular weight of the prepolymer is 4000-9000, coefficient of dispersion 1.2-3.0.
In another preferred example, in the step a), solution concentration 0.05-5g/ml, 0.1-3g/ml or 0.15-1g/
Ml or 0.2-0.5g/ml.
It in another preferred example, is 0.0001%-0.01% or 0.001%- by mass volume ratio in the step a)
0.01% or 0.005%-0.01% stannous octoate is dissolved in the solution of step a).
It is each that the bioelastomer can regulate and control it by the content of regulation polyethylene glycol and hexamethylene diisocyanate
Class performance can simultaneously be prepared in a mild condition.
The third aspect of the present invention, provides the preparation method of bioelastomer described in first aspect, and solvent adding amount is
It 0 times, comprises the steps of
(a) dried polyethylene glycol decanedioic acid glyceride performed polymer and mass volume ratio are lower than polyethylene glycol-
The catalyst of poly- decanedioic acid glyceride performed polymer 0.05% is uniformly mixed；
(b) hexa-methylene for being 0.2~1.5 with the molar ratio of glycerol in mixture obtained in step a), will be added
Diisocyanate simultaneously stirs and evenly mixs rapidly；
(c) mixture obtained in step b) is placed under dry environment, the reaction was continued 8-24 hours (preferably
12-14 hours) to get arrive macromolecular elastomer.
In another preferred example, catalyst is selected from the step b): stannous octoate, dibutyltin dilaurate, two
(dodecyl sulphur) dibutyl tin, dibutyltin diacetate, bismuth neodecanoate, zinc Isoocatanoate etc..
In another preferred example, step a), by dried polyethylene glycol decanedioic acid glyceride performed polymer and quality
Volume ratio lower than polyethylene glycol decanedioic acid glyceride performed polymer 0.0001%-0.05%, 0.001%-0.05% or
The catalyst of 0.005%-0.05% is uniformly mixed.
The fourth aspect of the present invention, provides a kind of modified material, and the modified material includes base material, and load
Bioelastomer on the base material.
The present invention is by the bioelastic liquid solution of various concentration, the mode through drop coating, the table coated on required modified object
Face, then to get the material for arriving modification after solvent volatilization and solvent removal step.
Preferably, the concentration of the bioelastic liquid solution is 0.01~∞ g/ml.
It is highly preferred that the concentration of the bioelastic liquid solution is 0.1g/ml, 0.2g/ml, 0.3g/ml or ∞ (solvent
For 0ml).
Preferably, it is hydrophobic to be selected from the brittleness brackets or PEEK, PMMA etc. such as calcium microcosmic salt bracket, MBG bracket for the base material
Property material.
The bioelastomer can be used for inorganic or high molecular material compound or modified.Through loading bioelastomer, base
The mechanical property of bottom material is enhanced.
The fifth aspect of the present invention, provides a kind of drug release material, and the drug release material includes bioelastic
Body, and the active factors being supported on the bioelastomer.
The bioelastomer can be used for preparing the carrier of cell culture or prepare the bioelastomer material of different-shape
Material, and can be used for albumen or drug loading and controlled release.
Through 0% solvent route prepare bioelastomer, without demoulding and in the drop coating of surface concentration be suitable for it is active because
Sub- solution.After freeze-dried, on the load factor bioelastomer surface prepared, another layer of bioelastomer in re-coating,
To get the bioelastomer film for arriving the carrying active factor after reaction in 12 hours.
Preferably, the active factors are selected from the factor that albumen or drug etc. have bioactivity.
Preferably, the bioelastomer is membranaceous, can preferably prepare multilayer.More electedly, bioelastomer film can
2~4 layers of preparation.
Preferably, bioelastomer film can be selected from the combination of different performed polymers.
Bioelastomer material of the invention has the function of height customization, in the tissue repair for being applied to different parts
When, it can be by the way that the content of component realizes object similar with application tissue site in controlled material in the synthesis process of elastomer
Change property, while two kinds of preparation methods in the present invention, can be prepared into corresponding when simulating the physicochemical property of surrounding tissue
Shape to be bonded surrounding tissue, meanwhile, mild reaction condition can also assign the load that the material can be used for active factors, into
The regeneration of one step promotion tissue, it is believed that the bioelastic physical efficiency that this height customizes provides more for associated biomolecule medical application
Ideal new material.
It should be understood that above-mentioned each technical characteristic of the invention and having in below (eg embodiment) within the scope of the present invention
It can be combined with each other between each technical characteristic of body description, to form a new or preferred technical solution.Institute in specification
The each feature disclosed can be replaced by any alternative characteristics for providing identical, impartial or similar purpose.As space is limited, exist
This is no longer repeated one by one.
Detailed description of the invention
Fig. 1 is the synthetic route of bioelastomer of the present invention, and (A) is the preparation of PGS-U, and (B) is the preparation of PEGS-U.
Fig. 2 is the extension test figure (A) and cyclic tension test chart (B) of bioelastomer of the present invention.
Fig. 3 shows bioelastomer contact angle (A) of the present invention and 30 days external degradations (B).
Fig. 4 shows bioelastomer of the present invention and BMSCs stem cell co-cultures result.
Fig. 5 is bioelastomer subcutaneous implantation of the present invention 7 days and 30 days H&E stained slice figures.
Fig. 6 is the material of various shapes that is prepared into of bioelastomer of the present invention, (a) is membrane material, (b) be porous support,
It (c) is tubing.
Fig. 7 is that bioelastomer of the present invention enhances inorganic material, and (A) is to compress the pattern of front and back under 6% coating content,
It (B) is the stress-strain diagram of compound rest.
Fig. 8 is that bioelastomer of the present invention is used for drug release, and (A) is that activity, (B) are the release of albumen in 3 days for 24 hours
Curve.
Specific embodiment
Present inventor by depth studying extensively, in polyester-based polymer performed polymer, while introducing poly-
Ethylene glycol and hexamethylene diisocyanate obtain a kind of low-temperature setting bioelastomer material that biocompatibility is excellent, gather
The introducing of ethylene glycol assigns poly- decanedioic acid glyceride excellent hydrophily, viscoplasticity and excellent biocompatibility, six methylenes
The addition of group diisocyanate assigns the macromolecule and forms under relatively mild conditions, simplifies molding condition and assigns
The stronger mechanical property of material, while can be used for the load of active factors.On this basis, the present invention is completed.
Term explanation
Unless otherwise defined, otherwise whole technologies used herein and scientific term all have the neck as belonging to the present invention
The normally understood identical meanings of the those of ordinary skill in domain.
As used herein, in use, term " about " means that the value can be from enumerating in mentioning the numerical value specifically enumerated
Value changes not more than 1%.For example, as used herein, statement " about 100 " include 99 and 101 and between whole values (for example,
99.1,99.2,99.3,99.4 etc.).
As used herein, term " containing " or " including (including) " can be open, semi-enclosed and enclosed.
In other words, the term also include " substantially by ... constitute " or " by ... constitute ".
As used herein, term " CPC ", " calcium phosphate bone cement " are used interchangeably.
As used herein, term " PEGS ", " polyethylene glycol decanedioic acid glyceride " are used interchangeably.
As used herein, term " PEG ", " polyethylene glycol " are used interchangeably.
As used herein, term " PEGS20 " and " PEGS40 " refer to the polyethylene glycol last of the ten Heavenly stems two of different polyethyleneglycol contents
Acid glyceride, wherein polyethylene glycol is respectively 20% and 40% relative to the molar fraction of glycerol, is used interchangeably.
As used herein, term " PGS-U " and " PEGS-U " refer to that hexamethylene diisocyanate is crosslinked poly- decanedioic acid glycerol
Ester or polyethylene glycol decanedioic acid glyceride.
As used herein, term " X-P-mU " " X-P-mU-F ", X refer to the letter of prepolymer used in synthesising biological elastomer
Claim, wherein 20 indicate PEGS20,40 indicate PEGS40；Y refers to the molar ratio of the hexamethylene diisocyanate and glycerol
Y；Solvent is not added during referring to bioelastomer preparation by F.
Preparation method
As shown in Figure 1, in a preferred embodiment, it is under argon atmosphere, 2g PEGS series performed polymer or PGS is pre-
Aggressiveness is dissolved in the anhydrous DMF solvent of 10ml.Then, the stannous octoate relative to total solvent volume 0.01% is dissolved in 5ml
DMF in, it is to be mixed uniformly after be transferred together and reacted in ball bottle with high molecular solution.Under argon atmosphere, by corresponding agent
The hexamethylene diisocyanate of amount is dissolved in the DMF of 5ml, is mixed back and is transferred in charger.Above-mentioned apparatus is transferred to
In heater, 55 DEG C are warming up to, to after ten minutes, with the rate of 10 drop per minute, by the molten of hexamethylene diisocyanate
Drop is added in Polymer Solution, and is allowed to continue to 5 hours of reaction.Solvent is removed to get bioelastomer material is arrived
PEGS-U or PGS-U.
In the present invention, bioelastomer can be prepared in the case where adding solvent, i.e., by polyethylene glycol decanedioic acid
Glyceride performed polymer reacts to obtain the bioelastomer in a solvent with hexamethylene diisocyanate,
Wherein, the solvent is benzene,toluene,xylene, pentane, hexane, octane, hexamethylene, cyclohexanone, toluene hexamethylene
Ketone, chlorobenzene, dichloro-benzenes, methylene chloride, methanol, ethyl alcohol, isopropanol, ether, propylene oxide, methyl acetate, ethyl acetate, vinegar
Propyl propionate, acetone, espeleton, methylisobutylketone, glycol monoethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, acetonitrile,
Pyridine, phenol, N, N- dimethylformamide, tetrahydrofuran or two or more mixed solvents.
In another preferred example, the preparation method further includes the steps that catalyst, the catalyst are added in a solvent
It is selected from: stannous octoate, dibutyltin dilaurate, two (dodecyl sulphur) dibutyl tins, dibutyltin diacetate, the new last of the ten Heavenly stems
Sour bismuth, zinc Isoocatanoate etc..
In another preferred example, the solvent adding amount is the 0 of polyethylene glycol decanedioic acid glyceride prepolymer mass
~100 times.
In another preferred example, when the solvent adding amount is not 0 times, the preparation of bioelastomer is comprised the steps of
(a) under the atmosphere of argon gas, dried polyethylene glycol decanedioic acid glyceride performed polymer is dissolved in anhydrous N, N-
In dimethylformamide, solution concentration is 0.01~∞ g/ml；
(b) under the atmosphere of argon gas, mass volume ratio is dissolved in the solution of step a) lower than 0.01% stannous octoate；
(c) under the atmosphere of argon gas, the solution of step b) is transferred in reaction unit, and connects Xi Laike operating system,
10~20min is heated at 20~65 DEG C；
(d) under argon atmosphere, the hexamethylene diisocyanate of corresponding mole is added in the device of step 3),
It is slowly dropped in solution；
(e) under argon atmosphere, the reaction was continued 5~12 hours in 20~65 DEG C for solution in step d), and taking-up is transferred to four
In fluorine mold, it is stored at room temperature 2 days, is dried in vacuo 48 hours at room temperature, obtains bioelastomer.
Preferably, the number-average molecular weight of the prepolymer is 4000-9000, coefficient of dispersion 1.2-3.0.
It is each that the bioelastomer can regulate and control it by the content of regulation polyethylene glycol and hexamethylene diisocyanate
Class performance can simultaneously be prepared in a mild condition.
Further, it is also possible to prepare bioelastomer in the case where not using solvent, i.e., solvent adding amount is 0 times, includes
The following steps:
(a) dried polyethylene glycol decanedioic acid glyceride performed polymer and mass volume ratio are lower than polyethylene glycol-
The catalyst of poly- decanedioic acid glyceride performed polymer 0.05% is uniformly mixed；
(b) hexa-methylene for being 0.2~1.5 with the molar ratio of glycerol in mixture obtained in step a), will be added
Diisocyanate simultaneously stirs and evenly mixs rapidly；
(c) mixture obtained in step b) is placed under dry environment, the reaction was continued 8-24 hours (preferably
12-14 hours) to get arrive macromolecular elastomer.
In another preferred example, catalyst is selected from the step b): stannous octoate, dibutyltin dilaurate, two
(dodecyl sulphur) dibutyl tin, dibutyltin diacetate, bismuth neodecanoate, zinc Isoocatanoate etc..
Present invention will be further explained below with reference to specific examples.It should be understood that these embodiments are merely to illustrate this hair
It is bright rather than limit the scope of the invention.In the following examples, the experimental methods for specific conditions are not specified, usually according to routine
Condition (such as Sambrook et al., molecular cloning: laboratory manual (New York:Cold Spring Harbor
Laboratory Press, 1989) condition described in) or according to the normal condition proposed by manufacturer.Unless otherwise stated,
Otherwise percentage and number are weight percent and parts by weight.
Unless otherwise defined, known to all professional and scientific terms as used herein and one skilled in the art
Meaning is identical.In addition, any method similar to or equal to what is recorded and material can be applied to the method for the present invention.
The preferred methods and materials described herein are for illustrative purposes only.
Embodiment 1
The present embodiment is related to the synthesis and purifying of PEGS0
PEGS0 performed polymer is synthesized by two-step process:
(a) under the atmosphere of argon gas, the decanedioic acid and glycerol that molar ratio is 1:1 react 24 hours at 130 DEG C；
(b) the reaction was continued under 150 DEG C, vacuum condition 6 hours for step a) product, obtains PEGS0 performed polymer.
Prepolymer product is purified by the dissolution of ethyl alcohol repeatedly-water settling operation, removes unreacted monomer and small point
Son obtains purifying PEGS0 performed polymer (poly- decanedioic acid glyceride).Number-average molecular weight is 6023Da, specific dispersivity 3.21.
Embodiment 2
The present embodiment is related to the synthesis and purifying of PEGS20 (20% polyethylene glycol decanedioic acid glyceride)
(i) under the atmosphere of argon gas, by the decanedioic acid of 14.14g and 20.00gPEG (number-average molecular weight 1000g/mol)
It is reacted 2 hours at 130 DEG C；
(ii) by the product of step (a), the reaction was continued under 130 DEG C, vacuum condition 24 hours, obtains decanedioic acid and PEG
Linear performed polymer；
(iii) glycerol of 7.36g and the decanedioic acid of 14.14g are added into the product of step (b), in 130 DEG C, vacuum item
The reaction was continued under part 48 hours.PEG is 20% relative to the molar content of glycerol in the reaction, and the hydroxyl and carboxylic of overall reaction
The molar ratio of base is 1.
Prepolymer product is purified by the dissolution of ethyl alcohol repeatedly-water settling operation, removes unreacted monomer and small point
Son obtains purifying PEGS20 performed polymer.The content of practical PEG is 19%, number-average molecular weight 7085Da, and specific dispersivity is
1.95。
Embodiment 3
The present embodiment is related to the synthesis and purifying of PEGS80 (80% polyethylene glycol decanedioic acid glyceride)
(a) under the atmosphere of argon gas, by the decanedioic acid of 16.18g and 80.00gPEG (number-average molecular weight 1000g/mol)
It is reacted 2 hours at 130 DEG C；
(b) by the product of step (a), the reaction was continued under 130 DEG C, vacuum condition 24 hours, obtains decanedioic acid and PEG
Linear performed polymer；
(c) glycerol of 1.8414g and the decanedioic acid of 6.0675g are added into the product of step (b), in 130 DEG C, vacuum
Under the conditions of the reaction was continued 48 hours.In the reaction PEG relative to glycerol molar content be 80%, and the hydroxyl of overall reaction with
The molar ratio of carboxyl is 1:1.
Prepolymer product is purified by the dissolution of ethyl alcohol repeatedly-water settling operation, removes unreacted monomer and small point
Son obtains purifying PEGS80 performed polymer.The content of practical PEG is 76%, number-average molecular weight 6308Da, and specific dispersivity is
2.42。
Embodiment 4
The present embodiment is related to solvent method approach preparation 0-P-1.0U bioelastomer
(a) under the atmosphere of argon gas, dried 4g PEGS0 performed polymer is dissolved in the anhydrous N of 20ml, N- dimethylformamide
In, obtain Polymer Solution；
(b) under the atmosphere of argon gas, 0.002g stannous octoate is dissolved in the solution of step a)；
(c) under the atmosphere of argon gas, the solution of step b) is transferred in reaction unit, and connects Xi Laike operating system,
10~20min is heated at 55 DEG C；
(d) under argon atmosphere, 1.969g hexamethylene diisocyanate is added in the device of step c), is slowly dripped
It is added in solution；
(e) under argon atmosphere, 55 DEG C of solution in step d) are reacted 5 hours.
The solution that above-mentioned reaction obtains is transferred in the mold of the discoid polytetrafluoroethylene (PTFE) of 10cm, stands 48 at room temperature
It after hour, is transferred under vacuum condition, drying at room temperature 72 hours is to get arriving membranaceous bioelastomer material 0-P-1.0U.
Embodiment 5
The present embodiment is related to solvent method approach preparation 20-P-1.0U bioelastomer
(a) under the atmosphere of argon gas, dried 4g PEGS20 performed polymer is dissolved in the anhydrous N of 20ml, N- dimethyl acyl
In amine, Polymer Solution is obtained；
(b) under the atmosphere of argon gas, 0.002g stannous octoate is dissolved in the solution of step a)；
(c) under the atmosphere of argon gas, the solution of step b) is transferred in reaction unit, and connects Xi Laike operating system,
10~20min is heated at 55 DEG C；
(d) under argon atmosphere, 1.06g hexamethylene diisocyanate is added in the device of step c), is slowly added dropwise
Into solution；
(e) under argon atmosphere, 55 DEG C of solution in step d) are reacted 5 hours.
The solution that above-mentioned reaction obtains is transferred in the mold of the discoid polytetrafluoroethylene (PTFE) of 10cm, stands 48 at room temperature
It after hour, is transferred under vacuum condition, drying at room temperature 72 hours is to get arriving membranaceous bioelastomer material 20-P-1.0U.
Embodiment 6
The present embodiment is related to solvent method approach preparation 80-P-1.0U bioelastomer
(a) under the atmosphere of argon gas, dried 4g PEGS80 performed polymer is dissolved in the anhydrous N of 20ml, N- dimethyl acyl
In amine, Polymer Solution is obtained；
(b) under the atmosphere of argon gas, 0.002g stannous octoate is dissolved in the solution of step a)；
(c) under the atmosphere of argon gas, the solution of step b) is transferred in reaction unit, and connects Xi Laike operating system,
10~20min is heated at 55 DEG C；
(d) under argon atmosphere, 0.134g hexamethylene diisocyanate is added in the device of step c), is slowly dripped
It is added in solution；
(e) under argon atmosphere, 55 DEG C of solution in step d) are reacted 5 hours.
The solution that above-mentioned reaction obtains is transferred in the mold of discoid 10cm polytetrafluoroethylene (PTFE), stands 48 at room temperature
It after hour, is transferred under vacuum condition, drying at room temperature 72 hours is to get arriving membranaceous bioelastomer material 80-P-1.0U.
Embodiment 7
The present embodiment is related to solvent method preparation 40-P-1.0U bioelastomer.
The present embodiment is substantially the same manner as Example 5, the difference is that the macromolecule is that PEGS40 is being dissolved in solvent
Afterwards, the hexamethylene diisocyanate of the 0.601g of addition.40-P- is obtained to after the reaction was completed, shift and remove solvent
The bioelastomer of 1.0U.
Embodiment 8
The present embodiment is related to solvent method preparation 60-P-1.0U bioelastomer
The present embodiment is substantially the same manner as Example 5, the difference is that the macromolecule is that PEGS60 is being dissolved in solvent
Afterwards, the hexamethylene diisocyanate of the 0.321g of addition.40-P- is obtained to after the reaction was completed, shift and remove solvent
The bioelastomer of 1.0U.
Embodiment 9
The present embodiment is related to solvent method approach 0-P-0.5U bioelastomer
The present embodiment is substantially the same manner as Example 5, the difference is that the amount for the hexamethylene diisocyanate being added
For 0.984g.The bioelastomer for obtaining 0-P-0.5U to after the reaction was completed, shift and remove solvent.
Embodiment 10
The present embodiment is related to solvent method approach 20-P-0.5U bioelastomer
The present embodiment is substantially the same manner as Example 5, the difference is that the amount for the hexamethylene diisocyanate being added
For 0.531g.The bioelastomer for obtaining 0-P-0.5U to after the reaction was completed, shift and remove solvent.
Embodiment 11
The present embodiment is related to solvent method preparation 40-P-0.5U bioelastomer.
The present embodiment is substantially the same manner as Example 5, the difference is that the amount for the hexamethylene diisocyanate being added
For 0.0.300g.The bioelastomer for obtaining 0-P-0.5U to after the reaction was completed, shift and remove solvent.
Embodiment 12
The present embodiment is related to solvent method preparation 60-P-0.5U bioelastomer.
The present embodiment is substantially the same manner as Example 5, the difference is that the amount for the hexamethylene diisocyanate being added
For 0.161g.The bioelastomer for obtaining 0-P-0.5U to after the reaction was completed, shift and remove solvent.
Embodiment 13
The present embodiment is related to solvent method preparation 80-P-0.5U bioelastomer.
The present embodiment is substantially the same manner as Example 5, the difference is that the amount for the hexamethylene diisocyanate being added
For 0.067g.The bioelastomer for obtaining 0-P-0.5U to after the reaction was completed, shift and remove solvent.
Embodiment 14
The present embodiment is related to 20-P-1.0U-F elastomer when solvent is 0.
(a) dried PEGS20 performed polymer 4g and mass volume ratio is pre- lower than polyethylene glycol decanedioic acid glyceride
The stannous octoate of aggressiveness 0.05% is uniformly mixed；
(b) two isocyanide of hexa-methylene for being 1 with the molar ratio of glycerol in mixture obtained in step a), will be added
Acid esters simultaneously stirs and evenly mixs rapidly；
(c) mixture obtained in step b) is placed under dry environment, the reaction was continued 12 hours to get arrive high score
Elastic body 20-P-1.0U-F.
Embodiment 15
The present embodiment is related to the characterization of bioelastomer material
PEGS-U is reacted by the hydroxyl on macromolecule performed polymer with the isocyanate groups on hexamethylene diisocyanate
It is made.The content (amount of the substance relative to hydroxyl substance) of polyethylene glycol in control performed polymer is respectively 0%,
20%, 40%, 60%, 80%, the hexamethylene diisocyanate relative to glycerol 50%~100% is added up to some column
Material is labeled as 0-P-0.5U, 0-P-1.0U, 20-P-0.5U, 20-P-1.0U, 40-P-0.5U, 40-P-1.0U, 60-P-
0.5U,60-P-1.0U,80-P-0.5U,80-P-1.0U.To the structure of these materials, thermal property and internal external contact compatibility etc.
Various properties are characterized respectively.
Data result: its structure is confirmed by nuclear magnetic spectrogram.The biological bullet of DSC experiment display X-P-mU series
The glass transition temperature of elastomer material is below room temperature, shows that this kind of bioelastomer material is bullet near human body temperature
(table 1) of property.Stretching (A in Fig. 2) and cyclic tension (B in Fig. 2) experiment confirms that X-P-mU series of biologic elastomer has well
Mechanical property and creep-resistant property.Contact angle (A in Fig. 3) and external degradation (B in Fig. 3) experiment in 30 days show that X-P-mU is raw
Object elastomer hydrophily and degradability are controllable, these are the experimental results showed that and pass through polyethylene glycol and hexa-methylene diisocyanate
The content of ester controls the performance of bioelastomer.
60-P-0.5U, 60-P-1.0U, 80-P-0.5U, 80-P-1.0U elastomer, mechanical strength are lower than 0.3MPa,
And break-draw is lower than 40%.And after performed polymer of the PEG content at 20 and 40 is crosslinked, mechanical strength reaches as high as
4.27MPa, tension failure rate 272%.
The mechanical property and glass transition temperature of the bioelastomer under room temperature of table 1
Embodiment 16:
The present embodiment is related to BMSC co-cultivation
1, with mouse mesenchymal stem cell (rBMSCs), (1, rat 80-100g or so take off neck and put to death, 75% alcohol bubble
10min。
2, sterile removing femur, shin bone, then the muscle on bone to the greatest extent is shelled with gauze.
3, metaphysis is cut, is drawn with 5ml syringe and (does not inactivate) L-DMEM culture medium flushing bone containing 10% fetal calf serum
Pulp cavity blows and beats the single cell suspension of system.
4,1000r/min, centrifugation 5min are centrifuged.
5, supernatant is abandoned, cell is resuspended in culture medium, blows and beats into cell suspension, is seeded in culture bottle and cultivates) it is model, make
With the state of confocal laser scanning microscope cell on the surface of the material.
It is as shown in Figure 4: by 1 × 105Rear PBS is cleaned three times for 24 hours on material for the cell culture in a/hole, and 2.5% penta 2
It is dyed 40 minutes after the fixed 15min of aldehyde with the phalloidine (FITC-Phalloidin) of marked by fluorescein isothiocyanate, PBS is clear
5 times, each 5min are washed, is observed under laser co-focusing after mounting fluid-tight piece.Phenomenon shows on 4,5,7 material of embodiment
The cell spreading area that cell adherence quantity rises with the increase of PEG content with state of sprawling, and adheres on bracket also with
The increase of PEG content and coated weight and increase.
Embodiment 17:
The present embodiment is related to the evaluation of zoopery and vivo biodistribution safety
1) it is subcutaneously implanted with C57 mouse as model, the bioelastomer material of embodiment 4,5 is implanted into respectively 8 weeks big
The dorsal sc position of male C57 mouse.After the implantation 1 week, 4 weeks mouse put to death where every group of embodiment respectively, by material
Material takes out together with surrounding tissue, for being sliced and dyeing use.
2) after slice being made in the material of taking-up and surrounding tissue, the paraffin in slice is sloughed with dimethylbenzene, then through concentration
The alcohol solution dipping successively reduced, is finally washed with distilled water.
3) 2) slice in after distilling water washing impregnated several minutes through hematoxylic solution, soaked in sour water and ammonium hydroxide
Steep the several seconds after, then with flowing water rinse and distilled water respectively rinse 1 hour.
4) 3) slice in is also dyed 3 minutes after ethanol solution is dehydrated with eosin stains, then through ethyl alcohol and diformazan
After benzene processing, gummy mounting obtains H&E stained slice in drop.
It can be seen that by Fig. 5, bioelastomer prepared by embodiment 4,5,7 all shows good biocompatibility.
Embodiment 18:
The present embodiment is related to the preparation of 20-P-1.0U-F film, porous support and tubular material
According to embodiment 7, the membranaceous bioelastomer material can be prepared by step described in embodiment 7.
Mixture in 7 step b) of embodiment is poured into poroid or circular groove the shape that a diameter is 0.5~3cm
Tetrafluoro mold in, and the mold for being loaded with mixture is placed in moist environment, passes through reacting for isocyanates and vapor
The CO released2Gas obtains the porous column holder material of a 20-P-1.0U-F, as shown in B in Fig. 6.
Mixture in 7 step b) of embodiment is transferred in a customization composable mold, wherein the composable mold is by two
Part forms.The composable mold is placed in a dry environment and allows it the reaction was continued 12 hours, demoulding takes out to manage
Shape bioelastomer material, as shown in C in Fig. 6.
Embodiment 19
The present embodiment is related to the preparation of porous calcium microcosmic salt bracket
The mixing of the quality such as the drilling salt (300-500 microns) by the calcium phoshate bone cement powder and after being sieved, Xiang Fenmo
Middle addition saturated salt solution (solid-to-liquid ratio: 1g/0.3mL) is used as solidify liquid, is modulated into uniform slurry rapidly, is placed in stainless steel
Mold in, the pressure maintaining compression moulding in 1 minute at 2MPa with tablet press machine.By the cylindrical sample after compression moulding at 37 DEG C,
72 hours progress curing reactions are placed under 100% damp condition, the material being cured then are impregnated 3 days in ultrapure water, no
Disconnected stirring changes the new ultrapure water of a batch for every 12 hours, porous C PC bracket is made after NaCl particle dissolves out completely.
Embodiment 20
The present embodiment is related to the preparation of bioelastomer/CPC compound rest and its performance characterization of each coating content
It is still the liquid with mobility after reacting 5h by solution described in 5 step e) of embodiment, it will with pipette tips
The liquid with 20 μ l/ times, altogether the coated weight of 4 80ul in total uniformly coat and infiltrate through prepared in embodiment 19 it is porous
In bracket, stands and fully penetrate into bracket and evenly dispersed to it, be then placed on the branch of coating in draught cupboard 48 hours, it will
Solvent volatilization is most of.Then bracket is placed in a vacuum drying oven, 37 DEG C of vacuum under conditions of 72 hours, obtain biology
Elastomer composite porous C PC bracket.
It is described according to 5 step a) of embodiment, regulate and control it is high molecular feed intake can the solution concentration made from step e) be 0.1
~0.3g/ml, according to coated content, last compound rest macromolecule content (high molecule mass/CPC bracket matter obtained
Amount) it is 6%.
As shown in fig. 7, (A) figure is pattern of the compound rest after compression verification under 6% coating content, (B) figure is to change
Coat the compressive deformation figure of material under content.
By compression test it is found that relative to unmodified CPC porous support, the compound rest coated with bioelastomer,
Its mechanical strength has a degree of enhancing.
Embodiment 21
The present embodiment is related to controlled release of the bioelastomer for active factors
According to described in 14 step d) of embodiment, after reacting 12 hours in drier, without demoulding, obtain being attached to glass
The membranaceous bioelastomer of glass on piece.In a manner of drop coating, will delay dissolved with the horseradish peroxidase solution of 10mg/ul
Slow drop coating is on the surface of the material.By frozen dried, in the bioelastomer membrane material for being loaded with bioactie agent, repeat
Step a) in embodiment 14 d), obtains the film for being loaded with horseradish peroxidase with structure layer by layer.
Above-mentioned load enzyme film is immersed in PBS solution, is subsequently placed into 37 DEG C of constant temperature oscillation casees, in the scheduled time
(1,2,4,8,12,24,36,48,72) PBS solution of release, and the PBS more renewed simultaneously are collected.Here, existed with the enzyme
Distinctive absorbance value goes to measure its content at 405nm, and then by the concentration dilution of enzyme solutions to 0.1ug/ml, colour developing is added
Liquid (TMB one pack system developing solution) measures it and characterizes in catalysis absorptivity after ten minutes the activity of enzyme.
24 hours enzymatic activitys in Fig. 8 in A the result shows that, it is still with higher with the catalase that this programme loads
Activity, when the content of PEG rises, the enzymatic activity released is also relatively high.
From in Fig. 8 in B as can be seen that this new bio elastomeric material has the function of sustained release, and containing with PEG
Amount rises, and the rate of release of enzyme also rises.
According to the area of membrane material, the amount of drop coating is controlled in 126ul/cm2, meanwhile, dissolved with the solution of bioactie agent
Concentration can do adjustment appropriate according to application site.
Be dependent on application site, membrane material composition can be selected from hexamethylene diisocyanate be crosslinked poly- decanedioic acid glyceride,
Hexamethylene diisocyanate cross-linked polyethylene glycol-poly- decanedioic acid glyceride etc..
It is dependent on application site, the composition of membrane material is not limited only to 2 layers, can appropriately adjust in this range.
Embodiment 22
The present embodiment is related to controlled release of the bioelastomer for drug
According to described in 14 step d) of embodiment, after reacting 12 hours in drier, without demoulding, obtain being attached to glass
The membranaceous bioelastomer of glass on piece.By dissolved with the dexamethasone solution of 10mg/ul in a manner of drop coating, slow drop coating
On the surface of the material.By frozen dried, in the bioelastomer membrane material for being loaded with drug, the step in embodiment 14 is repeated
Rapid a) d obtains the load medicine film with structure layer by layer.
Above-mentioned load medicine film is immersed in PBS solution, is subsequently placed into 37 DEG C of constant temperature oscillation casees, in the scheduled time
(1,2,4,8,12,24,36,48,72) PBS solution of release, and the PBS more renewed simultaneously are collected.By measuring the small molecule
Absorbance value measurement of the drug at 240nm wavelength carries the drug of medicine film release.
According to the area of membrane material, the amount of drop coating is controlled in 126ul/cm2, meanwhile, dissolved with the solution of bioactie agent
Concentration can do adjustment appropriate according to application site.
Be dependent on application site, membrane material composition can be selected from hexamethylene diisocyanate be crosslinked poly- decanedioic acid glyceride,
Hexamethylene diisocyanate cross-linked polyethylene glycol-poly- decanedioic acid glyceride etc..
It is dependent on application site, the composition of membrane material is not limited only to 2 layers, can appropriately adjust in this range.
Comparative example 1
The concrete scheme and earlier patent application CN201510107574.3 and document (Ma Y, Zhang of this comparative example
W,Wang Z,Wang Z,Xie Q,Niu H,et al.Acta Biomater 2016；44:110-24.) identical.
Performed polymer described in embodiment 1,2,3 after high-temperature vacuum is crosslinked, tensile strength 100kPa~1MPa it
Between, elongation at break is between 20~80%.
And be crosslinked by obtaining hexamethylene diisocyanate mode described in this programme, mechanical property has great improvement,
And adjustable extent is big, and Young's modulus draws high intensity and elongation at break respectively in 1.01-14.23 MPa, and 0.32-
Between 7.63MPa and 53.63-272.84%.
Comparative example 2
By hexamethylene diisocyanate described in this programme, (number average molecular weight is lower than with the lesser prepolymer of molecule
4000) it reacts, obtains product after removing solvent.The product is in DMF, and the part more than 70% still can dissolve, and mechanics
Tensile strength and mechanics are respectively lower than 10%, 0.3MPa.
And the prepolymer of (number-average molecular weight 4000-9000) is through two isocyanide of hexa-methylene in this programme molecular weight area
After acid esters crosslinking, a cross-linked network can be effectively established, and it is stretched and mechanical strength is also more excellent.
Comparative example 3
By the excessively high prepolymer of molecule described in this programme (number average molecular weight is higher than 9000) and hexa-methylene diisocyanate
Ester reaction, the reaction are being far below plastic in the stipulated time, meanwhile, there are still part isocyanate group in reaction.
And the prepolymer of (number-average molecular weight 4000-9000) and hexamethylene diisocyanate are mixed in this programme section
, can be under relatively mild reaction condition after conjunction, energy is slow and effectively forms cross-linked network, and after discarding solvent, there is one section
The time of processing can be operated.
Comparative example 4
Using the immobilized active factors of heat cross-linking method
By albumen or drug molecule, (solution or solid) and performed polymer described in embodiment 1,2,3 are straight in the right way
Connect mixing.In tetrafluoro mold after 130~150 DEG C of vacuum are crosslinked, make solvent for heat cross-linking side with buffer solutions such as PBS
The release of the formula supported active factor.The mode of the low temperature supported active factor described in comparative example 9, heat cross-linking mode are negative
The factor of load has lost its activity.
All references mentioned in the present invention is incorporated herein by reference, just as each document coverlet
It is solely incorporated as with reference to such.In addition, it should also be understood that, after reading the above teachings of the present invention, those skilled in the art
Member can make various changes or modifications the present invention, and such equivalent forms equally fall within the application the appended claims and limited
Fixed range.
Claims (10)
1. a kind of bioelastomer, it includes following structural units are as follows:
The integer that n is 10~80；
The integer that m is 2~14.
2. bioelastomer as described in claim 1, which is characterized in that in the bioelastomer, decanedioic acid and glycerol and
The molar ratio of polyethylene glycol is 0.65~2.8.
3. bioelastomer as described in claim 1, which is characterized in that in the bioelastomer, polyethylene glycol and glycerol
Molar ratio≤4；The molar ratio of hexamethylene diisocyanate and glycerol is 0.2~1.5.
4. a kind of preparation method of bioelastomer as described in claim 1, which is characterized in that the preparation method include with
Lower step:
It reacts polyethylene glycol decanedioic acid glyceride performed polymer to obtain the life with hexamethylene diisocyanate in a solvent
Object elastomer,
Wherein the solvent is benzene,toluene,xylene, pentane, hexane, octane, hexamethylene, cyclohexanone, toluene cyclohexanone, chlorine
Benzene, dichloro-benzenes, methylene chloride, methanol, ethyl alcohol, isopropanol, ether, propylene oxide, methyl acetate, ethyl acetate, propyl acetate,
Acetone, espeleton, methylisobutylketone, glycol monoethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, acetonitrile, pyridine, benzene
Phenol, N, N- dimethylformamide, tetrahydrofuran or two or more mixed solvents.
5. preparation method as claimed in claim 4, which is characterized in that the preparation method further includes that catalysis is added in a solvent
The step of agent, the catalyst are selected from: stannous octoate, dibutyltin dilaurate, two (dodecyl sulphur) dibutyl tins, two
Acetic acid dibutyl tin, bismuth neodecanoate, zinc Isoocatanoate or two or more mixed catalysts.
6. preparation method as claimed in claim 5, which is characterized in that the preparation of the bioelastomer comprises the steps of
(a) under the atmosphere of argon gas, dried polyethylene glycol decanedioic acid glyceride performed polymer is dissolved in anhydrous N, N- dimethyl
In amide, solution concentration is 0.01~∞ g/ml；
(b) under the atmosphere of argon gas, mass volume ratio is dissolved in the solution of step a) lower than 0.01% stannous octoate；
(c) under the atmosphere of argon gas, the solution of step b) is transferred in reaction unit, and connects Xi Laike operating system, in 20
10~20min is heated at~65 DEG C；
(d) under argon atmosphere, the hexamethylene diisocyanate of corresponding mole is added in the device of step 3), is slowly dripped
It is added in solution；
(e) under argon atmosphere, the reaction was continued 5~12 hours in 20~65 DEG C for solution in step d), and taking-up is transferred to tetrafluoro mould
In tool, it is stored at room temperature 2 days, is dried in vacuo 48 hours at room temperature, obtains bioelastomer.
7. a kind of preparation method of bioelastomer as described in claim 1, which is characterized in that under the preparation method includes
Column step:
(a) dried polyethylene glycol decanedioic acid glyceride performed polymer and mass volume ratio are lower than the polyethylene glycol last of the ten Heavenly stems two
The catalyst of acid glyceride performed polymer 0.05% is uniformly mixed；
(b) it in mixture obtained in step a), will be added different for 0.2~1.5 hexa-methylene two with the molar ratio of glycerol
Cyanate simultaneously stirs and evenly mixs rapidly；
(c) mixture obtained in step b) is placed under dry environment, the reaction was continued 8-24 hours (preferably 12-14
Hour) to get arrive macromolecular elastomer.
8. preparation method as claimed in claim 7, which is characterized in that catalyst is selected from the step b): stannous octoate, two
Butyl tin dilaurate, two (dodecyl sulphur) dibutyl tins, dibutyltin diacetate, bismuth neodecanoate, zinc Isoocatanoate or two
Kind or more mixed catalyst.
9. a kind of modified material, which is characterized in that the modified material includes base material, and is supported on the base material
On bioelastomer.
10. a kind of drug release material, which is characterized in that the drug release material includes bioelastomer, and is supported on
Active factors on the bioelastomer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810077797.3A CN110078880B (en) | 2018-01-26 | 2018-01-26 | Isocyanate cross-linked polyethylene glycol-polysebacic acid glyceride biological elastomer and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810077797.3A CN110078880B (en) | 2018-01-26 | 2018-01-26 | Isocyanate cross-linked polyethylene glycol-polysebacic acid glyceride biological elastomer and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110078880A true CN110078880A (en) | 2019-08-02 |
| CN110078880B CN110078880B (en) | 2022-06-28 |
Family
ID=67412636
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810077797.3A Active CN110078880B (en) | 2018-01-26 | 2018-01-26 | Isocyanate cross-linked polyethylene glycol-polysebacic acid glyceride biological elastomer and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110078880B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111892703A (en) * | 2020-06-28 | 2020-11-06 | 东华大学 | Biodegradable thermoplastic polyester elastic material and preparation method thereof |
| CN111956864A (en) * | 2020-08-18 | 2020-11-20 | 华东理工大学 | 3D printing composite support and preparation method and application thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1642916A1 (en) * | 2004-10-04 | 2006-04-05 | Bayer MaterialScience LLC | Polyester-polyurethane composites |
| CN103289349A (en) * | 2013-06-28 | 2013-09-11 | 南通华盛高聚物科技发展有限公司 | Biodegradable resin composition |
| CN103319865A (en) * | 2013-06-08 | 2013-09-25 | 上海博疆新材料科技有限公司 | Polylactic acid alloy membrane and application thereof |
| CN104629026A (en) * | 2015-02-15 | 2015-05-20 | 东华大学 | Biomedical polybasic copolymerized crosslinked polyester elastomer material and preparation method thereof |
| CN104645417A (en) * | 2015-03-11 | 2015-05-27 | 华东理工大学 | Mesoporous bioactive glass/poly-decyl diacid glyceride composite support as well as preparation method and application thereof |
| CN104825490A (en) * | 2015-04-23 | 2015-08-12 | 华东理工大学 | Hydroxyapatite nanoparticle with antitumor activity, preparation method and application thereof |
-
2018
- 2018-01-26 CN CN201810077797.3A patent/CN110078880B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1642916A1 (en) * | 2004-10-04 | 2006-04-05 | Bayer MaterialScience LLC | Polyester-polyurethane composites |
| CN103319865A (en) * | 2013-06-08 | 2013-09-25 | 上海博疆新材料科技有限公司 | Polylactic acid alloy membrane and application thereof |
| CN103289349A (en) * | 2013-06-28 | 2013-09-11 | 南通华盛高聚物科技发展有限公司 | Biodegradable resin composition |
| CN104629026A (en) * | 2015-02-15 | 2015-05-20 | 东华大学 | Biomedical polybasic copolymerized crosslinked polyester elastomer material and preparation method thereof |
| CN104645417A (en) * | 2015-03-11 | 2015-05-27 | 华东理工大学 | Mesoporous bioactive glass/poly-decyl diacid glyceride composite support as well as preparation method and application thereof |
| CN104825490A (en) * | 2015-04-23 | 2015-08-12 | 华东理工大学 | Hydroxyapatite nanoparticle with antitumor activity, preparation method and application thereof |
Non-Patent Citations (4)
| Title |
|---|
| MARIA JOSÉ NUNES PEREIRA等: ""A Highly Tunable Biocompatible and Multifunctional Biodegradable Elastomer"", 《ADVANCED MATERIALS》 * |
| SO MI CHOI，等: ""Synthesis and Characterization of In Situ Gellable Poly(glycerol sebacate)-co-Poly(ethylene glycol) Polymers"", 《MACROMOLECULAR RESEARCH》 * |
| WANG, ZIHAO等: ""Urethane-based low-temperature curing, highly-customized and multifunctional poly(glycerol sebacate)-co-poly(ethylene glycol) copolymers"", 《ACTA BIOMATERIALIA》 * |
| YIFAN MA等: ""PEGylated poly(glycerol sebacate)-modified calcium phosphate scaffolds with desirable mechanical behavior and enhanced osteogenic capacity"", 《ACTA BIOMATERIALIA》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111892703A (en) * | 2020-06-28 | 2020-11-06 | 东华大学 | Biodegradable thermoplastic polyester elastic material and preparation method thereof |
| CN111892703B (en) * | 2020-06-28 | 2021-07-20 | 东华大学 | Biodegradable thermoplastic polyester elastic material and preparation method thereof |
| CN111956864A (en) * | 2020-08-18 | 2020-11-20 | 华东理工大学 | 3D printing composite support and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110078880B (en) | 2022-06-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Kathuria et al. | Synthesis and characterization of elastic and macroporous chitosan–gelatin cryogels for tissue engineering | |
| Frydrych et al. | Biomimetic poly (glycerol sebacate)/poly (l-lactic acid) blend scaffolds for adipose tissue engineering | |
| Xue et al. | Biodegradable and biomimetic elastomeric scaffolds for tissue-engineered heart valves | |
| Elomaa et al. | Three-dimensional fabrication of cell-laden biodegradable poly (ethylene glycol-co-depsipeptide) hydrogels by visible light stereolithography | |
| Gunatillake et al. | Designing biostable polyurethane elastomers for biomedical implants | |
| Samourides et al. | The effect of porous structure on the cell proliferation, tissue ingrowth and angiogenic properties of poly (glycerol sebacate urethane) scaffolds | |
| Tran et al. | Synthesis and characterization of a biodegradable elastomer featuring a dual crosslinking mechanism | |
| US20150099853A1 (en) | Novel Biodegradable Elastomeric Scaffold for Tissue Engineering and Light Scattering Fingerprinting Methods for Testing the Same | |
| Daemi et al. | A robust super-tough biodegradable elastomer engineered by supramolecular ionic interactions | |
| Hafeman et al. | Injectable biodegradable polyurethane scaffolds with release of platelet-derived growth factor for tissue repair and regeneration | |
| Sharifpoor et al. | Synthesis and characterization of degradable polar hydrophobic ionic polyurethane scaffolds for vascular tissue engineering applications | |
| Pereira et al. | A highly tunable biocompatible and multifunctional biodegradable elastomer | |
| Kim et al. | Synthesis and evaluation of novel biodegradable hydrogels based on poly (ethylene glycol) and sebacic acid as tissue engineering scaffolds | |
| Da et al. | Composite elastomeric polyurethane scaffolds incorporating small intestinal submucosa for soft tissue engineering | |
| Zhang et al. | Synthesis and characterization of biocompatible, degradable, light‐curable, polyurethane‐based elastic hydrogels | |
| US20090130174A1 (en) | Poly (ester urethane) urea foams with enhanced mechanical and biological properties | |
| US20030118692A1 (en) | Biodegradable polymer | |
| Frydrych et al. | Thermoresponsive, stretchable, biodegradable and biocompatible poly (glycerol sebacate)-based polyurethane hydrogels | |
| Wang et al. | Urethane-based low-temperature curing, highly-customized and multifunctional poly (glycerol sebacate)-co-poly (ethylene glycol) copolymers | |
| JP2008049170A (en) | Use of thermoplastically processable polyurethane, and medical article | |
| EP1448656B1 (en) | Biodegradable polymer | |
| Gyawali et al. | Citric-acid-derived photo-cross-linked biodegradable elastomers | |
| Mostafavi et al. | Highly tough and ultrafast self-healable dual physically crosslinked sulfated alginate-based polyurethane elastomers for vascular tissue engineering | |
| Wang et al. | Polymerization of hydrogel network on microfiber surface: synthesis of hybrid water-absorbing matrices for biomedical applications | |
| CN110078880A (en) | Isocyanate-crosslinked polyethylene glycol decanedioic acid glyceride bioelastomer and its preparation method and application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |