CN106957434A - Triblock copolymer and porous laminated support and preparation method thereof - Google Patents
Triblock copolymer and porous laminated support and preparation method thereof Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 26
- 229920000428 triblock copolymer Polymers 0.000 title claims abstract description 24
- 238000006243 chemical reaction Methods 0.000 claims abstract description 29
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 14
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 14
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims abstract description 11
- 230000032050 esterification Effects 0.000 claims abstract description 6
- 238000005886 esterification reaction Methods 0.000 claims abstract description 6
- 229920000642 polymer Polymers 0.000 claims abstract description 6
- 239000001384 succinic acid Substances 0.000 claims abstract description 6
- 239000002994 raw material Substances 0.000 claims abstract description 5
- 239000000178 monomer Substances 0.000 claims abstract description 3
- 238000006068 polycondensation reaction Methods 0.000 claims abstract description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 57
- 239000002202 Polyethylene glycol Substances 0.000 claims description 24
- 229920001223 polyethylene glycol Polymers 0.000 claims description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 15
- 238000002347 injection Methods 0.000 claims description 13
- 239000007924 injection Substances 0.000 claims description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 12
- 229920001577 copolymer Polymers 0.000 claims description 12
- WERYXYBDKMZEQL-UHFFFAOYSA-N butane-1,4-diol Chemical compound OCCCCO WERYXYBDKMZEQL-UHFFFAOYSA-N 0.000 claims description 10
- 238000010438 heat treatment Methods 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 238000001291 vacuum drying Methods 0.000 claims description 8
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 claims description 7
- 229940014800 succinic anhydride Drugs 0.000 claims description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- 238000010521 absorption reaction Methods 0.000 claims description 6
- 239000003513 alkali Substances 0.000 claims description 6
- 239000007789 gas Substances 0.000 claims description 6
- 238000001556 precipitation Methods 0.000 claims description 6
- 238000005292 vacuum distillation Methods 0.000 claims description 6
- 229920001427 mPEG Polymers 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 4
- 238000002474 experimental method Methods 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- 238000010792 warming Methods 0.000 claims description 4
- 230000033228 biological regulation Effects 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 3
- 230000003197 catalytic effect Effects 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 3
- 230000007423 decrease Effects 0.000 claims description 3
- 239000005457 ice water Substances 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 3
- 238000000465 moulding Methods 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 238000007493 shaping process Methods 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 230000007480 spreading Effects 0.000 claims description 3
- 238000000967 suction filtration Methods 0.000 claims description 3
- 238000003828 vacuum filtration Methods 0.000 claims description 3
- -1 Chlorine sulfoxide Chemical class 0.000 claims description 2
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 238000013019 agitation Methods 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 230000006837 decompression Effects 0.000 claims description 2
- 238000003808 methanol extraction Methods 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 230000004044 response Effects 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims description 2
- 239000002585 base Substances 0.000 claims 1
- 125000003963 dichloro group Chemical group Cl* 0.000 claims 1
- 238000002844 melting Methods 0.000 claims 1
- 230000008018 melting Effects 0.000 claims 1
- 150000003462 sulfoxides Chemical class 0.000 claims 1
- 239000000463 material Substances 0.000 abstract description 10
- CDQSJQSWAWPGKG-UHFFFAOYSA-N butane-1,1-diol Chemical compound CCCC(O)O CDQSJQSWAWPGKG-UHFFFAOYSA-N 0.000 abstract description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- 229920002961 polybutylene succinate Polymers 0.000 description 6
- 239000004631 polybutylene succinate Substances 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000001035 drying Methods 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229920003232 aliphatic polyester Polymers 0.000 description 1
- 230000002429 anti-coagulating effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000007334 copolymerization reaction Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000010224 hepatic metabolism Effects 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 238000001746 injection moulding Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000005311 nuclear magnetism Effects 0.000 description 1
- 230000000242 pagocytic effect Effects 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- RINCXYDBBGOEEQ-UHFFFAOYSA-N succinic anhydride Chemical class O=C1CCC(=O)O1 RINCXYDBBGOEEQ-UHFFFAOYSA-N 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000010148 water-pollination Effects 0.000 description 1
Classifications
-
- 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
- C08G81/00—Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/56—Porous materials, e.g. foams or sponges
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/58—Materials at least partially resorbable by the body
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Dermatology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dispersion Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Other Resins Obtained By Reactions Not Involving Carbon-To-Carbon Unsaturated Bonds (AREA)
- Polyesters Or Polycarbonates (AREA)
Abstract
The invention belongs to the preparing technical field of Medical rack, and in particular to a kind of triblock copolymer and porous laminated support and preparation method thereof.The preparation method of triblock copolymer comprises the steps：1)：Using Isosorbide-5-Nitrae succinic acid and Isosorbide-5-Nitrae butanediol as reaction monomers, using esterification and melt polycondensation reaction, obtain a series of hydroxy-end capped, the PBS prepolymers with different molecular weight；2):Using MPEG as raw material, MPEG COOH are obtained by esterification, it is that can obtain MPEG COCl to continue acylated；3)：The synthesis of triblock polymer：HO PBS OH and MPEG COCl are polymerize, you can obtain triblock polymer.The triblock copolymer material of synthesis has higher molecular weight, preferable mechanical strength, possesses preferable hydrophilic-hydrophobic balance and biological degradability, meets the average operating as Medical rack material.
Description
Technical field
The invention belongs to the preparing technical field of Medical rack, and in particular to a kind of triblock copolymer and porous laminated branch
Frame and preparation method thereof.
Background technology
The high hydrophobicity of poly butylene succinate (PBS) molecular skeleton, intermolecular force is weak and is difficult to reconcile
Hydrophilic/hydrophobic is balanced, and presence the problems such as lack reactivity site, largely constrains PBS in bio-medical
Application of the material especially as Medical rack Material Field.And polyethylene glycol (PEG) is a kind of extremely wide polyethers of purposes
High-molecular compound, it can be applied to the various fields such as medicine, health, food, chemical industry.PEG has excellent biocompatibility
And water solubility.In the synthesis and modification of novel biomaterial, PEG will assign material new characteristic as a part for material
And function, such as hydrophily, flexibility, anticoagulant property, anti-macrophage are phagocytic.
By PEG and PBS copolymerization, while holding PEG original good biocompatibilities, moreover it is possible to improve gained copolymer
Hydrophilicity.In addition, this amphipathic copolymer also has biodegradability, PEG is very easy to by liver metabolism, and is gathered
The hydrophobic segment of esters then can be degraded into molecule by the effect of internal hydrolase, be drained by normal physiological metabolism process
To external.Therefore, will be in targeting if PBS is modified and is modified in terms of active reaction sites and controlled degradation is provided
Controlled release drug carrier and intelligentized tissue engineering bracket material field expand huge applications.
The content of the invention
It is an object of the invention to the shortcoming for overcoming prior art, there is provided a kind of triblock copolymer and porous laminated support
And preparation method thereof.
To achieve the above object, the technical solution adopted by the present invention is：
A kind of preparation method of triblock copolymer, comprises the steps：
1)：HO-PBS-OH preparation, using 1, 4- succinic acid and BDO as reaction monomers, using esterification and
Melt polycondensation reaction, obtains a series of hydroxy-end capped, the PBS prepolymers HO-PBS-OH with different molecular weight；Such as formula (I)
Show：
2):Terminal acyl groups PEG synthesis：Using methoxy poly (ethylene glycol) MPEG as raw material, end is obtained by esterification
The polyethylene glycol MPEG-COOH of end carboxyl, described MPEG-COOH is acylated and can obtain MPEG-COCl；Such as formula
(II is shown)
3)：Triblock polymer MPEG-PBS-MPEG synthesis：By step 1) obtained HO-PBS-OH and step 2)
Obtained MPEG-COCl is polymerize, you can obtain triblock polymer MPEG-PBS-MPEG.
Wherein, step 1) in 1, 4- succinic acid and BDO mol ratio be 1:1.0-1.5, obtained HO-PBS-
OH Mn is 5000-15000.
Specifically, step 1) concretely comprise the following steps：
1, 4- succinic acid, BDO and catalyst are added in reactor flask device, heating response device is simultaneously passed through
Nitrogen for a period of time after, reaction temperature is slowly increased to 170 DEG C, 2h or so is reacted at such a temperature, until no longer producing water droplet；
240 DEG C are then heated to, pressure gradually decreases to below 60Pa, accelerate stir about 3h.After reaction terminates, product chloroform dissolves
Again with methanol precipitates to obtain milky fluffy solid afterwards.It is standby that sample dries 24h in 50 DEG C of vacuum drying ovens.
Specifically, step 2) concretely comprise the following steps：
Add in the reactor after methoxy poly (ethylene glycol) and toluene Hybrid Heating backflow 30min, heating is azeotroped off
Water in MPEG, adds the succinic anhydride of 1.5 times of -2 times of MPEG moles, and temperature control is at 80 DEG C, after reacting 6 hours, then
It is warming up to 100 DEG C and then carries out vacuum filtration, terminates reaction after 2 hours；With water pump vacuum distillation until remaining a small amount of toluene, is used
A large amount of ether washing precipitations, remove excessive succinic anhydride and toluene, and obtaining MPEG-COOH, to be put into vacuum drying chamber standby；
The MPEG-COOH of terminal carboxyl group obtained above is dissolved in toluene, 4-8 moles times of MPEG-COOH is added
Thionyl chloride, lead to nitrogen protection, the gas generated in being reacted with alkali liquor absorption.Confined reaction device, temperature control is at 50 DEG C
Reaction terminates experiment in about 16 hours；Vacuum distillation goes out after most of toluene, add 60mL toluene continue to be distilled off it is excessive
Thionyl chloride, that is, can obtain the polyethylene glycol MPEG-COCl of end chloride.
Specifically, step 3) concretely comprise the following steps：
The MPEG-COCl of the HO-PBS-OH and 1.5-2 molar equivalents of 1 molar equivalent is added to reaction in ice-water bath
In device, using chloroform as solvent, and the pyridine of catalytic amount is added.The gas of generation, the lower magnetic force of nitrogen protection are reacted with alkali liquor absorption
Stirring, confined reaction is put.After reaction one hour, continue at room temperature after reacting 4 hours, then that temperature is transferred to 60 degree of reactions is 3 small
When, terminate experiment；Then product is added in excessive cold diethyl ether, Precipitation, after decompression suction filtration, then it is small by 24
When vacuum drying obtain triblock copolymer.
Present invention additionally comprises a kind of triblock copolymer, obtained using above-mentioned preparation method.
A kind of preparation method of porous laminated support, using described 8-10 mass parts triblock copolymer and 1 mass
Part polyethylene glycol oxide PEO is raw material, is sufficiently mixed in rotary drum blender mixer, puts into injection machine hopper, regulates and controls injection pressure；Carry out
Injection, cooling and shaping, obtain dumbbell shape injection batten；Molding batten is put into 37 DEG C of water immediately after and soaked, in blend
Water miscible PEO will be gradually leached out, and weight keeps constant, finally gives porous laminated structure stand.
Present invention additionally comprises a kind of porous layer support, prepared using above-mentioned preparation method.
Compared with prior art, the beneficial effects of the invention are as follows：
The three block aliphatic polyester material of synthesis has higher molecular weight, preferable mechanical strength, possessed preferably
Hydrophilic-hydrophobic balance and biological degradability, meet as Medical rack material average operating；With traditional use
Porous support prepared by PLA (PLA) material is compared, and MPEG-PBS-MPEG porous layer supports prepared by injection molding method have
Layer structure, higher porosity, the aperture size being evenly distributed, interconnected opening gap structure and well hydrophilic
Property.Copolymer brace aperture rate is more than 92.5%；Macropore size range is at 100-300 μm；The radial strength of copolymer support reaches
To 7.8kPa；The spreading rate of copolymer support is in 4%-6% or so, and support longitudinally shortens rate less than 9%；Copolymer support water connects
Feeler is below 25 degree.
Brief description of the drawings
Fig. 1 is the triblock copolymer MPEG-PBS-MPEG of present invention synthetic route chart.
Fig. 2 is the triblock copolymer MPEG-PBS-MPEG of present invention nuclear-magnetism figure.
Fig. 3 is the scanning electron microscope (SEM) photograph of the porous laminated supports of MPEG-PBS-MPEG of the present invention.
Fig. 4 is the porous laminated support preparation flow schematic diagram of the present invention.
Embodiment
In order that those skilled in the art more fully understand technical scheme, below in conjunction with the accompanying drawings and most
The present invention is described in further detail for good embodiment.
Embodiment：Fig. 1 shows the triblock copolymer MPEG-PBS-MPEG of present invention synthetic route chart.
1.1HO-PBS-OH synthesis
23.6 grams of 1,4- succinic acid (SA), 21.6 grams of 1,4- butanediols (BD) and catalyst chlorine are added in four-hole boiling flask
Change stannous 0.03g and p-methyl benzenesulfonic acid 0.03g, (BD and SA mol ratio are 1.2:1) when, being placed in heating mantle and being passed through one section of nitrogen
Between after, reaction temperature is slowly increased to 170 DEG C, 2h or so is reacted at such a temperature, until no longer producing water droplet；Then heat to
240 DEG C, pressure gradually decreases to below 60Pa, accelerates stir about 3h.After reaction terminates, obtain newborn with methanol extraction after chloroform dissolving
White fluffy solid.It is standby in 50 DEG C of baking 24h of vacuum drying oven.
1.2 terminal carboxyl group MPEG synthesis
10g methoxy poly (ethylene glycol)s (MPEG) and 150mL toluene Hybrid Heating backflow 30min are added in four-hole boiling flask
Afterwards, heating azeotropic is steamed after the water that 80mL toluene is removed in PEG, adds 2g succinic anhydrides, and temperature control is at 80 DEG C, and reaction 6 is small
When after, then be warming up to 100 DEG C then carry out vacuum filtrations, after 2 hours terminate reaction.With water pump vacuum distillation until remaining few
Toluene is measured, precipitation is washed with a large amount of ether, excessive succinic anhydride and toluene is removed, is put into vacuum drying chamber standby.
1.3 end chloride MPEG synthesis
The MPEG-COOH of 10 grams of carboxylated of addition, which weighs, in four-hole boiling flask is dissolved in 100ml toluene, adds 6 times moles
The thionyl chloride of amount, leads to nitrogen protection, the gas generated in being reacted with alkali liquor absorption.Confined reaction device.Temperature control is 50
DEG C reaction about 16 hours terminate experiment.Then vacuum distillation goes out after most of toluene, adds 60mL toluene and continues to be distilled off
Excessive thionyl chloride, product drying for standby.
1.4MPEG-PBS-MPEG synthesis
The end chloride MPEG of HO-PBS-OH and 2 times of mole is added in four-hole boiling flask in ice-water bath, chloroform
For solvent, and add the pyridine of catalytic amount.The gas of generation is reacted with alkali liquor absorption.The lower magnetic agitation of nitrogen protection, it is closed anti-
It should put.After reaction one hour, allow it to continue at room temperature after reacting 4 hours, then temperature is transferred to 60 degree of reactions and terminate within 3 hours real
Test.Then be added into excessive cold diethyl ether, there is Precipitation, by depressurizing suction filtration after, it is then true by 24 hours
Empty drying to obtain MPEG-PBS-MPEG triblock copolymers.
Fig. 1 shows MPEG-PBS-MPEG nuclear magnetic spectrogram, as we know from the figure：Chemical shift (δ) divides for 1.7,4.1 peak
- CH2-proton resonance peaks that Wei be on 1,4- butanediol segments at position 1 and position 4；δ be 2.6 at be 1,4- succinic acid chains
- CH2-proton resonance peaks in section at position 3；δ be 3.6 at be that at position 2-CH2-proton resonance peaks in PEG chain segment, say
Bright MPEG-PBS-MPEG triblock copolymers are successfully prepared.
Embodiment 2 is identical with the preparation method of embodiment 1 with embodiment 3, differs only in, the 1.1.HO- of embodiment 2
In PBS-OH synthesis, 1, 4- succinic acid, the mol ratio of BDO are 1:1, and 1, 4- succinic acid, Isosorbide-5-Nitrae in embodiment 3-
The mol ratio of butanediol is 1:1 mol ratio is 1:1.5.Embodiment 4 is identical with the preparation method of embodiment 1 with embodiment 5, area
It is not only that, during 1.2-1.3 synthesis MPEG-COCl, the MPEG of embodiment 4 and the mol ratio of succinic anhydride are 1:1.5
And it is 4 moles times that MPEG-COOH, which prepares the addition equivalent of the dimethyl sulfoxide during MPEG-COCl, and the MPEG of embodiment 5 with
The mol ratio of succinic anhydride is 1:The addition equivalent that 2 and MPEG-COOH prepares the dimethyl sulfoxide during MPEG-COCl rubs for 8
You are again.
The preparation of 1.5 porous laminated structure stands：
Embodiment 6：
As Fig. 4 is shown, the MPEG-PBS-MPEG triblock copolymers and polyethylene glycol oxide for first obtaining embodiment 1
(PEO) it is sufficiently mixed according to true part by weight (90/10) in rotary drum blender mixer, input injection machine hopper (I), regulation and control injection work
Skill condition, described Shooting Technique is the maximum injection temperature T range of regulation and control at 140-160 DEG C；Injection pressure P scopes are in 40MPa-
60MPa；40 DEG C of mould temperature is molded；Cooling and shaping (II) cool time 10-20s, obtains dumbbell shape injection batten；Immediately after
Molding batten is put into 37 DEG C of water immersion (III) for a long time, until weight keeps constant, porous laminated structure stand is obtained
(IV)。
Embodiment 7 is identical with the preparation method of embodiment 6 with embodiment 8, differs only in MPEG-PBS-MPEG three blocks
Copolymer is different from the mass ratio of polyethylene glycol oxide (PEO), and the mass ratio of embodiment 7 is 8:1 and the mass ratio of embodiment 8
Example is 10:1.
Wherein, embodiment 6 is optimum embodiment, and Fig. 3 shows the scanning electron microscope (SEM) photograph of porous layer support, its obtained porous layer
Brace aperture rate is more than 92.5%；Macropore size range is at 100-300 μm；The radial strength of porous layer support is more than 7.8kPa；
The spreading rate of copolymer support is 4%-6%, and support longitudinally shortens rate less than 9%；Copolymer support water contact angle 25 degree with
Under.
The above is only the preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, under the premise without departing from the principles of the invention, some improvements and modifications can also be made, these improvements and modifications also should
It is considered as protection scope of the present invention.
Claims (9)
1. a kind of preparation method of triblock copolymer, it is characterised in that comprise the steps：
1)：HO-PBS-OH preparation, using 1, 4- succinic acid and BDO as reaction monomers, using esterification and melting
Polycondensation reaction, obtains a series of hydroxy-end capped, the PBS prepolymers HO-PBS-OH with different molecular weight；As formula (I) is shown：
2):Terminal acyl groups PEG synthesis：Using methoxy poly (ethylene glycol) MPEG as raw material, end carboxylic is obtained by esterification
The polyethylene glycol MPEG-COOH of base, described MPEG-COOH is acylated and can obtain MPEG-COCl；Such as formula, (I I show
Go out):
3)：Triblock polymer MPEG-PBS-MPEG synthesis：By step 1) obtained HO-PBS-OH and step 2) obtain
MPEG-COCl polymerize, you can obtain triblock polymer MPEG-PBS-MPEG.
2. the preparation method of triblock copolymer according to claim 1, it is characterised in that step 1) in 1, 4- succinic acid
Mol ratio with 1,4- butanediols is 1:1.0-1.5, obtained HO-PBS-OH Mn are 5000-15000.
3. the preparation method of triblock copolymer according to claim 1, it is characterised in that step 1) specific steps
For：
1, 4- succinic acid, BDO and catalyst are added in reactor flask device, heating response device is simultaneously passed through nitrogen
After a period of time, reaction temperature is slowly increased to 170 DEG C, 2h or so is reacted at such a temperature, until no longer producing water droplet；Then
240 DEG C are warming up to, pressure gradually decreases to below 60Pa, accelerate stir about 3h；Reaction terminate after, product chloroform dissolve after again
Milky fluffy solid is obtained with methanol extraction；It is standby that sample dries 24h in 50 DEG C of vacuum drying ovens.
4. the preparation method of triblock copolymer according to claim 1, it is characterised in that step 2) specific steps
For：
Add in the reactor after methoxy poly (ethylene glycol) and toluene Hybrid Heating backflow 30min, heating is azeotroped off in MPEG
Water, add the succinic anhydride of 1.5 times of -2 times of MPEG moles, temperature control after reaction 6 hours, then is warming up at 80 DEG C
100 DEG C and then progress vacuum filtration, terminate reaction after 2 hours；With water pump vacuum distillation until remaining a small amount of toluene, uses a large amount of second
Ether washing precipitation, removes excessive succinic anhydride and toluene, and obtaining MPEG-COOH, to be put into vacuum drying chamber standby；
The MPEG-COOH of terminal carboxyl group obtained above is dissolved in toluene, the two of 4-8 moles times of MPEG-COOH are added
Chlorine sulfoxide, leads to nitrogen protection, the gas generated in being reacted with alkali liquor absorption.Confined reaction device, temperature control is in 50 DEG C of reactions
Terminate experiment within about 16 hours；Vacuum distillation goes out after most of toluene, adds 60mL toluene and continues that excessive dichloro is distilled off
Sulfoxide, that is, can obtain the polyethylene glycol MPEG-COCl of end chloride.
5. the preparation method of triblock copolymer according to claim 1, it is characterised in that step 3) specific steps
For：
The MPEG-COCl of the HO-PBS-OH and 1.5-2 molar equivalents of 1 molar equivalent is added in reactor in ice-water bath,
Using chloroform as solvent, and add the pyridine of catalytic amount.The gas of generation is reacted with alkali liquor absorption, nitrogen protects lower magnetic agitation,
Confined reaction is put.Reaction one hour after, at room temperature continue react 4 hours after, then temperature be transferred to 60 degree react 3 hours, knot
Beam is tested；Then product is added in excessive cold diethyl ether, Precipitation, after decompression suction filtration, then by 24 hours
Vacuum drying obtains triblock copolymer.
6. a kind of triblock copolymer, it is characterised in that obtained using the preparation method described in claim any one of 1-5.
7. a kind of preparation method of porous laminated support, it is characterised in that embedding using the 8-10 mass parts three described in claim 6
Section copolymer and 1 mass parts polyethylene glycol oxide PEO be raw material, be sufficiently mixed in rotary drum blender mixer, put into injection machine hopper,
Regulate and control Shooting Technique；Be molded, cooling and shaping, obtain dumbbell shape injection batten；Molding batten is put into 37 DEG C immediately after
Soaked in water, water miscible PEO will be gradually leached out in blend, weight keeps constant, finally gives porous laminated structure branch
Frame.
8. a kind of preparation method of porous laminated support, it is characterised in that described Shooting Technique is the maximum injection temperature T of regulation and control
Scope is at 140-160 DEG C；Injection pressure P scopes are in 40MPa-60MPa；40 DEG C of mould temperature；Cool time 10-20s.
9. a kind of porous laminated support, it is characterised in that prepared using preparation method described in claim 7 or 8；Described is more
Aperture layer brace aperture rate is more than 92.5%；Macropore size range is at 100-300 μm；The radial strength of porous layer support is more than
7.8kPa；The spreading rate of copolymer support is 4%-6%, and support longitudinally shortens rate less than 9%；Copolymer support water contact angle exists
Less than 25 degree.
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Cited By (2)
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| US10994057B2 (en) | 2018-03-01 | 2021-05-04 | Tepha, Inc. | Articles of poly(butylene succinate) and copolymers thereof |
| US11786632B2 (en) | 2018-03-01 | 2023-10-17 | Tepha, Inc. | Hernia repair, breast reconstruction and sling devices containing poly(butylene succinate) and copolymers thereof |
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| CN103242523A (en) * | 2013-05-10 | 2013-08-14 | 方剑群 | Synthesis method of triblock copolymer PEI-PEG-PEI |
| CN104892912A (en) * | 2015-06-08 | 2015-09-09 | 厦门普瑞安生物科技有限公司 | Poly lactic acid-glycolic acid (PLGA)-polyethylene glycol (PEG)-PLGA triblock copolymer and preparation method thereof |
| CN105085927A (en) * | 2015-08-19 | 2015-11-25 | 河南省眼科研究所 | Tri-block copolymer, preparation method thereof and eye drop prepared from tri-block copolymer |
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| CN1840199A (en) * | 2006-01-24 | 2006-10-04 | 中国科学院长春应用化学研究所 | Amphiphilic tri-block copolymer-paclitaxel bonded drug and preparation method thereof |
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| US10994057B2 (en) | 2018-03-01 | 2021-05-04 | Tepha, Inc. | Articles of poly(butylene succinate) and copolymers thereof |
| US11786632B2 (en) | 2018-03-01 | 2023-10-17 | Tepha, Inc. | Hernia repair, breast reconstruction and sling devices containing poly(butylene succinate) and copolymers thereof |
| US11878087B2 (en) | 2018-03-01 | 2024-01-23 | Tepha, Inc. | Oriented implants containing poly(butylene succinate) and copolymer, and methods of use thereof |
| US11896734B2 (en) | 2018-03-01 | 2024-02-13 | Tepha, Inc. | Surgical mesh implants containing poly(butylene succinate) and copolymers thereof |
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