CN105754078A - Block copolymerization method of PLLA and PEG in supercritical carbon dioxide - Google Patents

Abstract

The invention provides a method for block copolymerization of PLLA and PEG in supercritical carbon dioxide. The specific steps include: mixing lactide monomer, stannous octoate and polyethylene glycol according to the ratio of 60-100:0.2-0.8:10-30 The molar ratio is put into the reaction; 0-10wt% of the stabilizer PCL?b?PDMS?b?PCL is added; _CO is introduced into the reactor until the pressure in the reactor reaches 16-20Mpa, at 80-100°C, Keep the pressure and temperature in the kettle constant, and continue the reaction for 12-48 hours; obtain the block copolymer of PLLA and PEG. The method of the present invention successfully prepares PLLA?b?PEG?b?PLLA block copolymerization product with good comprehensive properties, the conversion rate of lactide monomer can reach more than 92%, the reaction time is short, the reaction conditions are mild, and the process The method is simple; no organic solvent is needed, and is in line with the development direction of green chemistry; the method of the invention is a biological material synthesis method with development potential and has broad application prospects.

Description

A kind of method of PLLA and PEG block copolymerization in supercritical carbon dioxide

technical field

The invention relates to a method for block copolymerization of PLLA and PEG, in particular to a method for block copolymerization of PLLA and PEG in supercritical carbon dioxide.

Background technique

As a new type of degradable material, linear aliphatic polyester has been widely concerned and applied in recent years. However, the traditional preparation method involves defects and deficiencies such as the use of organic solvents, excessively high reaction temperature, and uncontrollable product characteristics. Due to its excellent properties such as non-toxic, non-polluting, and reactive inertness, CO ₂ has gradually become a popular choice as a solvent in the current polymer synthesis process, and has also become a hot topic in "green chemistry" research in recent years. As the most commonly used solvent in supercritical fluid technology, supercritical carbon dioxide has many advantages: carbon dioxide is rich in sources, easy to recycle and use, and has no solvent residue; carbon dioxide molecules are stable and will not cause side reactions.

There are a large number of ester bonds in L-lactic acid (PLLA), and its hydrophilicity is poor, which reduces its biocompatibility; in addition, PLLA has a long degradation cycle, high brittleness, poor toughness, and poor impact resistance. Polyethylene glycol (PEG) is a degradable material with good hydrophilicity. The copolymerization of PEG and PLLA can improve the hydrophilicity of PLLA, and PEG can be used as the initiator of PLLA polymerization to form block copolymerization by insertion. According to the ratio of raw material monomers, the structure and molecular weight of its copolymer can be conveniently designed.

Supercritical carbon dioxide can dissolve most low molecular weight non-polar molecules and some polar molecules, but most industrially widely used polymers cannot be dissolved under milder conditions, only amorphous fluoropolymers and Siloxane polymers are completely soluble in supercritical carbon dioxide, therefore, most of the polymerization reactions in supercritical carbon dioxide are heterogeneous, that is, precipitation polymerization. Precipitation polymerization has some disadvantages, such as low conversion rate, small molecular weight of product and irregular shape of product.

Contents of the invention

The object of the present invention is to provide a kind of preparation method of polylactic acid and polyethylene glycol triblock PLLA-b-PEG-b-PLLA copolymer with good biodegradability; This method can realize dispersion in supercritical carbon dioxide environment Polymerization, improve the low conversion rate of raw materials, synthesize molecules with larger molecular weight, and at the same time, improve the regularity of product molecular morphology.

To achieve the above object, the invention provides a method for block copolymerization of PLLA and PEG in supercritical carbon dioxide, the specific steps are as follows:

S1. Dry the lactide monomer (L-LA) under reduced pressure at 30°C for 8-12 hours;

S2. Put the lactide monomer, stannous octoate and polyethylene glycol (PEG) into the reaction kettle according to the molar ratio of 60～100:0.2～0.8:10～30, stir to obtain the reaction liquid; A stabilizer PCL-b-PDMS-b-PCL is added to the liquid, and the amount of the stabilizer PCL-b-PDMS-b-PCL is 0 to 10 wt% of the reaction liquid;

Wherein, stannous octoate (Sn(Oct) ₂ ) is a catalyst; Polyethylene glycol (PEG) is a macromolecular initiator; PCL-b-PDMS-b-PCL is a stabilizer, and the stabilizer used in the present invention is based on the patent It is obtained from "Supercritical Carbon Dioxide Dispersion Polymerization Stabilizer and Its Preparation Method and Application Method (ZL2013101210958)".

S3, vacuumize the reactor;

This step is mainly to further remove the moisture that may exist in the monomer, catalyst and initiator.

S4, _CO Purging the reactor and the connecting pipeline with the reactor;

This step is mainly to further remove the air and moisture in the pipeline and in the kettle;

S5. Introduce _CO into the reactor until the pressure in the reactor reaches 16-20MPa, and at the same time, heat the reactor until the temperature in the reactor reaches 80-100°C; keep the pressure and temperature in the reactor constant, and continue Reaction 12～48h;

S6, using ice water to cool the reactor to below the critical temperature of supercritical carbon dioxide;

S7. Release the pressure until the _CO is completely released, and the product is taken out to obtain the PLLA and PEG block copolymer.

In a preferred manner, the molar ratio of the lactide monomer to the polyethylene glycol in step S2 is 80:20; the added amount of the stabilizer PCL-b-PDMS-b-PCL is the reaction liquid 5wt%.

In a preferred manner, step S5 is: introducing _CO into the reactor until the pressure in the reactor reaches 18MPa, and at the same time, heating the reactor until the temperature in the reactor reaches 100°C; keeping the pressure and temperature in the reactor unchanged , Continuous reaction for 24h.

The advantages of the present invention are:

1. The method of the present invention has successfully prepared a PLLA-b-PEG-b-PLLA block copolymerization product with good comprehensive properties, the conversion rate of lactide monomer can reach more than 92%, and the amount of stabilizer only needs 3% , the reaction time is significantly reduced, the reaction conditions are mild, the separation and purification only need to depressurize and get rid of carbon dioxide, and the process is simple; except for catalysts and initiators, no organic solvents are needed, which is in line with the development direction of green chemistry; the method of the present invention is a method with The potential biomaterial synthesis method has broad application prospects.

2. The method of the present invention successfully realizes dispersion polymerization, overcomes the existing shortcoming of precipitation polymerization common in supercritical carbon dioxide environment to a large extent, and under the effect of stabilizer, it can form a certain amount at the polymer and solvent interface. The active force of physical adsorption or chemical grafting produces steric hindrance to prevent the aggregation of particles; the inventive method improves reaction efficiency and yield, and the inventive method can be used for polymerizing polylactic acid, polycaprolactone and poly(caprolactone) in supercritical carbon dioxide Its copolymers and other linear aliphatic polyesters.

The present invention uses supercritical fluid as a solvent, which can avoid the use of commonly used organic solvents in the prepared biodegradable materials, which is more environmentally friendly, and the subsequent separation is simple, with less solvent residue. The polymerization reaction in supercritical fluid is a kind of good Foreground synthetic process method.

Description of drawings

Fig. 1 is a synthetic route diagram of PLLA-b-PEG-b-PLLA;

Fig. 2 is the PLLA-b-PEG-b-PLLA block copolymerization experiment device figure in the supercritical carbon dioxide;

Fig. 3 is the 1H-NMR spectrogram of PLLA-b-PEG-b-PLLA block copolymerization product;

Fig. 4 is the DSC spectrum of the PLLA-b-PEG-b-PLLA block copolymerization product.

detailed description

The route of PLLA and PEG block copolymerization reaction involved in the following examples in supercritical carbon dioxide, as shown in Figure 1; The reaction device involved in the examples is: volume 50ml has sapphire visible window, is equipped with electromagnetic stirring system And the high-pressure reactor of the numerical control electric heating system (maximum operating pressure 30MPa, maximum operating temperature 150 ℃), the reactor is cleaned with dichloromethane and fully dried with hot air before use.

The process flow chart of the reaction is shown in Figure 2: among them, 1 is the CO gas cylinder, ₂ is the pressure gauge of the gas cylinder, 3 is the valve of the gas cylinder, 4 is the cooler, 5 is the plunger pump, 6 is the pressure gauge, 7 Is the inlet valve of the reaction kettle, 8 is the pressure gauge, 9 is the sapphire viewing window, 10 is the magnetic stirring device, 11 is the electric heating jacket, 12 is the exhaust valve, 13 is the heating belt, 14 is the collection device, 15 is the liquid discharge valve , 16 is a flow meter.

The process of the embodiment of the present invention is summarized as follows:

Dry the monomer at 30°C under reduced pressure overnight to remove water; wash the reactor with dichloromethane and dry it fully with hot air before the experiment; mix the monomer (L-LA), catalyst (Sn(Oct)2) and The macromolecular initiator (PEG) is put into the reactor according to the molar ratio of 60:0.2:10～100:0.8:30, and the dosage of adding the self-made stabilizer is 0～10wt%; Remove the moisture that may exist in the body, catalyst, and initiator; use _CO to purge the reactor and pipeline to remove the air and moisture in the pipeline and the kettle; close the outlet valve, and use the plunger pump to feed CO into the reactor. _2. At the same time, heat the reactor, and adjust the pressure and temperature to the set value according to the needs; keep the pressure and temperature constant for a reaction time of 12 to 48 hours, and then use ice water to cool the reactor below the critical temperature; open the outlet valve, slowly release the pressure, and when the CO ₂ is completely released, open the reaction kettle and take out the product.

The present invention will be further described below through several specific implementation examples.

Example 1

The block copolymerization dispersion polymerization of L-lactide (L-LA) and polyethylene glycol (PEG) was carried out in a 50ml stainless steel reactor, as shown in Figure 2. Dry the monomer at 30°C under reduced pressure overnight to remove water; clean the reactor with dichloromethane and dry it fully with hot air before the experiment; add monomer L-LA1.6g, PEG0.4g, 0.1g (5% ) stabilizer, 45mg stannous octoate and polytetrafluoroethylene rotor, sealed reaction kettle. Slowly pass CO ₂ for 5 minutes, then heat, and at the same time turn on the plunger pump to pressurize the system. After reaching the experimental temperature (80°C) and reaction pressure (18MPa), start the stirrer; react for 24 hours, stop heating and stirring, and the reaction kettle is naturally stirred Cool down to room temperature and slowly deflate. The reactor was opened to collect a white powdery product with a number average molecular weight (Mn) of 12800, a molecular weight distribution (PDI) of 1.18, and a yield of 78%.

Example 2

Concrete operation is the same as example 2, add monomer L-LA1.6g, PEG 0.4g, 0.1g (5%) stabilizer, 45mg stannous octoate, experiment temperature (90 ℃), reaction pressure (18MPa), reaction time 24h, The product is a white powder with a number average molecular weight (Mn) of 15255 and a molecular weight distribution (PDI) of 1.13. Yield 88%.

Example 3

Concrete operation is the same as example 2, add monomer L-LA1.6g, PEG 0.4g, 0.1g (5%) stabilizer, 45mg stannous octoate, experiment temperature (100 ℃), reaction pressure (18MPa), reaction time 24h, The product is a white powder, the number average molecular weight (Mn) is 15380, the molecular weight distribution (PDI) is 1.15, and the yield is 90%.

Fig. 3 is monomer L-LA1.6g, PEG 0.4g, 0.1g (5%) stabilizer, 45mg stannous octoate, experiment temperature (90 ℃), reaction pressure (18MPa), reaction time 24h, PLLA-b- 1H-NMR spectrum of PEG-b-PLLA block copolymerization product. The sharper peak at 1.5ppm is the characteristic peak of the -CH3 repeating unit in PLLA, and the peak at 5.2ppm is the peak corresponding to -CH-. The combination of the two can prove the presence of PLLA in the product; at 3.6ppm The single peak at O-CH2-CH2-O- is the characteristic peak of the repeating structure of ethylene glycol, which is the conclusive evidence of the presence of PEG in the structural unit; and the structure corresponding to the weak peak at 4.3ppm is- COOCH2-C-, the presence or absence of this peak determines whether the copolymerization occurs. The peak here is the peak at the junction of the PEG and PLLA structural blocks. The presence of the peak here indicates that the product is a block copolymer of PEG and PLLA rather than PLLA and PLLA. For PEG blends, it can be concluded from Figure 3 that the target copolymer was synthesized in the experiment.

Fig. 4 is the DSC spectrum of the PLLA-b-PEG-b-PLLA block copolymerization product. Comparing the DSC curves of PLLA-b-PEG-b-PLLA and PLLA in the figure, we can clearly see the difference in thermophysical properties between the two. There are two obvious peaks in the copolymer, which are located at about 125°C and 150°C respectively, which represent the melting peaks of PEG and PLLA respectively, while the melting peak of pure PLLA is around 160°C, and the PEG segment in the PLLA structure The introduction of β destroys the regularity of its chain segments to a certain extent, which makes its crystallization performance decrease, and the thermal stability is also significantly weakened. The slight decrease in the melting temperature of the PLLA segments may be due to the decreased thermal stability due to the reduced length of the individual PLLA segments. In the DSC curves of the two polymers, there is no obvious peak corresponding to the glass transition temperature, which shows that the crystallization properties of the two products are good, and the isotactic properties of the products are good.

In the method of the present invention, the temperature has a significant impact on the conversion of the product. As the temperature increases, the conversion of the product tends to increase significantly, and the molecular weight of the product also increases, especially when the temperature increases from 80°C to 90°C. more obvious. 1H-NMR analysis proves that a triblock PLLA-b-PEG-b-PLLA copolymer with well-defined structure was obtained by polymerization. DSC and TGA showed that the thermophysical properties of the copolymerized modified product changed significantly, and the melting point of PLLA-b-PEG-b-PLLA decreased significantly compared to PLLA. Particle size analysis shows that with the increase of the content of PEG in the copolymer, the average particle size and particle size distribution range of the product have a significant increase trend, which is mainly due to the reduction of the melting point temperature is the product at the reaction temperature. Softens and adheres.

The above is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto, and any person familiar with the technical field within the technical scope disclosed in the present invention, according to the technical solution of the present invention Any equivalent replacement or change of the inventive concepts thereof shall fall within the protection scope of the present invention.

Claims (3)

1. PLLA and the method for PEG block copolymerization in a supercritical carbon dioxide, it is characterised in that tool Body step is as follows:

S1, by lactide monomer drying under reduced pressure 8～12h at 30 DEG C；

S2, by lactide monomer, stannous octoate and polyethylene glycol according to 60～100:0.2～0.8:10～30 mole Than putting in reactor, stir, obtain reactant liquor；Stabilizer is added in described reactant liquor PCL-b-PDMS-b-PCL, the addition of described stabilizer PCL-b-PDMS-b-PCL is described reactant liquor 0～10wt%；

S3, described reactor is vacuumized；

S4、CO₂Purge described reactor and the connecting line with described reactor；

S5, in described reactor, it is passed through CO₂To still, pressure reaches 16～20MPa, and meanwhile, heating is described Reactor to temperature in the kettle reaches 80～100 DEG C；Keep pressure in described still, temperature-resistant, sustained response 12～48h；

Reactor is cooled to below supercritical carbon dioxide critical-temperature by S6, use frozen water；

S7, pressure release to CO₂Release completely, is taken out product, is obtained PLLA and PEG block copolymer.

PLLA and the method for PEG block copolymerization in supercritical carbon dioxide the most according to claim 1, It is characterized in that, lactide monomer described in step S2 is 80:20 with the mol ratio of described polyethylene glycol；Institute State the 5wt% that addition is described reactant liquor of stabilizer PCL-b-PDMS-b-PCL.

PLLA and the method for PEG block copolymerization in supercritical carbon dioxide the most according to claim 1, It is characterized in that, step S5 is: be passed through CO in described reactor₂To still, pressure reaches 18MPa, with Time, heat described reactor to temperature in the kettle and reach 100 DEG C；Keep pressure in described still, temperature-resistant, hold Continuous reaction 24h.