Narrow-distribution polycaprolactone synthesized under microwave-assisted solvent-free system as well as preparation method and application of narrow-distribution polycaprolactone

Abstract

The invention belongs to the technical field of high polymer materials, and particularly relates to polycaprolactone with narrow molecular weight distribution synthesized under a microwave-assisted solvent-free system as well as a preparation method and application of the polycaprolactone. Epsilon-caprolactone and a catalyst are used as raw materials and subjected to ring opening polymerization under inert gas protection and microwave radiation, and the epsilon-caprolactone polymer is obtained. The condition of the microwave radiation is that the microwave with the power of 500-750W is adopted for treatment. The polycaprolactone prepared by the method has the advantages of high efficiency, environmental protection, controllable molecular weight and narrow molecular weight distribution, and has a good application prospect.

Description

Technical Field

[0001] The present invention belongs to the technical field of polymer materials, and specifically relates to a narrow distribution polycaprolactone synthesized in a microwave-assisted solvent-free system, a preparation method thereof, and uses thereof. Background Art

[0002] Polycaprolactone (PCL) is an aliphatic polyester with good biocompatibility and biodegradability. It is usually produced through the ring-opening polymerization reaction of caprolactone monomers. The molecular chain structure is relatively regular, with a low melting point (around 60°C) and glass transition temperature (around -60°C), which makes PCL have good flexibility and plasticity during processing. Moreover, the degradation rate of PCL can be controlled to a certain extent by adjusting the molecular weight and other means. In the biomedical field, it can be used to manufacture absorbable sutures, tissue engineering scaffolds, etc. It can gradually degrade into carbon dioxide and water in the body, without the need for secondary surgery to remove it; in the packaging field, as an environmentally friendly material, it helps to reduce white pollution.

[0003] Traditional methods for synthesizing poly(caprolactone) (PCL) typically utilize bulk or solution polymerization of ε-caprolactone catalyzed by stannous octoate. However, these methods present several bottlenecks: 1) long reaction times, typically requiring 20-48 hours; 2) strong solvent dependence, with organic solvents such as toluene and chloroform difficult to completely remove, posing a risk of residual toxicity; 3) a broad molecular weight distribution (PDI > 1.8), which impacts the mechanical properties of the material; and 4) high catalyst residues, requiring complex post-processing. Prior art methods have incorporated microwave treatment into PCL synthesis, such as in "CN1323844A - A Method for Preparing Poly(ε-Caprolactone)." This method addresses the issues of long reaction times and residual organic solvents to a certain extent. However, the resulting product still suffers from a broad molecular weight distribution.

[0004] Therefore, there is still a need to develop new synthesis processes to prepare PCL materials with narrower molecular weight ranges and better mechanical properties. Summary of the Invention

[0005] In view of the problems of the prior art, the present invention provides a polycaprolactone with narrow molecular weight distribution synthesized in a microwave-assisted solvent-free system, a preparation method thereof, and uses thereof.

[0006] A polycaprolactone with narrow molecular weight distribution synthesized in a microwave-assisted solvent-free system is obtained by ring-opening polymerization of ε-caprolactone and a catalyst as raw materials under inert gas protection and microwave irradiation. The microwave irradiation condition is as follows: microwave treatment with a power of 500-750W is used.

[0007] Preferably, the catalyst is selected from an organometallic compound catalyst, and the organometallic compound catalyst is preferably at least one of stannous octoate, aluminum isopropoxide or n-butyl titanate.

[0008] Preferably, the weight ratio of the ε-caprolactone to the catalyst is 100:0.2 to 100:0.5.

[0009] Preferably, the raw materials further include a capping agent, and the capping agent is selected from alkyl alcohol or a polymer of alkyl alcohol, preferably polyethylene glycol with a weight average molecular weight of 400 to 5000 Da.

[0010] Preferably, the usage ratio of the ε-caprolactone and the end-capping agent is 1:0.01 to 0.50.

[0011] Preferably, the microwave radiation procedure is: preheating the reaction system to 80-85°C, using microwaves with a power of 200-300W to initiate the ring-opening reaction; heating the reaction system to 110-135°C, preferably 120°C, and setting the microwaves with a power of 500-750W in pulse mode for further treatment.

[0012] Preferably, one pulse cycle of the microwave in the pulse mode includes 10-60s of radiation and 5-20s of pause;

[0013] And / or, the microwave radiation determines the reaction endpoint by real-time viscosity detection;

[0014] and / or, the microwave-induced ring-opening reaction is carried out for a treatment time of 0.5 to 1 hour;

[0015] And / or, the duration of the further microwave treatment in pulse mode in the microwave irradiation is 4.5-15.7 hours.

[0016] Preferably, the weight average molecular weight of the narrow molecular weight distribution polycaprolactone is in the range of 10k-100kDa, preferably 10k-30kDa;

[0017] And / or, the molecular weight distribution index PDI of the narrow molecular weight distribution polycaprolactone is ≤1.52;

[0018] And / or, the viscosity of the narrow molecular weight distribution polycaprolactone is in the range of 0.2 to 0.9 dl / g, preferably 0.2 to 0.5 dl / g.

[0019] The present invention also provides a method for preparing the above-mentioned polycaprolactone with narrow molecular weight distribution, comprising the following steps: subjecting ε-caprolactone and a catalyst as raw materials to ring-opening polymerization under inert gas protection and microwave irradiation to obtain the polycaprolactone; the microwave irradiation condition is: using microwaves with a power of 500 to 750 W for treatment.

[0020] The present invention also provides use of the above-mentioned narrow molecular weight distribution polycaprolactone in the preparation of drug carriers, medical devices, tissue engineering scaffolds, degradable plastics or 3D printing materials.

[0021] In the present invention, the polycaprolactone terminated by an alkyl alcohol or a polymer of an alkyl alcohol has the following structure:

[0022] Wherein, R is an alkyl group or a polymer of an alkyl alcohol.

[0023] The present invention provides a catalytic system that utilizes microwave radiation and chemical catalysis to synthesize polycaprolactone. The technical solution of the present invention achieves the following beneficial technical effects:

[0024] 1. The present invention can significantly shorten the reaction time.

[0025] 2. By introducing microwave radiation treatment and optimizing the microwave radiation process parameters, the molecular weight distribution of polycaprolactone products can be significantly narrowed, which is beneficial to improving the mechanical properties of the product.

[0026] 3. The present invention abandons the traditional solvent system and directly uses ε-caprolactone as the reaction medium, eliminating the risk of solvent residue and the product purity is ≥99.5%.

[0027] 4. By adjusting the microwave power (200-750W) and pulse frequency (intermittent radiation mode) in real time, the chain growth rate can be precisely controlled to achieve customized production of molecular weight (10k-90k Da).

[0028] In summary, the present invention has the advantages of high efficiency, environmental protection, controllable molecular weight and narrow molecular weight distribution, and has good application prospects.

[0029] Obviously, based on the above contents of the present invention, according to common technical knowledge and customary means in this field, without departing from the above basic technical ideas of the present invention, other various forms of modifications, replacements or changes can be made.

[0030] The following further describes the above content of the present invention in detail through specific embodiments in the form of examples. However, this should not be construed as limiting the scope of the above subject matter of the present invention to the following examples. All technologies implemented based on the above content of the present invention fall within the scope of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 The following are the monitoring results of the viscosity trend of the reaction solution in the embodiment;

[0032] Figure 2 This is the GPC test pattern of the embodiment;

[0033] Figure 3 This is the GPC detection spectrum of the comparative example. DETAILED DESCRIPTION

[0034] In the following examples and experimental examples, reagents and raw materials not specifically described are all commercially available.

[0035] Example 1

[0036] The reaction bottle is placed in a microwave reactor, 51.625g of methoxy polyethylene glycol 400 (mPEG400) and 500g of ε-caprolactone (ε-CL) are added to the reaction bottle, and a catalyst stannous octoate (0.2wt% ε-caprolactone) is added. An inert gas (nitrogen) is introduced to replace the oxygen in the reaction bottle for 2h. The temperature is raised to 120°C (in other embodiments, the temperature of this step is controlled at 110-135°C, and products with similar molecular weight distribution can be obtained), set to pulse mode (duty cycle: 30s radiation / 10s pause), power 750W. React for 8.3 hours, the viscosity is detected to be approximately 281.8cP, and the reaction system is cooled to 30°C. 2 L of dichloromethane was added to the reaction system, filtered through a 50 μm filter membrane (PTFE), purified, concentrated, precipitated with 1500 g of anhydrous methanol, and dried in vacuo to obtain 452.5 g of white solid methoxypolyethylene glycol 400-polycaprolactone (mPEG400-PCL12000) with a yield of 82.03%.

[0037] Example 2

[0038] A reaction flask was placed in a microwave reactor. 51.625 g of methoxypolyethylene glycol 400 (mPEG400) and 500 g of ε-caprolactone (ε-CL) were added to the flask. A catalyst, stannous octoate (0.2 wt% ε-caprolactone), was added. Inert gas (nitrogen) was introduced to displace the oxygen in the flask for 2 hours. The temperature was raised to 120°C and the power was set to 750 W. The reaction was allowed to react for 10.7 hours, with a viscosity of approximately 276.5 cP. The reaction system was then cooled to 30°C. 2 L of dichloromethane was added to the reaction system, and the mixture was purified by filtration through a 50 μm PTFE filter. The mixture was concentrated, precipitated with 1500 g of anhydrous methanol, and dried under vacuum to obtain 447.3 g of methoxypolyethylene glycol 400-polycaprolactone (mPEG400-PCL12000) as a white solid in an 81.09% yield.

[0039] Example 3

[0040] The reaction bottle was placed in a microwave reactor, 51.625 g of methoxy polyethylene glycol 400 (mPEG400) and 500 g of ε-caprolactone (ε-CL) were added to the reaction bottle, and a catalyst of stannous octoate (0.2 wt %) was added.

[0041] ε-caprolactone). Inert gas (nitrogen) was introduced to displace the oxygen in the reaction flask for 2 hours. The temperature was raised to 120°C and the power was set to 500W. The reaction was allowed to proceed for 13.5 hours, and the viscosity was approximately 264.2 cP. The reaction system was then cooled to 30°C. 2 L of dichloromethane was added to the reaction system, and the mixture was purified by filtration through a 50 μm PTFE filter. The solution was concentrated, precipitated with 1500 g of anhydrous methanol, and dried under vacuum to obtain 416.2 g of methoxypolyethylene glycol 400-polycaprolactone (mPEG400-PCL12000) as a white solid, with a yield of 75.45%.

[0042] Example 4

[0043] The reaction bottle was placed in a microwave reactor, 51.625 g of methoxy polyethylene glycol 400 (mPEG400) and 500 g of ε-caprolactone (ε-CL) were added to the reaction bottle, and a catalyst of stannous octoate (0.2 wt %) was added.

[0044] ε-caprolactone). Inert gas (nitrogen) was introduced to displace the oxygen in the reaction flask for 2 hours. The temperature was raised to 80°C, and the initial power was set to 200W and maintained for 0.5 hours. The temperature was raised to 120°C, the power was set to 750W, and the reaction was switched to pulse mode (duty cycle: 30s radiation / 10s pause). After 4.5 hours of reaction, when the viscosity measured approximately 293.7 cP, the reaction system was cooled to 30°C. 2L of dichloromethane was added to the reaction system, and the mixture was purified by filtration through a 50μm PTFE filter, concentrated, and precipitated with 1500g of anhydrous methanol. The mixture was dried under vacuum to obtain 489.7g of methoxypolyethylene glycol 400-polycaprolactone (mPEG400-PCL12000) as a white solid, with a yield of 88.77%.

[0045] Example 5

[0046] The preparation method of this example is the same as that of Example 4, except that the microwave irradiation procedure is as follows: the temperature is raised to 85°C, the initial power is set to 300W, and the temperature is maintained for 1 hour. The temperature is raised to 120°C, the power is set to 550W, and the microwave is switched to pulse mode (duty cycle: 60s irradiation / 20s pause). The reaction is allowed to proceed for 15.7 hours, and the viscosity is measured to be approximately 272.4 cP. 458.9 g of methoxypolyethylene glycol 400-polycaprolactone (mPEG400-PCL12000) as a white solid is obtained, with a yield of 83.19%.

[0047] Example 6

[0048] The preparation method of this example is the same as that of Example 4, except that the microwave irradiation procedure is as follows: the temperature is raised to 85°C, the initial power is set to 300W, and the temperature is maintained for 2 hours. The temperature is raised to 120°C, the power is set to 750W, and the microwave is switched to pulse mode (duty cycle: 10s irradiation / 5s pause). The reaction is allowed to proceed for 4.7 hours, and the viscosity is detected to be approximately 296.3 cP. 466.6 g of methoxypolyethylene glycol 400-polycaprolactone (mPEG400-PCL12000) as a white solid is obtained, with a yield of 84.59%.

[0049] Comparative Example

[0050] This example provides the preparation of polyethylene glycol 400-polycaprolactone (PEG400-PCL12000) material, and the preparation steps are as follows:

[0051] 51.625g of methoxy polyethylene glycol 400 (mPEG400) and 500g of ε-caprolactone (ε-CL) were added to a reaction flask. After azeotropic dehydration with anhydrous toluene, a catalyst (stannous octoate (0.2wt% ε-caprolactone)) was added and the reaction was carried out at 110°C for 22h. After completion of the reaction, the product was dissolved in dichloromethane and purified by extraction with brine and distilled water, respectively. After precipitation with methanol, the product was dried in an oven to obtain 435.6g of methoxy polyethylene glycol 400-polycaprolactone (mPEG400-PCL12000) as a white solid with a purity of 78.97%.

[0052] The process parameters and product performance parameters of the above embodiments and comparative examples are compared, and the results are shown in Table 1. Figure 1-3 As shown:

[0053] Table 1 Comparison of experimental data and product test data

[0054] project Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Comparative Example Reaction time 8.3h 10.7h 13.5h 4.5h 15.7h 4.7h 22h Solvent use Solvent-free Solvent-free Solvent-free Solvent-free Solvent-free Solvent-free Toluene Weight average molecular weight (Mw) 25821Da 25469Da 24472Da 26586Da 25772Da 26967Da 23905Da Molecular weight distribution coefficient 1.56 1.51 1.61 1.35 1.52 1.43 1.62 Viscosity (dl / g) 0.23dl / g 0.23dl / g 0.24dl / g 0.23dl / g 0.24dl / g 0.24dl / g 0.22dl / g Yield 82.03％ 81.09％ 75.45％ 88.77％ 83.19％ 84.59％ 78.97％

[0055] It can be seen that the embodiment of the present invention is shorter in reaction time, and when not using a solvent, obtains a product with a weight-average molecular weight close to that of the comparative example. The molecular weight distribution of the product is narrower, the viscosity is higher, and the synthesis yield is higher, and embodiment 4 has the best result. This shows that the introduction of microwave radiation is conducive to improving the performance of polycaprolactone. Therefore, technical scheme of the present invention has good application prospects in the synthesis of polycaprolactone.

Claims

1. A polycaprolactone with narrow molecular weight distribution synthesized in a microwave-assisted solvent-free system, characterized in that: The method comprises the following steps: using ε-caprolactone and a catalyst as raw materials to carry out ring-opening polymerization under the protection of inert gas and microwave radiation to obtain the product; the microwave radiation condition is: using microwaves with a power of 500-750W for treatment.

2. The polycaprolactone with narrow molecular weight distribution according to claim 1, characterized in that: The catalyst is selected from an organometallic compound catalyst, and the organometallic compound catalyst is preferably at least one of stannous octoate, aluminum isopropoxide, or n-butyl titanate.

3. The polycaprolactone with narrow molecular weight distribution according to claim 1, characterized in that: The usage ratio of the ε-caprolactone and the catalyst is 100:0.2 to 100:0.5 by weight.

4. The polycaprolactone with narrow molecular weight distribution according to claim 1, characterized in that: The raw materials also include a capping agent, which is selected from alkyl alcohol or alkyl alcohol polymers, preferably polyethylene glycol with a weight average molecular weight of 400 to 5000 Da.

5. The polycaprolactone with narrow molecular weight distribution according to claim 4, characterized in that: The usage ratio of the ε-caprolactone and the end-capping agent is 1:0.01-0.

50.

6. The polycaprolactone with narrow molecular weight distribution according to claim 1, characterized in that: The microwave radiation procedure is as follows: preheating the reaction system to 80-85° C., using microwaves with a power of 200-300W to initiate a ring-opening reaction; heating the reaction system to 110-135° C., and setting a microwave power of 500-750W in pulse mode for further treatment.

7. The polycaprolactone with narrow molecular weight distribution according to claim 6, characterized in that: One pulse cycle of the microwave in the pulse mode includes 10-60s of radiation and 5-20s of pause; And / or, the microwave radiation determines the reaction endpoint by real-time viscosity detection; and / or, the microwave-induced ring-opening reaction is carried out for a treatment time of 0.5 to 1 hour; And / or, the duration of the further microwave treatment in pulse mode in the microwave irradiation is 4.5-15.7 hours.

8. The polycaprolactone with narrow molecular weight distribution according to claim 1, characterized in that: The weight average molecular weight of the narrow molecular weight distribution polycaprolactone is in the range of 10k-100kDa, preferably 10k-30kDa; And / or, the molecular weight distribution index PDI of the narrow molecular weight distribution polycaprolactone is ≤1.52; And / or, the viscosity of the narrow molecular weight distribution polycaprolactone is in the range of 0.2 to 0.9 dl / g, preferably 0.2 to 0.5 dl / g.

9. The method for preparing polycaprolactone with narrow molecular weight distribution according to any one of claims 1 to 8, characterized in that: The method comprises the following steps: taking ε-caprolactone and a catalyst as raw materials and carrying out ring-opening polymerization under inert gas protection and microwave irradiation to obtain the product; the microwave irradiation condition is: using microwaves with a power of 500-750W for treatment.

10. Use of the polycaprolactone with narrow molecular weight distribution according to any one of claims 1 to 8 in the preparation of drug carriers, medical devices, tissue engineering scaffolds, degradable plastics or 3D printing materials.

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