CN115386075B

CN115386075B - Degradable branched polycaprolactone and preparation method thereof

Info

Publication number: CN115386075B
Application number: CN202211197476.XA
Authority: CN
Inventors: 钟爱民
Original assignee: Yangzhou Polytechnic Institute
Current assignee: Yangzhou Polytechnic Institute
Priority date: 2022-09-29
Filing date: 2022-09-29
Publication date: 2023-06-02
Anticipated expiration: 2042-09-29
Also published as: CN115386075A

Abstract

The scheme relates to a degradable branched polycaprolactone and a preparation method thereof, and the preparation method comprises the following steps: adding metered alpha-bromo-epsilon-caprolactone, 1, 4-butanediol and a catalyst into a reaction kettle, uniformly stirring, decompressing, dehydrating, and filling nitrogen to remove air in the system; adding metered phenyl glycidyl ether to carry out ring-opening polymerization reaction; after the reaction is finished, performing reduced pressure distillation and purification to obtain PCL-PGE; dissolving PCL-PGE in tetrahydrofuran, adding 2-methylene-1, 3-dioxepane and methacrylate monomers, adding catalytic amount of CuBr/bpy, introducing nitrogen to remove air in the system, and heating to 90 ℃ for ATRP polymerization; after the reaction was completed, the product was precipitated in methanol. Compared with pure polycaprolactone, the prepared degradable branched polycaprolactone has improved mechanical properties and degradation rate, and is expected to be applied to the biomedical field.

Description

Degradable branched polycaprolactone and preparation method thereof

Technical Field

The invention relates to the field of degradable high polymer materials, in particular to a degradable branched polycaprolactone and a preparation method thereof.

Background

With the rapid development of social economy, the problems of resource shortage and environmental pollution are also increased. Plastic products are developed to replace natural resources at the earliest time, are low in cost and easy to obtain and are widely used by people. However, non-degradable plastic articles place a great burden on the environment. Accordingly, researchers are working to develop degradable polymeric materials to address this problem. At present, the common degradable polymer is mainly polyester, and the molecular chain of the degradable polymer contains ester bonds which are easy to hydrolyze and are easy to decompose in the nature. Examples of the electrically-conductive aliphatic polyester include Polyglycolide (PGA), polylactide (PLA), and Polycaprolactone (PCL).

PCL is a thermoplastic semi-crystalline polymer, has excellent biocompatibility and degradability, belongs to environment-friendly plastics, and has important application prospects in the fields of biomedicine and the like. However, PCL belongs to a semi-crystalline polymer, and has limited practical applications due to poor hydrophilicity, low mechanical strength, slow degradation rate, and the like.

Disclosure of Invention

Aiming at the defects in the prior art, the invention prepares the branched PCL based on caprolactone and 2-methylene-1, 3-dioxycycloheptane, thereby reducing the crystallinity and having faster degradation rate.

In order to achieve the above purpose, the present invention provides the following technical solutions:

a method for preparing degradable branched polycaprolactone, comprising the following steps:

s1: adding metered alpha-bromo-epsilon-caprolactone, 1, 4-butanediol and a catalyst into a reaction kettle, uniformly stirring, decompressing, dehydrating, and filling nitrogen to remove air in the system; adding metered phenyl glycidyl ether to carry out ring-opening polymerization reaction; after the reaction is finished, performing reduced pressure distillation and purification to obtain PCL-PGE;

s2: dissolving PCL-PGE in tetrahydrofuran, adding 2-methylene-1, 3-dioxepane and methacrylate monomers, adding catalytic amount of CuBr/bpy, introducing nitrogen to remove air in the system, and heating to 90 ℃ for ATRP polymerization; after the reaction is completed, precipitating in methanol to obtain a product;

wherein the methacrylate monomer is a cyclohexyl methacrylate monomer, and the structural formula is as follows:

further, in the step S1, the molar ratio of the alpha-bromo-epsilon-caprolactone to the 1, 4-butanediol to the phenyl glycidyl ether to the catalyst is 1:0.5-0.8:0.4-1:0.02; the catalyst is a 1:1 composite catalyst of n-butyl lithium and stannous octoate.

Further, the reaction condition of the step S1 is 140-160 ℃ for 2-4 h.

Further, in the step S2, the molar ratio of PCL-PGE to 2-methylene-1, 3-dioxepane to the methacrylate monomers is 1:50-100:50-0.

The present invention further provides a degradable branched polycaprolactone prepared by the preparation method.

Compared with the prior art, the invention has the beneficial effects that: firstly, preparing a random copolymer containing a CL chain segment by using alpha-bromo-epsilon-caprolactone and phenyl glycidyl ether, wherein a phenyl functional group can improve the rigidity of a molecular chain, so that the mechanical property of the random copolymer is improved; meanwhile, the steric hindrance effect between the molecular chains of the random copolymer is increased, so that the molecular chains are disordered, and the crystallinity is reduced. However, the amount of phenyl glycidyl ether used cannot be excessive, the molar ratio of the phenyl glycidyl ether to the alpha-bromo-epsilon-caprolactone is optimally 0.4:1 during preparation, and when the ratio is too high, the phenyl glycidyl ether chains inserted into the polymer chains are excessive, so that the degradation rate is influenced, and the phenyl glycidyl ether is difficult to completely degrade into small molecules.

ATRP polymerization can be carried out through bromine at the alpha position of caprolactone, and PCL side chains of the same type are grafted on the main chain; in the scheme, a monomer 2-methylene-1, 3-dioxycycloheptane capable of undergoing free radical polymerization is selected, a chain segment similar to PCL is formed after ring opening, the overall degradability of the polymer is maintained, in addition, a cyclohexyl methacrylate monomer is used as a comonomer, on one hand, the existence of a cyclohexyl group is also used for increasing the steric hindrance effect, and the distance between macromolecular chains is pulled, so that rapid degradation is promoted; other polymer chains are inserted into the PCL chain segment, so that the crystallinity of the polymer can be effectively reduced, and the functionality of the polymer chain is increased due to rich functional groups; on the other hand, the pyrrolidone group is arranged at the para position of the cyclohexyl group, so that the hydrophilic property of the polymer is improved, the hydrolyzed molecular chain is broken to migrate to water molecules, and the hydrolysis is promoted; but also is hopeful to be applied to the field of biological medicine due to good biodegradability.

Detailed Description

FIG. 1 is a graph showing the relationship between the weight loss ratio and time under the hydrolysis conditions of the respective materials of example 1.

FIG. 2 is a graph showing the relationship between the weight loss ratio and time under the enzymatic hydrolysis conditions of the materials in example 1.

FIG. 3 is a graph showing the relationship between the weight loss ratio and time under the enzymolysis conditions of the materials of example 2.

Detailed Description

The technical solutions of the present invention will be clearly and completely described in connection with the embodiments, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.

In addition, the technical features of the different embodiments of the present invention described below may be combined with each other as long as they do not collide with each other.

The raw materials used in the scheme are all available in the market unless otherwise specified.

The preparation method of the 2-methylene-1, 3-dioxycycloheptane refers to the synthesis process research of the 2-methylene-1, 3-dioxycycloheptane, shandong chemical industry, volume 46 in 2017.

The preparation route of the cyclohexyl methacrylate monomer is as follows:

example 1:

adding metered alpha-bromo-epsilon-caprolactone (Br-CL), 1, 4-Butanediol (BDO) and a catalyst into a reaction kettle, uniformly stirring, decompressing, dehydrating, and filling nitrogen to remove air in a system; adding metered Phenyl Glycidyl Ether (PGE) to carry out ring-opening polymerization reaction, and reacting for 2-4 h at 140-160 ℃; after the reaction is finished, performing reduced pressure distillation and purification to obtain PCL-PGE; wherein, the molar ratio of Br-CL, BDO, PGE to the catalyst is 1:0.5-0.8:0.4-1:0.02. The following samples were obtained by varying the feed ratio of Br-CL, BDO, PGE.

TABLE 1

	Ratio of	Conv.％	Mn/g·mol ^-1	PDI	Tensile strength MPa
						PCL-PGE-1	1:0.5:0.4	90.4	7700	1.44	50.5
PCL-PGE-2	1:0.5:0.6	95.5	8100	1.21	52.6
						PCL-PGE-3	1:0.5:1	93.2	7900	1.68	54.1
PCL-PGE-4	1:0.5:1.2	90.6	8600	1.72	55.7
						PCL-PGE-5	1:0.5:1.6	88.4	8500	1.77	56.2

The degradability of the polymer is verified through hydrolysis and enzymolysis, for the convenience of experiments, the material is firstly made into a film, PCL-PGE is dried to constant weight in vacuum, the film with the thickness of 0.5mm is formed through hot pressing, and then the film is cut into a plurality of small blocks with the thickness of 1 multiplied by 2 cm.

The hydrolysis steps are as follows: preparing a buffer solution by adopting disodium hydrogen phosphate and dipotassium hydrogen phosphate, taking five clean test tubes, adding 10ml of the prepared buffer solution, respectively adding PCL-PGE-1-5 samples into the test tubes, performing hydrolysis under the condition of 40 ℃, sampling and weighing at regular intervals, calculating the weight loss rate, and drawing to obtain the figure 1.

The enzymolysis steps are as follows: a mixed solution (1 mg/mL) of lipase and PBS was prepared, and the other steps were the same as those of the hydrolysis test, and the weight loss ratio was plotted as shown in FIG. 2.

The molecular weight of the samples after the last enzymatic hydrolysis was tested and recorded in table 2.

TABLE 2

	PCL-PGE-1	PCL-PGE-2	PCL-PGE-3	PCL-PGE-4	PCL-PGE-5
						G/mol before degradation	7700	8100	7900	8600	8500
G/mol after enzymolysis	1100	1100	2000	2400	3100

Referring to FIGS. 1-2 in combination with tables 1-2, it is seen that PGE content affects polymer properties during polymerization, and that increased PGE increases polymer tensile strength, but degradation rate and degradation rate are not positively correlated with PGE content. PCL is a semi-crystalline polymer, and the degradation rate is generally slow, and by inserting polyether structures into the polymer chains, the spacing between macromolecules is pulled, and at the same time, the existence of phenyl groups further increases the steric hindrance, so that the degradation rate can be improved. However, when the PGE content is too high, the degradation rate is reduced, PGE is difficult to degrade, and when the degradation is completed, a larger molecular weight remains, and the degradation rate is low. Wherein, the comprehensive performance of the PCL-PGE-2 sample is optimal.

Example 2:

dissolving PCL-PGE-2 in tetrahydrofuran, adding 2-methylene-1, 3-dioxepane (MDO) and methacrylate monomers, adding catalytic amount of CuBr/bpy, introducing nitrogen to remove air in the system, and heating to 90 ℃ for ATRP polymerization; after the reaction is completed, precipitating in methanol to obtain a product; wherein the mol ratio of PCL-PGE, MDO and methacrylate monomers is 1:50-100:50-0. PCL-PGE (Mn/g.mol) ^-1 =8100 g/mol) and the following final samples were obtained by changing the feed ratio.

TABLE 3 Table 3

	Ratio of	Mn/g·mol ^-1	Tensile strength Mpa
				PCL-PGE-2-1	1:50:50	25600	45.5
PCL-PGE-2-2	1:60:40	22900	43.3
				PCL-PGE-2-3	1:70:30	20500	41.2
PCL-PGE-2-4	1:80:20	19500	40.1
				PCL-PGE-2-5	1:100:0	14900	34.2

The enzymolysis step is the same as that described above, and the enzymolysis rate is shown in FIG. 3.

By grafting the MDO with the polymer chain of the cyclohexyl methacrylate monomer at the branched chain, the tensile strength of the polymer is reduced, but the degradation rate of the polymer is further promoted. The degradation rate of PCL-PGE-2-1-5 at the early degradation stage (0-5 h) is slower than that of PCL-PGE-2, because the molecular weight is increased after ATRP polymerization, and the molecular chain length is increased; the middle degradation rate is obviously improved, hydrophilic groups promote migration of water molecules into the material, the degradation degree is obviously increased, the rate is reduced to 15h, and the weight loss rate approaches balance. The proportion of the monomer to be fed is changed, and when the reaction system only contains MDO monomer, the molecular weight is lower. As the PCL chain formed after the MDO is opened is low in crystallinity and higher in degradation rate than the PCL chain formed after the pure caprolactone is opened, the degradation rate and the degradation completion (weight loss rate) of the PCL-PGE-2-5 of the finally obtained material are higher than those of PCL-PGE-2-4, but the tensile strength of the PCL-PGE-2-2 is lowest, and in the comprehensive view, the PCL-PGE-2-2 has the best performance, namely, when the feeding ratio of the MDO to the cyclohexyl methacrylate monomer is 60:40, the mechanical performance and the degradation performance of the PCL-PGE-2-2 reach better balance.

Although embodiments of the present invention have been disclosed above, it is not limited to the use of the description and embodiments, it is well suited to various fields of use for the invention, and further modifications may be readily apparent to those skilled in the art, and accordingly, the invention is not limited to the particular details without departing from the general concepts defined in the claims and the equivalents thereof.

Claims

1. The preparation method of the degradable branched polycaprolactone is characterized by comprising the following steps:

2. the method for preparing the degradable branched polycaprolactone according to claim 1, wherein in the step S1, the molar ratio of α -bromo- ε -caprolactone, 1, 4-butanediol, phenyl glycidyl ether and catalyst is 1:0.5-0.8:0.4-1:0.02; the catalyst is a 1:1 composite catalyst of n-butyl lithium and stannous octoate.

3. The method for preparing the degradable branched polycaprolactone according to claim 1, wherein the reaction condition of the step S1 is 140-160 ℃ for 2-4 hours.

4. The method for preparing the degradable branched polycaprolactone according to claim 1, wherein in the step S2, the molar ratio of PCL-PGE, 2-methylene-1, 3-dioxepane and methacrylate monomers is 1:50-100:50-0.

5. A degradable branched polycaprolactone made by the method of any one of claims 1-4.