CN111892703A - A kind of biodegradable thermoplastic polyester elastic material and preparation method thereof - Google Patents

Abstract

The invention relates to a biodegradable thermoplastic polyester elastic material and a preparation method thereof. The method comprises: mixing sebacic acid and polyethylene glycol, stirring, esterification reaction under vacuum condition, adding catalyst, pre-condensation reaction under vacuum condition, continuing reaction of the obtained prepolymer for purification. The reaction monomer used in the method is relatively simple, non-toxic and non-irritating, and has good biological safety, and is widely used in biomedicine, and the obtained material has good biocompatibility and biodegradability.

Description

A kind of biodegradable thermoplastic polyester elastic material and preparation method thereof

technical field

The invention belongs to the field of biodegradable polymer materials and preparation thereof, in particular to a biodegradable thermoplastic polyester elastic material and a preparation method thereof.

Background technique

Biodegradable polymer materials are of great significance in biomedicine and are widely used in tissue engineering, drug release, biosensing and other fields. Biodegradable polyesters are the most common type of biodegradable polymer materials, and they include thermoplastic and thermosetting. Thermoplastic biodegradable polyesters such as polylactic acid, polyglycolic acid, polycaprolactone and their copolymers, etc., have good processing properties and high mechanical strength, and have been used in surgical sutures, fracture internal fixation, tissue engineering, drugs. Sustained release and other fields have been successfully applied, but they are not suitable for soft tissue engineering applications due to high crystallinity, high modulus, poor elasticity, and slow degradation. Polyglycerol sebacate and polyglycol citric acid, as well as their derived polymers, are several thermosetting biodegradable polyester materials that have been studied more. They have good elasticity and degradability, and are more suitable for It is used in soft tissue engineering such as myocardium, blood vessels, nerve conduits, etc., but its preparation conditions are harsh, the material needs to be cured, and the cured material is cross-linked, which is neither soluble in any solvent, nor can it be subjected to secondary melting processing, making it It is very limited in practical application. Thermoplastic elastomer is a special kind of polymer material. It is characterized by combining the processability of thermoplastic materials with the high elasticity of thermosetting materials, so that it has the advantages of plasticity and high elasticity at the same time. At present, there are few reports on thermoplastic elastomers in biodegradable polymer materials. The development of biodegradable thermoplastic elastomers is of great significance for promoting the solution of many problems in the field of biomedicine.

Sebacic acid and polyethylene glycol are two kinds of reaction monomers commonly used in the preparation of biodegradable polymer materials, and a variety of biodegradable materials prepared directly from sebacic acid and polyethylene glycol have also been reported. For example, polyethylene glycol is dicarboxylated, and then reacted with sebacic acid to obtain poly(sebacic acid-polyethylene glycol) anhydride (Chemical Reagents, 2007, 29(3): 161-163); Polyethylene glycol reaction to obtain polysebacic anhydride-polyethylene glycol block copolymer (Ion Exchange and Adsorption, 2008, 24(3): 246-253); or solution polymerization by sebacic acid chloride and polyethylene glycol PEG-SA polyesters were obtained (Polymer, 2006, 47:3760-3766). These materials mainly use the high hydrophilicity of polyethylene glycol to improve the hydrophilicity of polyanhydride materials, or form hydrophilic-hydrophobic block copolymers to form hydrogels with certain water absorption and water retention functions. Ethylene glycol has a higher molecular weight (Mn≥400). Such materials are mainly used as functional materials for the construction of drug controlled release carriers or hydrogels, and cannot be used as structural materials, nor do they have the properties of thermoplastic elastomers.

SUMMARY OF THE INVENTION

The technical problem to be solved by the present invention is to provide a biodegradable thermoplastic polyester elastic material and a preparation method thereof, so as to fill in the blank of the prior art.

The invention provides a biodegradable thermoplastic polyester elastic material, which is obtained by melting polycondensation of sebacic acid and polyethylene glycol under catalyst, through the reaction of hydroxyl and carboxyl groups between molecules, dehydration condensation polymerization, and purification.

The polyester elastic material is a high molecular weight linear poly(sebacic acid-polyethylene glycol) ester, and the structural formula of the poly(sebacic acid-polyethylene glycol) ester is:

其中n≥50，m＝2～8。

Wherein n≥50, m=2～8.

The number-average molecular weight (Mn) of the polyester elastic material can reach more than 13×10 ⁴ g·mol ^-1 , and the polydispersity index (Mw/Mn) is between 1.2-4.

The molecular weight of the polyethylene glycol is 100-400 g·mol ⁻¹ .

The catalyst is one of stannous octoate, stannous chloride, stannous octoate/p-toluenesulfonic acid, and stannous chloride/p-toluenesulfonic acid.

The polymerization reaction temperature is 120°C-280°C, the pressure is lower than 3325Pa, and the reaction time is 4-50 hours.

The present invention also provides a preparation method of the biodegradable thermoplastic polyester elastic material, comprising:

Mix sebacic acid and polyethylene glycol with a molar ratio of 0.99:1-1.10:1, stir, esterify under vacuum conditions, add catalyst, pre-condensate under vacuum conditions, and continue to react the obtained prepolymer, Purification to obtain a biodegradable thermoplastic polyester elastic material.

The stirring is as follows: stirring under nitrogen protection at 120-160° C. until the sebacic acid is completely dissolved.

The process parameters of the esterification reaction are as follows: the reaction temperature is 120-180° C., the pressure is 0.1-4000 Pa, and the reaction time is 0.5-8 hours.

The catalyst is any one or several of the catalysts that can catalyze the polymerization of polyester; preferably tin catalysts; more preferably, stannous octoate, stannous chloride, stannous octoate/p-toluenesulfonic acid, stannous chloride/p-toluene One of the sulfonic acids, the molar weight of p-toluenesulfonic acid is equal to the molar weight of stannous octoate or stannous chloride, and the molar weight of stannous octoate or stannous chloride is 0.0005- of the molar weight of hydroxyl or carboxyl in the reaction system 0.02 times (preferably 0.001-0.02 times).

The process parameters of the pre-condensation reaction are: the reaction temperature is 120-180° C., the pressure is 0.1-3000 Pa, and the reaction time is 2-20 hours.

The process parameters for the continued reaction are: the reaction temperature is 180-280° C., the pressure is lower than 3000 Pa, and the reaction time is 1-20 hours.

The purification method is as follows: firstly dissolving the initial polyester product in a good solvent, stirring to dissolve the polyester to obtain a polymer solution, and then dropping the polymer solution into the poor solvent to produce a precipitation, which is a purified product; The steps can be performed multiple times; the good solvent and the poor solvent can be combined arbitrarily.

The good solvent is any of tetrahydrofuran, acetone, chloroform, dichloromethane, N,N-dimethylformamide, dimethyl sulfoxide, 1,4-dioxane, and hexafluoroisopropanol. A sort of.

The poor solvent is any one of water, methanol, ethanol, ether and petroleum ether.

The mass volume ratio of the polyester primary product to the good solvent is 5%-30%, and the volume ratio of the good solvent to the poor solvent is 1:2-1:10.

The purification times are 1-5 times.

The invention also provides an application of the biodegradable thermoplastic polyester elastic material.

In the present invention, the polymerization reaction is directly melt polycondensation of sebacic acid and polyethylene glycol, and the reaction system does not contain any other components except the monomer and the catalyst. The product obtained after the synthesis reaction is an initial product, and its molecular weight distribution is wider, and a product with a higher relative molecular weight can be obtained after a certain purification step.

In the present invention, the molecular chain of the biodegradable thermoplastic polyester elastic material is linear, and the material is soluble in various organic solvents, such as tetrahydrofuran, acetone, chloroform, dichloromethane, dimethyl sulfoxide, N,N-dichloromethane Methylformamide, 1,4-dioxane, hexafluoroisopropanol, etc., insoluble in water, methanol, ethanol, ether, etc. The material is semi-crystalline solid at room temperature, its glass transition temperature is lower than 0°C, the material is in a high elastic state at room temperature, the elastic modulus is 0.01-2MPa, and the elongation at break exceeds 1700%. The polyester material has good solubility, processability, mechanical strength, high elasticity, and good biocompatibility, biodegradability and thermoplasticity.

beneficial effect

(1) The reaction monomer used in the present invention is relatively simple, non-toxic and non-irritating, and has good biological safety. It is widely used in biomedicine, and the obtained material has good biocompatibility and biodegradability.

(2) The thermoplastic polyester elastic material in the present invention has good solubility, processing performance and high elasticity, and its elastic modulus matches the soft tissue of human body, which can meet the needs of many biomedical applications.

Description of drawings

Fig. 1 is the infrared spectrogram of embodiment 1 gained material;

Fig. 2 is the hydrogen nuclear magnetic resonance spectrum ( ¹ H-NMR) diagram of the material obtained in Example 1;

3 is a uniaxial tensile stress-strain curve diagram of the material obtained in Example 1;

4 is a cyclic tensile stress-strain curve diagram of the material obtained in Example 1;

FIG. 5 is a uniaxial tensile stress-strain curve diagram of the material obtained in Example 1 and the material obtained in Comparative Example 1. FIG.

Detailed ways

The present invention will be further described below in conjunction with specific embodiments. It should be understood that these examples are only used to illustrate the present invention and not to limit the scope of the present invention. In addition, it should be understood that after reading the content taught by the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the appended claims of the present application.

Example 1

(1) Add 0.05mol sebacic acid (Sinopharm, AR) and 0.05mol polyethylene glycol-200 (Wokai) into a 250ml two-necked flask, stir at 140°C for 0.5h under nitrogen protection, after the sebacic acid is completely dissolved , the system forms a clear and transparent liquid;

(2) At 140°C, the pressure of the reaction system was reduced to 3000Pa, and the reaction was stirred for 6h;

(3) 0.0001mol of stannous octoate and 0.0001mol of p-toluenesulfonic acid were added to the reaction system, and the reaction was carried out at 160°C and 3000Pa for 6h;

(4) slowly raise the temperature to 260°C within 4h, then reduce the pressure to 100Pa, and continue the reaction for 8h to obtain the primary product of high molecular weight polyester elastic material;

(5) Dissolving the obtained polyester primary product in tetrahydrofuran to obtain a 10% (w/v) polymer solution, adding the solution dropwise to methanol, the volume ratio of tetrahydrofuran and methanol is 1:4, resulting in precipitation; repeat purification 3 times, and vacuum-drying the precipitate obtained at the last time for 2 days to obtain a purified polyester elastic material.

Fig. 1 shows: the infrared spectrum of the material obtained in Example 1, there is a strong stretching vibration peak of ester bond C=O at 1730cm ^-1 , indicating that hydroxyl and carboxyl groups have occurred between sebacic acid and polyethylene glycol-200. The dehydration and condensation reaction resulted in the formation of ester bonds, and the broad absorption peak of hydroxyl groups at 3400 cm ^-1 was very weak, indicating that the hydroxyl groups in polyethylene glycol-200 were almost completely consumed.

Figure 2 shows: the hydrogen spectrum of the material obtained in Example 1 has characteristic peaks of sebacic acid and polyethylene glycol, wherein the three peaks of δ1.30, 1.61 and 2.35ppm belong to the sebacic acid molecule, δ3.67, The three peaks of 3.70 and 4.23 ppm belong to polyethylene glycol-200, and the molar ratio of polyethylene glycol and sebacic acid is obtained by calculating the peak area, which is 1:1.02, which is consistent with the theoretical feeding ratio.

Figure 3 shows that the material obtained in Example 1 has good mechanical properties, its elastic modulus is about 0.2 MPa, which is close to the elastic modulus of many natural soft tissues, and the elongation at break of the obtained material exceeds 1700%, indicating that the material has Good elasticity and toughness, not easy to be broken, far exceeding the elongation at break of natural arterial and venous vessels (<500%). (The test temperature is room temperature and the tensile rate is 10mm/min)

Figure 4 shows that the material obtained in Example 1 has good elasticity and recovery ability. When the material is pulled to a strain of 100%, the material can quickly return to its original state after the external force is removed. After 10 uninterrupted 100% strain After stretching, the shape of the obtained material can still recover quickly, indicating that the obtained material is a good elastic material. (The test temperature is room temperature, the stretching rate is 10mm/min, the strain range is 20-100%, the number of cycles is 10, and the dwell time is 0s)

Example 2

(1) Add 0.05mol sebacic acid (Sinopharm, AR) and 0.05mol polyethylene glycol-200 (Wokai) into a 250ml two-necked flask, stir at 140°C for 0.5h under nitrogen protection, after the sebacic acid is completely dissolved , the system forms a clear and transparent liquid;

(2) At 140°C, the pressure of the reaction system was reduced to 3325Pa, and the reaction was stirred for 6h;

(3) 0.00025mol of stannous octoate and 0.00025mol of p-toluenesulfonic acid were added to the reaction system, and the reaction was carried out at 180°C and 3000Pa for 4h;

(4) slowly raise the temperature to 260°C within 4h, then reduce the pressure to 100Pa, and continue the reaction for 4h to obtain the primary product of high molecular weight polyester elastic material;

(5) Dissolving the obtained polyester primary product in tetrahydrofuran to obtain a 10% (w/v) polymer solution, adding the solution dropwise to methanol, the volume ratio of tetrahydrofuran and methanol is 1:4, resulting in precipitation; repeat purification 3 times, and vacuum-drying the precipitate obtained at the last time for 2 days to obtain a purified polyester elastic material.

Example 3

(1) Add 0.05mol sebacic acid (Sinopharm, AR) and 0.05mol polyethylene glycol-200 (Wokai) into a 250ml two-necked flask, stir at 140°C for 0.5h under nitrogen protection, after the sebacic acid is completely dissolved , the system forms a clear and transparent liquid;

(2) At 140°C, the pressure of the reaction system was reduced to 3000Pa, and the reaction was stirred for 6h;

(3) 0.001mol of stannous octoate and 0.001mol of p-toluenesulfonic acid were added to the reaction system together, the temperature was slowly raised from 140°C to 260°C within 6h at 3000Pa, and then the pressure was reduced to 100Pa, and the reaction was continued for 1h, Obtain high molecular weight polyester elastic material primary product;

(4) Dissolving the obtained polyester primary product in tetrahydrofuran to obtain a 10% (w/v) polymer solution, adding the solution dropwise to methanol, the volume ratio of tetrahydrofuran and methanol is 1:4, resulting in precipitation; repeat purification 3 times, and vacuum-drying the precipitate obtained at the last time for 2 days to obtain a purified polyester elastic material.

Comparative Example 1

(1) Add 0.05mol of sebacic acid (Sinopharm, AR) and 0.05mol of glycerol (Sinopharm, AR) into a 250ml single-neck flask, stir at 140°C for 0.5h under nitrogen protection, after the sebacic acid is completely dissolved, the system to form a clear and transparent liquid;

(2) 120℃, under nitrogen protection, stirring reaction for 24h;

(3) 120°C, reducing the pressure to 3000Pa, stirring and reacting for 48h to obtain a prepolymer of polyglycerol sebacate;

(4) curing the poly(trimethylene sebacate) prepolymer obtained in step (3) at 120° C. under a pressure of 100 Pa for 48 h to obtain a cured poly(trimethylene sebacate) elastomer.

Figure 5 shows that the material obtained in Example 1, as a thermoplastic material, has a modulus of elasticity close to that of the thermosetting material obtained in Comparative Example 1, but the elongation at break of the material obtained in Example 1 is much greater than that in Comparative Example 1. The elongation at break of the material.

Claims (10)

1. A biodegradable thermoplastic polyester elastic material is prepared from sebacic acid and polyethanediol through fusion polycondensation in the presence of catalyst, reaction between hydroxy and carboxyl, dewatering, condensation polymerization and purifying.

2. The material of claim 1, wherein the polyester elastomer is a high molecular weight linear poly (sebacic acid-polyethylene glycol) ester having the formula:

wherein n is more than or equal to 50, and m is 2-8.

3. The material as claimed in claim 1, wherein the molecular weight of the polyethylene glycol is 100-400 g-mol^-1(ii) a The catalyst is one of stannous octoate, stannous chloride, stannous octoate/p-toluenesulfonic acid and stannous chloride/p-toluenesulfonic acid.

4. A method for preparing a biodegradable thermoplastic polyester elastic material comprises the following steps:

mixing sebacic acid and polyethylene glycol in a molar ratio of 0.99:1-1.10:1, stirring, carrying out esterification reaction under a vacuum condition, adding a catalyst, carrying out pre-condensation reaction under the vacuum condition, continuously reacting the obtained prepolymer, and purifying to obtain the biodegradable thermoplastic polyester elastic material.

5. The method of claim 4, wherein the agitating is: stirring the mixture at the temperature of 160 ℃ under the protection of nitrogen until the sebacic acid is completely dissolved.

6. The method according to claim 4, wherein the esterification reaction has the following process parameters: the reaction temperature is 120 ℃ and 180 ℃, the pressure is 0.1-4000Pa, and the reaction time is 0.5-8 hours.

7. The method according to claim 4, wherein the catalyst is one of stannous octoate, stannous chloride, stannous octoate/p-toluenesulfonic acid and stannous chloride/p-toluenesulfonic acid, the molar amount of the p-toluenesulfonic acid is equal to that of the stannous octoate or the stannous chloride, and the molar amount of the stannous octoate or the stannous chloride is 0.0005-0.02 times of that of hydroxyl or carboxyl in the reaction system.

8. The method according to claim 4, wherein the pre-condensation reaction has the following process parameters: the reaction temperature is 120-180 ℃, the pressure is 0.1-3000Pa, and the reaction time is 2-20 hours.

9. The method of claim 4, wherein the process parameters of the continuous reaction are: the reaction temperature is 180 ℃ and 280 ℃, the pressure is lower than 3000Pa, and the reaction time is 1-20 hours.

10. Use of a polyester elastomer material according to claim 1.

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