CN104231578A - Completely biodegradable polyester material and preparation and application of completely biodegradable polyester - Google Patents

Abstract

The invention discloses a fully biodegradable polyester material and its preparation and application. The composition of the material includes 98% to 60% of poly-L-lactic acid and 2% to 40% of poly(L-lactic acid-caprolactone ester) copolymer, the molecular weight of the copolymer is 10,000 to 100,000, the ratio of lactic acid units to caprolactone units is 95:5 to 20:80, and contains 1 to 6 arms of a specific structure. The preparation method of the material: dissolving poly-L-lactic acid in an organic solvent capable of dissolving polylactic acid, adding the amount of the copolymer described in the recipe, stirring fully to dissolve the polymer completely, then adding the polymer solution to water or water/alcohol In the mixed solution, the blend is precipitated, filtered and dried to obtain the fully biodegradable polyester material to be prepared. The material can be used in the preparation of corresponding products in the fields of artificial bone body, tissue engineering scaffold, interventional medical device and the like in biomedicine, and the prepared product has excellent mechanical properties and biodegradability.

Description

A kind of fully biodegradable polyester material and its preparation and application

technical field

The invention relates to the technical field of polymer biodegradable materials, and more specifically relates to a fully biodegradable polymer material and its preparation method and application. the

Background technique

Biodegradable polymer materials are a kind of polymer materials that can be degraded in the body after performing corresponding functions in the human body and are gradually absorbed or excreted. They will not remain permanently in the body as foreign objects and affect human physiology and life. With the development of modern medicine, more and more biodegradable polymer materials are used in many products that do not need to be stored in the body for a long time. the

Degradable polymer material-polylactic acid is a commonly used degradable polymer material in biomedicine, and its molecular weight and crystallinity greatly affect its mechanical properties. Polylactic acid has adjustable strength, but its brittleness often affects its application range. Although the elongation at break of the material can be increased by adding a small molecule nucleating agent [CN200910045012.5] or a plasticizer [CN201010205306.2], in the biomedical field, small molecules tend to migrate under the action of body fluids, resulting in invalidated. The use of polymer plasticizers can avoid migration like small molecule plasticizers [CN201210548826.2], but the degraded diamines of materials that use diisocyanate chain extension may be toxic to the human body. the

Polycaprolactone is also a degradable polymer with good biocompatibility, and the multiple methylene groups in the caprolactone unit provide flexibility to its molecule. However, pure polycaprolactone has poor strength and low glass transition temperature, and it is difficult to meet the requirements of medical device products when used alone. It is a reasonable choice to use flexible biodegradable polymer polycaprolactone to form polylactic acid/polycaprolactone blends to improve the brittleness of polylactic acid [Engineering Fracture Mechanics 74(2007) 1872–1883]. The publication number is CN201210114155.9 patent document, which proposes to add polybutylene succinate and diphenylmethane diisocyanate when polylactic acid and polycaprolactone are blended, although adding each single-component material can overcome their own shortcomings , Combining the advantages of each single-component material, but the residue of diisocyanate or its degradation products prevent it from being used in the biomedical field. Due to the poor compatibility of polylactic acid and polycaprolactone, when they are blended, it is often necessary to add a compatibilizer when a chemical coupling agent such as diisocyanate is not used. In the biomedical field, the compatibilizer must also be a substance with good biocompatibility. Therefore, some researchers use polyethylene glycol/polypropylene glycol block copolymers or polylactic acid-polycaprolactone copolymers as blending compatibilizers. Adding polyethylene glycol/polypropylene glycol block copolymer [Energy Procedia 34 (2013) 542–548] or adding poly(lactic acid-caprolactone) copolymers can help improve the co-existence of polylactic acid and polycaprolactone. Mixture [Journal of Applied Polymer Science, Vol.86, 1892–1898 (2002)]. In any case, these systems all involve three different materials, and the system is very complicated; the pure polycaprolactone in the system partially degrades too slowly; moreover, these studies are also limited to the compatibility and crystallinity of the blend system. Changes, less attention has been paid to the changes in the mechanical properties of materials. the

Contents of the invention

In view of the deficiencies and current situation of biodegradable polymer materials in the prior art, the purpose of the present invention is to provide a fully biodegradable polyester material, which is used for artificial bone bodies, tissue engineering scaffolds, and interventional medical treatments in biomedicine. Appropriate products can be prepared in the field of equipment and other fields, so as to overcome the disadvantages of unsatisfactory performance of products prepared from degraded polymers provided by the prior art. the

The basic idea of the present invention is to directly mix poly(L-lactic acid-caprolactone) copolymer with polylactic acid, and utilize poly(L-lactic acid-caprolactone) copolymer to not degrade too slowly like pure polycaprolactone , and compatible with pure polylactic acid, flexibility is provided by multiple methylene units in the caprolactone chain link in the copolymer, thereby improving the brittleness of the blend, and poly(L-lactic acid-caprolactone) copolymerization The substance itself can also reduce the crystallinity of pure polylactic acid, so that the material has better mechanical properties. the

The fully biodegradable polyester material provided by the present invention comprises 98% to 60% of poly-L-lactic acid by mass and 2% to 40% by mass of poly(L-lactic acid-caprolactone) copolymer, the poly(L - Lactic acid-caprolactone) copolymer has a molecular weight of 10,000 to 100,000, a ratio of lactic acid units to caprolactone units of 95:5 to 20:80, and contains 1 to 6 arms of the following structure:

In the structural arm, n=10-1000 integers, m=5-200 integers. the

In the above technical solution of the present invention, the poly(L-lactic acid-caprolactone) copolymer preferably has a ratio of lactic acid units to caprolactone units of 90:10 to 40:60 and a molecular weight of 10,000 to 80,000 poly(L-lactic acid-caprolactone) copolymer. Further, the poly(L-lactic acid-caprolactone) copolymer is prepared by the following method: mix 0.01-1 part of initiator with 5-100 parts of cyclic lactone, dry in vacuum, and then add cyclic Mixed with 0.01-5% catalyst in terms of mass of lactone, dried at 0.01-100mmHg, room temperature-100°C for 1-24 hours, vacuum-sealed and reacted at 100-180°C for 1-120 hours to obtain biodegradable poly(L-lactic acid-caprolactone) copolymer. the

The initiator used for preparing the poly(L-lactic acid-caprolactone) copolymer is preferably a unit alcohol or a polyol with a hydroxyl group. Mono alcohols include alcohols with 4 to 16 carbon atoms, such as butanol, pentanol, hexanol, heptanol, etc.; polyols include dihydric alcohols, trihydric alcohols, tetrahydric alcohols, pentahydric and hexahydric alcohols, etc. Wherein dibasic alcohol can be ethylene glycol, propylene glycol or, butanediol etc.; Tribasic alcohol can be glycerol, tri(hydroxymethyl)ethane etc.; Tetrol can be pentaerythritol etc.; Xylitol, etc.; the hexavalent alcohol can be dipentaerythritol, mannitol, sorbitol, etc. Initiators are particularly preferably the aforementioned compounds in which the boiling point is above 150°C. The structure of the initiator is determined by the structure of the poly(L-lactic acid-caprolactone) copolymer. When the initiator is a unit alcohol or a glycol, the structure of the copolymer is linear, and the copolymer is one arm or two arms; When the initiator is ternary and more than three alcoholic hydroxyl groups, the structure of the copolymer is a multi-arm structure. the

The cyclic lactone used to prepare the poly(L-lactic acid-caprolactone) copolymer is preferably a cyclic lactone with a ratio of lactic acid units to caprolactone units of 95:5 to 20:80 and a molecular weight of 1 to 100,000 ; It is further preferred to select a cyclic lactone with a ratio of lactic acid unit to caprolactone unit of 90:10 to 40:60 and a molecular weight of 10,000 to 80,000. the

If it is considered that the color of the prepared poly(L-lactic acid-caprolactone) copolymer is relatively dark, or the purity requirement is high, the obtained poly(L-lactic acid-caprolactone) copolymer can be purified. As the method of purification, a method generally used for purification of polyester can be adopted. the

The method for preparing the above-mentioned fully biodegradable polyester material provided by the present invention can be taken by dissolving poly-L-lactic acid in 1 to 10 times the organic solvent capable of dissolving polylactic acid, adding a formula amount of poly(L-lactic acid-hexyl Lactone) copolymer, after fully stirring to dissolve the polymer completely, add the polymer solution to water or water/alcohol mixture 5 to 100 times the polymer solution, to precipitate the blend, filter and dry That is, a fully biodegradable material with toughening effect is obtained. The poly(L-lactic acid-caprolactone) copolymer is preferably a purified poly(L-lactic acid-caprolactone) copolymer. the

In the method for preparing fully biodegradable polyester materials, the organic solvent is preferably dichloromethane, chloroform, chloroethane, 1,2-dichloroethane, 1,1,1-trichloroethane , 1,1,2-trichloroethane, 1,1,1,2-tetrachloroethane, 1,1,2,2-tetrachloroethane, acetone, ethyl acetate, tetrahydrofuran, acetonitrile, N, At least one of N-dimethylformamide and N,N-dimethylacetamide. the

To prepare the above-mentioned fully biodegradable polyester material, for the blending of poly-L-lactic acid and poly(L-lactic acid-caprolactone), the common method of polymer blending can also be used, especially for polylactic acid with a larger molecular weight. Melt blending is more suitable. The specific operation can be taken. After fully drying the poly-L-lactic acid and poly(L-lactic-caprolactone) copolymer of the formula amount, they are added to the twin-screw extruder, and the screw speed is controlled to be 10 to 150 rpm. The outlet temperature is 130-200°C, the residence time of the material is 1-15 minutes, and the desired product can be obtained. The control parameters of the melt blending twin-screw extruder are preferably selected with a screw speed of 10-100 rpm, an extrusion temperature of 140-190°C, and a residence time of materials of 1-10 minutes. Before melt blending, it is best to place it in a vacuum oven and dry it under vacuum at 45-100°C. the

The fully biodegradable polyester material provided by the present invention can be used as bone material, tissue engineering scaffold material, interventional medical device material, etc., and can be used to make corresponding medical device products, such as ligature nails and clips used in medical operations. . The preparation of corresponding medical device products can directly adopt the addition of poly(L-lactic acid-caprolactone) copolymer in the substrate poly-L-lactic acid, and then add it to the barrel of the injection molding machine after passing through the solution blending or blending extruder , to obtain biodegradable medical device products by injection molding. the

In the fully biodegradable polyester material provided by the present invention, poly(L-lactic acid-caprolactone) copolymer is added to polylactic acid as a macromolecule with a toughening effect to improve its brittleness and maintain its strength. or have not been reported in other literatures. Further, by adjusting the molecular weight of polylactic acid and adding an appropriate amount of polymer poly(L-lactic acid-caprolactone) copolymer with toughening effect, a new material can be obtained for the preparation of degradable products. Until the present invention is completed, the inventor has not seen relevant reports in patent documents or other documents. the

The biodegradable polyester material provided by the present invention is a polylactic acid-based material, which is based on poly(L-lactic acid) and an appropriate amount of fully degradable polymer poly(L-lactic acid-caprolactone) with a toughening effect is added. ester) copolymer, a fully biodegradable material obtained by blending. Adding poly(L-lactic acid-caprolactone) copolymer with toughening effect to polylactic acid improves the brittleness of polylactic acid and maintains its strength. The biodegradable polylactic acid-based material provided by the present invention can be seen in the 500-fold magnified electron microscope image of the brittle section, and the two components in the blended material are mixed very uniformly, and the 2500-fold magnified electron microscope image can be seen between the two components. There is basically no phase interface, and it is a completely biodegradable material with a new structure. The material has excellent mechanical properties, and the elongation at break is 10-200% higher than that of pure poly(L-lactic acid) with the same molecular weight. The elongation at break and degradability of the blends can be adjusted according to the percentage of poly(L-lactic acid-caprolactone) copolymer in the blend and the ratio of lactic acid units to caprolactone units in the copolymer. The invention effectively improves the flexibility of the biodegradable polylactic acid under the premise of maintaining complete biodegradation and high mechanical strength of the material. Therefore, the fully biodegradable material prepared by the present invention has excellent mechanical properties, good biocompatibility and controllable degradation rate, has broad application prospects in the field of biomedicine, and is especially suitable for preparing fully biodegradable, Injection molding products in the body such as ligature nail clip products. the

The biodegradable material provided by the invention does not produce component migration, and has excellent mechanical properties, which can obviously improve the defects of poor toughness and brittleness of polylactic acid, and the elongation at break can reach 200% of polylactic acid with the same molecular weight. It can be widely used in various medical device fields such as bone material, tissue engineering scaffold material, interventional medical device (such as ligature clip, etc.) material. All the component raw materials used in the preparation are approved by the Food and Drug Administration and are safe and reliable. the

Description of drawings

Fig. 1 is the nuclear magnetic spectrum of poly(L-lactic acid-caprolactone) copolymer synthesized by the present invention;

Figure 2-1 to Figure 2-3 are magnified electron microscope images of the brittle section of the fully biodegradable polyester material of the present invention, wherein Figure 2-1 is an electron microscope image magnified 500 times, and Figure 2-2 is an electron microscope image magnified 2500 times Figures; Figure 2-3 is a 500 times magnified electron microscope image of the brittle section of the pure polylactic acid material under the same conditions. the

Fig. 3 is a graph showing the test results of mechanical properties of the fully biodegradable polyester material provided by the present invention, and the three different curves are the results of three measurements of the same sample. the

The data listed in Table 1 are the average of three test results. the

Detailed ways

The present invention is specifically described below by way of examples. It is necessary to point out that the following examples are only used to further illustrate the present invention, and can not be interpreted as the limitation of the protection scope of the present invention, some non-essential improvements and adjustments made by those skilled in the art according to the content of the above-mentioned present invention , still belong to the protection scope of the present invention. the

In the following examples, the parts, percentages, and ratios of each component are parts by mass (grams), percent by mass, and ratio by mass unless otherwise specified. the

Example 1

Mix 0.05 parts of n-decyl alcohol initiator with 25 parts of purified cyclic lactone (the ratio of lactic acid monomer to caprolactone monomer is 90:10), vacuum dry, and then add 0.01 parts based on the mass of cyclic lactone % of catalyst mixed, filled with nitrogen to drive away oxygen, vacuumize, repeat three times, control the vacuum degree of 0.05mmHg, vacuum seal the tube and react at 130°C for 48 hours to obtain a degradable poly(L-lactic acid-caprolactone) copolymer . The number average molecular weight of the obtained product after purification was determined to be 8.1×10 ⁴ g/mol.

Dissolve 6 parts/gram of poly L-lactic acid in 20 mL of dichloromethane solvent, add 4 parts/gram of the poly(L-lactic acid-caprolactone) copolymer prepared above, stir well to completely dissolve the polymer, and then gradually Add dropwise to 100mL of 1:1 water/ethanol mixture to precipitate the blend, filter and dry to obtain a fully biodegradable polyester material with mechanical properties. the

Example 2

After drying 20 parts of poly(L-lactic acid-caprolactone) obtained in Example 1 and 180 parts of poly-L-lactic acid at 80°C for 5 hours, they were added to a twin-screw extruder, and the screw speed was controlled at 15 rpm , the extrusion temperature is 180°C, and the residence time of the material is 5 minutes, that is, a fully biodegradable polyester material with excellent mechanical properties is obtained. the

Example 3

Mix 0.1 part of tris(hydroxymethyl)ethane initiator with 50 parts of purified cyclic lactone (the ratio of lactic acid monomer to caprolactone monomer is 90:10), vacuum dry and follow the method described in Example 1 Synthesis of degradable poly(L-lactic acid-caprolactone) copolymers. The number average molecular weight of the obtained product was determined to be 5.8×10 ⁴ g/mol after purification.

Dissolve 7.5 parts/gram of poly-L-lactic acid in 30 mL of dichloromethane solvent, add 2.5 parts/gram of poly(L-lactic acid-caprolactone) copolymer, stir well to dissolve the polymer completely, then gradually add to 200 mL The blend is precipitated in the water, filtered, and dried to obtain a fully biodegradable polyester material with excellent mechanical properties. the

Example 4

Mix 0.5 parts of tris(hydroxymethyl)ethane initiator with 100 parts of purified cyclic lactone (the ratio of lactic acid monomer to caprolactone monomer is 50:50), vacuum dry and follow the method described in Example 1 Synthesis of degradable poly(L-lactic-caprolactone). The number average molecular weight of the obtained product after purification was determined to be 5.7×10 ⁴ g/mol.

Dissolve 9.8 parts/gram of poly L-lactic acid in 20 mL of dichloromethane solvent, add 0.2 parts/gram of poly(L-lactic acid-caprolactone) copolymer, stir well to dissolve the polymer completely, then gradually add it dropwise to 300 mL1 :1 in a water/ethanol mixture, the blend is precipitated, filtered, and dried to obtain a fully biodegradable polyester material with mechanical properties. the

Example 5

Mix 0.5 parts of dodecyl alcohol initiator with 50 parts of purified cyclic lactone (the ratio of lactic acid monomer and caprolactone monomer is 50:50), and after vacuum drying, synthesize degradable polystyrene according to the method described in Example 1. (L-lactic acid-caprolactone). The number average molecular weight of the obtained product after purification was determined to be 1.8×10 ⁴ g/mol.

After drying 66 parts of the obtained poly(L-lactic acid-caprolactone) and 134 parts of poly-L-lactic acid at 80°C for 8 hours, they were added to a twin-screw extruder, and the screw speed was controlled to be 10 rpm, and extruded The temperature is 182° C., and the residence time of the material is 5 minutes, and a fully biodegradable polyester material with mechanical properties is obtained. the

Example 6

Dissolve 95 parts of poly-L-lactic acid in 200 mL of chloroform solvent, add 5 parts of poly(L-lactic acid-caprolactone) obtained in Example 5, stir well to completely dissolve the polymer, and then gradually add it dropwise to 1000 mL1: 1 in the water/ethanol mixture, the blend is precipitated, filtered, and dried to obtain a fully biodegradable polyester material with mechanical properties. the

Example 7

Mix 1.0 parts of dipentaerythritol initiator with 100 parts of purified cyclic lactone (the ratio of lactic acid monomer to caprolactone monomer is 40:60), and after vacuum drying, synthesize degradable poly( L-lactic acid-caprolactone). The number average molecular weight of the obtained product was determined to be 2.3×10 ⁴ g/mol after purification.

Dissolve 9.3 parts of poly-L-lactic acid in 10 mL of 1,1,2,2-tetrachloroethane solvent, add 0.7 parts of poly(L-lactic acid-caprolactone) copolymer, stir well to completely dissolve the polymer, and gradually Add dropwise to 200mL of 1:1 water/ethanol mixture to precipitate the blend, filter and dry to obtain a fully biodegradable polyester material with mechanical properties. the

Example 8

Mix 1 part of n-heptanol initiator with 100 parts of purified cyclic lactone (the ratio of lactic acid monomer to caprolactone monomer is 80:20), and after vacuum drying, synthesize a degradable polymer according to the method described in Example 1. (L-lactic acid-caprolactone). The number average molecular weight of the obtained product after purification was determined to be 1.1×10 ⁴ g/mol.

After drying 15 parts of the obtained poly(L-lactic acid-caprolactone) and 85 parts of poly L-lactic acid at 80°C for 6 hours, they were added to a twin-screw extruder, and the screw speed was controlled to be 20 rpm, and extruded The temperature is 185° C., and the residence time of the material is 3 minutes to obtain a fully biodegradable polyester material with mechanical properties. the

Table 1. Relevant properties of the fully biodegradable materials prepared in Examples 1 to 8

Claims (10)

1. a fully biodegradable polyester material, it is characterized in that, composition component comprises the poly (l-lactic acid) of quality 98% ~ 60% and poly-(Pfansteihl-caprolactone) multipolymer of quality 2% ~ 40%, the molecular weight of described poly-(Pfansteihl-caprolactone) multipolymer is 10,000 ~ 100,000, lactic acid units and caprolactone units number are than being 95:5 to 20:80, the arm containing 1 ~ 6 following structure:

N=10 ~ 1000 integer in structural arm, m=5 ~ 200 integer.

2. fully biodegradable polyester material according to claim 1, is characterized in that, the lactic acid units of described poly-(Pfansteihl-caprolactone) multipolymer is with caprolactone units number than being 90:10 to 40:60, and molecular weight is 10,000 ~ 80,000.

3. fully biodegradable polyester material according to claim 1 and 2, it is characterized in that, described poly-(Pfansteihl-caprolactone) multipolymer is prepared by following method: mixed with 5 ~ 100 mass parts annular lactones by 0.01 ~ 1 mass parts initiator, after vacuum-drying, add in the catalyst mix of annular lactone quality 0.01 ~ 5% again, vacuum tightness 0.01 ~ 100mmHg, at 10 DEG C ~ 100 DEG C dry 1 ~ 24 hour, vacuum sealing tube, in 100 ~ 180 DEG C of reactions 1 ~ 120 hour, namely obtains degradable poly-(Pfansteihl-caprolactone) multipolymer.

4. fully biodegradable polyester material according to claim 3, is characterized in that, described initiator is unit alcohol with hydroxyl or polyvalent alcohol.

5. fully biodegradable polyester material according to claim 4, is characterized in that, described initiator is that boiling point is not less than 150 DEG C, with the unit alcohol of hydroxyl or polyvalent alcohol.

6. fully biodegradable polyester material according to claim 1 and 2, is characterized in that, described poly-(Pfansteihl-caprolactone) multipolymer is poly-(Pfansteihl-caprolactone) multipolymer of purified process.

7. the preparation method of the described fully biodegradable polyester material of one of claim 1 to 6, it is characterized in that, poly (l-lactic acid) is dissolved in 1 ~ 10 times can dissolve in the organic solvent of poly(lactic acid), add poly-(Pfansteihl-caprolactone) multipolymer of formula ratio, after abundant stirring makes polymkeric substance dissolve completely, polymers soln is joined 5 ~ 100 times in the water of polymers soln or water/alcohol mixed solution, blend is precipitated out, after filtration, the dry i.e. obtained completely biodegradable material with toughening effect.

8. the preparation method of fully biodegradable polyester material according to claim 7, is characterized in that, described organic solvent is methylene dichloride, trichloromethane, monochloroethane, 1,2-ethylene dichloride, 1，1，1-trichloroethane, 1,1,2-trichloroethane, 1,1,1,2-tetrachloroethane, 1,1,2, at least one in 2-tetrachloroethane, acetone, ethyl acetate, tetrahydrofuran (THF), acetonitrile, DMF, N,N-dimethylacetamide.

9. the preparation method of the fully biodegradable polyester material that one of claim 1 to 6 is described, the poly (l-lactic acid) of formula ratio and poly-(Pfansteihl-caprolactone) multipolymer is it is characterized in that to insert in twin screw extruder, controlling screw speed is 10 ~ 150 revs/min, extrusion temperature is 130 ~ 200 DEG C, residence time of material be 1 ~ 15 minute blended, extrude and namely prepare fully biodegradable polyester material to be prepared.

10. the application of the described fully biodegradable polyester material of one of claim 1 to 6, is characterized in that preparing the application in diaphysis, tissue engineering bracket, interventional medical device article.