Degradable medical stent as well as preparation method and application thereof

Abstract

The invention relates to the technical field of degradable medical materials, in particular to a degradable medical stent as well as a preparation method and application thereof. The composite material comprises the following components in percentage by weight: 5-15% of polylactic acid-glycolic acid nanofibers, 8-12% of modified salix mongolica fibers, 10-25% of toughened polylactic acid, 10-20% of degradable polyester and 1-5% of a functional aid, the polylactic acid-glycolic acid nanofiber is prepared by the following steps: stretching an organic polymer into nanofiber by adopting an electrostatic spinning technology, collecting the nanofiber by using a balloon to form a nanofiber membrane, and loading paclitaxel onto the polylactic acid-glycolic acid nanofiber membrane by utilizing an ultrasonic spraying technology. The prepared material has excellent toughness and also has excellent crystallization property, so that the high-toughness heat-resistant composite material can be obtained after short-time thermal annealing treatment, and the composite material is completely biodegradable.

Description

Technical Field

[0001] The present invention relates to the technical field of degradable medical materials, and more specifically, to a degradable medical stent and a preparation method and application thereof. Background Art

[0002] As the trend of population aging intensifies, degenerative diseases have become a major challenge facing society and medicine. Data show that about 50% of the population over 65 years old is troubled by osteoarthritis (OA), and knee OA is the main cause of chronic pain and disability in the elderly. As one of the diseases with the highest disability rate, knee OA poses a heavy burden on the global economy. As an overall joint disease, OA patients show cartilage damage, synovial inflammation and abnormal subchondral bone reconstruction. The poor self-repair ability of articular cartilage and the inflammatory environment pose a huge challenge to cartilage regeneration. Studies have shown that in the course of OA disease, the structural integrity of the cartilage-bone interface (CBI) is destroyed, causing blood vessels in the subchondral bone to invade the cartilage area, and the media and factors in the joint cavity also penetrate into the bone tissue, which then causes damage to both the cartilage and the subchondral bone.

[0003] Polylactic acid-glycolic acid copolymer (PLGA) is a high molecular polymer formed by cross-linking polylactic acid (PLA) and polyglycolic acid (PGA). It is a degradable implant material approved by the US Food and Drug Administration (FDA) and has good cell compatibility and drug loading performance. The degradation rate of PLGA polymer in vivo is related to the cross-linking polymerization ratio of PLA and PGA. Studies have found that PLGA with a mass ratio of PLA and PGA of 50:50 has strong hydrophilicity, low crystallinity, low mechanical strength and elastic modulus.

[0004] Poly(lactic acid-glycolic acid) copolymers have low mechanical strength and are prone to deformation or fracture, especially under high stress environments, which limits their use in applications that require high-strength support. Summary of the invention

[0005] The present invention provides a degradable medical stent and a preparation method and application thereof. The prepared material has excellent toughness and excellent crystallization performance, so that a high-toughness and heat-resistant composite material can be obtained after a short-time thermal annealing treatment, and the composite material is also completely biodegradable.

[0006] In a first aspect, the present invention provides a degradable medical stent material, which comprises, by weight percentage, 5-15% of polylactic acid-glycolic acid nanofibers, 8-12% of modified Salix psammophila fibers, 10-25% of toughened polylactic acid, 10-20% of degradable polyester, and 1-5% of functional additives;

[0007] The polylactic acid-glycolic acid nanofibers are prepared by using an electrostatic spinning technique to stretch organic polymers into nanofibers, which are collected by a balloon to form a nanofiber membrane, and paclitaxel is then loaded onto the polylactic acid-glycolic acid copolymer nanofiber membrane by using an ultrasonic spraying technique.

[0008] Preferably, in terms of weight percentage, it includes 10-15% of polylactic acid-glycolic acid nanofibers, 10-12% of modified salix tamarisk fibers, 18-25% of toughened polylactic acid, 15-20% of degradable polyester, and 3-5% of functional additives.

[0009] Preferably, calculated by weight percentage, it includes 12% polylactic acid-glycolic acid nanofibers, 10% modified salix tamarisk fibers, 21% toughened polylactic acid, 18% degradable polyester, and 3% functional additives.

[0010] Preferably, the method for preparing the polylactic acid-glycolic acid nanofibers comprises the following steps:

[0011] A1: Preparation of polylactic acid-glycolic acid cross-linked nanofiber balloons: dissolving polylactic acid-glycolic acid in a mixed solution of dichloromethane and NN dimethylformamide, stirring for 8-10 hours to obtain a polylactic acid-glycolic acid solution, applying electrospinning technology to the polylactic acid-glycolic acid solution to obtain nanofiber balloons, and vacuum drying the prepared nanofiber balloons;

[0012] A2: Ultrasonic coating of paclitaxel: Weigh paclitaxel and iopromide, then measure anhydrous ethanol and distilled water, place them in an ultrasonic cleaning machine for oscillation and dissolution, the resulting solution is clear and transparent, and the paclitaxel drug is completely and evenly dissolved, and then loaded onto the polylactic acid-glycolic acid copolymer nanofiber membrane using ultrasonic spraying technology.

[0013] Preferably, the modified Salix psammophila fiber is prepared by modifying Salix psammophila fiber with silane coupling agent KH550, silane coupling agent KH570, titanate coupling agent 201, or maleic anhydride coupling agent.

[0014] Preferably, the toughened polylactic acid comprises an impact modifier BPM520, 2-4% CaCO 3 , processing aids and polylactic acid are mixed evenly to obtain the product.

[0015] Preferably, the degradable polyester is one or more of polybutylene terephthalate-butylene adipate copolymer, polycaprolactone, polybutylene succinate, polybutylene succinate-butylene adipate copolymer, and polyhydroxyalkanoate.

[0016] Preferably, the functional auxiliary agent is one or more of dihydrolevorotatory glucosone, calcium chloride, silver chloride, mineral oil, and vegetable oil.

[0017] In a second aspect, the present invention provides a method for preparing a degradable medical stent material, comprising the following steps:

[0018] (1) melt-blending polylactic acid-glycolic acid nanofibers, modified Salix psammophila fibers, and toughened polylactic acid at 30-50° C. to obtain a blend;

[0019] (2) The toughened polylactic acid, the degradable polyester and the functional additive are melt-blended with the blend to prepare a degradable medical stent material.

[0020] In a third aspect, the present invention provides an application of a degradable medical stent material in the field of medical consumables.

[0021] In a fourth aspect, the present invention provides a degradable medical stent, wherein the degradable medical stent comprises the degradable medical stent material.

[0022] In summary, the present invention has the following beneficial effects:

[0023] 1. The paclitaxel / polylactic acid-glycolic acid electrospun nanofiber membrane drug-loaded balloon of the present invention can be applied to the field of drug delivery for cardiovascular stenosis. The polylactic acid-glycolic acid copolymer nanofiber membrane is used as the base layer and then the paclitaxel drug that inhibits cell proliferation is coated by ultrasonic spraying technology to obtain a drug balloon with a uniform surface coating.

[0024] 2. The polar groups after hydrolysis and condensation of silane in the modified Salix tamarisk fibers of the present invention form hydrogen bonds with the hydroxyl groups in the Salix tamarisk fibers, reducing the number of hydroxyl groups in the fibers and the phenomenon of fiber agglomeration, and improving the uniformity of the dispersion of the Salix tamarisk fibers in the polylactic acid matrix; the non-polar group at one end is grafted with the polylactic acid molecular chain to form a long alkyl chain structure, which enhances the interfacial compatibility. The alkoxy group at one end of the titanate is hydrolyzed and forms hydrogen bonds with the hydroxyl groups in the Salix tamarisk fibers, and the group at the other end is physically entangled with the polylactic acid molecular chain, and the metal central atom titanium forms a monomolecular adsorption layer on the surface of the Salix tamarisk fibers, thereby generating a coupling effect. The carboxyl group in maleic anhydride forms hydrogen bonds with the hydroxyl groups in the Salix tamarisk fibers, maleic anhydride can combine with the hydrophilic Salix tamarisk fibers by forming ester bonds, and the hydrophobic chain ends in maleic anhydride are entangled with the polylactic acid matrix, which enhances the interfacial compatibility of the composite material, thereby having better mechanical properties.

[0025] 3. The main components of the composite material of the present invention are polylactic acid and degradable polyester, both of which are biodegradable materials and conform to the concept of green environmental protection.

[0026] It should be understood that the foregoing general description and the following detailed description are exemplary and explanatory only and are not intended to limit the scope of protection of the present invention. DETAILED DESCRIPTION

[0027] The present invention is further described in detail below in conjunction with the examples. It is particularly noted that if no specific conditions are specified in the following examples, the reactions are carried out according to conventional conditions or conditions recommended by the manufacturer. Unless otherwise specified, the raw materials used in the following examples can be obtained from common commercial sources.

[0028] Preparation Example

[0029] The preparation method of polylactic acid-glycolic acid nanofiber comprises the following steps:

[0030] A1: Preparation of polylactic acid-glycolic acid cross-linked nanofiber balloons: polylactic acid-glycolic acid was dissolved in dichloromethane and NN dimethylformamide in a mass ratio of 1:2, and stirred for 10 hours to obtain a polylactic acid-glycolic acid solution, and the polylactic acid-glycolic acid solution was subjected to electrospinning technology to obtain a nanofiber balloon, and the prepared nanofiber balloon was vacuum dried;

[0031] A2: Ultrasonic coating of paclitaxel: Weigh paclitaxel and iopromide, then measure anhydrous ethanol and distilled water, place them in an ultrasonic cleaning machine for oscillation and dissolution, the resulting solution is clear and transparent, and the paclitaxel drug is completely and evenly dissolved, and then loaded onto the polylactic acid-glycolic acid copolymer nanofiber membrane using ultrasonic spraying technology.

[0032] Example

[0033] Example 1

[0034] A degradable medical stent material, comprising, by weight percentage, 5% polylactic acid-glycolic acid nanofiber, 8% modified Salix psammophila fiber, 10% toughened polylactic acid, 10% degradable polyester, and 1% functional additive;

[0035] The modified Salix psammophila fiber is prepared by modifying the Salix psammophila fiber with a maleic anhydride coupling agent;

[0036] Toughened polylactic acid will be impact modifier BPM520, 2% CaCO 3 , a processing aid and polylactic acid are uniformly mixed to obtain the product;

[0037] The degradable polyester is a polybutylene terephthalate-butylene adipate copolymer;

[0038] The functional auxiliary agent is dihydrolevorotatory glucosone.

[0039] A method for preparing a degradable medical stent material comprises the following steps:

[0040] (1) melt-blending polylactic acid-glycolic acid nanofibers, modified Salix psammophila fibers, and toughened polylactic acid at 40° C. to obtain a blend;

[0041] (2) The toughened polylactic acid, the degradable polyester and the functional additive are melt-blended with the blend at a blending temperature of 190° C. to obtain a degradable medical stent material.

[0042] Example 2

[0043] A degradable medical stent material, comprising, by weight percentage, 8% polylactic acid-glycolic acid nanofiber, 10% modified Salix psammophila fiber, 12% toughened polylactic acid, 12% degradable polyester, and 2% functional additives;

[0044] The modified Salix psammophila fiber is prepared by modifying the Salix psammophila fiber with a maleic anhydride coupling agent;

[0045] Toughened polylactic acid will be impact modifier BPM520, 3% CaCO 3 , a processing aid and polylactic acid are uniformly mixed to obtain the product;

[0046] The degradable polyester is a polybutylene terephthalate-butylene adipate copolymer;

[0047] The functional auxiliary agent is dihydrolevorotatory glucosone.

[0048] A method for preparing a degradable medical stent material comprises the following steps:

[0049] (1) melt-blending polylactic acid-glycolic acid nanofibers, modified Salix psammophila fibers, and toughened polylactic acid at 30° C. to obtain a blend;

[0050] (2) The toughened polylactic acid, the degradable polyester and the functional additive are melt-blended with the blend at a blending temperature of 190° C. to obtain a degradable medical stent material.

[0051] Example 3

[0052] A degradable medical stent material, comprising, by weight percentage, 13% polylactic acid-glycolic acid nanofibers, 12% modified Salix psammophila fibers, 20% toughened polylactic acid, 18% degradable polyester, and 4% functional additives;

[0053] The modified Salix psammophila fiber is prepared by modifying the Salix psammophila fiber with a maleic anhydride coupling agent;

[0054] Toughened polylactic acid will be impact modifier BPM520, 4% CaCO 3 , a processing aid and polylactic acid are uniformly mixed to obtain the product;

[0055] The degradable polyester is a polybutylene terephthalate-butylene adipate copolymer;

[0056] The functional auxiliary agent is dihydrolevorotatory glucosone.

[0057] A method for preparing a degradable medical stent material comprises the following steps:

[0058] (1) melt-blending polylactic acid-glycolic acid nanofibers, modified Salix psammophila fibers, and toughened polylactic acid at 30° C. to obtain a blend;

[0059] (2) The toughened polylactic acid, the degradable polyester and the functional additive are melt-blended with the blend at a blending temperature of 190° C. to obtain a degradable medical stent material.

[0060] Example 4

[0061] A degradable medical stent material, comprising, by weight percentage, 15% polylactic acid-glycolic acid nanofiber, 12% modified Salix psammophila fiber, 25% toughened polylactic acid, 20% degradable polyester, and 5% functional additives;

[0062] The modified Salix psammophila fiber is prepared by modifying the Salix psammophila fiber with a maleic anhydride coupling agent;

[0063] Toughened polylactic acid will be impact modifier BPM520, 2% CaCO 3 , a processing aid and polylactic acid are uniformly mixed to obtain the product;

[0064] The degradable polyester is a polybutylene terephthalate-butylene adipate copolymer;

[0065] The functional auxiliary agent is dihydrolevorotatory glucosone.

[0066] A method for preparing a degradable medical stent material comprises the following steps:

[0067] (1) melt-blending polylactic acid-glycolic acid nanofibers, modified Salix psammophila fibers, and toughened polylactic acid at 40° C. to obtain a blend;

[0068] (2) The toughened polylactic acid, the degradable polyester and the functional additive are melt-blended with the blend at a blending temperature of 190° C. to obtain a degradable medical stent material.

[0069] Comparative Example 1

[0070] The preparation was carried out in the same manner as in Example 1, except that the polylactic acid-glycolic acid nanofibers were not added.

[0071] Comparative Example 2

[0072] The preparation was carried out in the same manner as in Example 1, except that no toughened polylactic acid was added.

[0073] Performance testing

[0074] The degradable medical stent materials prepared in Examples 1-4 and Comparative Examples 1-2 were subjected to toughness tests and impact tests.

[0075] The toughness test is carried out in accordance with the standard GB / T1040-2018 "Determination of tensile properties of plastics", and the elongation at break is used to indicate the quality of toughness.

[0076] The impact test was carried out in accordance with the standard GB / T 1043-2008 “Determination of impact properties of simply supported plastic beams” and was expressed using impact strength. The specific test results are shown in Table 1.

[0077] Table 1 Performance test results

[0078] Elongation at break / % <![CDATA[Impact strength / kJ / m 2 > Example 1 12.85 6.12 Example 2 12.52 5.95 Example 3 12.31 5.89 Example 4 12.64 6.08 Comparative Example 1 6.23 3.16 Comparative Example 2 5.35 3.21

[0079] Combining Examples 1-4 and Comparative Examples 1-2 and Table 1, it can be seen that Examples 1-4 of the present application use paclitaxel / polylactic acid-glycolic acid electrospun nanofibers and toughened polylactic acid in combination, and use modified Salix psammophila fibers; the resulting degradable medical stent material has high toughness and impact strength, and can be degraded, wherein the elongation at break of the composite material is above 12.31%, and the impact strength is 5.89 kJ / m 2 above.

[0080] The above is only an exemplary embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any changes or substitutions that can be easily thought of by a person skilled in the art within the technical scope disclosed by the present invention should be included in the protection scope of the present invention. Therefore, the protection scope of the present invention should be based on the protection scope of the claims.

Claims

1. A degradable medical stent material, characterized in that: According to the weight percentage, it includes 5-15% of polylactic acid-glycolic acid nanofiber, 8-12% of modified Salix psammophila fiber, 10-25% of toughened polylactic acid, 10-20% of degradable polyester, and 1-5% of functional additives; The polylactic acid-glycolic acid nanofibers are prepared by using an electrostatic spinning technique to stretch organic polymers into nanofibers, which are collected by a balloon to form a nanofiber membrane, and paclitaxel is then loaded onto the polylactic acid-glycolic acid copolymer nanofiber membrane by using an ultrasonic spraying technique.

2. The degradable medical stent material according to claim 1, characterized in that: Calculated by weight percentage, the invention comprises 10-15% of polylactic acid-hydroxyacetic acid nanofiber, 10-12% of modified salix tamarisk fiber, 18-25% of toughened polylactic acid, 15-20% of degradable polyester and 3-5% of functional additives.

3. The degradable medical stent material according to claim 1, characterized in that: The preparation method of the polylactic acid-glycolic acid nanofiber comprises the following steps: A1: Preparation of polylactic acid-glycolic acid cross-linked nanofiber balloons: dissolving polylactic acid-glycolic acid in a mixed solution of dichloromethane and NN dimethylformamide, stirring for 8-10 hours to obtain a polylactic acid-glycolic acid solution, applying electrospinning technology to the polylactic acid-glycolic acid solution to obtain nanofiber balloons, and vacuum drying the prepared nanofiber balloons; A2: Ultrasonic coating of paclitaxel: Weigh paclitaxel and iopromide, then measure anhydrous ethanol and distilled water, place them in an ultrasonic cleaning machine for oscillation and dissolution, the resulting solution is clear and transparent, and the paclitaxel drug is completely and evenly dissolved, and then loaded onto the polylactic acid-glycolic acid copolymer nanofiber membrane using ultrasonic spraying technology.

4. The degradable medical stent material according to claim 1, characterized in that: The modified Salix psammophila fiber is prepared by modifying the Salix psammophila fiber with silane coupling agent KH550, silane coupling agent KH570, titanate coupling agent 201 and maleic anhydride coupling agent.

5. The degradable medical stent material according to claim 1, characterized in that: The toughened polylactic acid is prepared by uniformly mixing an impact modifier BPM520, 2-4% of CaCO3, a processing aid and polylactic acid.

6. The degradable medical stent material according to claim 1, characterized in that: The degradable polyester is one or more of polybutylene terephthalate-butylene adipate copolymer, polycaprolactone, polybutylene succinate, polybutylene succinate-butylene adipate copolymer, and polyhydroxyalkanoate.

7. The degradable medical stent material according to claim 1, characterized in that: The functional auxiliary agent is one or more of dihydrolevorotatory glucosone, calcium chloride, silver chloride, mineral oil and vegetable oil.

8. The method for preparing the degradable medical stent material according to any one of claims 1 to 7, characterized in that: The following steps are involved: (1) melt-blending polylactic acid-glycolic acid nanofibers, modified Salix psammophila fibers, and toughened polylactic acid at 30-50° C. to obtain a blend; (2) The toughened polylactic acid, the degradable polyester and the functional additive are melt-blended with the blend to prepare a degradable medical stent material.

9. Use of the degradable medical stent material according to any one of claims 1 to 7 in the field of medical consumables.

10. A degradable medical stent, comprising the degradable medical stent material according to any one of claims 1 to 7.