Medical external fixation material and preparation method thereof

Abstract

The invention discloses a medical external fixation material and a preparation method thereof. The medical external fixation material is prepared from the following components: 40 to 60 parts of poly (3-hydroxybutyrate) / 4-hydroxybutyrate copolymer P3HB4HB, 10 to 30 parts of poly (butylene succinate) PBS, 5 to 20 parts of polyglycolic acid PGA, 5 to 10 parts of compatilizer and 0.5 to 10 parts of antibacterial agent, the medical external fixation material prepared by the preparation method provided by the invention not only has excellent mechanical properties, but also has good antibacterial properties, can be used on medical material instrument braces, and has good application prospects.

Description

Technical Field

[0001] The invention relates to the technical field of polymer materials, and in particular to a medical external fixation material and a preparation method thereof. Background Art

[0002] Thermoplastic board is a kind of plastic that becomes soft when heated, and can be divided into high-temperature thermoplastic board and low-temperature thermoplastic board. It has the advantages of shape memory function, strong plasticity, multiple thermoplasticity, easy operation, and biodegradability after disposal. It is suitable for making delicate and complex braces for upper limbs and hands.

[0003] At present, polycaprolactone (PCL) is widely used as a medical external fixation material in medical fields such as orthopedics, radiology, and rehabilitation. However, the mechanical properties of polycaprolactone are relatively weak and cannot withstand excessive tension and pressure, which may cause it to break or deform during some complex surgical repairs. In addition, medical antibacterial plates also need to have high antibacterial properties and be able to effectively inhibit the growth and reproduction of microorganisms such as bacteria and fungi.

[0004] Therefore, it is necessary to continue to develop new medical external fixation materials, which not only require better mechanical properties and the ability to withstand the pressure of complex operations, but also must have broad-spectrum antibacterial capabilities and be able to inhibit a variety of bacteria and fungi, thereby reducing the occurrence of infections in the environment or during use. Summary of the invention

[0005] The purpose of the present invention is to provide a medical external fixation material and a preparation method thereof, which not only has excellent antibacterial ability but also has good mechanical properties and meets the use requirements in the medical field.

[0006] To this end, the present invention adopts the following technical solutions:

[0007] The present invention provides a medical external fixation material, which comprises the following components by weight:

[0008] 40-60 parts of poly 3-hydroxybutyrate / 4-hydroxybutyrate copolymer P3HB4HB, 10-30 parts of polybutylene succinate PBS, 5-20 parts of polyglycolic acid PGA, 5-10 parts of compatibilizer and 0.5-10 parts of antibacterial agent.

[0009] Furthermore, the preparation method of the antibacterial agent is:

[0010] S1, MgCl 2 、AlCl 3 , caustic soda is dissolved in deionized water with a molar ratio of 3:1:(0.5-1.2) and then

[0011] Slowly add sodium hydroxide solution dropwise under nitrogen atmosphere, control the pH value to be stable at 10, the temperature to be 70-90°C, stir the reaction for 6-24h, centrifuge, wash, and dry to obtain product A;

[0012] S2, MgCl 2 、AlCl 3 , American saponin B in a molar ratio of 3:1:(0.5-1.2) dissolved in deionized water with no carbon dioxide

[0013] In a nitrogen atmosphere, slowly add sodium hydroxide solution dropwise, control the pH value to be stable at 10, the temperature to be 70-90° C., stir the reaction for 6-24 hours, centrifuge, wash, and dry to obtain product B;

[0014] S3, compounding product A and product B in a mass ratio of (1-3):(1-3), mixing them evenly, and obtaining the antibacterial agent.

[0015] Preferably, the compatibilizer is modified maleic anhydride.

[0016] Furthermore, the preparation method of the modified maleic anhydride comprises: dissolving maleic anhydride and ethyl acrylate in a solvent, and heating the mixture under the action of an initiator for a certain period of time to obtain the modified maleic anhydride.

[0017] Furthermore, the preparation method of the modified maleic anhydride comprises: 1) dissolving maleic anhydride and ethyl acrylate in a solvent, and heating the mixture under the action of an initiator for a certain time; 2) adding a borate coupling agent to the reaction product of step 1), stirring the mixture for a certain time, removing the solvent, and drying the mixture to obtain the modified maleic anhydride.

[0018] Preferably, the mass ratio of maleic anhydride to ethyl acrylate is (1-5):1.

[0019] Preferably, the initiator is potassium persulfate; and / or the solvent is alcohol or ether; and / or the reaction temperature is 60-80° C.; and / or the reaction time is 10-40 min.

[0020] Preferably, in step 2), the weight proportion of the borate coupling agent in the compatibilizer is 1-10%, and the stirring time is

[0021] 10-20min.

[0022] Preferably, the medical external fixation material further comprises a reinforcing material.

[0023] Preferably, the reinforcing material is carbon fiber or plant fiber.

[0024] Preferably, the medical external fixation material further comprises one or more of an antioxidant, a plasticizer, and a filler.

[0025] The present invention also provides a method for preparing a medical external fixation material, comprising the following steps:

[0026] (1) Weigh each component according to the ratio, dissolve P3HB4HB, PGA, and PBS in chloroform respectively, place in a 50-55°C water bath and stir to fully dissolve;

[0027] (2) P3HB4HB solution and PGA solution were mixed, stannous octoate catalyst was added, stirred for reaction for 0.5-2h, PBS was added and stirred for reaction for 0.5-2h, the solvent was removed, and dried to obtain P3HB4HB-PGA-PBS;

[0028] (3) P3HB4HB-PGA-PBS, a compatibilizer, an antibacterial agent and an optional reinforcing material are melt-blended in a melt-blending apparatus to obtain a product.

[0029] The invention also provides a medical external fixation material for use in a medical device brace.

[0030] Preferably, the medical device brace includes a neck collar, a shoulder abduction fixator, a shoulder fixation strap, an adjustable knee brace protector, an adjustable elbow brace protector, an adjustable ankle brace protector, a waist fixation strap, a forearm fixation strap, a brace, an abdominal belt, a fixed splint and other orthopedic orthotics.

[0031] Compared with the prior art, the present invention has the following beneficial effects:

[0032] The medical external fixation material provided by the present invention adopts P3HB4HB, PGA and PBS as matrix resins, and is matched with the antibacterial agent and the prepared compatibilizer prepared by the present invention, and has excellent strength, toughness and antibacterial performance.

[0033] The present invention adopts P3HB4HB, PGA and PBS in a scientific ratio to react and obtain P3HB4HB-PGA-PBS, which has better mechanical properties than single component resin.

[0034] The modified maleic anhydride provided by the present invention is used as a compatibilizer to further improve the tensile strength and elongation at break of the base resin and enhance the mechanical properties of the material.

[0035] The medical external fixation material provided by the present invention can be shaped according to needs to be made into different types of clamps, and has excellent antibacterial properties, reduces skin infections, and can be widely used in the medical field. DETAILED DESCRIPTION

[0036] Below by specific embodiment, the specific implementation mode of this explanation technical scheme is further described, these embodiments are for the detailed description of this technical scheme, rather than for limiting this technical scheme. Based on the embodiment in this description, all other embodiments obtained by those of ordinary skill in the art without making creative work premise belong to the scope of protection of this description. Unless otherwise specified, the reagent, method and equipment used in the present invention are conventional reagents, methods and equipment in the art, and the reagents and materials used in the following examples are all commercially available.

[0037] Poly 3-hydroxybutyrate-4-hydroxybutyrate (P3HB4HB) was purchased from Zhuhai Medfa Biotechnology Co., Ltd.;

[0038] Polyglycolic acid was purchased from Suzhou Huantong Technology Co., Ltd.;

[0039] Polybutylene succinate was purchased from Shanghai Oushuo Plastic Co., Ltd.;

[0040] Maleic anhydride was purchased from Wuxi Yiyuan New Material Technology Co., Ltd.;

[0041] Oleoresin, CAS No. 483-15-8, purchased from Jiangsu Chuangsheng Bioengineering Co., Ltd.;

[0042] Phytolaccae saponin B, CAS No. 60820-94-2, was purchased from Hubei Guangao Biotechnology Co., Ltd.

[0043] Example 1

[0044] A medical external fixation material comprises, by weight, 60 parts of poly 3-hydroxybutyrate / 4-hydroxybutyrate copolymer P3HB4HB, 15 parts of polybutylene succinate PBS, 10 parts of polyglycolic acid PGA, 10 parts of a compatibilizer and 5 parts of an antibacterial agent.

[0045] The preparation method of the modified maleic anhydride is as follows: 10 g of maleic anhydride and 5 g of ethyl acrylate are weighed and dissolved in 100 mL of ether, 0.1 g of initiator potassium persulfate is added, the temperature is raised to 65° C., and the reaction is carried out for 20 minutes.

[0046] The preparation method of the antibacterial agent comprises the following steps:

[0047] S1, MgCl 2 、AlCl 3 , caustic soda was dissolved in deionized water with a molar ratio of 3:1:0.9, and sodium hydroxide solution was slowly added dropwise under a nitrogen atmosphere, the pH was controlled to be stable at 10, the temperature was 80°C, the reaction was stirred for 20 hours, centrifuged, washed, and dried to obtain product A;

[0048] S2, MgCl 2、AlCl 3 1. Dissolve phytolaccaside B in deionized water with carbon dioxide removed in a molar ratio of 3:1:1, slowly add sodium hydroxide solution dropwise under a nitrogen atmosphere, control the pH value to be stable at 10, the temperature to be 80°C, stir and react for 20 hours, centrifuge, wash, and dry to obtain product B;

[0049] S3, compounding product A and product B in a mass ratio of 1:1, mixing them evenly, to obtain the antibacterial agent.

[0050] The preparation method of the above-mentioned medical external fixation material is:

[0051] (1) Weigh each component according to the ratio, dissolve P3HB4HB, PGA, and PBS in chloroform respectively, and stir in a 55°C water bath to fully dissolve;

[0052] (2) P3HB4HB solution and PGA solution were mixed, stannous octoate catalyst was added, stirred for reaction for 1 hour, PBS was added, stirring for reaction for another 1 hour, the solvent was removed, and dried to obtain P3HB4HB-PGA-PBS;

[0053] (3) P3HB4HB-PGA-PBS, a compatibilizer, and an antibacterial agent are melt-blended in a melt-blending apparatus to obtain the product.

[0054] Example 2

[0055] A medical external fixation material comprises, by weight, 50 parts of poly 3-hydroxybutyrate / 4-hydroxybutyrate copolymer P3HB4HB, 10 parts of polybutylene succinate PBS, 10 parts of polyglycolic acid PGA, 5 parts of a compatibilizer and 3 parts of an antibacterial agent.

[0056] The preparation method of the modified maleic anhydride is as follows: 10 g of maleic anhydride and 5 g of ethyl acrylate are weighed and dissolved in 100 mL of ether, 0.1 g of initiator potassium persulfate is added, the temperature is raised to 65° C., and the reaction is carried out for 20 minutes.

[0057] The preparation method of the antibacterial agent comprises the following steps:

[0058] S1, MgCl 2 、AlCl 3 , caustic soda was dissolved in deionized water with carbon dioxide removed in a molar ratio of 3:1:1, sodium hydroxide solution was slowly added dropwise under a nitrogen atmosphere, the pH was controlled to be stable at 10, the temperature was 80°C, the reaction was stirred for 18 hours, centrifuged, washed, and dried to obtain product A;

[0059] S2, MgCl 2 、AlCl 31. Dissolve phytolaccaside B in deionized water with carbon dioxide removed in a molar ratio of 3:1:1, slowly add sodium hydroxide solution dropwise under a nitrogen atmosphere, control the pH value to be stable at 10, the temperature to be 80°C, stir the reaction for 18 hours, centrifuge, wash, and dry to obtain product B;

[0060] S3, compounding product A and product B in a mass ratio of 1.5:1, mixing them evenly, and obtaining the antibacterial agent.

[0061] The preparation method of the above-mentioned medical external fixation material is:

[0062] (1) Weigh each component according to the ratio, dissolve P3HB4HB, PGA, and PBS in chloroform respectively, and stir in a 55°C water bath to fully dissolve;

[0063] (2) P3HB4HB solution and PGA solution were mixed, stannous octoate catalyst was added, stirred for reaction for 1 hour, PBS was added, stirring for reaction for another 1 hour, the solvent was removed, and dried to obtain P3HB4HB-PGA-PBS;

[0064] (3) P3HB4HB-PGA-PBS, a compatibilizer, and an antibacterial agent are melt-blended in a melt-blending apparatus to obtain the product.

[0065] Example 3

[0066] A medical external fixation material comprises, by weight, 60 parts of poly 3-hydroxybutyrate / 4-hydroxybutyrate copolymer P3HB4HB, 10 parts of polybutylene succinate PBS, 20 parts of polyglycolic acid PGA, 10 parts of a compatibilizer and 6 parts of an antibacterial agent.

[0067] The preparation method of the modified maleic anhydride is as follows: (1) weighing 10 g of maleic anhydride and 5 g of ethyl acrylate, dissolving them in 100 mL of ether, adding 0.1 g of initiator potassium persulfate, heating to 65° C., and reacting for 20 min; (2) adding 0.5 g of borate coupling agent to step (1), mixing well, and stirring for 15 min.

[0068] The preparation method of the antibacterial agent comprises the following steps:

[0069] S1, MgCl 2 、AlCl 3 , caustic soda was dissolved in deionized water with a molar ratio of 3:1:1.05, and sodium hydroxide solution was slowly added dropwise under a nitrogen atmosphere, the pH was controlled to be stable at 10, the temperature was 85°C, the reaction was stirred for 24 hours, centrifuged, washed, and dried to obtain product A;

[0070] S2, MgCl 2 、AlCl 3, phytolaccarin B was dissolved in deionized water with carbon dioxide removed in a molar ratio of 3:1:1.05, and sodium hydroxide solution was slowly added dropwise under a nitrogen atmosphere, the pH was controlled to be stable at 10, the temperature was 85°C, the reaction was stirred for 24 hours, centrifuged, washed, and dried to obtain product B;

[0071] S3, compounding product A and product B in a mass ratio of 1:1.5, mixing them evenly, and obtaining the antibacterial agent.

[0072] The preparation method of the above-mentioned medical external fixation material is:

[0073] (1) Weigh each component according to the ratio, dissolve P3HB4HB, PGA, and PBS in chloroform respectively, and stir in a 50°C water bath to fully dissolve;

[0074] (2) P3HB4HB solution and PGA solution were mixed, stannous octoate catalyst was added, stirred for reaction for 1 hour, PBS was added, stirring for reaction for another 1 hour, the solvent was removed, and dried to obtain P3HB4HB-PGA-PBS;

[0075] (3) P3HB4HB-PGA-PBS, a compatibilizer, and an antibacterial agent are melt-blended in a melt-blending apparatus to obtain the product.

[0076] Comparative Example 1

[0077] Compared with Example 1, the difference is that no antibacterial agent is added, and the other aspects are the same.

[0078] The preparation method is the same as Example 1.

[0079] Comparative Example 2

[0080] Compared with Example 1, the difference is that the antibacterial agent is replaced by an equal weight portion of lysine, and the other parts are the same.

[0081] The preparation method is the same as Example 1.

[0082] Comparative Example 3

[0083] Compared with Example 1, the difference is that the antibacterial agent is replaced by an equal weight portion of pokeweed saponin B, and the other parts are the same.

[0084] The preparation method is the same as Example 1.

[0085] Comparative Example 4

[0086] Compared with Example 1, the difference is that the antibacterial agent is replaced by equal parts by weight of schizonepeta and schizonepeta saponin B, the mass ratio of schizonepeta and schizonepeta saponin B is, and the other parts are the same.

[0087] The preparation method is the same as Example 1.

[0088] Comparative Example 5

[0089] Compared with Example 1, the difference is that the antibacterial agent is replaced by nanosilver in an equal weight portion, and the other parts are the same.

[0090] The preparation method is the same as Example 1.

[0091] Comparative Example 6

[0092] Compared with Example 1, the difference is that no compatibilizer is included, and the other aspects are the same.

[0093] The preparation method is the same as Example 1.

[0094] Comparative Example 7

[0095] Compared with Example 1, the difference is that the compatibilizer is replaced by maleic anhydride in equal parts by weight, and the other parts are the same.

[0096] The preparation method is the same as Example 1.

[0097] Comparative Example 8

[0098] Compared with Example 1, the difference is that the preparation method of the medical external fixation material is different, and the other aspects are the same.

[0099] The preparation method of the medical external fixation material of this comparative example is: P3HB4HB, PGA, PBS, a compatibilizer and an antibacterial agent are mixed, and melt-blended in a melt-blending instrument to obtain the material.

[0100] Comparative Example 9

[0101] Compared with Example 1, the difference is that polybutylene succinate is not included, and the other parts are the same.

[0102] The preparation method is the same as Example 1.

[0103] Comparative Example 10

[0104] Compared with Example 1, the difference is that polyglycolic acid is not included, and the other aspects are the same.

[0105] The preparation method is the same as Example 1.

[0106] Comparative Example 11

[0107] Compared with Example 1, the difference is that polybutylene succinate and polyglycolic acid are not included, and the other parts are the same.

[0108] The preparation method is the same as Example 1.

[0109] Performance Testing:

[0110] 1. Antibacterial performance test

[0111] Test method: Refer to GB / T 31402-2015 standard test. Test the antibacterial rate against Escherichia coli, Staphylococcus aureus and Streptococcus.

[0112] Table 1 Antibacterial rate test results

[0113]

[0114] As can be seen from Table 1, the external fixation materials prepared in Examples 1-3 of the present invention have excellent antibacterial properties, and have good antibacterial rates against Escherichia coli, Staphylococcus aureus, and Streptococcus, with the highest rate reaching 99.99%. Comparative Examples 1-5 use different antibacterial materials, and their antibacterial properties are not as good as the antibacterial agent prepared in the present invention.

[0115] 2. Mechanical properties

[0116] Test method: The materials of the embodiment and comparative example were used to prepare a film with a thickness of 60 μm, the processing temperature of which was 190-210°C, and the film was cut into 10×5 mm strips. The film was stretched at a rate of 800 mm / min and then oriented by 4 times and 6 times respectively to obtain the stretched strip samples of the embodiment and comparative example. The tensile strength and elongation at break of the strip samples were measured in accordance with the provisions of GB / T 1043.1-2008.

[0117] The test results are shown in Table 2.

[0118] Table 2 Performance test results

[0119] Tensile strength(MPa) Elongation at break (%) Example 1 39.63 838.65 Example 2 38.49 772.48 Example 3 42.27 963.72 Comparative Example 1 37.43 847.46 Comparative Example 2 39.69 840.28 Comparative Example 3 39.82 844.35 Comparative Example 6 28.84 508.76 Comparative Example 7 30.57 865.31 Comparative Example 8 34.86 667.72 Comparative Example 9 31.74 692.63 Comparative Example 10 27.95 575.47 Comparative Example 11 23.39 304.15

[0120] It can be seen from Table 2 that the sample strips of the external fixation material prepared in Examples 1-3 have better tensile strength and elongation at break.

[0121] Compared with Example 1, in Comparative Example 1, the antibacterial agent prepared by the present invention is not added, and the tensile strength decreases slightly, but the elongation at break is better.

[0122] Compared with Example 1, in Comparative Examples 2 and 3, the antibacterial agent was replaced with an equal weight portion of phytolaccarubi or an equal weight portion of phytolaccarubi saponin B, and the tensile strength and elongation at break were slightly increased.

[0123] Compared with Example 1, in Comparative Example 6, the compatibilizer prepared by the present invention was not added, and the tensile strength and elongation at break were significantly reduced.

[0124] Compared with Example 1, in Comparative Example 7, the compatibilizer is replaced with maleic anhydride in equal parts by weight, and both the tensile strength and the elongation at break decrease, but are higher than those of Comparative Example 6.

[0125] Compared with Example 1, Comparative Example 8 has a different preparation method, and both the tensile strength and the elongation at break are lower.

[0126] Compared with Example 1, in Comparative Example 9, no polybutylene succinate was added, and both the tensile strength and the elongation at break decreased.

[0127] Compared with Example 1, in Comparative Example 10, no polyglycolic acid was added, and both the tensile strength and the elongation at break decreased.

[0128] Compared with Example 1, in Comparative Example 11, both polybutylene succinate and polyglycolic acid were not added, and the tensile strength and elongation at break were significantly reduced, and the reduction was greater than that of Comparative Examples 9 and 10.

[0129] The invention shows that the antibacterial agent prepared by the invention can enhance the tensile strength, the compatibilizer prepared by the invention can enhance the tensile strength and elongation at break, and the invention prepares P3HB4HB, PGA and PBS by compounding P3HB4HB-PGA-PBS, which can enhance the tensile strength and elongation at break of the material. The invention adopts P3HB4HB, PGA and PBS to coordinate with the prepared antibacterial agent and compatibilizer to jointly enhance the mechanical properties of the material and improve the strength and toughness of the material.

[0130] Although the embodiments of the present description have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present description, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A medical external fixation material, characterized in that: By weight, it includes the following components: 40-60 parts of poly 3-hydroxybutyrate / 4-hydroxybutyrate copolymer P3HB4HB, 10-30 parts of polybutylene succinate PBS, 5-20 parts of polyglycolic acid PGA, 5-10 parts of compatibilizer and 0.5-10 parts of antibacterial agent.

2. The medical external fixation material according to claim 1, characterized in that: The preparation method of the antibacterial agent is: S1, dissolve MgCl2, AlCl3, and caustic soda in a molar ratio of 3:1:(0.5-1.2) in deionized water free of carbon dioxide, slowly add sodium hydroxide solution dropwise under a nitrogen atmosphere, control the pH to be stable at 10, the temperature to be 70-90°C, stir the reaction for 6-24h, centrifuge, wash, and dry to obtain product A; S2, dissolving MgCl2, AlCl3, and phytolaccaside B in a molar ratio of 3:1:(0.5-1.2) in deionized water free of carbon dioxide, slowly adding sodium hydroxide solution dropwise under a nitrogen atmosphere, controlling the pH to be stable at 10, the temperature to be 70-90° C., stirring the reaction for 6-24 hours, centrifuging, washing, and drying to obtain product B; S3, compounding product A and product B in a mass ratio of (1-3):(1-3), mixing them evenly, and obtaining the antibacterial agent.

3. The medical external fixation material according to claim 1, characterized in that: The compatibilizer is modified maleic anhydride.

4. The medical external fixation material according to claim 3, characterized in that: The preparation method of the modified maleic anhydride comprises: dissolving maleic anhydride and ethyl acrylate in a solvent, and heating the mixture under the action of an initiator for a certain period of time to obtain the modified maleic anhydride.

5. The medical external fixation material according to claim 3, characterized in that: The preparation method of the modified maleic anhydride comprises: 1) dissolving maleic anhydride and ethyl acrylate in a solvent, and heating the mixture under the action of an initiator for a certain time; 2) adding a borate coupling agent to the reaction product of step 1), stirring the mixture for a certain time, removing the solvent, and drying the mixture to obtain the modified maleic anhydride.

6. The medical external fixation material according to claim 4 or 5, characterized in that: The mass ratio of maleic anhydride to ethyl acrylate is (1-5):

1.

7. The medical external fixation material according to claim 4 or 5, characterized in that: The initiator is potassium persulfate; and / or the solvent is alcohol or ether; and / or the reaction temperature is 60-80° C.; and / or the reaction time is 10-40 min.

8. The medical external fixation material according to claim 5, characterized in that: In the step 2), the weight proportion of the borate coupling agent in the compatibilizer is 1-10%, and the stirring time is 10-20 minutes.

9. A method for preparing the medical external fixation material according to any one of claims 1 to 8, characterized in that: The following steps are involved: (1) Weigh each component according to the ratio, dissolve P3HB4HB, PGA, and PBS in chloroform respectively, place in a 50-55℃ water bath and stir to fully dissolve; (2) P3HB4HB solution and PGA solution were mixed, stannous octoate catalyst was added, stirred for reaction for 0.5-2h, PBS was added, stirring was continued for reaction for 0.5-2h, the solvent was removed, and dried to obtain P3HB4HB-PGA-PBS; (3) P3HB4HB-PGA-PBS, a compatibilizer, an antibacterial agent and an optional reinforcing material are melt-blended in a melt-blending apparatus to obtain a product.

10. Use of the medical external fixation material according to any one of claims 1 to 8 or the medical external fixation material prepared by the preparation method according to claim 9 in medical device braces.

Images