Preparation method of hydroxyapatite / curcumin antibacterial composite material with ultrasonic response

Abstract

The invention discloses a preparation method of a hydroxyapatite / curcumin antibacterial composite material with ultrasonic response, and relates to the technical field of biomedical composite materials. In order to solve the problems of postoperative infection risk and antibiotic resistance of materials, the invention provides a preparation method of a composite material with biocompatibility and ultrasonic response antibacterial property. The preparation method comprises the following steps: dissolving calcium nitrate tetrahydrate and curcumin in deionized water to obtain a mixed solution A; dissolving diammonium hydrogen phosphate in deionized water to obtain a mixed solution B; slowly dropwise adding B into A, enabling the molar ratio of calcium to phosphorus to be 1.67, adjusting the pH value to be 8-10 by using ammonia water, stirring to obtain a reaction precursor, and carrying out hydrothermal reaction at 110-140 DEG C for 10-24 hours; centrifugally washing with deionized water to be neutral, and freeze-drying to obtain the material. The preparation method is simple, conditions are mild, no harmful gas is generated, and the obtained material can effectively generate active oxygen under ultrasonic stimulation, has an excellent antibacterial effect on escherichia coli and staphylococcus aureus and is suitable for the biomedical fields of bone repair, implant material coatings and the like.

Description

Technical Field

[0001] This invention relates to the field of biomedical composite materials technology, specifically a method for preparing an ultrasonically responsive hydroxyapatite / curcumin antibacterial composite material. Background Technology

[0002] Biomedical materials are functional materials used for the diagnosis, treatment, repair, or replacement of human tissues or organs, and are widely used in orthopedics, dentistry, drug delivery, and other fields. Among them, hydroxyapatite has become a research hotspot due to its excellent biocompatibility, osteoconductivity, and chemical stability. Nano-hydroxyapatite powder has a higher specific surface area and bioactivity, and can promote cell adhesion and bone tissue regeneration, thus showing broad application prospects in bone repair and implant materials.

[0003] However, implanted materials often face the risk of postoperative infection during clinical application. Traditional antibacterial strategies mainly rely on antibiotics, but the overuse of antibiotics can easily lead to the emergence of drug-resistant bacteria, and it is difficult to maintain local drug concentrations. In recent years, antibacterial strategies based on reactive oxygen species have received widespread attention due to their broad-spectrum bactericidal effect and low likelihood of inducing drug resistance. Ultrasound, as a non-invasive and highly penetrating external stimulation method, can stimulate certain materials to generate reactive oxygen species, thereby achieving non-invasive antibacterial therapy.

[0004] Curcumin is a natural polyphenol compound with good biocompatibility, anti-inflammatory, antioxidant, and antibacterial activities. Under ultrasound, curcumin can be activated to produce reactive oxygen species such as singlet oxygen, exhibiting excellent ultrasonic-responsive antibacterial properties. Therefore, combining curcumin with hydroxyapatite to prepare a composite material with both good bioactivity and ultrasonic-responsive antibacterial properties has significant research value and application prospects. Summary of the Invention

[0005] The purpose of this invention is to provide a method for preparing an ultrasonically responsive hydroxyapatite / curcumin antibacterial composite material. The prepared material has good biocompatibility and ultrasonically responsive antibacterial properties, and can generate reactive oxygen species under ultrasonic stimulation to effectively inhibit bacterial growth.

[0006] The technical solution of this invention is: a method for preparing an ultrasonically responsive hydroxyapatite / curcumin antibacterial composite material, characterized by comprising the following steps: Dissolve 5.8-6.0 g of calcium nitrate tetrahydrate in 25-30 mL of deionized water, add 0.1-1.0 g of curcumin, and stir for 30-50 minutes to obtain mixture A; dissolve 1.9-2.0 g of diammonium hydrogen phosphate in 25-30 mL of deionized water, and stir for 30-50 minutes to obtain mixture B; slowly add mixture B dropwise to mixture A to make the calcium-to-phosphorus molar ratio 1.67, adjust the pH to 8-10 with 10-30% ammonia water, and continue stirring for 30-60 minutes to obtain the reaction precursor; transfer the reaction precursor solution to a polytetrafluoroethylene-lined reactor, and hydrothermally react at 110-140 °C for 10-14 hours, then remove after natural cooling; centrifuge the reaction product, wash it three times with deionized water until neutral, and freeze-dry it at -50-60 °C for 20-30 hours to obtain the ultrasonically responsive hydroxyapatite / curcumin composite material.

[0007] The calcium-to-phosphorus molar ratio in the above steps is 1.67.

[0008] The amount of curcumin added in the above steps is 0.1-1.0 g.

[0009] The pH value is adjusted using ammonia water at a volume ratio of 10-30% in the aforementioned steps.

[0010] The hydrothermal reaction temperature in the above steps is 110-140 ℃, and the reaction time is 10-14 hours.

[0011] The freeze-drying temperature in the above steps is -55 to 60 ℃, and the drying time is 20 to 30 hours.

[0012] A method for preparing an ultrasonically responsive hydroxyapatite / curcumin antibacterial composite material is characterized by the following steps: dissolving 5.9 g of calcium nitrate tetrahydrate in 25 mL of deionized water, adding 0.736 g of curcumin, and stirring for 30 minutes to obtain mixture A; dissolving 1.98 g of diammonium hydrogen phosphate in 25 mL of deionized water, and stirring for 30 minutes to obtain mixture B; slowly adding mixture B dropwise to mixture A to make the calcium-to-phosphorus molar ratio 1.67, adjusting the pH to 8.7 with 25% ammonia water, and continuing to stir for 1 hour to obtain the reaction precursor; transferring the reaction precursor solution to a polytetrafluoroethylene-lined reactor, hydrothermally reacting at 130°C for 12 hours, and removing it after natural cooling; centrifuging the reaction product, washing it three times with deionized water until neutral, and freeze-drying it at -55°C for 24 hours to obtain the ultrasonically responsive hydroxyapatite / curcumin antibacterial composite material.

[0013] The technical effects of this invention are as follows: (1) The present invention uses a hydrothermal method to synthesize hydroxyapatite / curcumin composite material in one step. The process is simple, the conditions are mild, and no harmful gases are generated, making it suitable for large-scale production. (2) Curcumin is uniformly distributed in the prepared composite material, which has good ultrasonic response performance and can effectively generate reactive oxygen species under ultrasonic stimulation, thus exhibiting excellent antibacterial effect. (3) Composite materials have good biocompatibility and are suitable for biomedical fields such as bone repair and implant material coating. Attached Figure Description

[0014] Figure 1 Transmission electron microscopy image of hydroxyapatite / curcumin composite material (Example 4).

[0015] Figure 2 Acoustoelectric current diagrams of hydroxyapatite / curcumin composites with different curcumin contents.

[0016] Figure 3 Plate images showing the antibacterial properties of hydroxyapatite / curcumin composites with different curcumin contents against Escherichia coli and Staphylococcus aureus. Detailed Implementation

[0017] To better understand the present invention, the present invention will be further described in detail below with reference to the accompanying drawings and embodiments, but the scope of protection of the present invention is not limited to the scope shown in the embodiments. Example

[0018] A method for preparing an ultrasonically responsive hydroxyapatite / curcumin antibacterial composite material, characterized by comprising the following steps: 5.9 g of calcium nitrate tetrahydrate was dissolved in 25 mL of deionized water, and 0.184 g of curcumin was added. The mixture was stirred for 30 minutes to obtain mixture A. 1.98 g of diammonium hydrogen phosphate was dissolved in 25 mL of deionized water and stirred for 30 minutes to obtain mixture B. Mixture B was slowly added dropwise to mixture A to make the calcium-to-phosphorus molar ratio 1.67. The pH was adjusted to 8.7 with 25% ammonia water, and the mixture was stirred for 1 hour to obtain the reaction precursor. The reaction precursor solution was transferred to a polytetrafluoroethylene-lined reactor and hydrothermally reacted at 130 °C for 12 hours. After natural cooling, the product was removed. The reaction product was centrifuged, washed three times with deionized water until neutral, and freeze-dried at -55 °C for 24 hours to obtain the ultrasonically responsive hydroxyapatite / curcumin antibacterial composite material.

[0019] Test results: The prepared hydroxyapatite / curcumin composite material was uniformly loaded and showed a weak response under ultrasonic radiation, generating an acoustic current. Example

[0020] A method for preparing an ultrasonically responsive hydroxyapatite / curcumin antibacterial composite material, characterized by comprising the following steps: 5.9 g of calcium nitrate tetrahydrate was dissolved in 25 mL of deionized water, and 0.368 g of curcumin was added. The mixture was stirred for 30 minutes to obtain mixture A. 1.98 g of diammonium hydrogen phosphate was dissolved in 25 mL of deionized water and stirred for 30 minutes to obtain mixture B. Mixture B was slowly added dropwise to mixture A to make the calcium-to-phosphorus molar ratio 1.67. The pH was adjusted to 8.7 with 25% ammonia water, and the mixture was stirred for 1 hour to obtain the reaction precursor. The reaction precursor solution was transferred to a polytetrafluoroethylene-lined reactor and hydrothermally reacted at 130 °C for 12 hours. After natural cooling, the product was removed. The reaction product was centrifuged, washed three times with deionized water until neutral, and freeze-dried at -55 °C for 24 hours to obtain the ultrasonically responsive hydroxyapatite / curcumin antibacterial composite material.

[0021] Test results: The prepared hydroxyapatite / curcumin composite material was uniformly loaded and showed a weak response under ultrasonic radiation, generating an acoustic current. Example

[0022] A method for preparing an ultrasonically responsive hydroxyapatite / curcumin antibacterial composite material, characterized by comprising the following steps: 5.9 g of calcium nitrate tetrahydrate was dissolved in 25 mL of deionized water, and 0.553 g of curcumin was added. The mixture was stirred for 30 minutes to obtain mixture A. 1.98 g of diammonium hydrogen phosphate was dissolved in 25 mL of deionized water and stirred for 30 minutes to obtain mixture B. Mixture B was slowly added dropwise to mixture A to make the calcium-to-phosphorus molar ratio 1.67. The pH was adjusted to 8.7 with 25% ammonia water, and the mixture was stirred for 1 hour to obtain the reaction precursor. The reaction precursor solution was transferred to a polytetrafluoroethylene-lined reactor and hydrothermally reacted at 130℃ for 12 hours. After natural cooling, the product was removed. The reaction product was centrifuged, washed three times with deionized water until neutral, and freeze-dried at -55℃ for 24 hours to obtain the ultrasonically responsive hydroxyapatite / curcumin antibacterial composite material.

[0023] Test results: The prepared hydroxyapatite / curcumin composite material was uniformly loaded and showed a weak response and acoustic current generation under ultrasonic radiation. It had an inhibitory effect on Staphylococcus aureus and exhibited significant antibacterial effect under ultrasound. Example

[0024] A method for preparing an ultrasonically responsive hydroxyapatite / curcumin antibacterial composite material, characterized by comprising the following steps: 5.9 g of calcium nitrate tetrahydrate was dissolved in 25 mL of deionized water, and 0.736 g of curcumin was added. The mixture was stirred for 30 minutes to obtain mixture A. 1.98 g of diammonium hydrogen phosphate was dissolved in 25 mL of deionized water and stirred for 30 minutes to obtain mixture B. Mixture B was slowly added dropwise to mixture A to make the calcium-to-phosphorus molar ratio 1.67. The pH was adjusted to 8.7 with 25% ammonia water, and the mixture was stirred for 1 hour to obtain the reaction precursor. The reaction precursor solution was transferred to a polytetrafluoroethylene-lined reactor and hydrothermally reacted at 130 °C for 12 hours. After natural cooling, the product was removed. The reaction product was centrifuged, washed three times with deionized water until neutral, and freeze-dried at -55 °C for 24 hours to obtain the ultrasonically responsive hydroxyapatite / curcumin antibacterial composite material.

[0025] Test results: The prepared hydroxyapatite / curcumin composite material was uniformly loaded and showed a weak response and acoustic current generation under ultrasonic radiation. It had an inhibitory effect on Staphylococcus aureus and exhibited significant antibacterial effect under ultrasound. Example

[0026] A method for preparing an ultrasonically responsive hydroxyapatite / curcumin antibacterial composite material, characterized by comprising the following steps: 5.9 g of calcium nitrate tetrahydrate was dissolved in 25 mL of deionized water, and 0.921 g of curcumin was added. The mixture was stirred for 30 minutes to obtain mixture A. 1.98 g of diammonium hydrogen phosphate was dissolved in 25 mL of deionized water and stirred for 30 minutes to obtain mixture B. Mixture B was slowly added dropwise to mixture A to make the calcium-to-phosphorus molar ratio 1.67. The pH was adjusted to 8.7 with 25% ammonia water, and the mixture was stirred for 1 hour to obtain the reaction precursor. The reaction precursor solution was transferred to a polytetrafluoroethylene-lined reactor and hydrothermally reacted at 130 °C for 12 hours. After natural cooling, the product was removed. The reaction product was centrifuged, washed three times with deionized water until neutral, and freeze-dried at -55 °C for 24 hours to obtain the ultrasonically responsive hydroxyapatite / curcumin antibacterial composite material.

[0027] Test results: The prepared hydroxyapatite / curcumin composite material was uniformly loaded and showed a weak response under ultrasonic radiation, generating an acoustic current.

[0028] It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, it should be understood that after reading the teachings of this invention, those skilled in the art can make various alterations or modifications to the invention, and these equivalent forms also fall within the scope defined by the appended claims.

Claims

1. The technical solution of the present invention is: a method for preparing a hydroxyapatite / curcumin antibacterial composite material with ultrasonic response, characterized in that... Includes the following steps: Dissolve 5.8-6.0 g of calcium nitrate tetrahydrate in 25-30 mL of deionized water, add 0.1-1.0 g of curcumin, and stir for 30-50 minutes to obtain mixture A; dissolve 1.9-2.0 g of diammonium hydrogen phosphate in 25-30 mL of deionized water, and stir for 30-50 minutes to obtain mixture B; slowly add mixture B dropwise to mixture A to make the calcium-to-phosphorus molar ratio 1.67, adjust the pH to 8-10 with 10-30% ammonia water, and continue stirring for 30-60 minutes to obtain the reaction precursor; transfer the reaction precursor solution to a polytetrafluoroethylene-lined reactor, and hydrothermally react at 110-140 °C for 10-14 hours, then remove after natural cooling; centrifuge the reaction product, wash it three times with deionized water until neutral, and freeze-dry it at -50-60 °C for 20-30 hours to obtain the ultrasonically responsive hydroxyapatite / curcumin composite material.

2. The method for preparing an ultrasonically responsive hydroxyapatite / curcumin antibacterial composite material according to claim 1, characterized in that: The amount of curcumin used in the above steps is 0.7-1.0g.

3. The method for preparing an ultrasonically responsive hydroxyapatite / curcumin antibacterial composite material according to claim 1, characterized in that: In the above steps, ammonia solution with a mass-to-volume ratio of 10%-30% is used to adjust the pH value, maintaining the solution pH at 8-10. After adjustment, stirring is continued for 30-60 minutes.

4. The method for preparing an ultrasonically responsive hydroxyapatite / curcumin antibacterial composite material according to claim 1, characterized in that: The hydrothermal reaction temperature in the above steps is 110-140℃, and the reaction time is 10-14 hours.

5. The method for preparing an ultrasonically responsive hydroxyapatite / curcumin antibacterial composite material according to claim 1, characterized in that: In step five, the freeze-drying temperature is -50 to 60°C, and the drying time is 20 to 30 hours.

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