Preparation method of a ph-temperature synergistically responsive drug-releasing bone cement

Abstract

The invention discloses a preparation method of pH-temperature synergistically responsive drug-releasing bone cement. Firstly, single-walled carbon nanotubes are truncated and purified to form carboxyl groups on the surface, and drug-loaded carbon nanotubes are prepared by impregnation. phase powder; then through the temperature-sensitive properties of poly(N-isopropylacrylamide), hydrogel microspheres are prepared, and the drug-loaded hydrogel microsphere solid phase powder is prepared through the connection of amide bonds, and finally the two are mixed to form a double For the stimuli-responsive hydrogel (pH-temperature) hydrogel microspheres, mix the pH-temperature synergistically responsive microspheres, calcium phosphate bone cement powder with the liquid phase, stir and solidify. The bone cement can release the drug slowly and autonomously in the inflammatory lesion area of ​​the bone defect. The amount of drug release is controlled by the acidity of the microenvironment and the temperature rise. When the pH and temperature of the local area return to normal, the release of the drug stops.

Description

technical field

[0001] The invention belongs to the technical field of medical biomaterials, and relates to a preparation method of a pH-temperature synergistic drug-releasing bone cement. Background technique

[0002] Calcium Phosphate Cement (CPC) is a typical representative of bio-organic polymer bone cement materials, because it undergoes hydration reaction under the conditions of temperature (37°C) and humidity (100%) to obtain a density similar to that of human bone tissue. The cured product - hydroxyapatite or permeabilite, has certain degradability and good biocompatibility, and is widely used in the revision of bone cemented or non-cemented prosthesis after joint replacement , to fill and repair part of the bone defect. Postoperative infection is one of the difficult problems in orthopedic surgery. In order to solve postoperative infection, adding antibiotics to bone cement is a common method in clinical medicine, that is, to control the infection focus through loc...

Examples

Embodiment 1

[0053] The preparation method of a pH-temperature synergistic response drug-releasing bone cement of the present invention is specifically implemented according to the following steps:

[0054] Step 1, preparing drug-loaded carbon nanotubes;

[0055] Step 1.1, weigh 0.5g single-walled carbon nanotubes and 10ml acid solution H 2 SO 4 / HNO 3 (Mixed acid of 98% concentrated sulfuric acid and 68% concentrated nitric acid, the volume ratio is 3:1) mixed to activate the carboxyl group, ultrasonicated at room temperature for 2 hours, diluted with deionized water, filtered with suction, washed with deionized water until neutral , dried under vacuum at room temperature for 16 hours to obtain carboxylated single-walled carbon nanotubes (SWCNT-COOH);

[0056] Step 1.2, weigh 0.5g of carboxylated single-walled carbon nanotubes (SWCNT-COOH) and 0.2g of vancomycin hydrochloride dissolved in 10ml of deionized water, mix the two, stir at room temperature for 2 hours, and vacuum dry for 16 ...

Embodiment 2

[0064] The preparation method of a pH-temperature synergistic response drug-releasing bone cement of the present invention is specifically implemented according to the following steps:

[0065] Step 1, preparing drug-loaded carbon nanotubes;

[0066] Step 1.1, weigh 1g of single-walled carbon nanotubes and 15ml of acid solution H 2 SO 4 / HNO 3 (The mixed acid of 98% concentrated sulfuric acid and 68% concentrated nitric acid has a volume ratio of 3:1) and mix them to activate the carboxyl groups. Ultrasound at room temperature for 3 hours, dilute with deionized water, filter with suction, wash with deionized water until neutral, Vacuum drying at room temperature for 18 hours to obtain carboxylated single-walled carbon nanotubes (SWCNT-COOH);

[0067] Step 1.2, weigh 1g of carboxylated single-walled carbon nanotubes (SWCNT-COOH) and 0.4g of vancomycin hydrochloride dissolved in 15ml of deionized water, mix the two at room temperature and stir for 4 hours, then vacuum dry for...

Embodiment 3

[0075] The preparation method of a pH-temperature synergistic response drug-releasing bone cement of the present invention is specifically implemented according to the following steps:

[0076] Step 1, preparing drug-loaded carbon nanotubes;

[0077] Step 1.1, weigh 1.5g single-walled carbon nanotubes and 20ml acid solution H 2 SO 4 / HNO 3 (The mixed acid of 98% concentrated sulfuric acid and 68% concentrated nitric acid has a volume ratio of 3:1) mixed to activate the carboxyl groups, ultrasonicated at room temperature for 4 hours, diluted with deionized water, filtered with suction, washed with deionized water until neutral, Vacuum drying at room temperature for 20 hours to obtain carboxylated single-walled carbon nanotubes (SWCNT-COOH);

[0078] Step 1.2, weigh 1.5g of carboxylated single-walled carbon nanotubes (SWCNT-COOH) and 0.6g of vancomycin hydrochloride dissolved in 20ml of deionized water, mix the two at room temperature and stir for 4 hours, then vacuum dry for...

technical field

[0001] The invention belongs to the technical field of medical biomaterials, and relates to a preparation method of a pH-temperature synergistic drug-releasing bone cement. Background technique

[0002] Calcium Phosphate Cement (CPC) is a typical representative of bio-organic polymer bone cement materials, because it undergoes hydration reaction under the conditions of temperature (37°C) and humidity (100%) to obtain a density similar to that of human bone tissue. The cured product - hydroxyapatite or permeabilite, has certain degradability and good biocompatibility, and is widely used in the revision of bone cemented or non-cemented prosthesis after joint replacement , to fill and repair part of the bone defect. Postoperative infection is one of the difficult problems in orthopedic surgery. In order to solve postoperative infection, adding antibiotics to bone cement is a common method in clinical medicine, that is, to control the infection focus through loc...

Examples

Embodiment 1

[0053] The preparation method of a pH-temperature synergistic response drug-releasing bone cement of the present invention is specifically implemented according to the following steps:

[0054] Step 1, preparing drug-loaded carbon nanotubes;

[0055] Step 1.1, weigh 0.5g single-walled carbon nanotubes and 10ml acid solution H 2 SO 4 / HNO 3 (Mixed acid of 98% concentrated sulfuric acid and 68% concentrated nitric acid, the volume ratio is 3:1) mixed to activate the carboxyl group, ultrasonicated at room temperature for 2 hours, diluted with deionized water, filtered with suction, washed with deionized water until neutral , dried under vacuum at room temperature for 16 hours to obtain carboxylated single-walled carbon nanotubes (SWCNT-COOH);

[0056] Step 1.2, weigh 0.5g of carboxylated single-walled carbon nanotubes (SWCNT-COOH) and 0.2g of vancomycin hydrochloride dissolved in 10ml of deionized water, mix the two, stir at room temperature for 2 hours, and vacuum dry for 16 ...

Embodiment 2

[0064] The preparation method of a pH-temperature synergistic response drug-releasing bone cement of the present invention is specifically implemented according to the following steps:

[0065] Step 1, preparing drug-loaded carbon nanotubes;

[0066] Step 1.1, weigh 1g of single-walled carbon nanotubes and 15ml of acid solution H 2 SO 4 / HNO 3 (The mixed acid of 98% concentrated sulfuric acid and 68% concentrated nitric acid has a volume ratio of 3:1) and mix them to activate the carboxyl groups. Ultrasound at room temperature for 3 hours, dilute with deionized water, filter with suction, wash with deionized water until neutral, Vacuum drying at room temperature for 18 hours to obtain carboxylated single-walled carbon nanotubes (SWCNT-COOH);

[0067] Step 1.2, weigh 1g of carboxylated single-walled carbon nanotubes (SWCNT-COOH) and 0.4g of vancomycin hydrochloride dissolved in 15ml of deionized water, mix the two at room temperature and stir for 4 hours, then vacuum dry for...

Embodiment 3

[0075] The preparation method of a pH-temperature synergistic response drug-releasing bone cement of the present invention is specifically implemented according to the following steps:

[0076] Step 1, preparing drug-loaded carbon nanotubes;

[0077] Step 1.1, weigh 1.5g single-walled carbon nanotubes and 20ml acid solution H 2 SO 4 / HNO 3 (The mixed acid of 98% concentrated sulfuric acid and 68% concentrated nitric acid has a volume ratio of 3:1) mixed to activate the carboxyl groups, ultrasonicated at room temperature for 4 hours, diluted with deionized water, filtered with suction, washed with deionized water until neutral, Vacuum drying at room temperature for 20 hours to obtain carboxylated single-walled carbon nanotubes (SWCNT-COOH);

[0078] Step 1.2, weigh 1.5g of carboxylated single-walled carbon nanotubes (SWCNT-COOH) and 0.6g of vancomycin hydrochloride dissolved in 20ml of deionized water, mix the two at room temperature and stir for 4 hours, then vacuum dry for...

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