CN115381854A - Injectable antibacterial composite material and preparation method and application thereof - Google Patents
Injectable antibacterial composite material and preparation method and application thereof Download PDFInfo
- Publication number
- CN115381854A CN115381854A CN202210792517.3A CN202210792517A CN115381854A CN 115381854 A CN115381854 A CN 115381854A CN 202210792517 A CN202210792517 A CN 202210792517A CN 115381854 A CN115381854 A CN 115381854A
- Authority
- CN
- China
- Prior art keywords
- alginate
- mesoporous material
- composite material
- injectable
- mesoporous
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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- 238000002360 preparation method Methods 0.000 title claims abstract description 16
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Abstract
The invention discloses an injectable antibacterial composite material and a preparation method and application thereof, wherein the injectable antibacterial composite material comprises nano silver, a mesoporous material and alginate; nano silver is loaded in the mesoporous material; alginate is coated on the surface of the mesoporous material; the mass ratio of the nano silver to the mesoporous material to the alginate is 1: (20 to 1000): (200-2000). The in-vitro silver ion release period and the antibacterial effect of the injectable antibacterial composite material can reach more than 21 days, and the injectable antibacterial composite material is more suitable for tissue repair and reconstruction under the condition of bacterial infection and has long-acting and lasting antibacterial effect. In addition, the mesoporous material can slowly and continuously release divalent ions such as calcium, zinc, magnesium, strontium and the like, and is favorable for maintaining the cross-linked structure of alginate on the premise of not influencing the biological safety, so that the composite material can keep certain mechanical strength for a long time, and can also promote the repair and reconstruction of tissues including bone tissues.
Description
Technical Field
The invention relates to the field of materials, in particular to an injectable antibacterial composite material and a preparation method and application thereof.
Background
The restoration and reconstruction of infectious bone defects caused by severe open fracture, orthopedic postoperative infection and acute and chronic osteomyelitis become a great challenge for clinicians, multiple operations are often needed, the application of early local antibiotics can effectively reduce open injured bone infection, and the antibacterial artificial bone scaffold material is expected to be used for treating infectious bone defects. The controlled release system of the drug which combines the antibacterial drug and the carrier is one of the choices for effectively solving the problem of bone infection, the controlled release system of the drug can directly or indirectly promote the prolonged release of the drug at the implantation part, besides the sustained and controllable drug delivery, the drug delivery carriers can also protect the active factors and protein molecules from dissociation or inactivation, and improve the overall bioavailability and clinical efficacy. Compared with systemic administration, local administration reduces the concentration of plasma drugs, thereby avoiding some adverse reactions or general toxicity; moreover, the local administration carrier targeting the bone infection part generally has certain osteoinductive activity, and the local administration system combining the antibacterial drug and the bone repair material has obvious advantages in the treatment of bone infection.
Research shows that the nano silver particles have strong inhibiting and killing effects on dozens of pathogenic microorganisms, have no drug resistance and cytotoxicity, and can promote wound healing. The effects of metal ions such as silver ions on bacteria are manifold and they create new differences in the concentration of intracellular and extracellular ions by changing the polarization state inside and outside the normal biofilm, hindering or destroying the transport of small and large molecular species that maintain the physiological function of the cell. Some metal ions, such as silver ions, may also enter the microbial cells, inactivating most enzymes and exerting antibacterial efficacy. However, when the concentration of metal ions such as silver ions is too high, biotoxicity is caused. Meanwhile, the nano silver material prepared by the traditional precipitation method has large granularity and wider size distribution, and the high efficiency of the antibacterial performance of the nano silver material is influenced. The surface of the nano mesoporous silicon-based material contains a plurality of nano microporous structures, has a huge specific surface area and a microporous structure, and has high activity. The mesoporous silica-based material has excellent adsorption performance and is an ideal inorganic antibacterial agent carrier.
Disclosure of Invention
In order to overcome the problems of the prior art, an object of the present invention is to provide an injectable antibacterial composite material.
The invention also aims to provide a preparation method of the injectable antibacterial composite material.
The invention also aims to provide a bone scaffold material.
The fourth purpose of the invention is to provide the application of the injectable antibacterial composite material in the tissue repair material or the regeneration material.
The fifth purpose of the invention is to provide the application of the injectable antibacterial composite material in preparing medicines or materials for treating orthopedic diseases.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
the first aspect of the invention provides an injectable antibacterial composite material, which comprises nano silver, a mesoporous material and alginate; nano silver is loaded in the mesoporous material; the alginate is coated on the surface of the mesoporous material; the mass ratio of the nano silver to the mesoporous material to the alginate is 1: (20 to 1000): (200-2000). The antibacterial composite material can be directly injected into the affected part of a human body through a syringe.
Preferably, the mass ratio of the nano silver to the mesoporous material is 1: (50-1000); further preferably, the mass ratio of the nano silver to the mesoporous material is 1: (50-800); still further preferably, the mass ratio of the nano silver to the mesoporous material is 1: (50-400).
Preferably, the mass ratio of the nano silver to the alginate is 1: (200-1500); further preferably, the mass ratio of the nano silver to the alginate is 1: (200-1200); still further preferably, the mass ratio of the nano silver to the alginate is 1: (400-800).
Preferably, the alginate comprises at least one of monovalent metal alginate, divalent metal alginate and trivalent metal alginate; further preferably, the alginate comprises at least one of divalent metal alginate and trivalent metal alginate; still more preferably, the alginate is a divalent metal alginate.
Preferably, the mesoporous material has a specific surface area of 50 to 800m 2 (ii)/g; more preferably, the mesoporous material has a specific surface area of 100 to 800m 2 (ii)/g; still more preferably, the mesoporous material has a specific surface area of 200 to 800m 2 /g。
Preferably, the particle size of the mesoporous material is 0.1-10 μm; more preferably, the particle size of the mesoporous material is 0.5 to 8 μm; still more preferably, the mesoporous material has a particle size of 0.5 to 5 μm.
Preferably, the average pore diameter of the mesoporous material is 2-50 nm; further preferably, the average pore diameter of the mesoporous material is 2 to 40nm; still more preferably, the mesoporous material has an average pore diameter of 2 to 30nm.
Preferably, the mesoporous material is mesoporous silicic acid divalent metal salt.
Preferably, the mesoporous material comprises at least one of mesoporous calcium silicate, mesoporous magnesium silicate, mesoporous zinc silicate and mesoporous strontium silicate. In the application process of the injectable antibacterial composite material, the mesoporous material can slowly and continuously release divalent ions such as calcium, zinc, magnesium, strontium and the like, and the divalent cations can be favorable for maintaining the cross-linked structure of the divalent metal alginate or the trivalent metal alginate on the premise of not influencing the biological safety, so that the composite material can keep certain mechanical strength for a long time; meanwhile, the sustained release of divalent cations such as calcium, zinc, magnesium, strontium and the like can also promote the repair and reconstruction of tissues including bone tissues.
Preferably, the mesoporous material is a pretreated mesoporous material, and the pretreatment specifically comprises: the alcohol solution containing the mesoporous material is reacted with alkali liquor to prepare the mesoporous material. When the mesoporous material is pretreated, the mesoporous material reacts with alkali liquor to generate silicate with strong binding power, higher strength, good acid resistance and heat resistance, which is beneficial to loading nano silver.
A second aspect of the present invention provides a method for preparing an injectable antibacterial composite material provided by the first aspect of the present invention, comprising the steps of:
s1: pretreating a mesoporous material, and then mixing and reacting the pretreated mesoporous material with a nano silver source;
s2: and (3) mixing the product obtained in the step (S1) with alginate to obtain the injectable antibacterial composite material.
The product in the step S1 is a mesoporous material with nano silver loaded inside.
Preferably, the nano-silver source comprises silver nitrate; further preferably, the nano silver source is a silver nitrate solution.
Preferably, the concentration of the silver nitrate is 1-20 g/L; further preferably, the concentration of the silver nitrate is 2-10 g/L; still further preferably, the concentration of the silver nitrate is 2 to 8g/L.
Preferably, the step of pretreating the mesoporous material in step S1 is: reacting alcohol liquid containing mesoporous materials with alkali liquor; further preferably, the step of pretreating the mesoporous material in step S1 is: dispersing the mesoporous material in an alcohol solution, adding alkali liquor for reaction, and obtaining the pretreated mesoporous material.
Preferably, the time required by the pretreatment step is 20-60 h; further preferably, the time required for the pretreatment step is 24 to 50 hours; still further preferably, the time required for the pretreatment step is 24 to 48 hours.
Preferably, the alcohol solution comprises at least one of methanol, ethanol, propanol, butanol, ethylene glycol and propylene glycol.
Preferably, the alkali liquor comprises at least one of sodium hydroxide solution, potassium hydroxide solution, calcium hydroxide solution and barium hydroxide solution; further preferably, the alkali liquor comprises at least one of sodium hydroxide solution and potassium hydroxide solution; still further preferably, the alkali liquor is a sodium hydroxide solution or a potassium hydroxide solution.
Preferably, the concentration of the sodium hydroxide solution is 0.03-0.5 mol/L; further preferably, the concentration of the sodium hydroxide solution is 0.08-0.5 mol/L; still more preferably, the concentration of the sodium hydroxide solution is 0.1 to 0.5mol/L.
Preferably, the step of mixing and reacting the pretreated mesoporous material with the nano silver source in step S1 specifically comprises: and dropwise adding a silver nitrate solution into the pretreated mesoporous material solution for reaction, and then centrifuging, cleaning and drying to obtain the mesoporous material with the nano silver loaded inside. The mesoporous material loaded with the nano silver inside is a brown black powdery material.
Preferably, the mass-volume ratio of the mesoporous material to the alcoholic solution is (0.01-0.05): 1g/mL; more preferably, the mass-to-volume ratio of the mesoporous material to the alcohol solution is (0.02 to 0.04): 1g/mL.
Preferably, the time required by the step of dropwise adding the silver nitrate solution into the pretreated mesoporous material solution is 10-60 min; further preferably, the time required by the step of dropwise adding the silver nitrate solution into the pretreated mesoporous material solution is 20-60 min; still further preferably, the time required for the step of dropwise adding the silver nitrate solution into the pretreated mesoporous material solution is 20-40 min.
Preferably, the AgNO 3 The reaction time of the solution and the pretreated mesoporous material is 5-60 min. AgNO 3 Solution and pretreated mediumThe reaction time of the porous material is timed from the time when the silver nitrate is completely added into the pretreated mesoporous material.
Preferably, the centrifugal temperature is 0-12 ℃; further preferably, the centrifugation temperature is 0 to 10 ℃; still further preferably, the centrifugation temperature is 2 to 8 ℃. The purpose of the centrifugation step is to precipitate the nanosilver particles in solution.
Preferably, the drying temperature is 50-80 ℃; further preferably, the drying temperature is 55-75 ℃; still further preferably, the drying temperature is 60 to 70 ℃. The purpose of the drying step is to remove the liquid component from the nanosilver solution.
The invention adopts the processes of low-temperature centrifugation and high-temperature drying to stably load the nano silver in the pores in the mesoporous material.
Preferably, the step S2 specifically includes: and (2) mixing the product obtained in the step (S1) with monovalent metal alginate, and then crosslinking the monovalent metal alginate with divalent metal salt or trivalent metal salt to obtain the injectable antibacterial composite material.
Preferably, the crosslinking time is 0.5-4 min; further preferably, the crosslinking time is 1-4 min; still more preferably, the crosslinking time is 2 to 4min.
Preferably, the divalent metal salt comprises at least one of calcium salt, zinc salt, magnesium salt and strontium salt. The divalent metal salt in the present invention functions as a crosslinking agent for the monovalent metal alginate, and the alginic acid is crosslinked with metal cations to produce the crosslinked divalent metal alginate.
Preferably, the divalent metal salt is a salt solution; further preferably, the concentration of the divalent metal salt solution is 0.5-5 mol/L; still further preferably, the concentration of the divalent metal salt solution is 1 to 5mol/L.
Preferably, the monovalent metal alginate is a monovalent metal alginate solution.
Preferably, the concentration of the monovalent metal alginate solution is 1-10 g/mL; further preferably, the concentration of the monovalent metal alginate solution is 2-8 g/mL; still more preferably, the concentration of the monovalent metal alginate solution is 2-5 g/mL.
Preferably, the monovalent metal alginate comprises at least one of sodium alginate and potassium alginate.
Preferably, the mass-volume ratio of the mesoporous material internally loaded with nano silver to the monovalent metal alginate salt aqueous solution is (0.005-0.08): 10g/mL.
Preferably, the mixing step in step S2 includes at least one of mechanical stirring and ultrasonic dispersion.
Preferably, the stirring speed of the mechanical stirring is 200-3000 rpm; further preferably, the stirring speed of the mechanical stirring is 500-3000 rpm; still more preferably, the stirring speed of the mechanical stirring is 500 to 2500rpm.
Preferably, the stirring time of the mechanical stirring is 5-60 min; further preferably, the stirring time of the mechanical stirring is 10-50 min; still more preferably, the stirring time of the mechanical stirring is 10 to 30min.
Preferably, the ultrasonic frequency in the ultrasonic dispersion is 10-40 KHz; further preferably, the ultrasonic frequency in the ultrasonic dispersion is 20 to 35KHz; still further preferably, the ultrasonic frequency in the ultrasonic dispersion is 20 to 25KHz.
Preferably, the power of the ultrasonic wave in the ultrasonic dispersion is 2-800W; further preferably, the power of the ultrasonic wave in the ultrasonic dispersion is 50-800W; still more preferably, the ultrasonic power in the ultrasonic dispersion is 100 to 800W.
Preferably, the ultrasonic time in the ultrasonic dispersion is 1-20 min; further preferably, the ultrasonic time in the ultrasonic dispersion is 5-20 min; still further preferably, the ultrasonic time in the ultrasonic dispersion is 10 to 20min.
A third aspect of the present invention provides a bone scaffold material comprising the injectable antimicrobial composite material according to the first aspect of the present invention.
A fourth aspect of the present invention provides the use of the injectable antimicrobial composite material provided by the first aspect of the present invention in a tissue repair material or a regeneration material.
Preferably, the tissue repair is tissue repair and reconstruction in the presence of bacterial infection.
A fifth aspect of the present invention provides a use of the injectable antibacterial composite material provided by the first aspect of the present invention in preparation of a medicament or material for treating orthopedic disorders.
Preferably, the orthopedic disorder comprises a bone fracture, an orthopedic post-operative infection, or an infectious bone defect.
The beneficial effects of the invention are: the in-vitro silver ion release period and the bacteriostatic effect of the injectable antibacterial composite material can reach more than 21 days, and the composite material is more suitable for tissue repair and reconstruction under the condition of bacterial infection and has long-acting and lasting bacteriostatic effect.
The preparation method disclosed by the invention is simple in process, low in requirements on equipment, rich in raw material source, low in cost and easy to realize industrial production.
In addition, in the application process of the injectable antibacterial composite material, the mesoporous material can slowly and continuously release divalent ions such as calcium, zinc, magnesium, strontium and the like, and the divalent cations can be favorable for maintaining the cross-linked structure of the divalent metal alginate or the trivalent metal alginate on the premise of not influencing the biological safety, so that the composite material can keep a certain mechanical strength for a long time; meanwhile, the sustained release of divalent cations such as calcium, zinc, magnesium, strontium and the like can also promote the repair and reconstruction of tissues including bone tissues.
Drawings
FIG. 1 is a graph showing in vitro silver ion release profiles of the composites of examples 1 to 5 of the present invention and comparative example 1.
Detailed Description
Specific embodiments of the present invention are described in further detail below with reference to the figures and examples, but the practice and protection of the present invention is not limited thereto. It is noted that the following processes, if not described in particular detail, are all realizable or understandable by those skilled in the art with reference to the prior art. The reagents or apparatus used are not indicated to the manufacturer, and are considered to be conventional products available by commercial purchase.
Example 1
The injectable antibacterial composite material in the embodiment is prepared by the following preparation method, and specifically comprises the following steps:
200mg of mesoporous strontium silicate is dispersed in 10mL of ethanol solution, and 5mL of 0.1mol/L sodium hydroxide aqueous solution is added for reaction for 36 hours to obtain a pretreated solution containing the mesoporous material. 15mL of 2g/L AgNO 3 Dropwise adding the solution into the pretreated solution containing the mesoporous material at a constant speed within 10min, reacting for 30min, centrifuging, cleaning and drying to obtain a brownish black powdery sample, namely the nano-silver loaded mesoporous material. Dispersing 75mg of mesoporous material loaded with nano silver into 15mL of 1g/mL sodium alginate aqueous solution, and mechanically dispersing for 20min (the rotating speed is 200 rpm); 3mL of 0.5mol/L calcium nitrate aqueous solution is added, and crosslinking is carried out for 0.5min, so as to obtain the injectable antibacterial composite material in the example.
Example 2
The injectable antibacterial composite material in the embodiment is prepared by the following preparation method, and specifically comprises the following steps:
100mg of mesoporous calcium silicate is dispersed in 10mL of methanol solution, and 5mL of 0.08mol/L sodium hydroxide aqueous solution is added for reaction for 24h to obtain a pretreated solution containing the mesoporous material. Mixing 5mL of AgNO at 8g/L 3 Dropwise adding the solution into the pretreated solution containing the mesoporous material at a constant speed within 30min, reacting for 10min, centrifuging, cleaning and drying to obtain a brownish black powdery sample, namely the nano-silver loaded mesoporous material. Dispersing 500mg of nano-silver loaded mesoporous material in 10mL, 3g/mL of sodium alginate solution, and mechanically dispersing for 30min (the rotating speed is 500 rpm); adding 1mL of 3mol/L calcium nitrate aqueous solution, and crosslinking for 3min to obtain the injectable antibacterial composite material in the example.
Example 3
The injectable antibacterial composite material in the embodiment is prepared by the following preparation method, and specifically comprises the following steps:
dispersing 200mg of mesoporous magnesium silicate in 10mL of methanol solution, adding 5mL of 0.03mol/L sodium hydroxide aqueous solution for reaction for 48h,obtaining a pretreated solution containing mesoporous materials. 4mL of AgNO at 8g/L 3 Dropwise adding the solution into the pretreated solution containing the mesoporous material at a constant speed within 25min, reacting for 60min, centrifuging, cleaning and drying to obtain a brownish black powdery sample, namely the nano-silver loaded mesoporous material. Dispersing 160mg of the mesoporous material loaded with the nano-silver into 2mL of 10g/mL sodium alginate solution, and performing ultrasonic dispersion for 1min (ultrasonic conditions are 25KHz and 800 w); 0.5mL of 5mol/L calcium nitrate aqueous solution is added for crosslinking for 1min, and the injectable antibacterial composite material in the example is obtained.
Example 4
The injectable antibacterial composite material in the embodiment is prepared by the following preparation method, and specifically comprises the following steps:
500mg of mesoporous magnesium silicate is dispersed in 10mL of isopropanol solution, and 5mL of 0.2mol/L sodium hydroxide aqueous solution is added for reaction for 24 hours to obtain a pretreated solution containing the mesoporous material. 6mL of 6g/L AgNO 3 Dropwise adding the solution into the pretreated solution containing the mesoporous material at a constant speed within 15min, reacting for 5min, centrifuging, cleaning and drying to obtain a brownish black powdery sample, namely the nano-silver loaded mesoporous material. 160mg of mesoporous material loaded with nano silver is dispersed in 8mL of 2g/mL of potassium alginate solution, and mechanical dispersion is carried out for 10min (the rotating speed is 3000 rpm); adding 1.5mL of 2mol/L calcium nitrate aqueous solution, and crosslinking for 2min to obtain the injectable antibacterial composite material in the example.
Example 5
The injectable antibacterial composite material in the embodiment is prepared by the following preparation method, and specifically comprises the following steps:
300mg of mesoporous zinc silicate is dispersed in 10mL of ethylene glycol solution, and 5mL of 0.5mol/L sodium hydroxide aqueous solution is added for reaction for 24h to obtain a pretreated solution containing the mesoporous material. 3.6mL of 10g/L AgNO 3 Dropwise adding the solution into the pretreated solution containing the mesoporous material at a constant speed within 60min, reacting for 20min, centrifuging, cleaning and drying to obtain a brownish black powdery sample, namely the nano-silver loaded mesoporous material. Dispersing 320mg of mesoporous material loaded with nano silver into 8mL of sodium alginate solution of 5g/mL,performing ultrasonic dispersion for 20min (ultrasonic conditions are 20KHz and 2 w); 2mL of 2mol/L calcium nitrate aqueous solution is added for crosslinking for 4min, and the injectable antibacterial composite material in the example is obtained.
Comparative example 1
The injectable antimicrobial composite material in this example differs from example 2 in that: in this example, no mesoporous material was used. The preparation method is prepared by the following steps:
mixing 5mL of AgNO at 8g/L 3 Dispersing the solution in 10mL and 3g/mL sodium alginate solution, and mechanically dispersing for 30min (the rotating speed is 500 rpm); adding 1mL of 3mol/L calcium nitrate aqueous solution, and crosslinking for 3min to obtain the injectable antibacterial composite material in the example.
Comparative example 2
The composite material in this example differs from example 2 in that: in this example, silver nitrate was not used. The preparation method is prepared by the following steps:
dispersing 100mg of mesoporous calcium silicate in 10mL of methanol solution, adding 5mL of 0.08mol/L sodium hydroxide aqueous solution for reaction for 24h to obtain a pretreated solution containing the mesoporous material, centrifuging, cleaning and drying to obtain a powdery sample, namely the pretreated mesoporous material. Dispersing 500mg of the pretreated mesoporous material in 10mL of 3g/mL of sodium alginate solution, and mechanically dispersing for 30min (the rotating speed is 500 rpm); 1mL of 3mol/L calcium nitrate aqueous solution was added, and crosslinking was performed for 3min to obtain a composite material in this example.
Comparative example 3
The composite material in this example differs from example 2 in that: the mesoporous material and silver nitrate were not used in this example. The preparation method is prepared by the following steps:
1mL of a 3mol/L aqueous calcium nitrate solution was added to 10mL of a 3g/mL sodium alginate solution, and crosslinking was performed for 3min to obtain a composite material in this example.
And (3) performance testing:
the composite materials prepared in examples 1 to 5 and comparative examples 1 to 3 were subjected to the following performance tests.
(1) In vitro cytotoxicity assessment
The composite materials prepared in examples 1-5 and comparative examples 1-3 were evaluated and scored according to the requirements of GB/T16886.5-2017. The results of the experiment are shown in table 1 below:
TABLE 1 results of in vitro cytotoxicity test of the composite materials prepared in examples 1 to 5 and comparative examples 1 to 3
| Example 1 | Example 2 | Example 3 | Example 4 | Example 5 | Comparative example 1 | Comparative example 2 | Comparative example 3 | |
| Scoring device | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
As can be seen from table 1, the injectable antibacterial composite materials prepared in examples 1 to 5 of the present invention have high safety and no cytotoxicity, and can be suitably used for human bone repair.
(2) In vitro silver ion release performance detection
The composite materials prepared in examples 1 to 5 and comparative example 1 were subjected to in vitro solute release evaluation. The evaluation method specifically comprises the following steps:
(1) Firstly, 2mg of the composite materials prepared in examples 1 to 5 and comparative example 1 were precisely weighed into a centrifuge tube, PBS buffer was added to a total volume of 5ml, and after sealing, the temperature was maintained at 37. + -. 1 ℃ and the centrifuge tube was shaken in a shaker at 100 rpm.
(2) Stopping shaking at a certain time interval, filtering the release medium by a microporous filter membrane, measuring the concentration of released silver ions, and calculating the percentage of the released silver ions according to the amount of the input silver ions and the volume of the sample.
(3) Fresh PBS buffer was added to the pellet to a total volume of 5ml, shaking was continued under the first step conditions, and then the procedure was repeated for 2-3 steps.
(4) The total release time is 21 days, and finally, the silver ion release curve is obtained according to the time and the cumulative release percentage.
The in vitro silver ion release curves of the composite materials prepared in examples 1 to 5 and comparative example 1 measured according to the above method are shown in fig. 1, and it can be seen from fig. 1 that the in vitro silver ion release period of the antibacterial composite material of the present invention can reach more than 21 days, and the cumulative release rate does not exceed 90% when the composite material is released for 21 days. In contrast, in comparative example 1, the in vitro silver ions of the composite material prepared without the mesoporous material are completely released within 24 hours, and the composite material does not have a long-acting slow release effect.
(3) Detection of antibacterial property of composite material
Taking fresh slant culture of Staphylococcus aureus and Escherichia coli, counting viable bacteria, and preparing into bacteria-containing solution with diluent (0.03 mol/L PBS (pH = 7.2-7.4) containing 1% peptone)The amount is 10X 10 6 cfu/ml bacterial suspension. The composite materials prepared in examples 1 to 5 and comparative examples 1 to 3 were placed in sterile petri dishes, 50 μ L of the bacterial suspension was applied to each material and the time of application was recorded, while the composite materials prepared in examples 1 to 5 and comparative examples 1 to 3 were placed in a 5ml nutrient broth tube. The bacterial suspension was inoculated into a blood plate medium 60min after the addition of bacteria, and the blood plate medium was used as a control, and contained no composite material of examples 1 to 5 and comparative examples 1 to 3. The blood plate culture medium inoculated with the bacteria and the nutrient broth tube are both put into a culture chamber at 37 ℃ for 48h, and the primary result is observed, and the culture is continued in the sterile growth tube until the 21 st day. Positive is indicated as (+) if the broth tube is turbid and the blood plate has bacteria growing; still clear as day 21, considered sterile growth, indicated by (-) at; the specific test results are shown in table 2 below:
table 2 antibacterial property test results of the composite materials prepared in examples 1 to 5 and comparative examples 1 to 3
In summary, the injectable antibacterial composite materials in examples 1 to 5 of the present invention all have long-acting silver ion releasing performance and bactericidal effect, wherein example 2 and comparative example 1 are based on silver ion loaded alginate. In example 2, a mesoporous material is used to load nano silver in the process of preparing the composite material, and a mesoporous material is not used in comparative example 1. Under the condition that no mesoporous material is preloaded with nano silver, silver ions in the alginate are released within 24 hours, and the long-acting antibacterial effect cannot be achieved.
While the embodiments of the present invention have been described in detail, the present invention is not limited to the embodiments, and various changes can be made without departing from the spirit of the present invention within the knowledge of those skilled in the art. Furthermore, the embodiments of the present invention and the features of the embodiments may be combined with each other without conflict.
Claims (10)
1. An injectable antimicrobial composite characterized by: comprises nano silver, mesoporous material and alginate; nano silver is loaded in the mesoporous material; the alginate is coated on the surface of the mesoporous material; the mass ratio of the nano silver to the mesoporous material to the alginate is 1: (20 to 1000): (200-2000).
2. An injectable antimicrobial composite material according to claim 1, characterized in that: the specific surface area of the mesoporous material is 50-800 m 2 /g。
3. An injectable antimicrobial composite material according to claim 2, characterized in that: the mesoporous material is mesoporous silicic acid divalent metal salt.
4. An injectable antimicrobial composite material according to claim 1, characterized in that: the alginate comprises at least one of monovalent metal alginate, divalent metal alginate and trivalent metal alginate.
5. An injectable antimicrobial composite according to any of claims 1 to 4, characterized in that: the mesoporous material is a pretreated mesoporous material, and the pretreatment specifically comprises the following steps: the alcohol solution containing the mesoporous material is reacted with alkali liquor to prepare the mesoporous material.
6. The method for preparing an injectable antibacterial composite material according to claim 5, characterized in that: the method comprises the following steps:
s1: pretreating a mesoporous material, and then mixing and reacting the pretreated mesoporous material with a nano silver source;
s2: and (3) mixing the product obtained in the step (S1) with alginate to obtain the injectable antibacterial composite material.
7. The method of preparing an injectable antimicrobial composite material according to claim 6, wherein: the step S2 specifically includes: and (2) mixing the product obtained in the step (S1) with monovalent metal alginate, and then mixing and reacting with divalent metal salt or trivalent metal salt to obtain the injectable antibacterial composite material.
8. A bone scaffolding material, characterized in that: an injectable antimicrobial composite material according to any one of claims 1 to 5.
9. Use of the injectable antimicrobial composite according to any one of claims 1 to 5 in tissue repair or regeneration materials.
10. Use of the injectable antimicrobial composite material according to any one of claims 1 to 5 for the preparation of a medicament or material for the treatment of orthopaedic diseases.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102499259A (en) * | 2011-11-18 | 2012-06-20 | 北京崇高纳米科技有限公司 | Clothing degerming liquid and preparation method thereof |
| CN103768643A (en) * | 2014-02-17 | 2014-05-07 | 周继胡 | Silver ion alginate sustained-release antibacterial gel and preparation method thereof |
| CN106994133A (en) * | 2016-01-25 | 2017-08-01 | 吉林省莱沃医疗科技有限公司 | Calcium zinc ion is combined antibacterial alginate slow-release material and preparation method thereof |
| CN113083174A (en) * | 2021-03-17 | 2021-07-09 | 武汉工程大学 | Preparation method of nano-silver/diatomite/calcium alginate composite antibacterial hydrogel microspheres |
| CN113499475A (en) * | 2021-06-10 | 2021-10-15 | 广东省科学院健康医学研究所 | Composite material for bracket and preparation method and application thereof |
| CN113511811A (en) * | 2021-03-16 | 2021-10-19 | 浙江大学 | Multifunctional mesoporous biomaterial, preparation method and application |
-
2022
- 2022-07-07 CN CN202210792517.3A patent/CN115381854B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102499259A (en) * | 2011-11-18 | 2012-06-20 | 北京崇高纳米科技有限公司 | Clothing degerming liquid and preparation method thereof |
| CN103768643A (en) * | 2014-02-17 | 2014-05-07 | 周继胡 | Silver ion alginate sustained-release antibacterial gel and preparation method thereof |
| CN106994133A (en) * | 2016-01-25 | 2017-08-01 | 吉林省莱沃医疗科技有限公司 | Calcium zinc ion is combined antibacterial alginate slow-release material and preparation method thereof |
| CN113511811A (en) * | 2021-03-16 | 2021-10-19 | 浙江大学 | Multifunctional mesoporous biomaterial, preparation method and application |
| CN113083174A (en) * | 2021-03-17 | 2021-07-09 | 武汉工程大学 | Preparation method of nano-silver/diatomite/calcium alginate composite antibacterial hydrogel microspheres |
| CN113499475A (en) * | 2021-06-10 | 2021-10-15 | 广东省科学院健康医学研究所 | Composite material for bracket and preparation method and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| 刘文著: "《全国中医药行业高等教育"十三五"规划教材 药用高分子材料学》", 北京：中国中医药出版社, pages: 113 - 115 * |
| 刘立华: "模板法合成介孔硅酸钙及其对重金属离子的吸附性能", 《环境化学》, vol. 35, no. 9, pages 1943 - 1951 * |
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