KR20050054349A - Biodegradable ceramic/polymer composite and preparation method of the same - Google Patents

Abstract

The present invention relates to a biodegradable organic-inorganic nanocomposite and a method for producing the organic-inorganic nanocomposite and its preparation by uniformly dispersing silver ion-carrying apatite and silver nanoparticles in a biodegradable polymer in order to enhance antimicrobial properties It is about how to. The organic-inorganic nanocomposite of the present invention includes silver, apatite hydroxide and a biodegradable polymer, and a method of preparing the same includes preparing a mixture by mixing apatite hydroxide nanoparticles and a biodegradable polymer solution, stirring the mixture, And drying the stirred mixture, wherein the apatite hydroxide nanoparticles are prepared by dissolving a Ca source and a P source in a solvent to prepare a precursor, adding a salt to the precursor, and stirring to prepare a spray solution. Spraying the spray liquid with an ultrasonic nebulizer, spraying the sprayed droplets into a preheated chamber, pyrolysing the spray, and collecting the synthetic powder produced after the pyrolysis; Washing the collected synthetic powder, and drying the washed synthetic powder, Carrying the antibacterial metal hydroxide to the apatite in order to enhance or may be added in the form of a powder.

Description

Organic-inorganic nanocomposite and its manufacturing method {BIODEGRADABLE CERAMIC / POLYMER COMPOSITE AND PREPARATION METHOD OF THE SAME}

The present invention relates to a biodegradable organic-inorganic nanocomposite and a method for manufacturing the same, and particularly to a method for producing an organic-inorganic nanocomposite by uniformly dispersing silver ions-carrying apatite hydroxide nanoparticles in a biodegradable polymer to enhance antimicrobial properties. It is about.

With the growing interest in health and hygiene in the development of modern society, it is possible to prevent infections of biomaterials or other harmful microorganisms that can replace and replace some parts of human tissues caused by accident or disease. Antimicrobial materials are being actively researched.

Hydroxyapatite, one of the biomaterials, is similar to the hard tissue component of the human body and has biocompatibility, adsorption capacity of heavy metals and bacteria. Hydroxyapatite, (Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ ), which has the same composition as the biological inorganic component, has excellent human friendliness so that the implants in bone or skin can be easily integrated with the surrounding biological tissues. It has a wide range of biomaterials. In the apatite hydroxide crystals, calcium tends to be eluted because defects tend to occur at the positions of the vertically arranged calcium (Ca), and thus, other cations such as silver (Ag), copper (Cu), and zinc (Zn) are used. Is easily substituted. At this time, when silver is substituted, it has excellent antibacterial properties, and silver hydroxide apatite can be used as an ion elution antibacterial material. For this purpose, silver hydroxide can be supported on the silver by ion-exchange method, and silver-supported apatite can be prepared and used by supporting it in a solution that can obtain silver ions such as silver nitrate. Therefore, conventionally, the apatite hydroxide having biocompatibility and bone conductivity is added with antibacterial function by supporting silver. For example, an antibacterial effect is required on the human body where deadly pathogens such as staphylococci can come into contact with, and as a coating material for such a site, silver hydroxide apatite can be easily applied and used throughout the life where antibacterial activity is required. It can be applied to over products.

Biodegradable polymers, which are one of the biomaterials, are polymers that decompose and disappear due to simple hydrolysis or action of an enzyme. Natural polymers, such as polypeptides, polysaccharides, polynucleotides and polyesters produced by microorganisms, are each degraded by their own degrading enzymes. Most synthetic polymers do not degrade, but some aliphatic polyesters or polycarbonates degrade slowly by hydrolysis. Degradable polymers in the body for medical use should not cause foreign body reactions in vivo, should be decomposed into harmless substances, and have appropriate processing characteristics and strength. In this respect, the enzyme-degradable polymer has the advantage of high biocompatibility, but this may also act as a disadvantage of inducing an immune response. In addition, enzymatically decomposable polymers are difficult to arbitrarily control biodegradation rate and mechanical properties compared to hydrolysable polymers that are decomposed by hydrolysis. On the other hand, hydrolyzable polymers have a low immune response in the body, easy control of mechanical properties and relatively simple structure changes depending on the use. In addition, most of these structures contain ester bonds, and when the ester bonds are broken by the hydration of water in the body, the molecular weight decreases. Thus, the low molecular weight polymers are transported through the blood to the outside of the body in the form of urine. Discharged. In practical applications, synthetic polymers such as aliphatic polyesters are widely used for various purposes.

The organic-inorganic composite may be manufactured in the form of fibers, films, sheets, tubes, rods, porous structures, etc. according to the application to the living body, and supports absorbent sutures, tissue adhesives, and broken bones used to bond wounds. Development is being actively used for use as a bone bonding material used, drug carriers used to deliver drugs. In other medical fields, such as urethral catheters, biliary tract ducts, surgical sutures, bone plates or screws that fix when bones are broken, pins, rods, or tissue adhesives that reinforce weakened bones or tendons, or drug delivery systems. It can be applied.

However, the disadvantage of using the biodegradable polymer as a bone substitute has the disadvantage that there is no bioactivity like the non-degradable polymer. In other words, not only spontaneous coupling with the bone in the body but also mechanical properties that are not suitable for supporting the load. Therefore, in order to overcome the disadvantages of existing biodegradable polymers, for example, mechanical strength, organic-inorganic complexes in which the biodegradable polymers are combined with apatite hydroxide have been manufactured, but a simple mixing method of melt blending, mixing and mixing in solution It is difficult to bring about an improvement in mechanical strength. That is, since the biodegradable polymer has a high viscosity, inorganic particles such as apatite hydroxide are hardly dispersed, and thus, suitable mechanical strength is not obtained.

Moreover, the conventional apatite hydroxide and biodegradable polymer composites are widely used as biomaterials due to their high biocompatibility, but there are still limitations in using them as biomaterials that require high antimicrobial properties.

SUMMARY OF THE INVENTION An object of the present invention is to solve the above-mentioned problems of the prior art, and to provide an organic-inorganic nanocomposite of biodegradable polymer having high biodegradability and high strength and apatite hydroxide, and a method of manufacturing the same.

Still another object of the present invention is to provide an organic-inorganic nanocomposite having improved antimicrobial properties and a method of manufacturing the same.

In order to achieve the above object, the method for producing apatite hydroxide nanoparticles according to the present invention comprises the steps of preparing a mixture by mixing the apatite hydroxide nanoparticles and a biodegradable polymer solution, the step of stirring the mixture, And drying the mixture, wherein the apatite hydroxide nanoparticles are prepared by dissolving a Ca source and a P source in a solvent to prepare a precursor, adding a salt to the precursor, and stirring to prepare a spray solution; Spraying the spray liquid with an ultrasonic atomizer, spraying the sprayed droplets into a preheated chamber, pyrolyzing the spray, collecting the synthetic powder produced after the pyrolysis, and collecting It can be prepared through the step of washing the synthetic powder, and the step of drying the washed synthetic powder.

The apatite hydroxide nanoparticles may be prepared including an apatite hydroxide carrying an antimicrobial metal.

Another method for producing apatite hydroxide nanoparticles according to the present invention comprises the steps of preparing a mixture by mixing apatite hydroxide nanoparticles and a biodegradable polymer solution, agitating the mixture, and drying the stirred mixture And the apatite hydroxide nanoparticles may include apatite hydroxide carrying an antimicrobial metal. The antimicrobial metal may comprise silver. The apatite hydroxide nanoparticles can carry silver using ion exchange, and the apatite hydroxide nanoparticles carrying silver can support 0.22% of silver. The preparing of the mixture may further include adding an antimicrobial metal nanopowder to the apatite hydroxide, wherein the antimicrobial metal nanopowder may include silver nanopowder. The preparing of the mixture may include dispersing the apatite hydroxide nanoparticles with a dispersant mixed in the biodegradable polymer solution. The biodegradable polymer may include polyglycol, polylactide, and polycaprolactone. , Polydioxanone, polyleucine, a mixture of two or more thereof, a copolymer prepared from the mixture, collagen, hyaluronic acid, chondroitin sulfate, chitin, chitosan, dextran, amylose, alginic acid. The biodegradable polymer solution may include a solution in which polylactide is dissolved in chloroform, the polylactide may be dissolved at a rate of 10wt% with respect to chloroform, and the apatite hydroxide nanoparticles may be 1wt based on polylactide. Can be%. Drying the mixture may include drying in a vacuum atmosphere.

The organic-inorganic nanocomposite according to the present invention may be prepared according to the preparation method of the organic-inorganic nanocomposite.

The organic-inorganic nanocomposite according to the present invention may be prepared including silver, apatite hydroxide, and a biodegradable polymer. The apatite hydroxide may include rod-shaped nanoparticles, and the biodegradable polymer may include polylactide.

The method for preparing a nanocomposite having high strength biodegradability and antimicrobial properties, which is an object of the present invention, prepares a nano-crystalline crystalline apatite and complexes it with a biodegradable polymer. In particular, in order to add antimicrobial properties thereto, apatite hydroxide loaded with an antimicrobial metal is used. In the following examples, silver is used as an example of the antimicrobial metal, and polylactide is used as the biodegradable polymer. Meanwhile, in order to further add antimicrobial properties, silver nanoparticles may be further added to the silver-supported apatite to complex with the biodegradable polymer. Biodegradable polymers and apatite hydroxides each do not have suitable mechanical strengths, and the mechanical strength and physical properties are enhanced through compounding. However, if the apatite hydroxides are not well dispersed, they do not obtain the required mechanical strengths. Good and well-dispersed apatite hydroxide can be prepared and used.

Therefore, in the embodiment of the present invention, in order to obtain a good crystallinity of the apatite hydroxide is prepared by the ultrasonic spray pyrolysis method of salt and then complexed with a biodegradable polymer. Apatite hydroxide prepared by the liquid phase method is poor in crystallinity and difficult to disperse when compounded with a biodegradable polymer due to strong aggregation of particles.

On the other hand, silver is further added in order to add antimicrobial activity to the organic-inorganic nanocomposite. As an example, silver-supported apatite hydroxide or silver nanoparticles are used to add the antibacterial activity required for medical use to the organic-inorganic composite. That is, a method of preparing a silver-supported apatite by supporting the apatite hydroxide in a silver ion solution or by preparing a silver nanoparticle by an electrolysis method and dispersing it together when dispersing the apatite may be used in combination with the biodegradable polymer.

Silver hydroxide loaded apatite is an ion-elevating inorganic antibacterial material. It is expected to be applied as a biomaterial or antibacterial material by adding antibacterial function to the advantages such as biocompatibility, heavy metal adsorption ability, and bacteria adsorption ability of existing apatite hydroxide. . To improve the cell trapping capacity of these antimicrobial devices or to increase the antimicrobial activity even with a small amount of antimicrobial devices, to facilitate the production of composite films and fibers with polymers, to improve the mechanical strength and to have excellent performance such as transparency (aesthetics). In order to manufacture nano antibacterial devices, that is, nano-sized apatite hydroxide is important.

In view of the above description, since the apatite hydroxide used in the present invention has excellent crystallinity as apatite hydroxide prepared by the salt-added ultrasonic spray pyrolysis method, an organic-inorganic material prepared by complexing with the apatite hydroxide nanoparticles prepared by such a method The complex has high bioactivity and mechanical strength. In particular, the apatite hydroxide nanoparticles having a good crystallinity in the form of rod-shaped crystals prepared by salted ultrasonic spray pyrolysis can be expected to have a larger effect when the silver ions are substituted, the surface area of the apatite hydroxide nanoparticles is wider. Therefore, nano-sized apatite hydroxide supported on silver results in an increase in antibacterial activity even with a small amount of silver. In other words, when silver is supported on the hydroxyapatite nanoparticles having a good crystallinity in the form of rod-shaped ultrasonic spray pyrolysis, the supported silver is eluted by moisture and has an antibacterial effect. Along with apatite, silver nanoparticles have a large surface area and can be expected to have a greater effect of antibacterial activity. Therefore, silver-supported nano-size apatite hydroxide and silver particles bring about an increase in antibacterial activity even with a small amount of silver.

Hybridization with organic materials can lead to dramatic improvements in mechanical properties that cannot be achieved through micron-level complexation. Biodegradable polymers include polyglycolide, polylactide, polycaprolactone, polydioxanone, polyleucine, mixtures of two or more thereof, copolymers prepared from the mixture, collagen, hyaluronic acid, chondroitin sulfate, chitin, chitosan , Can be selected from dextran, amylose, and alginic acid. Among them, polylactide, one of the most biodegradable polymers, is the most commonly used material, and is generally weak to heat and moisture, so it is easy to hydrolyze, and its unit structure is simple, so that its mechanical properties are high and its polarity (oxygen / carbon) is small. It has the advantage of slow decomposition.

First, a method for preparing crystalline apatite hydroxide having good crystallinity and weak cohesion will be described with reference to FIGS. 1 and 2.

1 shows a schematic configuration of an ultrasonic spray pyrolysis apparatus for producing apatite hydroxide nanoparticles for use in the present invention. First, before describing a specific manufacturing process of the apatite hydroxide, it will be briefly described the configuration and operation of the ultrasonic spray pyrolysis apparatus shown in FIG.

As illustrated in FIG. 1, the ultrasonic spray pyrolysis apparatus may be basically divided into three regions, an ultrasonic spraying zone A, a thermal reaction zone B, and a collecting zone C. The process in each of these areas of the ultrasonic spray pyrolysis apparatus is performed in the droplet vessel 100, the reactor 200, and the collector 300, respectively. The droplet container 100 is connected to the spray liquid source 110 and the carrier gas source 120, the lower portion of the droplet container 100 to be immersed in the container 111 containing the water. An ultrasonic vibrator 130 is mounted on the bottom surface of the container below the droplet container 100. Spray liquid source 110 supplies spray liquid 114 into droplet container 100. The ultrasonic vibrator 130 of the vessel 111 sprays the spray liquid supplied from the spray liquid source 110 into droplets of several microns in size. The sprayed droplets are moved into the chamber 210 of the reactor 200 using the carrier gas supplied from the carrier gas source 120. The reactor 200 is a device for maintaining the temperature in the chamber 210 at a desired value, and includes a heater 220 mounted around the chamber, a temperature sensor 230 and a temperature controller 240 mounted in the chamber. . The temperature controller 240 maintains the temperature in the chamber 210 at the set temperature by controlling the heater 220 based on the temperature in the chamber received from the temperature sensor 230. Droplets introduced into the chamber 210 of the reactor 200 together with the carrier gas are pyrolyzed at a set temperature. A collector 300 including a collecting filter 310 and a pump 320 is provided at the top of the reactor 200 to collect various powders generated at the same time while emitting various gases generated during the pyrolysis reaction. That is, in the chamber 210 of the reactor 200, the reaction powder and the various gases generated during the pyrolysis reaction are passed through the collector 300 by the pump 320, wherein the powder generated after the pyrolysis The silver is caught by the collecting filter 310, and various gases generated in the pyrolysis reaction are discharged to the outside through the collecting filter 310. At this time, all the manufacturing process is performed under atmospheric pressure.

A specific manufacturing process for obtaining apatite hydroxide nanoparticles using the salted ultrasonic spray pyrolysis method is shown as a flowchart in FIG. 2. Prepare a water-soluble Ca source and P source that can be dissolved in ultrapure or distilled water as raw materials. In this example, 0.1 M aqueous solution precursor is prepared by dissolving Ca ₉ (NO ₃ ) _{2 ·} 4H ₂ O as the Ca source and H ₃ PO ₄ as the P source in distilled water. The aqueous solution precursor is such that Ca and P have a stoichiometric ratio of 1.67: 1 (step S21). The stoichiometric ratio of Ca / P is irrelevant to the production of nanoparticles, and to obtain a pure apatite hydroxide phase. If the stoichiometric ratio of Ca / P is changed, TCP, DCP, CaO, etc. may be formed in addition to the apatite hydroxide phase. Non-stoichiometric phases such as TCP, DCP, CaO, etc. may be a cause of poor mechanical safety, for example, strength due to poor heat and moisture.

The aqueous solution precursor is added with a high water-soluble salt (NaNO ₃ ) and stirred sufficiently for 24 hours to completely dissolve and mix the aqueous solution to form a spray solution (step S22). The amount of salt added at this time is described below. Accordingly, the sprayed liquid becomes droplets having a uniform Ca / P molar ratio in the ultrasonic spraying process. Adding salts as described above not only prevents agglomeration of the primary particles but also facilitates the crystallization process of the particles to be obtained, thereby making it possible to produce single crystal particles having high crystallinity. That is, the salt used in the present invention serves to control the aggregation and growth of the apatite hydroxide primary particles, and the salt must be completely removed through washing while the apatite hydroxide nanoparticles are manufactured. As the water-soluble salts used, chlorides of Li, Na and K can be used, and these salts are washed by water in a subsequent washing process. Therefore, alcohol may also be used as the solvent as long as the salt is easily washed by alcohol or the like in a subsequent washing step.

The spray solution 114 prepared in this way has a constant height in the droplet container 100 from the spray solution source 110 through the supply pipe for ultrasonic spraying (solution height when the droplet generation is optimally maintained by the ultrasonic vibrator). Is supplied. The droplet container 100 is spaced apart from the container 111 at an appropriate interval (about 3 cm) so as not to directly contact the ultrasonic vibrator 130, and the container 111 is filled with water 113 and used as an ultrasonic delivery medium. Therefore, the ultrasonic vibration generated by the operation of the ultrasonic vibrator 130 vibrates the droplet container 100 indirectly through the water 113 as a transmission medium to spray fine droplets from the spray liquid 114 (step S23). . Since droplets are generated by ultrasonic vibration, and the apatite hydroxide nanoparticles are synthesized through condensation and synthetic pyrolysis due to evaporation of water in the chamber 210, uniform powders can be obtained to produce uniform powders. . The intensity of the ultrasonic vibration, the distance between the ultrasonic vibrator and the droplet container 100, the height of the droplet, and the like become variables for generating uniform droplets.

Air is used as a carrier gas for continuously supplying the fine spray droplets generated by the ultrasonic vibrator 130 to the reaction unit 200, which is provided by the carrier gas source 120 (step S24). The carrier gas may be air, oxygen, nitrogen, an inert gas or a mixture of these gases. In the reaction unit 200 capable of temperature control, by adjusting the temperature in the chamber 210 to a predetermined reaction temperature, the spray droplets shrink as the water evaporates and are synthesized pyrolyzed (step S25). Next, the synthetic powder is collected in the dry collecting device 300 (step S26). The collected synthetic powder is washed with distilled water to remove salt (step S27). For example, the powder obtained from the ultrasonic spray pyrolysis apparatus is placed in a filter such as filter paper for cleaning and poured with heated distilled water to remove salts in the apatite hydroxide particles. For fast cleaning, wet ball mills with distilled water can be used for grinding and cleaning. The ball mill is subjected to a wet ball mill cleaning process in which particles are pulverized to submicron or less to wash salts with distilled water, and then separated from the particles and the solution dissolved in the distilled water using a filter or a centrifuge. In order to easily clean a small amount of salt between the apatite hydroxide primary particles, the ultrasonic cleaning is performed by putting the apatite hydroxide particles in distilled water using a conventional ultrasonic cleaner using ultrasonic cavitation. After washing, the resultant is separated using a filter or a centrifugal separator to obtain only the apatite hydroxide particles as above, followed by drying using a drier or freeze drying (step S28). Since there is a difference in the solubility of the salt according to the amount of distilled water, it may be repeated several times or washed with a large amount of distilled water.

3A and 3B are scanning micrographs of apatite hydroxides having a nano size of 30 nm and 100 nm, respectively, prepared by the above-described ultrasonic spray pyrolysis and salt addition decomposition. As shown in the photograph of FIG. 3b, the shape of the apatite hydroxide crystal having a nano size of 100 nm is rod-shaped. The apatite hydroxide obtained by the above method has a high crystallinity as a single crystal, and it can be seen from the transmission electron micrograph and the diffraction pattern image of the apatite hydroxide of FIGS. 4A and 4B. Since the rod-shaped apatite has a large surface area, the contact area with the bacteria will be expanded, and by using this, it is also possible to bring about an improvement in the antibacterial ability by supporting silver ions having an antibacterial function on the apatite. Inducing a uniform dispersion of the apatite hydroxide to form a biodegradable polymer and an organic-inorganic complex, it can be expected to further enhance the strength of the composite. Therefore, the use of the present invention is used in the present invention a rod-shaped apatite nanoparticles having a rod-shaped 100nm size having a stoichiometric and high crystallinity that can induce a uniform dispersion of the apatite hydroxide.

The organic-inorganic nanocomposite can be prepared by complexing only the apatite hydroxide and the biodegradable polymer. In the following examples, the preparation of the organic-inorganic nanocomposite with added antibacterial activity will be described.

<Example 1>

By using the ion exchange method, silver ions having antimicrobial properties are supported on apatite hydroxide, and the silver-supported apatite hydroxide nanoparticles and a biodegradable polymer such as polylactide are combined. Next, a method of preparing an organic-inorganic nanocomposite by complexing a silver-supported apatite with a biodegradable polymer to have high strength, biodegradability and antimicrobial properties according to the present invention will be described with reference to FIG. 5.

First, apatite hydroxide nanoparticles having good crystallinity, for example, apatite hydroxide nanoparticles having a size of 100 nm are prepared (step S51), and silver-supported apatite is prepared using an ion exchange method (step S52). At this time, silver-carrying apatite nanoparticles can be obtained by substituting silver instead of calcium in the molecular structure of apatite by putting apatite nanoparticles in a solution in which silver nitrate (AgNO ₃ ) is dissolved in distilled water. Apatite hydroxide nanoparticles become silver-supported apatite with the substitution of silver.The molecular formula is (Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ ) to (Ca _10-Z Ag _Z (PO ₄ ) ₆ (OH) _2-Z ) It becomes Next, the silver-supported apatite nanoparticles and the biodegradable polymer should be complexed. The solvent used to make the polylactide solution may be chloroform or dioxin. The melting point may vary depending on the viscosity or molecular weight of the polylactide. In this embodiment, the polylactide is dissolved in chloroform (step S53). At this time, the polylactide is dissolved by adding 10wt% by weight relative to chloroform to form a polylactide slurry.

Since the solution in which polylactide is dissolved in chloroform has a high viscosity, it is difficult to uniformly disperse inorganic substances such as silver-supported apatite hydroxide particles. Therefore, in order to uniformly disperse the particles, a small amount of dispersant, for example, acetone or methanol, is added to the silver-supported apatite to disperse the particles first to form a dispersion (step S54), and then the dispersion is a polylactide as a biodegradable polymer solution. Into the slurry and stirred for a long time, for example, 6 hours or more with a stirrer to mix uniformly well (step S55). In this case, in order to prepare the organic-inorganic nanocomposite that is decomposed after a predetermined time such as surgical suture, bone fixation plate, etc. to be discharged out of the body, the silver-supported apatite is approximately 1wt by weight relative to polylactide. You can use%.

After stirring sufficiently with the stirrer to prepare a film using a solvent casting (solvent casting), and dried in a vacuum oven at 130 ℃ to completely evaporate the solvent of chloroform, to prepare a silver-supported apatite hydroxide / polylactide nanocomposite (Step S56). In this case, the composite may be prepared in the form of a film and used for coating or characterization.

FIG. 6 is an X-ray diffraction graph of silver supported apatite and the peak shows a peak of pure apatite. In general, the main peak of the X-ray diffraction graph of the silver nanoparticles appears at about 38 degrees. In the graph, the silver peak does not appear because silver ions are substituted with calcium.

As shown in Table 1, the silver-supported apatite can be confirmed that calcium is substituted with silver through quantitative analysis of an ICP-AES (ICP-Atomic Emission Spectrometer). That is, as shown in the table, the average concentration of silver in the 100 nm sized apatite hydroxide nanoparticles was 0.22%, and the deviation (SD) was 0.048.

7 is a scanning electron micrograph of the organic-inorganic nanocomposites using silver-supported apatite / polylactide. The white parts are silver-supported apatite hydroxide nanoparticles and are relatively well dispersed on the surface. This is expected to show antimicrobial properties as the polylactide is biodegradable.

8 is a graph showing X-ray diffraction of the organic-inorganic nanocomposites using silver-supported apatite / polylactide. The peaks of the crystallized polylactide phase and the apatite hydroxide phase can be seen.

<Example 2>

Another embodiment of preparing an organic-inorganic nanocomposite having high strength, biodegradability and antimicrobial properties according to the present invention will be described with reference to FIG. 9. First, silver nanoparticles having a size of 30 nm are prepared by electrolysis (step S91), added to silver-supported apatite to be dispersed with a dispersant (step S92), and polylactide is dissolved in chloroform (step S93).

Silver nanoparticles have a greater antimicrobial activity with a smaller amount than the particles of the submicron unit. On the other hand, even in this case, since the solution prepared in Example 1 in which polylactide is dissolved in chloroform has a high viscosity, it is difficult to uniformly spray inorganic materials such as silver nanoparticles and silver-supported apatite hydroxide particles, and thus a dispersant may be used. It is preferable to use. Next, the dispersed silver-supported apatite is added to the polylactide slurry and stirred for a long time with a stirrer (step 94). The stirring solution is dried under vacuum at 130 ° C to prepare an organic-inorganic composite (step S95).

As an example of a method for producing silver nanoparticles, an example of applying an electrolysis method is shown in FIG. 10. The electrodes are connected to two rods 2 and 3 made of silver to flow a constant voltage and current. At this time, the cations dissolved in the positive electrode move to the negative electrode by the electrostatic attraction to obtain electrons to form silver particles. In this electrolysis process, the ultrasonic generator 4 and the magnetic stirrer 5 are operated to prevent the metal particles from staying at the cathode, thereby making the particle size small and uniform, and preventing the aggregation of the particles in the solution. It is also effective to facilitate the movement of ions can be obtained a uniform silver nanoparticles. In addition, the size control of the metal particles is possible by adjusting the voltage, current and time. FIG. 11 is a scanning micrograph of the silver nanoparticles prepared by the above method, and FIG. 12 is a scanning electron micrograph of a mixture of silver nanoparticles and silver-supported apatite hydroxide nanoparticles, which are represented by white circles. As shown in the picture, silver particles and rod-shaped silver supported apatite crystals are well dispersed. In this case, in order to manufacture the organic-inorganic nanocomposite that is produced after being decomposed after a predetermined time, such as a surgical suture, a bone fixation plate at the time of fracture, and discharged into the body, the ratio of silver / silver-supported apatite / polylactide mixed film It is 1: 1: 100 and the ratio of the addition amount of silver and silver supported apatite to biodegradable polymer can be different. FIG. 13 is a scanning electron micrograph of an organic-inorganic nanocomposite using silver and silver-supported apatite hydroxide and polylactide. Through this, it can be seen that the hydroxide hydroxide is relatively well dispersed, but silver particles having a few tens of nano-sizes are difficult to distinguish with the naked eye in the photograph. The silver nanoparticles are covered by polylactide, a biodegradable polymer, which exhibits antibacterial properties as the polylactide biodegrades with silver-bearing apatite on some surfaces.

Table 2 below shows the results of the antibacterial activity against E. coli and Staphylococcus aureus (O. D. test, optical density test).

O. D. is a measure of the amount of light scattered. If there are many particles suspended in the sample, passing the light through the sample will cause the light to collide with the particles, which will increase the amount of light scattered. That is, the absorbance increases when the amount of cells in the sample increases by using this. When the medium without any inoculation of the strain and no growth of the cell is 0, the value of O. D. increases as the cell grows more. In general, when the O. D. value is less than 2, it can be said to have antibacterial activity. That is, as shown in Table 2, the OD value of the silver supported apatite hydroxide / polylactide nanocomposite or the silver / silver supported apatite hydroxide nanoparticles / polylactide nanocomposite is 2 or less, and thus all have antibacterial activity. It can be seen. In particular, the silver / silver supported apatite hydroxide nanoparticles / polylactide nanocomposites were better than the silver supported apatite hydroxide nanoparticles / polylactide nanocomposites. It can be seen that the value is small, excellent antibacterial activity.

The manufacturing method of the organic-inorganic nanocomposite according to the embodiment of the present invention can be carried out by various modifications within the range allowed by the technical idea of the present invention without being limited to the above-described embodiments.

As described above, the organic-inorganic complex prepared by using a good crystallinity of the apatite hydroxide prepared by the salt-added ultrasonic spray pyrolysis method according to the present invention as shown in Fig. 7, 8, 12 or 13 Not only is it homogeneously well dispersed in the biodegradable polymer, but also high mechanical strength can be achieved.

On the other hand, the improvement of the antimicrobial activity of the organic-inorganic complex prepared by further adding silver-supported apatite or silver nanoparticles can be confirmed by Table 2.

As described above, the present invention provides a manufacturing method that can greatly improve the mechanical properties and antimicrobial function of the nanocomposite by uniformly dispersing silver hydroxide apatite particles having biocompatibility and antimicrobial properties with respect to the biodegradable organic polymer material. do. Therefore, not only as a living defect graft material, but also among various medical materials, pathogens such as staphylococci, which are fatal to the human body, may be contacted due to distribution to the outside such as urethral catheters, biliary pulmonary ducts, surgical sutures, etc. It can be easily used as a coating material, and can be applied to various household products that require antimicrobial activity.

1 is a schematic configuration diagram of an ultrasonic spray pyrolysis apparatus for producing apatite hydroxide nanoparticles for use in the present invention.

2 is a flowchart illustrating a process for producing apatite hydroxide nanoparticles for use in the present invention.

3a and 3b are scanning electron micrographs of apatite hydroxide having a nano size of 30nm, 100nm prepared by the salt addition ultrasonic spray pyrolysis method.

4A and 4B are transmission electron microscope photographs and diffraction pattern images of apatite hydroxide prepared by salt addition ultrasonic spray pyrolysis.

Figure 5 is a flow chart illustrating a process for producing an organic-inorganic nanocomposite according to Example 1 of the present invention.

6 is a graph showing X-ray diffraction of silver-supported attapitite;

7 is a scanning electron micrograph of the organic-inorganic complex according to Example 1.

8 is a graph showing X-ray diffraction of the organic-inorganic complex according to Example 1;

9 is a flow chart illustrating a process for producing an organic-inorganic nanocomposite according to Example 2 of the present invention.

10 is a manufacturing method of silver nanoparticles.

11 is a scanning electron micrograph of silver nanoparticles.

12 is a scanning electron micrograph of the nanoparticles mixed with silver and silver hydroxide apatite loaded according to Example 2 of the present invention.

13 is a scanning electron micrograph of the organic-inorganic complex according to Example 2.

<Explanation of symbols for the main parts of the drawings>

1: power

2, 3: silver bar

4: ultrasonic generator

5: stirrer

6: ammeter

7: voltmeter

100: drop container

110: spray liquid source

111: Courage

113: water

114: spray liquid

120: carrier gas source

130: ultrasonic vibrator

200: reactor

210: chamber

220: burner

230: temperature sensor

240: temperature controller

300: collector

310: capture filter

320: pump

Claims (18)

Preparing a mixture by mixing the apatite hydroxide nanoparticles and the biodegradable polymer solution, Stirring the mixture; Drying the stirred mixture, The apatite hydroxide nanoparticles are prepared by dissolving a Ca source and a P source in a solvent to prepare a precursor, adding a salt to the precursor, stirring to prepare a spray solution, and spraying the spray solution with an ultrasonic nebulizer. Spraying the sprayed droplets into a pre-heated chamber, pyrolysing the spray, collecting the synthetic powder produced after the pyrolysis, washing the collected synthetic powder, Method for producing an organic-inorganic nanocomposite, characterized in that the manufactured through the step of drying the washed synthetic powder. The method of claim 1, wherein the apatite hydroxide nanoparticles include apatite hydroxide carrying an antimicrobial metal. Preparing a mixture by mixing the apatite hydroxide nanoparticles and the biodegradable polymer solution, Stirring the mixture; Drying the stirred mixture, The apatite hydroxide nanoparticles manufacturing method of the organic-inorganic nanocomposite, characterized in that it comprises an apatite hydroxide carrying an antimicrobial metal. The method of claim 2 or 3, wherein the antimicrobial metal comprises silver. The method for producing an organic-inorganic nanocomposite according to claim 4, wherein the apatite hydroxide nanoparticles carry silver using an ion exchange method. The method for producing an organic-inorganic nanocomposite according to claim 4, wherein the silver-supported apatite hydroxide nanoparticles carry 0.22% silver. The method of claim 1, wherein the preparing of the mixture further comprises adding an antimicrobial metal nanopowder to the apatite hydroxide. The method of claim 7, wherein the antimicrobial metal nanopowder comprises a silver nanopowder. The organic-inorganic nanocomposite of claim 1, wherein the preparing of the mixture comprises dispersing the apatite hydroxide nanoparticles with a dispersant mixed in the biodegradable polymer solution. Manufacturing method. The method according to claim 1, wherein the biodegradable polymer is polyglycolide, polylactide, polycaprolactone, polydioxanone, polyleucine, a mixture of two or more thereof, prepared from the mixture. A method for producing an organic-inorganic nanocomposite characterized in that it is selected from a copolymer, collagen, hyaluronic acid, chondroitin sulfate, chitin, chitosan, dextran, amylose, and alginic acid. The method according to any one of claims 1 to 3, wherein the biodegradable polymer solution comprises a solution of polylactide dissolved in chloroform. The method of claim 11, wherein the polylactide is dissolved in a proportion of 10 wt% with respect to chloroform. The method of claim 12, wherein the apatite hydroxide nanoparticles are 1 wt% based on polylactide. The method of claim 1, wherein the drying of the mixture comprises drying in a vacuum atmosphere. An organic-inorganic nanocomposite according to any one of claims 1 to 3, which is prepared according to the method for producing an organic-inorganic nanocomposite. An organic-inorganic nanocomposite comprising silver, apatite hydroxide and a biodegradable polymer. The organic-inorganic nanocomposite of claim 16, wherein the apatite hydroxide comprises rod-shaped nanoparticles. The organic-inorganic nanocomposite of claim 16 or 17, wherein the biodegradable polymer comprises polylactide.