TWI534085B - Magnetic and hollow composite sphere and method for manufacturing the same - Google Patents

Description

Magnetic hollow composite ball and manufacturing method thereof

The present invention relates to a magnetic hollow composite ball and a method of manufacturing the same, and more particularly to a magnetic hollow composite ball having metal particles coated with cerium oxide and a method for producing the same.

Magnetic particles have a wide range of applications, especially in applications such as MRI, gene therapy and drug delivery.

Functional magnetic particles conventionally applied to biomedical materials are, for example, nano-iron oxide (Fe ₃ O ₄ ) in a high oxidation state. Nano-iron oxide produces superparamagnetic properties due to size effect. Therefore, nano-iron oxide can form a high-efficiency contrast reagent to assist the water-producing region. However, the superparamagnetic nano-iron oxide itself is toxic. To be applied to the human body, it is necessary to make the nano-iron oxide biocompatible. Therefore, iron oxide particles are often used as the core, and some biomedical polymers such as polyethylene glycol (PEG) and poly are modified on the surface. Vinyl alcohol (PVA) and polyethylene oxide (PEO) are used to alter the surface biocompatibility. The surface-modified nano-iron oxide must have good stable dispersibility, and must possess biological non-toxicity and compatibility. If nano-iron oxide is coagulated and precipitated in the living body, it will easily cause clogging in blood vessels or fine tissues.

At present, magnetic composite hollow spheres formed by mounting magnetic particles in hollow spheres still have the following problems: (1) the hollow spheres are insufficient in strength and easily collapse; (2) the hollow spheres are insufficient in size and are easily swallowed by cells; The space of the hollow sphere is insufficient so that the drug or the contaminant has no position to adsorb; (4) the magnetic particle has a risk of being phagocytized by the cell; and (5) the magnetic particle has the problem of being oxidized by air to form iron oxide. Researchers are working hard to develop magnetic composite hollow spheres that can solve the above problems (1) to (5).

In view of the above, the present invention provides a magnetic hollow composite ball capable of simultaneously solving the problems of the above (1) to (5) and a method of manufacturing the same.

The present invention provides a magnetic hollow composite ball comprising: a porous ceria shell; a ceria protective layer disposed on an inner side surface and an outer side surface of the porous ceria shell; and a plurality of ceria coated The metal particles are respectively distributed in the above porous ceria shell and the above-mentioned ceria protective layer.

In an embodiment of the invention, the metal particles are at least one selected from the group consisting of iron, cobalt, and nickel metal particles.

In an embodiment of the invention, the magnetic hollow composite ball has an outer diameter of 100 nm to 600 nm.

In an embodiment of the invention, the thickness of the porous ceria shell is It is 15 nm to 30 nm.

In an embodiment of the invention, the porous ceria shell has an average porosity of 10 nm to 20 nm.

In an embodiment of the invention, the magnetic hollow composite ball is used as a biomedical material.

In the magnetic hollow composite ball of the present invention, since the metal particles are coated with cerium oxide, oxidation and agglomeration of the metal particles can be avoided, so that the metal particles can be uniformly distributed in the porous ceria shell and the ceria protective layer, and by the second The ruthenium oxide protective layer can further prevent oxidation and agglomeration of the magnetic metal particles. Further, in the present invention, by setting the thickness and the average porosity of the porous ceria shell in the magnetic hollow composite ball to the above range, the magnetic hollow composite ball can have sufficient strength to remain hollow even after heat treatment. The integrity of the ball. In addition, the present invention can avoid phagocytosis by cells when used as a drug carrier by setting the outer diameter of the magnetic hollow composite sphere to the above range.

The present invention further provides a method for producing a magnetic hollow composite sphere, comprising: a step of adsorbing metal ions by a porous ceria hollow sphere; and a porous ceria hollow sphere having a metal ion adsorbed thereon, a solution containing a decalane oxygen compound, and The reducing agent is mixed to obtain a magnetic hollow composite ball.

In an embodiment of the invention, the step of preparing a porous ceria hollow sphere is further included.

In an embodiment of the invention, the step of preparing the porous ceria hollow sphere comprises: hydrolyzing a solution containing a decane oxygen compound on a polymer template a step of condensation; and a step of heat treatment.

In an embodiment of the invention, the metal ion is at least one selected from the group consisting of iron, cobalt, and nickel ions.

In an embodiment of the invention, the polymer template is made of a polyacrylate.

In an embodiment of the invention, the above decaneoxy compound is selected from the group consisting of tetramethoxy decane and tetraethoxy decane.

In an embodiment of the invention, the solution containing a decane oxygen compound contains a carbon number of 6 to 18 atoms.

In an embodiment of the invention, the alkane having 6 to 18 carbon atoms is n-dodecane.

In an embodiment of the invention, the reducing agent is NaBH ₄ .

In the present invention, the porous hollow ceria hollow sphere adsorbs metal ions, and then the metal ions are reduced to metal particles, and the hydrolyzed condensation reaction of the decaned oxygen compound and the oil-water emulsification reaction are carried out, whereby the magnetic hollow composite ball specified in the above-mentioned present invention can be obtained. In addition, by using polyacrylate as the polymer template and hydrolytic condensation reaction of a decane oxy-compound, the thickness and average porosity and outer diameter of the porous ceria shell can be made to meet the above range. Magnetic hollow composite ball.

The above described features and advantages of the invention will be apparent from the following description.

100‧‧‧Magnetic hollow composite ball

110‧‧‧ Porous cerium oxide shell

120‧‧‧ cerium oxide protective layer

130‧‧‧Multiple cerium oxide coated metal particles

140‧‧‧ holes

150‧‧‧ hollow part

BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a view showing the structure of a magnetic hollow composite ball according to an embodiment of the present invention.

Fig. 2 is a flow chart showing a method of manufacturing a magnetic hollow composite ball according to an embodiment of the present invention.

The present invention will be described in detail below with reference to the drawings. In the present invention, the magnetic hollow composite sphere refers to a hollow sphere comprising a composite material of a magnetic metal and cerium oxide (porous), and the detailed structure is as follows.

BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a view showing the structure of a magnetic hollow composite ball according to an embodiment of the present invention.

Referring to FIG. 1, the magnetic hollow composite ball 100 of the present invention comprises: a porous ceria shell 110; a ceria protective layer 120 disposed on the inner side surface and the outer side surface of the porous ceria shell 110; The ceria-coated metal particles 130 are distributed in the porous ceria shell 110 and the ceria protective layer 120, respectively. In an embodiment, the pores included in the porous ceria shell 110 are represented by holes 140.

<Porous cerium oxide shell>

The thickness of the porous ceria shell is not particularly limited, but is preferably 15 nm to 30 nm. If the thickness of the porous ceria shell is set to 15 nm to 30 nm, the strength of the magnetic hollow composite ball is sufficient, and the heat treatment can be maintained even after heat treatment at 400 ° C or higher. Hold the integrity of the hollow sphere.

The porous ceria shell has an average porosity of 10 nm to 20 nm. When the magnetic hollow composite ball of the present invention is used for a drug carrier or an adsorbent material of a biomedical material, it has sufficient surface area and activity to facilitate drug transport or pollutant adsorption. .

<cerium oxide protective layer>

The ceria protective layer is disposed on the inner side surface and the outer side surface of the porous ceria shell, thereby protecting the metal particles distributed in the porous ceria shell and the ceria protective layer. The thickness of the ceria protective layer may be appropriately selected as long as it can coat the metal particles.

<Multiple cerium oxide coated metal particles>

The metal particles in the plurality of ceria-coated metal particles are at least one selected from the group consisting of iron, cobalt, and nickel metal particles, and thus the magnetic hollow composite ball of the present invention has magnetic properties and can be applied to magnetic properties. field. The metal particles are preferably iron particles from the viewpoint of excellent magnetic properties. Further, the particle diameter of the metal particles is not particularly limited, and is preferably a nanometer-sized particle diameter. Although the magnetic nano metal particles are relatively easy to oxidize and the magnetic properties thereof are lowered, since the metal particles of the present invention are respectively coated with cerium oxide, they are not oxidized to lower their magnetic properties, and do not agglomerate and affect their application. .

<Magnetic hollow composite ball>

The outer diameter of the magnetic hollow composite ball is preferably from 100 nm to 600 nm. If the outer diameter of the magnetic hollow composite ball is 100 nm or more, when the magnetic hollow composite ball of the present invention is used for a drug carrier or an adsorbent material of a biomedical material, the magnetic hollow composite ball can be avoided. The problem of being swallowed by cells, and having enough cavity space to store drugs or adsorbates.

In the magnetic hollow composite ball of the present invention, since the metal particles are adsorbed on the porous ceria shell and coated with cerium oxide, the oxidation and agglomeration of the metal particles can be avoided, so that the metal particles can be uniformly distributed in the porous ceria shell and the second In the ruthenium oxide protective layer, the magnetic metal particles are more oxidized and agglomerated by the ruthenium dioxide protective layer. Further, in the present invention, by setting the thickness and the average porosity of the porous ceria shell in the magnetic hollow composite ball to the above range, the magnetic hollow composite ball can have sufficient strength to remain hollow even after heat treatment. The integrity of the ball, when used in a pharmaceutical carrier or adsorbent material for biomedical materials, has sufficient surface area and activity to facilitate drug delivery or contaminant adsorption. In addition, the present invention can avoid phagocytosis by cells when used as a drug carrier by setting the outer diameter of the magnetic hollow composite sphere to the above range.

The magnetic hollow composite ball of the present invention can be applied to, for example, environmentally-friendly catalyst carrier and adsorbent material due to the above-mentioned effects; drug carrier for biomedical engineering, drug magnetic guidance, hysteresis hyperthermia, nuclear magnetic resonance imaging; A catalyst carrier for a fuel cell, a carrier for a semiconductor oxide and an organic dye molecule in a dye-sensitized solar cell, a magnetic fluid sealing technique, and the like.

The method for producing a magnetic hollow composite sphere according to the present invention includes the steps of: adsorbing metal ions by a porous ceria hollow sphere; and a porous ceria hollow sphere adsorbing metal ions, a solution containing a decasiloxane compound, and reducing The agent is mixed to obtain a magnetic hollow composite ball. The invention is not limited to this, In one embodiment, the step of preparing a porous ceria hollow sphere is further included. In another embodiment, the step of preparing the porous ceria hollow sphere comprises the steps of: hydrolyzing a solution containing a decane oxygen compound onto a polymer template; and heat treating. Here, the porous ceria hollow sphere refers to a portion including the porous ceria shell 110 and the hollow portion 150 in the magnetic hollow composite ball 100 shown in FIG.

Fig. 2 is a flow chart showing a method of manufacturing a magnetic hollow composite ball according to an embodiment of the present invention. Referring to FIG. 2, a method for manufacturing a magnetic hollow composite ball according to the present invention includes: a step S1 of preparing a porous ceria hollow sphere; a step S2 of adsorbing a metal ion by a porous ceria hollow sphere; and adsorbing a metal ion The porous ceria hollow sphere, the solution containing the decane oxygen compound, and the reducing agent are mixed to obtain a step S3 of the magnetic hollow composite sphere. The above steps will be explained in more detail below.

<Step S1>

In the step S1, a known porous ceria hollow sphere can be used, and as long as its outer diameter, shell thickness, and average porosity fall within the above range, it can be used in the present invention. In addition, porous ceria hollow spheres can also be prepared by themselves. The method for producing the porous ceria hollow sphere is not particularly limited, and is not particularly limited as long as the outer diameter, the shell thickness, and the average porosity of the prepared porous ceria hollow sphere fall within the above range.

In the method for preparing a porous ceria hollow sphere, it is preferred to include a preparation method of: a solution containing a decane oxygen compound on a polymer template a step of hydrolytic condensation; and a step of heat treatment. In one embodiment, a solution containing a decyloxy compound having a hydrolytic condensation ability is added to a solution having a polymer template, and then the decane oxygen compound is hydrolyzed and condensed on the polymer template, followed by calcination at a predetermined temperature. The polymer template was removed, thereby preparing a porous ceria hollow sphere A.

The material of the polymer template may be used as long as it is an ester. However, from the viewpoint of preparing a porous ceria hollow sphere having an outer diameter, a shell thickness, and an average porosity falling within the above range, the polymer template is preferably agglomerated. Acrylate.

The decane oxygen compound having a hydrolytic condensation ability is, for example, tetramethoxy decane, tetraethoxy decane or the like. The method of hydrolyzing and condensing the solution containing a decane oxygen compound is not particularly limited, and a known hydrolysis condensation method of a decane oxygen compound can be used.

The temperature of the heat treatment is not particularly limited, and is preferably 400 ° C or more from the viewpoint of the removal property of the polymer template.

In the present invention, by adding a carbon number 6 to 18 alkane (hole forming agent) in step S1, pores are formed in the shell of the prepared porous ceria hollow sphere, thereby adjusting the porous ceria hollow sphere Average porosity. In one embodiment, a solution containing a decyloxy compound having a hydrolytic condensation ability and a carbon number of 6 to 18 are added to a solution having a polymer template to hydrolyze the decane oxygen compound, and then at a prescribed temperature. The porous stencil is removed to remove the polymer template, thereby preparing the porous ceria hollow sphere B. The porous ceria hollow sphere B obtained in this manner has an average porosity of the porous ceria hollow sphere B larger than that of the porous ceria hollow sphere A as compared with the above porous ceria hollow sphere A. Further, by adjusting the type and content of the alkane having 6 to 18 carbon atoms, the average porosity of the obtained porous ceria hollow sphere B can be changed, and the average porosity of the porous ceria hollow sphere can be controlled. The alkane having 6 to 18 carbon atoms is, for example, n-dodecane.

<Step S2>

In the step S2, the manner in which the porous ceria hollow spheres adsorb metal ions is not particularly limited, and it is preferred to immerse the porous ceria hollow spheres in a solution containing a metal salt to adsorb metal ions.

The metal ion is at least one selected from the group consisting of iron, cobalt, and nickel ions. The metal ion is preferably an iron ion from the viewpoint of excellent magnetic properties. The metal salt is suitably selected depending on the kind of metal ion to be adsorbed, and examples thereof include iron nitrate, iron sulfate, iron chloride, cobalt nitrate, cobalt sulfate, cobalt chloride, nickel nitrate, nickel sulfate, nickel chloride, and the like. Ferric chloride, cobalt chloride, and nickel chloride are less desirable because they tend to remain in the porous ceria hollow spheres and are not easily removed.

<Step S3>

In step S3, mixing the porous ceria hollow spheres, the solution containing the decane oxygen compound, and the reducing agent, which adsorb metal ions, generate at least three kinds of reactions, respectively, reduction reaction of metal ions to metal particles, and decane oxygen. Hydrolysis condensation reaction of compound, oil-water emulsification reaction.

The reducing agent is not particularly limited as long as it can reduce the metal ions to metal particles, and is preferably NaBH ₄ .

The solution containing a decane oxygen compound is not particularly limited, and may be appropriately selected as long as it is a hydrolysis condensation reaction capable of generating a decane oxygen compound and an oil-water emulsification reaction. Choose. Specifically, in order to hydrolyze and condense the decane oxygen compound, it is necessary to add a component which can hydrolyze and condense the decane oxygen compound in the solution containing the decane oxygen compound; in order to generate an emulsification reaction, it is necessary to add a solution containing a decane oxygen compound. The composition of the oil phase and the water phase. The above-described decane oxide-containing solution in the step S3 may contain the above-mentioned carbon number 6 to 12 alkyl groups as the oil phase component.

In step S3, due to the reduction reaction, the metal ions are reduced to metal particles, thereby forming metal particles; due to the oil-water emulsification reaction and the hydrophilic nature of the porous ceria hollow sphere, the reduction reaction of the metal ions is limited to the porous two. In the hollow sphere of cerium oxide, no excess metal particles are interposed between the obtained magnetic hollow composite spheres, and the risk of the metal particles being phagocytized by the cells due to being dispersed between the magnetic hollow composite spheres can be reduced. Here, if the metal reduction reaction is carried out in a single aqueous phase, many metal particles which are difficult to separate are obtained, which has a great adverse effect on the subsequent application of the magnetic hollow composite ball. In addition, a ruthenium dioxide protective layer is formed on the inner side surface and the outer side surface of the porous ceria shell due to the hydrolysis condensation reaction of the decane oxygen compound, and the ceria is coated with the metal particles, resulting in the porous second A plurality of cerium oxide-coated metal particles are formed in the cerium oxide shell and the cerium oxide protective layer. These metal particles are not oxidized by being coated with cerium oxide, and are not agglomerated with other metal particles, so that they can be uniformly distributed in the porous ceria shell and the ceria protective layer.

The method for producing a magnetic hollow composite sphere of the present invention can be obtained by adsorbing a metal ion by a porous ceria hollow sphere, and then reducing the metal ion to a metal particle while performing a hydrolysis condensation reaction of the decane oxygen compound and an oil-water emulsification reaction. The magnetic hollow composite ball specific to the above case is obtained. In addition, by using polyacrylate as the polymer template and hydrolytic condensation reaction of a decane oxy-compound, the thickness and average porosity and outer diameter of the porous ceria shell can be made to meet the above range. Magnetic hollow composite ball.

The invention will now be described in more detail by way of specific examples.

Example

<Preparation of porous ceria hollow spheres>

First, 2.4 g of polyacrylic acid (PAA) was dissolved in 36.5 ml of aqueous ammonia and stirred for 30 minutes, and then 730 ml of absolute ethanol was added and stirred for 40 minutes to form a polymer template solution. Next, 15 ml of Tetraethyl Orthosilicate (TEOS) was added to the polymer template solution at a rate of 3 ml per two hours, and then allowed to react for 2 hours. Thereafter, 2.83 ml of aqueous ammonia was added, and the mixture was further stirred for 8 hours to carry out a hydrolysis condensation reaction on a polymer template. After the reaction, the mixture was washed twice with ethanol, and concentrated and dried under reduced pressure to obtain a porous ceria hollow sphere A'. It was found by a low-magnification and high-magnification transmission electron microscope (TEM) image that the obtained porous ceria hollow sphere A' had an outer diameter of about 250 nm to 400 nm and a shell thickness of about 25 nm to 35 nm. The porous ceria hollow sphere A' analyzed by a BET specific surface area measuring instrument has an average porosity of about 10 nm.

<Adjustment of average porosity of porous ceria hollow spheres>

First, 0.8 g of PAA was dissolved in 12 ml of aqueous ammonia and stirred for 30 minutes, and then stirred by adding 240 ml of absolute ethanol for 40 minutes to form a polymer template solution. Next, 8 ml of TEOS and 3.12 ml of n-dodecane were added at a rate of 2.2 ml every two hours. After the mixed solution was added to the polymer template solution, the reaction was carried out for 2 hours. Thereafter, 1.5 ml of aqueous ammonia was added, and the mixture was further stirred for 4 hours to carry out a hydrolysis condensation reaction on the polymer template. After the reaction, the mixture was washed twice with ethanol, and concentrated and dried under reduced pressure to obtain a porous ceria hollow sphere. B'. It was found from the TEM images of low magnification and high magnification that the obtained porous ceria hollow sphere B' had an outer diameter of about 300 nm and a shell thickness of about 50 nm. The porous ceria hollow sphere B' obtained by analysis by a BET specific surface area measuring instrument has an average porosity of about 20 nm.

Further, after the above-mentioned porous ceria hollow spheres after washing were subjected to calcination at 400 ° C / 3 h, it was found from the TEM images of low magnification and high magnification that the hollow ceria hollow spheres after calcination were still intact.

<Preparation of magnetic hollow composite ball>

First, 0.045 g of porous ceria hollow spheres heat-treated at 400 ° C were dispersed in a mixed solution of 1.2 ml of water and 4.8 ml of absolute ethanol. After ultrasonic vibration for 30 minutes, 4 ml of an aqueous solution of iron ions was added, and ultrasonic waves were used for shattering. After 5 minutes of shaking, the solution was switched to an ultrasonic cleaner for 6 hours, during which ultrasonic vibration was used every two hours for 5 minutes to obtain a porous cerium hollow sphere aqueous solution with iron ions adsorbed thereon. . After removing the solvent with a vacuum concentrator, it was dispersed in 10 ml of the n-dodecane oil phase, and shaken for 15 minutes. Then, a small amount of TEOS and 5 ml of ethanol were added, respectively, and after shaking for 1 minute, 2 ml of 0.2 M NaBH was added. ₄ aqueous solution, shake for 5 minutes, reduce iron ions. Finally, after the product was washed twice with ethanol, a magnetic composite hollow sphere in which Fe particles were coated with SiO ₂ was obtained. The magnetic composite hollow spheres were dispersed in an aqueous solution, and the magnets were detected by magnets, and as a result, they exhibited a good magnetic attraction effect. Further, it was found from the high-magnification TEM image that the iron particles coated with SiO _{2 were} uniformly dispersed in the hollow sphere.

Although the present invention has been disclosed in the above embodiments, it is not intended to limit the present invention, and any one of ordinary skill in the art can make some changes and refinements without departing from the spirit and scope of the present invention. The scope of the invention is defined by the scope of the appended claims.

100‧‧‧Magnetic hollow composite ball

110‧‧‧ Porous cerium oxide shell

120‧‧‧ cerium oxide protective layer

130‧‧‧Multiple cerium oxide coated metal particles

140‧‧‧ holes

150‧‧‧ hollow part

Claims (10)

A magnetic hollow composite ball comprising: a porous ceria shell; a ceria protective layer disposed on an inner side surface and an outer side surface of the porous ceria shell; and a plurality of ceria-coated magnetic metals The particles are respectively distributed in the above porous ceria shell and the above-mentioned ceria protective layer. The magnetic hollow composite ball according to claim 1, wherein the magnetic metal particles are at least one selected from the group consisting of iron, cobalt, and nickel magnetic metal particles. The magnetic hollow composite ball according to claim 1, wherein the outer diameter is from 100 nm to 600 nm. The magnetic hollow composite ball according to claim 1, wherein the porous ceria shell has a thickness of 15 nm to 30 nm. A method for producing a magnetic hollow composite ball, comprising: a step of adsorbing magnetic metal ions by a porous ceria hollow sphere; and the above porous ceria hollow sphere having a magnetic metal ion adsorbed thereon, a solution containing a decasiloxane compound, and The reducing agent is mixed to obtain a magnetic hollow composite ball. The method for producing a magnetic hollow composite ball according to claim 5, further comprising the steps of: hydrolyzing and condensing a solution containing a decane oxygen compound on a polymer template; and heat-treating. The manufacturer of the magnetic hollow composite ball as described in claim 6 of the patent application scope The method wherein the polymer template is made of a polyacrylate. The method for producing a magnetic hollow composite ball according to claim 5, wherein the magnetic metal ion is at least one selected from the group consisting of iron, cobalt, and nickel ions. The method for producing a magnetic hollow composite ball according to claim 5, wherein the decaneoxy compound is selected from the group consisting of tetramethoxy decane and tetraethoxy decane. The method for producing a magnetic hollow composite ball according to claim 5, wherein the solution containing the decane oxygen compound contains a carbon number of 6 to 18 atoms.