KR20140078876A - Development of Detoxification System Containing Micronized Magnesium Using Rapid Expansion Supercritical Fluid - Google Patents

Abstract

The present invention relates to fine particle magnesium material using an environmentally friendly supercritical fluid process and a heavy metal detoxifying system wherein a method of producing a particle of ultrafine particle magnesium using a supercritical fluid process and an application of a heavy metal detoxifying system comprise: a step of generating magnesium particles by spraying and contacting a mixture solution, in which the magnesium is dissolved in an organic solvent, to a supercritical fluid; and a step of eliminating the organic solvent used in the mixture solution by introducing the supercritical fluid to the particle. The production method of the present invention can be used in the processing of the magnesium material for promoting effects to a skin by increasing a cross section through varying the degree of crystallinity of drug for miniaturizing the particle size of the drug through the variation of pressure and temperature which are the manipulation variables of a supercritical fluid process or through the flux variation of supercritical carbon dioxide and the solution of magnesium organic solvent.

Description

TECHNICAL FIELD [0001] The present invention relates to a method for preparing a heavy metal detoxifying agent containing magnesium microparticles using a rapidly expanding supercritical fluid,

The present invention relates to the development of a chelating heavy metal detoxification system containing magnesium microparticles using a rapidly expanding supercritical fluid, comprising the steps of spraying a mixed solution obtained by dissolving magnesium in an organic solvent into an environmentally supercritical fluid to cause magnesium particles And introducing a supercritical fluid into the particle to remove the organic solvent used in the mixed solution. The present invention relates to an application to the development of a heavy metal detoxification system for producing ultrafine magnesium particles using a rapidly expanding supercritical fluid will be.

In general, magnesium is the fourth most abundant mineral of minerals in our bodies. An adult with a body weight of 70 kg has about 24-25 g of magnesium, 60% of the total magnesium is contained in the bone, 99% of the remaining 40% is present in the intracellular fluid, and about 1% is present in the extracellular fluid . One third of the magnesium in the skeleton acts as a reservoir of magnesium and regulates the magnesium concentration in the extracellular fluid. Bone is considered to be a reservoir of magnesium, with about 30% of bone magnesium present on the bone surface and passive equilibrium with plasma magnesium, buffering changes in plasma magnesium concentration. Magnesium plays an important role in the biochemical and physiological processes. It acts as a cofactor in more than 300 enzyme systems and is involved in carbohydrate metabolism and plays an important role in the energy production process. It is also necessary for biochemical or physiological processes that occur in the body, such as synthesis of fat, proteins and nucleic acids, and contraction of muscles. Magnesium plays an essential role in the maintenance of cell membrane potentials in nerves and muscles and in the conduction of impulses in neuronal junctions.

The general microfabrication process uses microcapsules to form fine particles using organic solvents, but there are many cases involving side effects due to problems such as residual organic solvents.

On the other hand, supercritical fluid is an environmentally friendly fluid, which is an incompressible fluid under temperature and pressure above the critical point, and exhibits a unique characteristic that does not appear in conventional organic solvents. That is, supercritical fluids have excellent physical properties such as high density close to liquid, low viscosity close to gas, high diffusion coefficient, and very low surface tension. Since the supercritical fluid can continuously change the density from the lean state close to ideal gas to the high density state close to the liquid density, the fluid equilibrium property (solubility, entrainer effect), transfer property (viscosity, diffusion coefficient, Degree), molecular clustering, and the like. Therefore, if the supercritical fluid is easy to control the properties of the supercritical fluid, solvent characteristics comparable to various types of liquid solvents can be obtained with one solvent. Particularly, since carbon dioxide has a low critical temperature of 31.1 ° C, it is suitable for application to thermally denatured substances such as drugs. It is non-toxic, non-flammable and is very low in cost and can be recovered and reused. It is very ideal for application to medicinal materials because of its many advantages.

Recently, supercritical fluids have been studied in the field of selective extraction and extraction of substances by using these unique properties of supercritical fluids. In addition, supercritical fluids have been used as solvents or anti-solvent ) Have been actively studied to obtain recrystallization or fine particles.

Magnesium, which has been used previously, has a large particle size, which causes poor skin absorption. Further, if fine particles are obtained using an organic solvent, there is a side effect due to the residual organic solvent. In the present invention, supercritical carbon dioxide which does not use an organic solvent and does not require a separate separation step is used to obtain fine particles of magnesium.

The present inventors have developed a method for producing magnesium having increased skin absorption rate due to an increase in the effective cross-sectional area by making the particle size of magnesium small by using a supercritical fluid process using supercritical carbon dioxide, and the magnesium preparation prepared therefrom is used as a supercritical fluid process The crystallization of the drug itself is changed by changing the operating parameters such as the temperature and the pressure, the flow rate of the solution used together with the supercritical carbon dioxide, and the effective cross-sectional area is increased to obtain the finely divided magnesium particles, I want to complete it.

The magnesium obtained using the supercritical fluid process of the present invention can obtain ultrafine particles as compared with the conventional magnesium and has completed the process for preparing the ultrafine magnesium preparation which is expected to enhance the skin effect due to the increase of the effective cross sectional area. This microparticle magnesium can be applied to the development of a heavy metal detoxification system.

     Disclosure of Invention Technical Problem [8] Accordingly, the present invention has been made to solve the above-mentioned problems occurring in the prior art, and it is an object of the present invention to provide a preparation in which magnesium having a large particle size is refined using a supercritical fluid process to increase skin absorption rate.

Hereinafter, the present invention will be described in detail.

The present invention relates to a method for producing magnesium particles, comprising the steps of forming magnesium particles by spraying a mixed solution obtained by dissolving magnesium in an organic solvent into a supercritical fluid, and introducing a supercritical fluid into the particles to remove the organic solvent used in the mixed solution The present invention provides a method for preparing micronized magnesium using a supercritical fluid process,

The basic principle of the production method is that magnesium is dissolved in an appropriate amount of an organic solvent and then sprayed through a nozzle to a reaction vessel equilibrated with supercritical carbon dioxide to obtain particles, supercritical carbon dioxide is flowed several times to extract an organic solvent And then removing the carbon dioxide to produce finely divided magnesium.

More specifically, in the present invention, a method for producing a micronized magnesium using a supercritical fluid process comprises the steps of: 1) dissolving magnesium in an organic solvent and preparing a mixture thereof; 2) contacting the supercritical fluid with the mixed solution to form magnesium particles; 3) introducing a separate supercritical fluid into the particles to remove the organic solvent; 4) recovering the generated particles. The manufacturing method will be described in detail in each step as follows.

1) Preparation of mixed solution of magnesium for spraying

Methanol, ethanol or the like is used as the organic solvent in step 1), but ethanol which is less toxic to the human body is used in the present invention.

The organic solvent used is preferably used in an amount of 0.0001 to 0.50 parts by weight, more preferably 0.001 to 0.20 parts by weight, based on the weight of the organic solvent. When the amount is less than 0.0001 parts by weight, the amount of particles that can be obtained becomes too small, and when more than 0.50 parts by weight, magnesium is not dissolved in the organic solvent.

2) Generation of Particles through Partitioning of Mixture Solution into Supercritical Fluid

The supercritical fluid that can be used in the step 2) includes supercritical carbon dioxide, supercritical dinitrogen monoxide, supercritical methane trifluoride, supercritical propane, supercritical ethylene or supercritical xenon. In the present invention, Supercritical carbon dioxide was used.

The temperature and pressure of the stainless steel reactor were injected into the reaction vessel so that the temperature and pressure of the reactor were 31.1 and 73.8 bar, which is the critical point of the carbon dioxide, and the supercritical state was maintained by pressurization and warming. Wait until equilibrium is achieved. It is desirable to use a syringe pump to maintain a constant pressure and to know the exact amount of injection when pressurizing carbon dioxide, and to use a circulating thermostat or thermostat to keep the temperature constant. When the reaction vessel is equilibrated to the supercritical state, a mixed liquid of the magnesium and the additive prepared in the step 1) is injected into the reaction vessel at a constant rate using a small liquid pump capable of controlling the speed. In order to prevent clogging of the nozzle, it is preferable to inject a small amount of empty solvent before injection of the mixed solution, for example, about 3-4 ml, and as the amount of the co-solvent injected increases, The cleaning time by the fluid becomes longer. The injected mixed solution is injected through the nozzle, and the organic solvent in the injected mixed solution is mixed with supercritical carbon dioxide at a high speed to generate particles. A separate supercritical fluid may be injected to prevent saturation in the reaction vessel at the same time as the injection of the mixed solution.

3) Removal of organic solvent using supercritical fluid

After spraying of the mixed solution, a particle washing process is required to introduce a supercritical fluid to remove the organic solvent in the generated particles. In this process, the supercritical fluid is injected into the reactor at a constant rate, and the reactor is discharged through the outlet at the same rate as the injection rate so as to induce the reactor to a constant pressure. At this time, a back pressure regulator is connected to the outlet to regulate the discharge rate and maintain the pressure in the reaction vessel. A dual membrane filter with a 0.45μm hole size at the outlet is used to prevent the particles from escaping. When the solvent remains, the temperature and pressure are lowered to collect the particles. When the solvent is re-precipitated, the particles are re-dissolved to form agglomerates. Therefore, the washing process must be continued until the solvent is completely removed. The amount of supercritical fluid for washing depends on the amount of solvent used and the size of the reaction vessel, preferably about 2,000-3,000 ml.

4) Particle recovery

At the end of the cleaning process, the supply of supercritical fluid to the reactor is stopped and the supercritical fluid is drained. At this time, if the discharge is made too fast, the generated particles may be damaged, so it is preferable to discharge slowly. After removing all of the supercritical fluid in the reaction vessel, collect the particles from the wall or bottom of the reactor.

Hereinafter, comparative examples and examples of the present invention will be described in detail.

First, the comparative example shows pre-treatment magnesium having a particle size of 50-100 microns. In this example, the particle size of the magnesium particles produced under the following conditions was measured by a particle size analyzer and the fine particle size of 50 to 150 nm . The content of the mixed solution used for producing magnesium having a small surface area using a supercritical fluid process is 0.16 g of magnesium and 22.87 g of ethanol. The height of the sedimentation tank where the sedimentation takes place is 200 mm and the volume is 100 ml.

As shown in the following Table 1, the operating parameters in this embodiment are temperature and pressure, carbon dioxide flow rate, and solution flow rate. In Example 1-2, the temperature was controlled to change 313 and 333K, and in Example 3-4, Min of magnesium was obtained while varying the flow rate of carbon dioxide from 2.5 to 3.5 kg / hr in Example 5-6 and the flow rate of the solution from 0.5 to 1.5 ml / min in Example 7-8.

Working conditions and particle size by the four operating variables in Examples 1-8 Example Temperature (K) Pressure (bar) Carbon dioxide flow rate (kg / hr) Solution flow rate (ml / min) Particle Size (nm) Example 1 313 150 2.5 0.5 106 Example 2 333 150 2.5 0.5 125 Example 3 313 130 2.5 0.5 131 Example 4 313 170 2.5 0.5 74 Example 5 313 150 2.5 0.5 153 Example 6 313 150 3.5 0.5 52 Example 7 313 150 2.5 0.5 138 Example 8 313 150 2.5 1.5 53

The magnesium obtained using the supercritical fluid process of the present invention can obtain ultrafine particles as compared with the conventional magnesium and has completed the process for preparing the ultrafine magnesium preparation which is expected to enhance the skin effect due to the increase of the effective cross sectional area. This fine particle magnesium can be applied to a chelating heavy metal detoxification system or the like.

Claims (1)

A step of spraying a mixed solvent obtained by dissolving magnesium in an organic solvent into a supercritical fluid to form magnesium particles; and introducing a supercritical fluid to remove the organic solvent used in the mixed solution. The amount of magnesium in the organic solvent used is preferably in the range of 0.0001 to 0.50 parts by weight, more preferably in the range of 0.001 to 0.20 parts by weight, and the quasi- Application to.