KR20140078878A - Development of Hari Detoxification System Containing Micronized Zinc Using Supercritical Nano Particle System - Google Patents

Abstract

The present invention relates to a nanoparticle zinc preparation using an environmentally-friendly supercritical fluid process and a chelating heavy metal detoxification system containing the same, wherein a mixed solution obtained by dissolving zinc in an organic solvent is sprayed onto a supercritical fluid to form zinc particles And introducing a supercritical fluid into the particle to remove the organic solvent used in the mixed solution. A method of producing particles of ultrafine fine particle zinc using a supercritical fluid process, And to the use of a detoxification system. The manufacturing method of the present invention changes the crystallization degree of the drug itself by changing the temperature and pressure which are operating variables of the supercritical fluid process or by changing the flow rate of supercritical carbon dioxide and the solution of zinc and organic solvent, Can be usefully employed in the preparation of zinc preparations for which improvement of skin efficacy is expected.

Description

TECHNICAL FIELD The present invention relates to a method for preparing an antidote for hair heavy metals containing supercritical zinc nanostructures,

The present invention relates to the development of heavy metal antidotes containing zinc microparticles containing supercritical zinc nanostructures, comprising the steps of: dissolving zinc in an environmentally-friendly supercritical fluid and then spraying to contact to produce zinc particles; And removing the organic solvent used in the mixed solution. The present invention relates to an application of the rapid-expansion supercritical fluid to the development of a heavy metal detoxifier for producing ultrafine zinc particles.

In general, zinc is an essential component of 80 kinds of enzymes that plays an important role in the body and is an essential trace element deeply related to the action of hormones such as insulin. It is also an inorganic substance involved in nucleic acid synthesis and protein synthesis. 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.

Previously used zinc has a large particle size and has poor skin absorption rate. When fine particles are obtained using an organic solvent, there is a side effect due to the residual organic solvent. In the present invention, it is desired to obtain fine particles of zinc by using supercritical carbon dioxide without using an organic solvent and not requiring a separate separation step.

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

The zinc obtained by using the supercritical fluid process of the present invention was able to obtain ultrafine particles as compared with the conventional zinc, and completed the manufacturing process of the ultrafine zinc formulation, which is expected to enhance the skin effect due to the increase of the effective cross-sectional area. This microparticle zinc can be applied to the development of a chelating heavy metal detoxification system.

     Disclosure of Invention Technical Problem [9] 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 the skin absorption rate is increased by refining zinc having a large particle size using a supercritical fluid process.

Hereinafter, the present invention will be described in detail.

The present invention provides a method for producing zinc particles, comprising the steps of: preparing zinc particles by spraying a mixed solution obtained by dissolving zinc 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 To provide a method of making micronized zinc using a supercritical fluid process.

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

More specifically, in the present invention, a method for producing finely divided zinc using a supercritical fluid process comprises the steps of: 1) dissolving zinc in an organic solvent and preparing a mixture thereof; 2) contacting the supercritical fluid with the mixed solution to form zinc 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 zinc 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 preferably contains 0.0001 to 0.50 parts by weight of zinc, more preferably 0.001 to 0.20 parts by weight. When the amount is less than 0.0001 parts by weight, the amount of particles that can be obtained becomes too small, and when the amount is more than 0.50 parts by weight, zinc 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 zinc and the additive prepared in step 1) is injected into the reaction vessel at a constant rate by using a small liquid pump capable of controlling the exact 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 zinc of 50-100 micron particle size. The zinc particles produced in the following conditions were measured for particle size by a particle size analyzer, and the fine particle size of 50 to 150 nm . The mixed solution used for preparing zinc with a small surface area using a supercritical fluid process is 0.16 g of zinc and 22.23 g of ethanol. The height of the sedimentation tank where the precipitation occurs 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, Fine carbonized zinc could be obtained by changing the carbon dioxide flow rate from 2.5 to 3.5 kg / hr in Example 5-6 and the solution flow rate 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 0.5 114 Example 2 333 150 2.5 0.5 138 Example 3 313 130 2.5 0.5 131 Example 4 313 170 2.5 0.5 68 Example 5 313 150 2.5 0.5 155 Example 6 313 150 3.5 0.5 53 Example 7 313 150 2.5 0.5 139 Example 8 313 150 2.5 1.5 53

The zinc obtained by using the supercritical fluid process of the present invention was able to obtain ultrafine particles as compared with the conventional zinc, and completed the manufacturing process of the ultrafine zinc formulation, which is expected to enhance the skin effect due to the increase of the effective cross-sectional area. This fine particle zinc can be applied to a chelating heavy metal detoxification system or the like.

Claims (1)

Comprising the steps of: spraying a mixed solvent obtained by dissolving zinc in an organic solvent into a supercritical fluid to produce zinc particles; and introducing a supercritical fluid to remove the organic solvent used in the mixed solution. The amount of zinc is preferably 0.0001 to 0.50 parts by weight, more preferably 0.001 to 0.20 parts by weight in the organic solvent to be used, Application to.