KR20090007226A - Nano-particles containing calcium and method for preparing the same - Google Patents

Abstract

A manufacturing method of calcium containing nano particle is provided to control a size of calcium containing particles into 1 nm to 900 nm, to generate no coherence, to be mass-produced easily and to simplify a process. A manufacturing method of calcium containing nano particle comprises steps of: (1) dissolving a calcium supply source material in a solvent; (2) adding and agitating a polysaccharide compound in the solution obtained from the step (1); and (3) separating and refining calcium containing nano particle from the solution obtained from the step (2).

Description

Calcium-containing nanoparticles and its manufacturing method {NANO-PARTICLES CONTAINING CALCIUM AND METHOD FOR PREPARING THE SAME}

The present invention relates to nanoparticles containing calcium and a method of manufacturing the same, and more particularly, the absorption rate is superior to the conventional calcium agent, has a high purity and a certain type of nanostructure, the manufacturing process is simple and uses expensive equipment The present invention relates to a nanoparticle containing calcium and a method for producing the same, which are not easily mass-produced.

Calcium is one of the most abundant minerals in the body and is a must. About 2% of the total weight is made of calcium, and 99% of the body's calcium is in the bones. Calcium plays an important role in many parts of human enzyme activity as well as in the formation and maintenance of bones and teeth. It is also involved in the contraction of muscles and the release of neurotransmitters, regulation of the heart rate, blood clotting.

Lack of calcium in the body can cause rickets in children. Since the rickets disease may cause bone deformity and deterioration of growth development, a certain amount of calcium intake in adolescence is very important. In adults, calcium deficiency can lead to osteomalacia, low blood calcium levels can lead to muscle stiffness and leg cramps, and can also cause high blood pressure, osteoporosis and colon cancer.

Osteoporosis, in particular, literally means `` a hole in the bone, '' and in the United States more than 20 million people have osteoporosis.

Osteoporosis is generally experienced by both men and women over 40 years of bone mass loss, but women are at greater risk of developing osteoporosis. The osteoporosis is caused by a number of factors due to excessive bone loss, the form is also varied, the post-menopausal osteoporosis of women is the most common form. It is known that about one-fourth of women develop postmenopausal osteoporosis, and the loss of the spine, hips, and ribs is usually the largest, but in severe cases the entire skeleton can be affected by postmenopausal osteoporosis.

Since the bones in the human body carry large weights, they are sensitive to pain and malformations or fracture breakage. As a direct result of osteoporosis, at least 15 million fractures occur each year, about 2% of which are hip fractures, a very terrible injury for most patients. 12-20% of hip fractures are very fatal, with half of survivors undergoing long-term inpatient treatment, with one third of women and one-sixth of men experiencing hip fractures.

Conventionally, for the treatment of osteoporosis, ionized calcium liquid, calcium prepared using oyster shells, animal bones, milk, anchovies, and the like have been taken. However, when taking ionized calcium to increase bone density, the problem of adsorption of heavy metals in the body together with bones, and bones of animals can cause problems in the body. In addition, anchovies are currently very poorly absorbed, and only 1% of the anchovy's calcium content is absorbed into the body. Therefore, the conventional calcium supplementation has only a delay in the development of osteoporosis, which can be cured. Could not.

To solve this problem, many research teams and companies are spurring the development of calcium supplements with high purity, high absorption rate and easy ionization.

Calcium supplements that are currently taken and sold most are calcium carbonate. When the general public took the calcium supplement, which is the main ingredient of calcium carbonate, it was found that the degree of ionization by interacting with gastric juice was about 20%, and about 4% when the patient had little secretion of gastric juice. The cause of this phenomenon is that calcium carbonate must be easily dissolved and then reacted with gastric fluid to increase its ionization.The calcium carbonate has a high melting point (825 ℃) and is not soluble in water at room temperature. Not easy to do

However, if the size is manufactured in nano units, the surface area is maximized due to the characteristics of the nanomaterial, and thus the ionization degree is increased, thereby increasing the absorption rate in the human body. In order to produce nano-calcium having a particle size of the nano-level has been researched.

As is well known in the field of nanotechnology, unexpected properties can be found by rapid physico-chemical characterization when particles become smaller than the bore radius of the atoms that make up the material. Theoretically, since the bore radius of calcium is 0.19 nm, nano-calciums having sizes of tens to hundreds of nanometers do not have problems such as unexpected toxicity and have a significant increase in absorption compared to regular bulk calcium. have.

Korean Patent Laid-Open Publication No. 2006-91675 (Method for preparing oyster shell nanopowder having increased calcium absorption in the body) refers to a method for preparing nanocalcium having nano-level particle size by crushing abalone or oyster shell. Looking at the analysis table of nano calcium obtained by the crushing method described in the patent, Fe ₂ O ₃ , Al ₂ O ₃ , MgO, SiO ₂ , Pb, As, Ba, Mg, alkaline salts other than the calcium component Impurities are included. This means that long-term use of the nano calcium obtained by the above method can accumulate a significant amount of poisonous As (arsenic) and heavy metal Pb (lead) in the body, which may cause fatal effects on the human body.

Furthermore, the nano calcium presented in the patent has a nano particle form present in a nano size sphere. These nanoparticles tend to aggregate with each other in order to lower surface energy, and thus, it is difficult to expect an excellent improvement in absorption rate due to nanoization.

In order to solve the above-mentioned problems of the prior art, the present invention controls the size of the calcium-containing particles to a nanometer level, for example, in the range of 1 μm, more preferably 1 nm to 900 nm, no aggregation occurs, and is easy for mass production. It is a technical object of the present invention to provide a calcium-containing nanoparticle and a method for manufacturing the same, which are simplified in the process.

According to the present invention, there is provided a method for producing calcium-containing nanoparticles, wherein the polysaccharide compound is added to a solution in which a calcium source material and a solvent are mixed.

According to one embodiment of the present invention, the calcium-containing nanoparticles of the present invention

(1) dissolving the calcium source material in a solvent,

(2) adding and stirring a polysaccharide compound to the solution obtained in step (1), and

(3) is prepared through the step of separating and purifying the calcium-containing nanoparticles from the solution obtained in step (2).

In the present invention, the calcium source material is not particularly limited, and preferably a suitable calcium compound is used as the functional food or medical raw material. Specifically, calcium citrate, calcium gluconate, calcium hydroxide, calcium chloride, calcium nitrate, calcium lactate, tricalcium phosphate, dibasic calcium phosphate, calcium phosphate, calcium carbonate, calcium pantothenate, calcium propionate, calcium sulfate, calcium phosphate, and oxide Any one selected from the group consisting of calcium, calcium ascorbate, calcium alginate, calcium acetate, calcium sorbate, shell-derived calcium material, seaweed calcium and combinations thereof can be used as the calcium source material.

In the present invention, the solvent may be used without limitation as long as it can dissolve the calcium source material as described above at room temperature or by heating, and preferably a solvent suitable for the production of functional food or medical raw materials is used. Specifically, a solvent selected from the group consisting of water, lower alcohols (eg, alcohols having 1 to 6 carbon atoms such as methanol, ethanol propanol, etc.), acetone, acetic acid aqueous solution, and combinations thereof can be used.

In the present invention, the type of the polysaccharide compound is not particularly limited, and both natural and synthetic polysaccharide compounds may be used. Preferably, starch, chitin, chitosan, alginic acid, carboxymethyl cellulose (CMC), hydroxymethyl cellulose (HMC), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), hydroxypropyl methyl cellulose (HPMC ) And combinations thereof are used.

The calcium-containing nanoparticles prepared according to the present invention preferably have a diameter of 1 μm or less, more preferably 1 nm to 900 nm.

Through the present invention, it is possible to mass-produce calcium-containing nanoparticles by chemical synthesis using harmless raw materials. The prepared calcium-containing nanoparticles have a particle size adjusted to the nano level, have a high absorption rate and high purity, and can be adjusted so as not to undergo the absorption / digestion process in the gastrointestinal tract during the administration of the biomass. In the method of producing calcium-containing nanoparticles of the present invention, unlike conventional nanocalcium production techniques, expensive production is possible without using expensive equipment, and thus mass distribution is possible at a low price.

Hereinafter, the method for preparing calcium-containing nanoparticles of the present invention will be described in detail step by step.

(1) step: dissolution of calcium source material

The calcium source material is added to a solvent and then dissolved by heating and stirring as necessary.

There is no particular limitation on the kind of calcium source material, and preferably, suitable calcium compounds are used as functional food or medical raw materials. It is advisable to use ingredients that have been recognized as safe by the Food and Drug Administration. Specifically, calcium citrate, calcium gluconate, calcium hydroxide, calcium chloride, calcium nitrate, calcium lactate, tricalcium phosphate, dibasic calcium phosphate, calcium phosphate, calcium carbonate, calcium pantothenate, calcium propionate, calcium sulfate, calcium phosphate, and oxide Any one selected from the group consisting of calcium, calcium ascorbate, calcium alginate, calcium acetate, calcium sorbate, shell-derived calcium material, seaweed calcium and combinations thereof can be used as the calcium source material.

As the solvent, any solvent capable of dissolving the calcium source material can be used without limitation, and preferably a solvent suitable for the production of the functional food or medical raw material is used. Specifically, one selected from the group consisting of water, lower alcohols (for example, alcohols having 1 to 6 carbon atoms such as methanol, ethanol propanol, etc.), acetone, acetic acid aqueous solution, and combinations thereof can be used as the solvent. It is preferable to use water which is harmless to the human body.

The amount of calcium source material used may be appropriately selected in view of the solubility in the selected solvent. For example, when water is used as the solvent, it is preferable to allow the solution concentration of the calcium source to be determined within the concentration range of 0.001 M to 0.5 M, but is not limited thereto. However, if the amount of the calcium source material is used too little, the productivity and efficiency of the manufacturing process may be lowered. If the amount is too high, nanoparticles may not be effectively formed.

There is no particular restriction on the temperature conditions upon dissolution of the calcium source material. Thus, the calcium source material may be dissolved in the solvent even at room temperature, but heating is preferred to obtain more complete and rapid dissolution. There is no particular limitation on the heating temperature conditions, and for example, the boiling point of the solvent may be appropriately selected within the range of 25 to 150 ° C, preferably 90 to 110 ° C. Dissolution of the calcium source material may be performed for 0.5 to 24 hours, but is not limited thereto.

When dissolving the calcium source material, various reactions occur in the solvent depending on the type of raw material. For example, in the case of calcium carbonate, a reaction as in Scheme 1 below occurs.

CaCO ₃ (s) + 2H ⁺ (aq) → Ca ^{2 +} (aq) + CO ₂ (g) ↑ + H ₂ O

As shown in Scheme 1, when calcium carbonate is used as a raw material, when dissolved in water, it is ionized with calcium ions and carbon dioxide and water are generated. Carbon dioxide generated at this time becomes a gas and is discharged from the reactor.

(2) step: addition of the polysaccharide compound

The polysaccharide compound is added to the solution of the calcium source material obtained in step (1) and stirred to form calcium-containing nanoparticles. When a polysaccharide compound is added to a solution containing ionized calcium, it is determined that the polysaccharide compound forms a kind of complex structure while forming an ionic bond with calcium ions.

There is no particular restriction on the amount of the polysaccharide compound, and considering the solubility of the polysaccharide compound relative to the solvent, the polysaccharide compound is used within a range of 50 parts by weight per 100 parts by weight of the solvent. It is also desirable to select appropriately within the range of 0.01 to 10 moles per mole of calcium source material in solution. If the concentration of the polysaccharide compound is lower than the above-mentioned level, the size of the calcium-containing particles may be increased, and if it exceeds the above range, the use of excessive polysaccharide compounds may lead to a decrease in the purity and content of the calcium-containing nanoparticles.

As the polysaccharide compound, both natural or synthetic polysaccharide compounds can be used, and those that are harmless to humans and non-toxic are preferable. Specifically, starch, chitin, chitosan, alginic acid, carboxymethyl cellulose (CMC), hydroxymethyl cellulose (HMC), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), hydroxypropyl methyl cellulose (HPMC ) And combinations thereof are used.

There are no particular limitations on the temperature conditions upon addition and stirring of the polysaccharide compound, and for example, the boiling point of the solvent and the kind of the polysaccharide compound may be appropriately selected within the range of 25 to 150 ° C, preferably 90 to 110 ° C. Addition and stirring of the polysaccharide compound may be performed for 0.5 to 24 hours, but is not limited thereto.

(3) step: separation and purification of calcium-containing nanoparticles

A separation process is performed to selectively recover only calcium-containing nanoparticles from the solution obtained in step (2), and a purification process is performed to increase purity.

There is no particular limitation on the method of separation and purification, and the separation and purification methods and apparatus known in the art are carried out as it is or as appropriately modified. For example, separation and purification can be carried out by filter filtration, adsorption, electrophoresis, reverse osmosis, precipitation, and the like. A separation method using a micro filter is preferable in terms of mass production.

In the method for preparing calcium-containing nanoparticles of the present invention, in addition to the components and / or steps as described above, the method may further include additional ingredients and / or steps usable within the scope of achieving the object of the present invention. .

The calcium-containing nanoparticles obtained according to the present invention have a nanometer size size of less than 1 μm, preferably in the range of 1 nm to 900 nm nm.

On the contrary, the calcium-containing nanoparticles of the present invention have the advantage of being easily ionized and absorbed in the solution and the body since the aggregation of the particles of the present invention does not occur significantly between the fine calcium particles prepared by the conventional crushing method. Have Therefore, it is not only useful for the treatment and prevention of various diseases caused by calcium deficiency such as osteoporosis, rickets, osteomalacia, hypertension and colon cancer, but also in the form of health supplements such as various solid preparations or liquid drinks. . In addition, the calcium-containing nanoparticles of the present invention is directly transferred to the blood to increase the bone density, and the extra calcium-containing particles are excreted in vitro by the blood, it is possible to take a larger amount than conventional calcium supplements.

Therefore, according to another aspect of the present invention, there is provided a functional food for calcium supplement containing calcium-containing nanoparticles obtained according to the present invention. Functional food for calcium supplement which can be provided according to the present invention is characterized in that it comprises calcium-containing nanoparticles obtained according to the present invention as the main functional ingredient, and further includes various additive components such as excipients commonly used in functional food. can do. In addition, the preparation of the calcium supplement functional food can be prepared in a functional food formulation (such as tablets, capsules, suspensions, etc.) commonly known in the art, there is no particular limitation on the preparation method.

Hereinafter, preferred examples are provided to aid in understanding the present invention. However, the following examples are merely provided to more easily understand the present invention, and the contents of the present invention are not limited by the examples.

[ Example ]

Example  One

Calcium pantothenate was added to water to dissolve at 25 mM and then heated at 90 ° C. for 10 minutes. Chitosan was added thereto at a concentration of 12.5 mM and then mixed uniformly at the same temperature for 2 hours.

The obtained mixture was separated using a micro filter and dried to obtain calcium fine nanoparticles in the form of white fine powder, and the photograph is shown in FIG. 1.

The obtained calcium-containing nanoparticles were photographed in the form of particles using a field emission scanning electron microscope (FE-SEM). 2 is an FE-SEM photograph of the calcium-containing nanoparticles prepared in Example 1. Referring to FIG. 2, it can be seen that the nanoparticles prepared according to the present invention not only generate little agglomeration but also have a nanometer diameter of a small diameter of 1 nm to 900 nm.

In addition, EDX (Energy-dispersive X-ray spectroscopy) analysis was performed on the obtained calcium-containing nanoparticles, and the results are shown in FIG. 8.

Example  2

Calcium-containing nanoparticles were prepared in the same manner as in Example 1 except that calcium gluconate was used as the calcium source compound. As a result, white fine powder-containing calcium-containing nanoparticles were obtained, and FE-SEM observation confirmed that nanoparticles having a particle diameter of about 1 nm to about 900 nm were obtained in the same manner as in Example 1.

Example  3

Calcium-containing nanoparticles were prepared in the same manner as in Example 1 except that starch was used as the polysaccharide compound. As a result, white fine powder-containing calcium-containing nanoparticles were obtained, and FE-SEM observation confirmed that nanoparticles having a particle diameter of about 1 nm to about 900 nm were obtained in the same manner as in Example 1.

Example  4

Calcium-containing nanoparticles were prepared in the same manner as in Example 1 except that carboxymethylcellulose was used as the polysaccharide compound. As a result, white fine powder-containing calcium-containing nanoparticles were obtained, and FE-SEM observation confirmed that nanoparticles having a particle diameter of about 1 nm to about 900 nm were obtained in the same manner as in Example 1.

Comparative Experiment  One

For comparison with the calcium-containing nanoparticles obtained in Example 1, particle shapes were photographed using FE-SEM for commercially available nanocalcium products. The results are shown in FIGS. 3 to 5.

3 is a 1000 times magnification FE-SEM photograph of oyster shell nanocalcium nutritional supplement sold in CVS pharmacy in the United States, FIG. 4 is a 20000 times magnification FE-SEM photograph of oyster shell fractured nano calcium sold in Korea. Figure 5 is a 1000 times magnification FE-SEM picture of calcium nutritional supplement is also sold in Korea. 3 to 5, it can be seen that in the case of conventional commercially available nano calcium preparations, aggregation occurs severely.

Comparative Experiment  2

In order to determine the solubility of calcium nanoparticles in the aqueous solution, each of the nanoparticles prepared in Example 1 and commercially available nanocalcium (crushing method) were added to 0.2 ml of 100 ml of water at room temperature.

6 is a side (a) and a front photograph (b) showing the state after dissolving the nano calcium prepared by the crushing method in water, Figure 7 is a calcium-containing nanoparticles prepared in Example 1 dissolved in water Side (a) and front photograph (b) which show the post state.

According to Figure 6 it can be seen that in the case of the conventional nano calcium prepared by the shredding method, the degree of cohesion is very large and is hardly dissolved in water at room temperature. In comparison, the calcium-containing nanoparticles prepared according to the present invention, as shown in Figure 7, immediately dissolved in water at room temperature as soon as added to form a transparent solution, it can be seen that showed very excellent dissolution characteristics.

As described above, the calcium-containing nanoparticles prepared by the chemical synthesis method through the present invention can control the particle size to the nanometer level, and have advantages of high absorption rate and high purity. In addition, high-priced equipment is not used, and mass production at low cost is possible, and it is expected that the effect of distributing nano calcium agent at a low price.

1 is a photograph of the result prepared in Example 1.

2 is a field emission scanning electron microscope (FE-SEM) photograph of the calcium-containing nanoparticles prepared in Example 1. FIG.

3 is a 1000-fold magnification FE-SEM photograph of an oyster shell nanocalcium nutritional supplement sold in the CVS pharmacy of the United States.

Figure 4 is a 20000 times magnification FE-SEM picture of oyster shell crushed nano calcium sold in Korea.

Figure 5 is a 1000 times magnification FE-SEM picture of the calcium nutritional supplement that is sold in Korea.

Figure 6 is a side (a) and front view (b) showing the state after dissolving the existing nano-calcium product prepared by the shredding method in water.

7 is a side (a) and a front photograph (b) showing a state after dissolving the calcium-containing nanoparticles prepared in Example 1 in water.

8 is an EDX analysis spectrum of the calcium containing nanoparticles prepared in Example 1. FIG.

Claims (11)

A method for producing calcium-containing nanoparticles, comprising adding a polysaccharide compound to a solution in which a calcium source material and a solvent are mixed. The method of claim 1, (1) dissolving the calcium source material in a solvent, (2) adding and stirring a polysaccharide compound to the solution obtained in step (1), and (3) separating and purifying the calcium-containing nanoparticles from the solution obtained in the step (2). The method of claim 1, Calcium source materials include calcium citrate, calcium gluconate, calcium hydroxide, calcium chloride, calcium nitrate, calcium lactate, tricalcium phosphate, calcium diphosphate, monobasic calcium phosphate, calcium carbonate, calcium pantothenate, calcium propionate, calcium sulfate, calcium phosphate, A method for producing calcium-containing nanoparticles, characterized in that selected from the group consisting of calcium oxide, calcium ascorbate, calcium alginate, calcium acetate, calcium sorbate, calcium material derived from shells, seaweed calcium, and combinations thereof. The method of claim 1, The solvent is a method for producing calcium-containing nanoparticles, characterized in that selected from the group consisting of water, lower alcohol, acetone, aqueous acetic acid, and combinations thereof. The method of claim 1, The polysaccharide compound is calcium, characterized in that selected from the group consisting of starch, chitin, chitosan, alginic acid, carboxymethyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose and combinations thereof Method for producing a containing nanoparticles. The method of claim 2, Method for producing calcium-containing nanoparticles, characterized in that the dissolution of the calcium source material in step (1) is carried out at 25 to 150 ℃. The method of claim 2, The method of producing calcium-containing nanoparticles, characterized in that the addition and stirring of the polysaccharide compound in step (2) is carried out at 25 to 150 ℃. The method of claim 2, Separation and purification in step (3) is a method for producing calcium-containing nanoparticles, characterized in that carried out by one of the methods selected from filter filtration, adsorption, electrophoresis, reverse osmosis, precipitation. Calcium containing nanoparticles manufactured by the method of any one of Claims 1-8 and whose particle diameter is 1 micrometer or less. The method of claim 9, Calcium-containing nanoparticles having a particle diameter ranging from 1 nm to 900 nm 900. Functional food for calcium supplement containing calcium containing nanoparticles manufactured by the method of any one of Claims 1-8.

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