KR101468608B1 - Process for manufacturing composition containing aminolevulinic acid and selenium - Google Patents

Abstract

The present invention provides a method for preparing a composition comprising a first step of dissolving aminolevulinic acid and vitamin C in a solution containing an antioxidant and a second step of dissolving lyophilized selenium in the solution of the first step.

Description

TECHNICAL FIELD The present invention relates to a process for preparing a composition containing aminolevulinic acid and selenium,

The present invention relates to a method for preparing a composition comprising selenium, aminolevulinic acid and vitamin C, and more particularly to a method for producing a composition comprising selenium having a particle size of 20 to 200 nm at a concentration of 500 to 2000 ppm (w / v) (W / v) of vitamin C, and 5 to 10% (w / v) of vitamin C at a concentration of 100 to 2000 ppm (w / v) of aminolevulinic acid.

5-aminoLevulinic Acid (ALA) is a five-carbon aliphatic compound that is an essential precursor for all tetrapyrrole biosynthesis, including chlorophyll and heme in organisms. In vivo, tetrapyrrole is biosynthesized into heme, a coenzyme such as hemoglobin, chlorophyll, and vitamin B12, through various steps. Aminolevulinic acid can be used in various ways as an environmentally friendly biochemical pesticide and biological growth promoter. However, unstability and unevenness of the composition may be a problem in the method for producing a composition containing aminolevulinic acid.

The present invention seeks to provide a method for effectively producing a composition comprising selenium, aminolevulinic acid and vitamin C.

In order to accomplish the above object, the present invention provides a method for preparing a pharmaceutical composition comprising a first step of dissolving aminolevulinic acid and vitamin C in a solution containing an antioxidant and a second step of dissolving lyophilized selenium in a solution of the first step A method for preparing a composition is provided. The first and second steps may be performed sequentially, in reverse order or concurrently.

Hereinafter, the present invention will be described in detail.

First, the first step of the method for producing a composition according to the present invention will be described. The antioxidant used in the present invention serves to prevent the oxidation of selenium and vitamin C to be described later in the composition of the present invention. Specific examples of the antioxidant include, but are not limited to, sodium metaphosphate, sodium polyphosphate, erythroelysorbic acid, and / or dibutylhydroxytoluene (BHT).

The 5-aminoLevulinic Acid (ALA) used in the method of preparing the composition according to the present invention can be used in all biological systems to form tetrapyrroles such as heme, bacterio-chlorophyll, corrinoid, tetrapyrrole compounds. Hep synthesized in the liver contributes to the synthesis of cytochrome P450 (CYP450). As a result, the carcinogens and various heavy metals are detoxified.

In the composition according to the present invention, the amount of aminolevulinic acid is preferably 100 to 2000 ppm (w / v), more preferably 500 to 1000 ppm (w / v).

The vitamin C used in the present invention is also called as ascorbic acid as one of the trace elements for maintaining the function and health of the human body. Vitamin C helps the body resist infections, heal wounds and keep tissues healthy, and is one of the antioxidants that prevents free radical damage. The vitamin C according to the present invention is preferably 5 to 10% (w / v), more specifically 7 to 8% (w / v).

In the present invention, the combination of selenium and vitamin C maximizes the antioxidant effect, enhances nonspecific immunity, and alleviates stress. In addition, the pH of the whole solution can be lowered by vitamin C, and the stability of aminolevulinic acid can be enhanced.

In the first step according to the production method of the present invention, the antioxidant is dissolved in distilled water to prepare a first solution, a second solution prepared by dissolving aminolevulinic acid in separate distilled water is mixed with the first solution, A third solution made by dissolving vitamin C in separate distilled water can be mixed into the first and second solutions. In this case, by previously dissolving the antioxidant, it is possible to prevent the vitamin C, selenium and the like from being oxidized in the solution in advance.

 Next, the second step of the method for producing a composition according to the present invention will be described. Method 2 for the preparation of the composition according to the invention The step 2 comprises dissolving lyophilized selenium in the solution formed in one step.

However, it is also possible to dissolve the solution obtained by one step in the solution after completing the two steps. In other words, the first and second lines can be reversed and progressed at the same time.

First, selenium in the present invention is an essential trace element in the body. Selenium was first discovered in 1817 by a Swedish chemist, Berselius, and was named after the goddess of the moon in Greek mythology. In 1978, the World Health Organization (WHO) and the United Nations Food and Agriculture Organization (FAO) recognized selenium as an essential nutrient and set a recommended daily dose of 50-200 μg (1 μg for 0.001 g). Selenium is a component of glutathione peroxidase, a potent antioxidant enzyme that eliminates the harmful oxygen in the body. It enhances immune function and prevents cancer. Selenium has been shown to improve immune function against hepatitis and AIDS virus, alleviate arthritis symptoms and pain, and reduce cancer incidence by 50% or more. However, excessive intake of selenium may indicate addiction. Selenium is rich in milk, broccoli, cabbage, chicken, fish, seafood, and grains.

The selenium used in the present invention is preferably nano-selenium. Nanoselenium refers to selenium having a particle size of about 20 to 200 nm, which is smaller and faster to absorb than conventional inorganic selenium. It is known to be about 10 times less toxic than conventional inorganic selenium. The selenium used in the present invention is preferably 100 to 2000 ppm (w / v), more preferably 500 to 1000 ppm (w / v).

In the method for preparing a composition according to the present invention, freeze-dried selenium is used. That is, the method for preparing a composition according to the present invention includes freeze-drying selenium. It is possible to prevent aggregation and denaturation of selenium through the lyophilization process.

The lyophilization includes a preliminary freezing step, a vacuum step and a drying step. The preliminary freezing step may proceed at -40 ° C for more than 24 hours, and the vacuum step may be at -76 ° C and 80 mtorr or less. The drying step may be carried out at -40 ° C for 24 hours, at -5 ° C for 15 hours, at 10 ° C for 15 hours, or at 25 ° C for at least 24 hours.

In the case of lyophilization of selenium, a protective agent may be further used. Examples of the protecting agent include, but are not limited to, dextrin, trhalose, mannitol, and the like. These protectors prevent flocculation and reduced dry weight when freeze-drying only selenium. That is, it is easy to increase the amount, and the solubility can be improved even in the selenium liquid phase, thereby increasing the uniformity. As a result, even when powder is formed after drying, it is possible to inject a fixed amount at a fixed concentration, and it is also easy to crush after drying.

The composition of the present invention is prepared by adding ethylenediaminetetraacetic acid (ED) (hereinafter referred to as EDTA-Fe), ethylenediaminetetraacetic acid-Cu (hereinafter referred to as EDTA- Quot; Cu "), choline chloride and sorbitol. In step 3, a solution prepared by first dissolving EDTA-Fe and EDTA-Cu in distilled water and a solution prepared by dissolving choline and sorbitol in distilled water separately may be mixed with the solution after the second step. In this case, uniform mixing of EDTA-Fe and EDTA-Cu becomes possible. Sorbitol is not very viscous and can be added at the end to allow the solution to mix well.

 The choline chloride used in the production method of the present invention has an effect of improving liver function. Sorbitol promotes metabolism, EDTA-Fe and EDTA-Cu play a role in promoting the effects of aminolevulinic acid.

Preferably, the choline chloride is 5 to 15% (w / v), sorbitol is 10 to 15% (w / v), EDTA-Fe is 0.1 to 1% (w / v) 0.5% (w / v).

In another aspect, the present invention provides a method for preparing a composition comprising a first step of dissolving aminolevulinic acid and vitamin C in a solution containing an antioxidant and a second step of dissolving lyophilized selenium in the solution of the first step ≪ / RTI > compositions. The composition prepared by the method of the present invention as described above can be applied to a variety of feeds, feed additives, cosmetics, functional foods and the like.

For example, it can be used as feed for crustaceans or feed additives. At this time, crustaceans are crustaceans consisting of prawns and injuries consisting of Litopenaeus vannamei, Marsupenaeus japonicus, Penaeus monodon, Penaeus chinensis and Penaeus morguiensis Eriocheir sinensis, crabs consisting of crabs, but are not limited thereto.

By the method for preparing a composition according to the present invention, a composition containing selenium, aminolevulinic acid and vitamin C can be stably provided. In addition, homogeneous compositions are obtained and are helpful for subsequent storage and storage.

Hereinafter, the present invention will be described in detail with reference to examples. However, the examples are given for the purpose of helping understanding of the present invention, and thus the scope of the present invention is not limited thereto.

Example  1: Method for producing selenium solution

125 ml of selenium (Nano-selenium) having a concentrate concentration of 8,000 ppm was mixed with 675 ml of distilled water. 140 g of dextrin, 140 g of trehalose and 20 g of mannitol were mixed in 700 ml of distilled water, and mixing was carried out at a low speed of 300 rp or less so as not to generate bubbles. The agitator used was a DP-Q model from Labins. 200 ml of the mixed protector was mixed with the selenium solution, and an appropriate amount of distilled water was added to make the total amount of selenium solution to 1 liter. At this time, the selenium concentration is 1,000 ppm (w / v).

Example  2: preliminarily freezing the selenium solution.

The liquid selenium solution in the homogeneous state obtained by repeating Example 1 was uniformly dispensed into a 4 L capacity stainless steel freeze-drying tray by 3 liters. When the bubbles are dried, the hardness of the part is high, so it may be difficult to uniformize the bubbles when crushed. Before the selenium solution prepared in Example 1 was introduced, the CIP of the front shelf and the rear cooling trap of the freeze dryer (PVTFD-100 of Ilshin Bio-Bose Co., Ltd.) was performed and alcohol was sprayed I have. A sample tray was inserted into the front shelf of the freeze dryer, and a temperature sensor was attached to the selenium solution of Example 1 in the upper, middle, and lower portions to preliminarily freeze. The temperature of the front shelf was lowered to -40 ° C, and the temperature of the selenium solution was waited for 24 hours or more until it became equal to the shelf. At this stage, the sugar component contained in the selenium solution of Example 1 was completely frozen.

Example  3: Pre-lyophilized selenium in a vacuum.

When the temperature of the sample in the front shelf and the tray is maintained at -40 ° C, the temperature of the cold trap at the back of the freeze drier is lowered to -76 ° C. Then, the vacuum pump is operated and the inside of the freeze- .

Example  4: drying the selenium after the vacuum step.

When the degree of vacuum was kept stable, freeze-drying was carried out at the temperature and time of Table 1 (temperature and time conditions in the drying step) below.

order Shelf temperature time One Maintained at -40 ℃ Maintain over 24hr 2 Rising section from -40 ° C to -5 ° C Temperature rise for 3 hours 3 Maintained at -5 ° C 15hr temperature maintenance 4 Rise interval from -5 ℃ to 10 ℃ Temperature rise for 15hr 5 Maintained at 10 ° C 15hr temperature maintenance 6 The rising section from 10 ° C to 25 ° C 10hr temperature rise 7 Keep at 25 ℃ 24hr temperature maintenance

Example  5: Storing selenium after the drying step.

Selenium after the steps of Examples 1 to 4 was subjected to moisture measurement (water content was measured by Kett (FD610) to be less than 7%), and then pulverized to about 100 mesh and stored at a temperature lower than 10 ° C.

Example  6: Selenium and Aminolevulinic acid  ≪ / RTI > and the like.

First, 10 g of a mixture of sodium metaphosphate and sodium polyphosphate mixed as a antioxidant in a ratio of 1: 1 was dissolved in 100 ml of water. Then, 80 g of vitamin C was dissolved to prepare a first solution. Then, 1 g of the aminolevulinic acid powder was dissolved in 10 ml of distilled water separately to prepare a second solution, and then the first solution was stirred and the second solution was added. 14 g of selenium powder passed through Examples 1 to 5 was diluted in 100 ml of water to prepare a third solution, which was then added to a mixed solution of the first solution and the second solution while stirring. Then, 5 g of EDTA-Fe and 1 g of EDTA-Cu were added to the mixed solution, and then 100 ml of choline chloride and 120 ml of sorbitol were added while stirring the solution. Distilled water was added to adjust the total volume to 1 l.

Claims (16)

A first step of dissolving aminolevulinic acid and vitamin C in a solution containing an antioxidant;
A second step of dissolving lyophilized selenium in the solution of the first step; And
And a third step of dissolving EDTA-Fe, EDTA-Cu, choline chloride and sorbitol in the solution of the second step. The method according to claim 1,
Wherein the particle size of the selenium is 20 to 200 nm. The method according to claim 1,
Wherein the freeze-drying comprises a pre-freezing step, a vacuum step, and a drying step. The method of claim 3,
The preliminary freezing step is carried out at -40 DEG C for at least 24 hours,
Wherein the vacuum step is performed at -76 [deg.] C and 80 mtorr or less. The method of claim 3,
Wherein said drying step comprises maintaining at -40 占 폚 for 24 hours, at -5 占 폚 for 15 hours, at 10 占 폚 for 15 hours, and at 25 占 폚 for at least 24 hours. The method of claim 3,
Further comprising using a protective agent in the lyophilization step. The method according to claim 6,
Wherein the protecting agent is dextrin, tricalose, and mannitol. The method according to claim 1,
The first step is to dissolve the antioxidant in distilled water to make a first solution,
A second solution prepared by dissolving the aminolevulinic acid in distilled water is mixed with the first solution,
Wherein a third solution made by dissolving the vitamin C in separate distilled water is mixed with the first and second solutions. The method according to claim 1,
Wherein the selenium is 500 to 2000 ppm (w / v)
Wherein the aminolevulinic acid is 100 to 2000 ppm (w / v)
Wherein the vitamin C is 5-10% (w / v). The method according to claim 1,
Wherein the antioxidant is sodium metaphosphate and sodium polyphosphate. delete The method according to claim 1,
In the third step, a solution prepared by first dissolving EDTA-Fe and EDTA-Cu in distilled water and a solution prepared by dissolving choline and sorbitol in distilled water separately are mixed with the solution after the second step ≪ / RTI > The method according to claim 1,
The choline chloride is 5-15% (w / v)
The sorbitol is 10-15% (w / v)
The EDTA-Fe is 0.1 to 1% (w / v)
Wherein the EDTA-Cu is 0.01 to 0.5% (w / v). 14. The method of claim 13,
The selenium is 1000 ppm (w / v)
Wherein the aminolevulinic acid is 1000 ppm (w / v)
The vitamin C is 8% (w / v)
The choline chloride was 10% (w / v)
The sorbitol is 12% (w / v)
The EDTA-Fe was 0.5% (w / v)
Wherein the EDTA-Cu is 0.1% (w / v). The method according to any one of claims 1 to 10, 12 to 14,
Compositions made by the method of making the composition. 16. The method of claim 15,
The composition comprises at least one composition selected from the group consisting of Litopenaeus vannamei, Marsupenaeus japonicus, Penaeus monodon, Penaeus chinensis, Penaeus morguiensis, (Eriocheir sinensis), crabs consisting of crabs.