KR20080019966A - Liquid formulation containing calcium, magnesium and vitamin, and preparing method thereof - Google Patents

Abstract

A liquid formulation containing calcium, magnesium and vitamin is provided to improve absorption rate of calcium, magnesium and vitamin and shield bitter taste of calcium by improving stability of calcium, magnesium and vitamin in aqueous solution, so that it is useful for prevention of diseases including osteomalacia, osteoporosis, rickets and growth retardation of growing children. A liquid formulation contains 0.1-0.5 wt.% of calcium salt, 0.05-0.3 wt.% of magnesium salt and vitamin, and further contains 1-3 wt.% of organic acid, 1-5 wt.% of stabilizing agent and 0.02-0.1 wt.% of bittering agent, wherein the calcium salt is selected from calcium gluconate, calcium lactate and a mixture thereof; the magnesium salt is selected from magnesium oxide, magnesium carbonate, magnesium hydroxide and a mixture thereof; the organic acid salt is selected from maleic acid, citric acid, tartaric acid, ascorbic acid and a mixture thereof; the stabilizing agent is selected from polyvinylpyrrolidone, cyclodextrin and a mixture thereof; and the bittering agent is selected from stevioside, acesulfame potassium and aspartame mixture and a mixture thereof. A method for preparing the liquid formulation containing calcium, magnesium and vitamin comprises the steps of: mixing and agitating calcium and stabilizing agent to prepare transparent solution; adding an organic acid into the transparent solution and stirring the organic acid; adding magnesium into the solution and stirring the mixture at 0-40 deg. C; and adding bittering agent into the mixture.

Description

Liquid Formulation Containing Calcium, Magnesium and Vitamin, and Preparing Method Thereof}

The present invention is a liquid formulation containing calcium, magnesium and vitamins.

More specifically, in a composition containing calcium, magnesium and vitamins, by providing a liquid composition comprising an organic acid, a stabilizer and a bitter agent, it is not present in suspension in an existing aqueous solution or stable over time such as precipitation phenomenon. Solving the problem that has not been solved, there is a feature that is a liquid composition having stability in aqueous solution.

Calcium salts are well known for the treatment of calcium deficiency, and hence the syndrome. In acceptable and effective treatments, calcium salt-based calcium preparations should have high calcium ions content to facilitate body absorption.

Most commercially available calcium medicines include oral solid tablets (tablets, chewable tablets, capsules), and a single combination of calcium salt, calcium salt, vitamin D and its active agent, and magnesium salt.

These formulations contain more than the required amount of calcium and have a very low bioabsorption rate of 30% in actual calcium. In addition, in the case of chewable tablets that are large or chewable tablets, it is inconvenient to take in children or elderly people who are difficult to chew.

In addition, calcium salts, magnesium salts, vitamin D, or active agents included in the solid preparation of the calcium salt mono- or co-formulations are insoluble ingredients. Therefore, in recent years, the dose of vitamin D and its derivatives is increased in order to increase the absorption of calcium, or in the case of effervescent tablets, the tablets are dissolved in a glass of water and administered as foaming.

However, in the case of effervescent tablets, there is an inconvenience of preparing a container and water separately, and also has disadvantages of causing gastrointestinal disorders.

On the other hand, when calcium salts and magnesium salts are administered in the form of an aqueous solution, calcium and magnesium absorption can be expected to be increased, and they can be easily taken and alleviate side effects. However, there are many problems in preparing calcium and magnesium into liquid formulations containing a sufficient amount (more than 300 mg as calcium) to anticipate drug efficacy. The aqueous solution in the form of a liquid, such as is present in the suspension in the aqueous solution, it is not stable in the change over time, such as precipitation phenomenon and has the disadvantage of having to shield them because of the unpleasant taste, flavor, etc. peculiar to the mineral, but has been solved until now It does not provide a way to do it.

Accordingly, the present invention provides an inorganic supplement to prevent diseases such as osteomalacia, osteoporosis, rickets, and developmental development of children in lack of calcium intake, a sufficient amount for the purpose of improving the disadvantages and side effects of solids Calcium salt (300 mg as calcium), magnesium salt (100 mg as magnesium) and vitamins were prepared in a stable state in an aqueous solution to improve the absorption of calcium, magnesium and vitamins, as well as to shield the unique bitter taste of calcium. It is characterized by manufacturing.

The present invention is a liquid formulation containing calcium, magnesium and vitamins.

More specifically, in the composition containing calcium, magnesium and vitamins, by preparing a liquid composition comprising an organic acid, a stabilizer and a bitter agent, it is present as a suspension in an existing aqueous solution or is not stable over time changes such as precipitation phenomenon It solves a problem and provides the liquid composition which has stability also in aqueous solution.

In order to achieve the above object, the composition containing calcium salt, magnesium salt and vitamin according to the present invention can be made including an organic acid, stabilizer and bitter agent.

The calcium salt may be selected from the group consisting of calcium gluconate, calcium lactate, calcium carbonate and mixtures thereof, and may be 0.1 (w / v) to 0.5 (w / v) wt% based on the total weight of the composition. It can be included.

The magnesium salt may be selected from the group consisting of magnesium oxide, magnesium carbonate, magnesium hydroxide or a mixture thereof, and may be included in an amount of 0.05 (w / v) to 0.3 (w / v) wt% based on the total weight of the composition. Can be done.

The organic acid salt may be selected from the group consisting of malic acid, citric acid, tartaric acid, ascorbic acid or mixtures thereof, and may be 1 (w / v) to 3 (w / v) wt% based on the total weight of the composition. It can be included.

The stabilizer may be selected from the group consisting of polyvinylpyrrolidone, cyclodextrin liquid or mixtures thereof, and may be 1 (w / v) to 5 (w / v) wt% based on the total weight of the composition. It can be included.

The vitamin may be vitamin D.

The magnesium salt may be magnesium oxide.

The stabilizer may be a cyclodextrin solution.

The bitter agent is selected from the group consisting of steviosides, mixtures of acesulfa potassium and aspartame, and mixtures thereof, and comprises 0.02 (w / v) to 0.1 (w / v) weight% of the total weight of the composition. Can be.

Hereinafter, the present invention will be described in detail.

Still another object according to the present invention is a method for preparing a composition containing calcium salt, magnesium salt and vitamin, comprising the steps of mixing calcium and stabilizer to form a transparent solution; Mixing and stirring an organic acid in the stirring solution; And mixing magnesium and stirring the mixture at 0 ° C to 40 ° C.

The calcium source according to the present invention may be used at least one of calcium gluconate, calcium lactate, calcium carbonate. Preferably calcium gluconate or calcium lactate can be used. Calcium according to the present invention may be included to be 0.1 (w / v) to 0.5 (w / v) wt% of the total weight of the composition. If the content exceeds 0.5 (w / v) wt%, the calcium content drops and precipitates and discolors.

As a source of magnesium according to the present invention, one or more magnesium oxides, magnesium carbonates, and magnesium hydroxides may be used. Magnesium according to the present invention may be included to be 0.05 (w / v) to 0.3 (w / v) wt% of the total weight of the composition.

The organic acid according to the present invention may be one or more of malic acid citric acid, tartaric acid, ascorbic acid. Preferably malic acid may be used. The organic acid according to the present invention may be included to be 1 (w / v) to 3 (w / v) wt% of the total weight of the composition.

If it is less than 1 (w / v)% by weight, the solubility of calcium and magnesium decreases, causing precipitation, and the ability to mask the unique taste of calcium decreases.If the acid is used more than 3 (w / v)% by weight, It can irritate the gastric mucosa.

Vitamins according to the invention enhance the absorption of calcium in the composition. Preferred vitamin according to the present invention is vitamin D (cholecalciferol), the vitamin D can be mixed solubilized by a known method.

As the stabilizer according to the present invention, one or more polyvinylpyrrolidone and cyclodestrin solution may be used. Preferably cichdextrin liquid may be used, and the stabilizer according to the present invention may be included to be 1 (w / v) to 5% by weight of the total weight of the composition.

If it is less than 1 (w / v)% by weight, the active ingredients may not be sufficiently stabilized in solution, causing turbidity and precipitation, and an amount of more than 5 (w / v)% by weight interacts with the active ingredients to form coprecipitates. do.

As a bitter according to the present invention can be selected and used from the group consisting of steviosides, mixtures of acesulfa potassium and aspartame and mixtures thereof. The bitumen may be included in an amount of 0.02 (w / v) to 0.1 (w / v) wt% based on the total weight of the composition, more preferably 0.03 (w / v) to 0.08 (w / v It may be included in weight percent.

On the other hand, the process of preparing calcium and magnesium-containing liquids is temperature sensitive. Therefore, the liquid composition according to the present invention can be prepared at 40 ℃ or less. In case of magnesium salt, it should be prepared at 40 degrees C or less to prepare a clear solution of calcium and magnesium solution. Manufacturing above 40 degrees Celsius is undesirable due to discoloration and formation of precipitates.

Hereinafter, the present invention will be described in detail through Examples and Comparative Examples, but the purpose of the present invention is not limited to the limited scope of the Examples and Comparative Examples described.

Example 1

1.9 g of calcium gluconate, 1 g of calcium lactate, 3 g of cyclodextrin solution, and 60 mg of sodium benzoate were slowly added to 70 ml of purified water, followed by stirring at 95 ° C./40 min for dissolving into a completely clear solution. Prepared. 248.8 mg of magnesium oxide was slowly added to the stirred solution at 38 ° C. to prepare a clear solution, followed by sterile purified water to obtain 100 ml.

Comparative Example 1

1.9 g of calcium gluconate, 1 g of calcium lactate, and 60 mg of sodium benzoate were slowly added to 70 ml of purified water, followed by stirring at 95 ° C./40 minutes for dissolving into a completely clear solution.

248.8 mg of magnesium oxide was slowly added to the stirred solution at 38 ° C. to prepare a clear solution, and then sterile purified water was added to make 100 ml.

Comparative Example 2

1.9 g of calcium gluconate, 1 g of calcium lactate, and 60 mg of sodium benzoate were slowly added to 70 ml of purified water, followed by stirring at 95 ° C./40 minutes for dissolving into a completely clear solution.

248.8 mg of magnesium oxide was slowly added to the stirred solution at 38 ° C., 1.5 g of polyethylene glycol prepared in a clear solution state was added thereto, stirred and homogenized, and then sterilized to 100 ml.

Comparative Example 3

1.9 g of calcium gluconate, 1 g of calcium lactate, 3 g of cyclodextrin solution, and 60 mg of sodium benzoate were slowly added to 70 ml of purified water, followed by stirring at 95 ° C./40 min for dissolving into a completely clear solution. Prepared.

248.8 mg of magnesium oxide was slowly added to the stirred solution at 50 ° C. to prepare a clear solution, followed by sterile purified water to obtain 100 ml.

[Comparative Example 4]

To 70 ml of purified water, 3.8 g of calcium gluconate, 2 g of calcium lactate, 4.8 g of cyclodextrin solution, and 60 mg of sodium benzoate were slowly added and stirred for 95 ° C / 40 minutes, dissolved in a completely clear solution. A liquid was prepared.

248.8 mg of magnesium oxide was slowly added to the stirred solution at 38 ° C. to prepare a clear solution, and then sterile purified water was added to make 100 ml.

[Comparative Example 5]

To 70 ml of purified water, 6.3 g of calcium gluconate, 3.3 g of calcium lactate, 5 g of cyclodextrin solution, and 60 mg of sodium benzoate were slowly added to the solution. The mixture was stirred at 95 ° C / 40 minutes, dissolved in a completely clear solution. Was prepared.

248.8 mg of magnesium oxide was slowly added to the stirred solution at 38 ° C. to prepare a clear solution, and then sterile purified water was added to make 100 ml.

Example 2

The stable calcium-containing solution of Example 1 was mixed with vitamin D to aid the absorption of calcium.

Solubilization of vitamin D (400 IU) was prepared through known solubilization methods. In 70 ml of purified water, 1.9 g of calcium gluconate, 1 g of calcium lactate, 3 g of cyclodextrin solution, 60 mg of sodium benzoate, 1 g per bag, 4 g of sorbitol, and sodium succinate were slowly added as a copper and stirred for 95 ° C / 40 minutes to dissolve into a completely clear solution. After cooling slowly, 2 g of malic acid was added thereto to prepare a clear liquid.

248.8 mg of magnesium oxide was slowly added to the stirring solution at 38 ° C. to prepare a clear solution, and then the vitamin D solubilizing solution was added to the stirring solution in order, and then, sterile purified water was added to make 100 milliliters.

[Examples 3 to 8 and Comparative Examples 6 to 11]

To the solution prepared according to Example 2, the masking agent was added and mixed according to the composition shown in Table 1 below, and the flavoring agent was put in line with 100 ml and sealed in a container and sterilized.

Table 1

Stevioside Sasesulpam Potassium + Aspartame Acesulfame Potassium Aspartame Example 3 0.02% - - - Example 4 0.05% - - - Example 5 0.11% - - - Example 6 - 0.03% + 0.02% - - Example 7 - 0.03% + 0.04% - - Example 8 - 0.05% + 0.05% - - Comparative Example 6 - - 0.04% - Comparative Example 7 - - 0.06% - Comparative Example 8 - - 0.1% - Comparative Example 9 - - - 0.03% Comparative Example 10 - - - 0.05% Comparative Example 11 - - - 0.1%

[Test Example 1]

Through Example 1 and Comparative Examples 1 to 5 through the calcium salt and magnesium salt solubility test in the aqueous solution to determine the amount of calcium and magnesium that can be prepared as a liquid, to determine the production method ensured stability in the preparation thereof It was.

Prepared Examples and Comparative Examples Packed in a brown bottle and stored at room temperature, refrigerated, accelerated conditions to confirm the change in appearance (discoloration, precipitation generation) and the content change of the main components and the results are shown in Table 2 and Table 3 Described.

[Table 2]

Example 1 Comparative Example 1 Comparative Example 2 Comparative Example 3 Room temperature Acceleration Room temperature Acceleration Room temperature Acceleration Room temperature Acceleration discoloration - - - - - - 0 0 Precipitation - - - 0 0 0 0 0

Table 3

Example 2 Comparative Example 4 Comparative Example 5 Room temperature Acceleration Room temperature Acceleration Room temperature Acceleration Ca content change (%) 120 119.3 120 95 120 55 Mg content change (%) 102 101 103 83 102 47 Sedimentation - - 0 - 0 discoloration - - - 0 0 0

In the preparation of calcium and magnesium-containing liquid formulations, discoloration and precipitation were found in Comparative Example 3, in which the temperature exceeded 40 ° C. when magnesium oxide was administered. This is considered to be due to the interaction of magnesium oxide with calcium salts and other sugars. On the other hand, there was little change in the content of the liquid preparation prepared according to the preparation method of Example 1.

Comparative Example 4 (Calcium 5.9g) and Comparative Example 5 (Calcium 9.6g) were prepared as a liquid by precipitation and browning under accelerated conditions as a result of the content test and the stability test to confirm the solubility and stability by increasing the calcium content. It was confirmed that the stability was poor.

When the vitamin D was mixed with the stable calcium-containing solution of Example 1 through Example 2, discoloration, precipitation, and the like did not occur and the stable solution state was maintained.

[Test Example 2]

In Examples 3 to 8, and Comparative Examples 6 to 11, to investigate the taste preference of the liquid to improve the bitterness and bitterness peculiar to calcium, 21 adult men and women in their twenties and thirties were performed. 4 is shown.

Table 4

Artificial sweeteners Examples 3 to 5 Examples 6-8 Comparative Examples 6 to 8 Comparative Examples 9 to 11 Affinity (persons) 9 7 3 2

 The masking effect was shown in Examples 3 to 5 of the stevioside-containing solution and Examples 6 to 8 of the acesulpam potassium and aspartame-containing solution, especially Example 4 containing 0.5% stevioside was better. It was.

The present invention is a liquid composition containing calcium, magnesium, and vitamins, which is an excellent calcium liquid pharmaceutical composition that can be added to organic tablets and stabilizers to reduce the convenience of taking, improve the absorption rate, and reduce side effects compared to tablets and capsules.

Claims (10)

A composition comprising a calcium salt, a magnesium salt and a vitamin, wherein the liquid composition comprises an organic acid, a stabilizer and a bitter agent. The method of claim 1, The calcium salt is selected from the group consisting of calcium gluconate, calcium lactate, calcium carbonate and mixtures thereof, and is contained in an amount of 0.1 (w / v) to 0.5 (w / v) wt% based on the total weight of the composition. Liquid composition, characterized in that made. The method of claim 1, The magnesium salt is selected from the group consisting of magnesium oxide, magnesium carbonate, magnesium hydroxide, or mixtures thereof, and is comprised in an amount of 0.05 (w / v) to 0.3 (w / v) wt% based on the total weight of the composition. Liquid composition, characterized in that. The method of claim 3, wherein Liquid composition, characterized in that the magnesium salt is magnesium oxide. The method of claim 1, The organic acid salt is selected from the group consisting of malic acid, citric acid, tartaric acid, ascorbic acid or mixtures thereof, and is contained in an amount of 1 (w / v) to 3 (w / v) wt% based on the total weight of the composition. Liquid composition, characterized in that made. According to claim 1, wherein the stabilizer is selected from the group consisting of polyvinylpyrrolidone, cyclodextrin liquid or mixtures thereof, and 1 (w / v) to 5 (w / v) to the total weight of the composition It is contained in the weight% liquid composition characterized by the above-mentioned. The method of claim 6, The liquid composition, wherein the stabilizer is a cyclodextrin solution. The method of claim 1, Liquid composition, characterized in that the vitamin is vitamin D. The method of claim 1, The bitter agent is selected from the group consisting of steviosides, mixtures of sasesulfa potassium and aspartame, and mixtures thereof, and comprises 0.02 (w / v) to 0.1 (w / v) weight% based on the total weight of the composition. Liquid composition, characterized in that. In the method for producing a composition containing calcium salt, magnesium salt and vitamins, Mixing calcium and stabilizer to form a clear solution; Mixing and stirring an organic acid in the stirring solution; Mixing magnesium and stirring at 0 ° C to 40 ° C; And Adding a bitter; Method for producing a liquid composition containing calcium salt, magnesium salt and vitamins comprising a.