JPH04346926A - Syrup agent - Google Patents

Abstract

PURPOSE:To obtain an ascorbic acid-containing syrup widely usable as a drug for common use because an ascorbic acid as an active ingredient exists stably for a long period of time in ordinary preservation at room temperature and the content thereof will not reduce with time. CONSTITUTION:Ascorbic acid useful for drugs and cosmetics by specific physiological activity such as skin chromatosis preventing action, etc., for foods and quasi drugs as vitamin C and also for fats and oils foods, etc., as an antioxidant, a salt and a derivative thereof, as an active ingredient, is adjusted to pH 6.0-8.0, preferably pH 7.0-8.0 with sodium hydrogencarbonate, sodium carbonate, sodium hydroxide or potassium phosphate to give a syrup agent stably mixed with an ascorbic acid.

Description

[Detailed description of the invention]

0001

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a syrup stably containing ascorbic acids.

0002

[Prior Art] Ascorbic acid is used in pharmaceuticals and cosmetics due to its unique physiological activities such as preventing skin pigmentation, and is also used as vitamin C in foods and quasi-drugs, or as vitamin C in oils, fats, foods, etc. It is used in a wide range of fields, including as an antioxidant.

However, ascorbic acid has an enediol group in its molecular structure, and especially the enol groups bonded to the 2- and 3-position carbon atoms easily lose hydrogen atoms and are oxidized to become tautomerized to the keto form. Furthermore, it decomposes into diketogulonic acid, oxalic acid, threonine, etc. and becomes colored. Therefore, ascorbic acid has the property of being very unstable, especially in an aqueous solution. Furthermore, destruction is significantly accelerated in the presence of alkalinity and heavy metals.

[0004] Therefore, when blending into an aqueous composition,
Various stabilization measures have been adopted in the past. For example, it may be wrapped in cyclodextrin, liposome, or other oils or fats, or it may be blended with a non-aqueous water-soluble base of polyhydric alcohol such as glycerin.

[0005]

[Problems to be Solved by the Invention] However, these stabilization measures lead to a decrease in the activity of ascorbic acid and a decrease in the activity of vitamin C.
It is still unsatisfactory in terms of retention of action, side effects, and stability. Therefore, the development of a syrup formulation stably containing ascorbic acid, its salts, or its derivatives is expected.

[0006]

[Means for Solving the Problems] In view of the above-mentioned circumstances, the present inventors conducted intensive research to develop a stable ascorbic acid-containing syrup, and as a result, the pH of the syrup was adjusted to 6.0 with sodium bicarbonate or the like. 0-8. It was discovered that a decrease in the content of ascorbic acid can be prevented by adjusting it to a range of 0, and the present invention was completed based on this finding.

That is, the present invention uses ascorbic acid or its salts or its derivatives as an active ingredient, and has a pH of 6.
．． 0-8. The present invention relates to a syrup characterized in that the syrup is adjusted to a range of 0.

[0008] If the pH of the syrup is outside the above range, there is a problem that the properties change and decompose over time, making it necessary to store it in a cool place. Therefore, in the syrup of the present invention, the contents of sodium bicarbonate, phosphate, etc. are determined so that the syrup is within the above pH range.

In the present invention, the salts and derivatives of ascorbic acid include monoalkali metal salts obtained by neutralizing the hydroxyl group at the 3-position carbon of ascorbic acid with an alkali metal, such as sodium ascorbate or potassium ascorbate, and ascorbic acid. Ascorbic acid monoester derivatives such as monostearate, ascorbic acid monopalmitate, ascorbic acid monooleate, or ascorbic acid monophosphate, ascorbic acid distearate, ascorbic acid dipalmitate, a

001
0. Ascorbic acid dioleate or ascorbic acid diester derivatives such as ascorbic acid diphosphate, ascorbic acid triester derivatives such as ascorbic acid tristearate, ascorbic acid tripalmitate or ascorbic acid triphosphate, 6-stearoyl ascorbic acid, Alternatively, ascorbic acid derivatives such as acyl derivatives of ascorbic acid such as 6-palmitoyl ascorbic acid can be mentioned.

Raw materials for syrups include sugars such as white sugar, mannitol and sorbitol, and sweeteners such as saccharin. Examples of the pH adjuster include sodium hydrogen carbonate, sodium carbonate, sodium hydroxide, and potassium phosphate.

[0012] In addition to the above-mentioned essential ingredients, the syrup of the present invention may also contain, if necessary, antipyretics such as acetaminophen, phenacetin, and aspirin, antihistamines such as chlorpheniramine maleate, methylephedrine hydrochloride, Medicinal ingredients such as antitussives such as codeine phosphate, herbal medicines such as Senega extract, paraoxygen

[
Preservatives such as methyl benzoate, fragrances such as strawberry flavor, thickeners such as methylcellulose, emulsifiers such as glycerin fatty acid esters, coloring agents such as Food Red No. 102, etc. may be used in appropriate combinations. The blending amount may be such that the above-mentioned essential components of the present invention do not deviate from the purpose of the present invention.

[0014] As a method for preparing the syrup of the present invention, for example, sodium ascorbate, pH
As a conditioning agent, sodium hydrogen carbonate is added and dissolved in purified water under nitrogen substitution, and separately purified water is added to flavoring agents, preservatives, or other medicinal ingredients as necessary, and dissolved by heating etc. An example of this method is to mix and stir under nitrogen purge, add coloring agents, fragrances, etc. as appropriate, and make up the specified amount with purified water, but there are no particular limitations. A method can be used.

Specifically, for example, first, purified water 1
Add a preservative such as methyl paraoxybenzoate to 75 liters and heat to dissolve. Add 250 kg of white sugar to this and heat to dissolve. Next, sodium hydrogen carbonate 1. 4 kg and other medicinal ingredients, such as acetaminophen, are added and dissolved by heating if necessary.

[0016] Next, this liquid is cooled (below 30°C), and sodium ascorbate is added and dissolved under nitrogen substitution. Next, add fragrance under nitrogen substitution to bring the total volume to 500L.
pH7. 5 of the syrup of the present invention is obtained.

[0017] Based on the results of the storage test (Test Example 2) described below, it was determined that the content of the active ingredient, sodium ascorbate, in the syrup of the present invention decreased by less than 10% over a period of 3 years at room temperature, and therefore it cannot be used as a pharmaceutical product. It can be widely supplied.

[0018]

[Examples] Next, the present invention will be explained in more detail based on Examples, but the present invention is not limited to these. Example 1 A syrup containing sodium ascorbate was prepared according to the following recipe under nitrogen substitution (oxygen concentration of about 4%), and then adjusted to pH 6.0 using sodium hydrogen carbonate. 0,
7. 0 and 8. It was adjusted to 0 and filled into a brown bottle, filled with nitrogen (oxygen concentration of about 4%), and a sample was prepared and sealed.

(Prescription) Sodium ascorbate 7g White sugar
75
0g methyl paraoxybenzoate 250mg purified water
Appropriate amount: 1500 g The syrup prepared according to the above recipe is a colorless, slightly viscous liquid.

Comparative Example 1. After preparing with the same recipe as in Example 1 under nitrogen substitution, using sodium hydrogen carbonate, p
H is 5. It was adjusted to 0 and filled into a brown bottle, filled with nitrogen (oxygen concentration of about 4%), and a sample was prepared and sealed.

Test Example 1. For the samples of Example 1 and Comparative Example 1, changes in sodium ascorbate content over time were measured at 40°C and 50°C in an accelerated test. The sodium ascorbate content was measured according to the ascorbic acid quantitative method described below. Table 1 shows the residual rate of ascorbic acid in the syrup at 40°C and 50°C after one month and two months.

[0022]

[Table 1] As a result, the pH of Example 1 was 6. 0-8. It can be said that syrups in the range of 0 are stable.

Example 2. A syrup containing sodium ascorbate (pH 7.5) was prepared according to the following recipe under nitrogen substitution (oxygen concentration of about 4%), filled into a 60 ml amber bottle, and the space of the container was further filled with nitrogen and sealed. .

(Prescription) Sodium ascorbate 4
0g acetaminophen
60g white sugar
3500g Sodium bicarbonate 20g Sodium paraoxybenzoate 1g Purified water
Appropriate amount: 7000 ml The syrup prepared according to the above recipe is a colorless, slightly viscous liquid.

Test Example 2. The sample of Example 2 was left in a constant temperature chamber at 25° C. and 40° C., and the change in content of sodium ascorbate over time was measured (see the method for quantifying ascorbic acid described below). Table 2 shows the residual rate of sodium ascorbate in the syrup after 1, 2, 3, and 6 months of storage at 40°C, and 12 and 36 months of storage at 25°C.

[0026]

[Table 2] As a result, the content was maintained at 90% or more after storage at 25℃ for 36 months, and after storage at 40℃ for 6 months (25℃,
Since the content was maintained at over 90% even after storage for 3 years (equivalent to 3 years), we believe that this syrup can guarantee stability for 3 years at 25°C.

(Ascorbic acid determination method) The content of ascorbic acid, its salts, or its derivatives contained as an active ingredient in the syrup of the present invention was determined by the method shown below. Method: Accurately measure a certain amount of this product containing ascorbic acid, its salts, or its derivatives, perform pretreatment such as hydrolysis if necessary, add metaphosphoric acid/acetic acid test solution and hydrogen peroxide test solution, and shake. After that, titration 2
, 6-dichlorophenol Indophenol sodium test solution until the solution exhibits a light pink color that lasts for 5 seconds.

[0028]

Effects of the Invention: The syrup containing ascorbic acid, its salts, or its derivatives of the present invention can be stored normally for a long period of time at room temperature, and the content of the active ingredient ascorbic acid, its salts, or its derivatives decreases over time. It is stable over a long period of time. Therefore, it has the effect of being widely used not only in medical treatment but also as an over-the-counter drug.

Claims (2)

[Claims] Claim 1: The active ingredient is ascorbic acid, a salt thereof, or a derivative thereof, and the pH is 6. 0-8. 0
A syrup agent characterized by being adjusted to a range of. [Claim 2] pH is 7. 0-8. The syrup according to claim 1, wherein the syrup is adjusted to 0.