JPS61207322A - Foamable solid composition containing ascorbic acid - Google Patents

Abstract

PURPOSE:To provide the titled composition useful as medicinal drug, etc., and composed of mixture of an ascorbic acid-containing component coated with a polymeric substance having acidic group and a carbonate-containing component coated with a water-soluble neutral polymeric substance. CONSTITUTION:A foamable solid composition containing ascorbin in stable state can be produced by combining (A) an ascorbic acidcontaining component coated with a polymeric substance having acidic group (e.g. hydroxypropylmethylcellulose phthalate) (the amount of the coating material is 2-20wt% of the total amount of the component), (B) a carbonate-containing component (e.g. K2CO3) coated with a water-soluble neutral polymeric substance (e.g. hydroxyropylcellulose) and (C) a copper ion source such as CuCl2 to exhibit antimicrobial activity. The ratios of A:B:C are preferably (5-30):(10-60):(0.05-0.3).

Description

[Detailed Description of the Invention] The present invention is an ascorbic acid-containing foamable solid composition, more specifically, a foaming solid composition containing ascorbic acid that generates carbon dioxide and foams when mixed with water. The present invention relates to an effervescent solid composition useful as a pharmaceutical, cosmetic or food product.

BACKGROUND OF THE INVENTION Solid compositions that generate carbon dioxide and foam when mixed with water have been known as pharmaceuticals, cosmetics, or foods. These are usually compositions made by mixing an organic acid such as alcoholic acid or citric acid with a carbonate such as sodium carbonate, and the organic acid and carbonate react in water to generate carbon dioxide. However, this type of composition is highly hygroscopic, and organic acids and carbonates are highly reactive.
It is quite difficult to obtain a composition that can maintain commercial value for a long period of time while maintaining good foaming properties. Therefore, various methods have been proposed for maintaining the foamability of such compositions stably for a long period of time. For example, by storing the composition at a low temperature, coating the carbonate with a gum (U.S. Pat. No. 3,082,091), or coating the organic acid with a hydrophobic substance (U.S. Pat. No. 2,956,926), Methods are known to delay the reaction of salts. In addition, addition of dimethylpolysiloxane (Japanese Patent Application Laid-Open No. 57-564
No. 34), addition of natural protein (JP-A-49-39582)
), and the use of anhydrous carbonate (Japanese Patent Application Laid-open No. 7246/1983) has also been proposed.

However, these methods are not necessarily satisfactory, and when used by adding them to water, there are problems such as delayed dissolution, reduced foaming power, and formation of insoluble matter.

On the other hand, ascorbic acid is widely used as vitamin C and as an ingredient in convex pharmaceuticals, cosmetics, and foods due to its reducing action. It exhibits antimicrobial effects such as fungal, antibacterial, and antiviral effects, and is used as a disinfectant and cleaning agent.
It is also known that it can be used (U.S. Pat. No. 306,513)
No. 9). However, ascorbic acid is an unstable substance, especially in the presence of water, and it reacts with other formulation ingredients, causing it to lose its original function and cause coloration. Various methods of stabilizing ascorbic acid have been attempted when using ascorbic acid. For example, a method of stabilizing ascorbic acid by goating it with a polymeric substance containing polyethylene glycol is known (Japanese Patent Publication No. 45-1074). issue).

The problem that Hoho is trying to solve When ascorbic acid reacts with carbonate in water, it generates carbon dioxide and foams, just like organic acids.

Therefore, if ascorbic acid and carbonate, as well as copper ions, can be stably blended with them, pharmaceuticals and cosmetics containing ascorbic acid, including disinfectants and detergents, can be used.
It is possible to add a new commercial value of foaming properties to foods, etc., and it becomes possible to more effectively demonstrate the efficacy of ascorbic acid.

However, ascorbic acid, like the organic acids used in conventional foamable solid compositions, is highly reactive with carbonates and is also a very unstable substance. Therefore, even if the conventional method of maintaining the foamability of a foamable solid composition as described above is maintained stably for a long period of time, or even if the known ascorbic acid stabilization method is used, the combination of ascorbic acid and carbonate, It is difficult to obtain a foamable solid composition that can maintain foamability and good commercial value over a long period of time.

In view of these circumstances, the present inventors have conducted extensive studies in order to obtain a composition containing ascorbic acid and carbonate that can maintain good commercial value over a long period of time. As a result, they discovered that the desired composition could be obtained by coating ascorbic acid and carbonate individually with a specific polymeric substance.

Means for Solving the Problems The present invention provides an ascorbic acid compound comprising a mixture of an ascorbic acid compounding component coated with a polymeric substance having acidic groups and a carbonate compounding component coated with a neutral water-soluble polymeric substance. An acid-containing foamable solid composition is provided. In the solid state of the composition of the present invention, the reaction between ascorbic acid and carbonate is suppressed, and the foaming property is well maintained, and the ascorbic acid itself is also extremely It has been stabilized. Moreover, when mixed with water, the carbonate coated with a neutral water-soluble polymeric substance first dissolves quickly to form a basic solution, and then, due to its action,
Ascorbic acid coated with a polymeric substance having acidic groups dissolves and quickly reacts with carbonate to generate carbon dioxide, resulting in delayed dissolution and decreased foaming power as in conventional foamable solid compositions. It exhibits good foaming properties without problems such as insoluble formation, and at the same time exhibits the excellent efficacy of ascorbic acid. Additionally, if a steel ion source is added to the carbonate compound, it will react with ascorbic acid to exhibit an excellent antimicrobial effect. Such effects can only be obtained by coating the ascorbic acid component with a polymeric substance having acidic groups and coating the carbonate component with a neutral water-soluble polymeric substance, as in the present invention. However, this cannot be achieved by replacing the polymeric material used for coating each component or by replacing it with another polymeric material.

An acidic polymeric substance having an acidic group such as a carboxyl group is used as the polymeric substance having an acidic group, which is used for coating the ascorbic acid compound. Alternatively, a substance having one type of ester group and soluble in water at a pH of 5 or higher, particularly a cellulose-based or acrylic acid-based polymer substance is preferable. In particular, a polymeric substance having a carboxyl group corresponding to a molecular weight of 105 or more is preferred.

Examples of such polymeric substances include hydroquinepropylmethylcellulose phthalate, carboxymethylethylcellulose, methyl methacrylate-methacrylic acid copolymer, and ethyl acrylate-methacrylic acid copolymer.

As the ascorbic acid compounding component, ascorbic acid itself may be used alone, or ascorbic acid may be appropriately combined with organic acids such as tartaric acid and citric acid, and excipients such as lactose. Ascorbic acid may be free ascorbic acid itself or derivatives thereof such as salts, ethers, and ester derivatives, and in the present invention, erythorbic acid as an isomer or derivatives thereof may be used.

Coating with ascorbic acid components can be carried out according to conventional methods, for example, using an ethanol or aqueous ethanol solution of the acidic polymer substance described above, a fluidized bed method,
This can be carried out by a spouted bed method, a transport bed method, or the like. Furthermore, coating can be applied to powdered ascorbic acid-containing components or to ascorbic acid-containing components that have been granulated in advance according to a conventional method. From the viewpoint of stabilizing effect, solubility when mixed with water, and foamability, the coating amount is preferably 2 to 20% (wt%, same hereinafter) based on the total weight of ascorbic acid compounded components.

As the neutral water-soluble polymeric substance used for coating the carbonate component, any known polymeric substance can be used, such as hydroxypropylcellulose, hydroxyethylcellulose, sodium carboxomethylcellulose, polyvinylpyrrolidone, vinylpyrrolidone. -Vinyl acetate copolymer, polyvinyl alcohol, sodium polyacrylate, hydroxypropyl methylcellulose and the like.

Examples of carbonates used include potassium carbonate, sodium carbonate, ammonium carbonate, potassium bicarbonate, sodium bicarbonate, and sodium sesquicarbonate. In the present invention, these carbonates alone may be used as the carbonate compounding component, and in order to exhibit an antimicrobial effect,
Copper ion sources such as cupric chloride, copper sulfate, hydrates thereof, and copper oleate may be combined as appropriate.

The carbonate component can be coated in the same manner as the ascorbic acid component, except that the above-mentioned neutral water-soluble polymer substance is used, and the amount of coating may be the same.

The effervescent solid composition of the present invention can be prepared by mixing the coated ascorbic acid component and the carbonate component according to a conventional method, and, if desired, granulating, tableting, and encapsulating them according to a conventional method. The resulting solid composition is in the form of powder, fine particles, granules, tablets, capsules, etc. The mixing ratio of the coated ascorbic acid and carbonate components can be selected as appropriate, but typically the ascorbic acid (as the free acid) is based on the total composition.
The content of carbonate is 10-60%, and when using a copper ion source, the content of copper ion source is 0.05%.
It is preferable to set the content to 0.3%. If desired, additives such as excipients, sweeteners, flavoring agents, coloring agents, and other medicinal agents that do not affect the stability and effervescence of ascorbic acid can also be combined.

Thus, the foamable solid composition of the present invention can be used in various pharmaceuticals, cosmetics, and foods that take advantage of the efficacy and foaming properties of ascorbic acid. For example, as an effervescent vitamin C agent, you can put it directly in your mouth to enjoy its effervescent properties, or you can dissolve it in water and drink it, making use of the whitening effect of vitamin C and the blood circulation promoting effect of effervescent carbon dioxide. It can be used as a bath additive. Furthermore, when a copper ion source is added, it can be used as a disinfectant for contact lenses and dentures, a disinfectant for disinfecting water in toilets and bathtubs, and the like.

Supervised by X Next, the present invention will be explained in more detail with reference to Examples.

Example 1 Foaming bath agent ingredients % Ascorbic acid Ingredients Ascorbic acid 20 Tartaric acid
10 lactose
IO Hydroquine Propyl Methyl 5 Cellulose Phthalate Carbonate Ingredients Sodium Bicarbonate 45 Pigments and Fragrances 2 Hydroxypropyl Cellulose 8 Mix ascorbic acid, tartaric acid and lactose, use a 7% ethanol solution of hydroxypropyl methyl cellulose phthalate, and coat using a fluidized bed coating machine. Coat the mixture with and dry (40°C)
As a result, a coated ascorbic acid-containing component was obtained. Similarly, a 4% ethanol solution of hydroxypropyl cellulose was used to coat the carbonate formulation. The entire amount of each coated component was mixed and compressed into 10 g tablets according to a conventional method, and each tablet was wrapped in aluminum foil to obtain an effervescent bath agent. When taking a bath, add an appropriate number of tablets to the hot water in the bathtub.

Example 2 Sparkling powdered beverage ingredients % Ascorbic acid Ingredients Ascorbic acid 20 Citric acid 15 Powdered sugar
37 fragrance
2 Carboxymethylethyl cellulose 6 Carbonate base fertilizer synthetic component Sodium bicarbonate 13 Pigment
lHydroxyethylcellulose 6 Mix ascorbic acid, citric acid, powdered sugar, and flavoring, coat the mixture with a 7% ethanol solution of carboxymethylethylcellulose while granulating it with a fluidized bed coating machine, dry it, and size it. Granules of ascorbic acid-containing ingredients coated with a particle size of 80 mesh or more were obtained. Similarly, using a 4% ethanol solution of hydroxyethylcellulose, coated granules of carbonate compounding ingredients with a particle size of 80 mesh or more were obtained. The coated ascorbic acid compounding ingredient granules and carbonate compounding ingredient granules were added to
:20 weight ratio and packaged in sticks of 1.5 g each.

Add this bag to a regular cup of water for drinking.

Example 3 Tablet Confectionery To the mixture obtained in Example 2, twice the weight of glucose and lactose were added and mixed well, and tablets of 2 g each were formed by direct compression according to a conventional method. This is bottled and served as food.

Example 4 Contact lens sterilization and cleaning agent tablet ingredients % Ascorbic acid Containing ingredients Ascorbic acid 30 Lactose
20 Methyl methacrylate - methacrylic acid 7 River polymer (manufactured by West German Rohm Pharma, Eudragit L I 00) Carbonate ingredients Sodium bicarbonate 14 Copper sulfate pentahydrate 01 Sodium chloride 0.6 Neutralizing agent
Appropriate amount Hydroxypropylcellulose 5 Lactose 100%
In the same manner as in Example 1, each component was coated using a 6% ethanol solution of methyl methacrylate-methacrylic acid copolymer and a 4% ethanol solution of hydroxypropyl cellulose, mixed, and prepared into 100 mg tablets each. did. Bottle this. This tsl is 10
Dissolve in ml of water and use to sterilize and clean contact lenses.

Example 5 Foaming Kurashiki Tablet Ingredients % Ascorbic acid Ingredients Ascorbic acid 3° Malic acid 2° Powdered sugar
5 fragrances
1.8 Acrylic acid-methacrylic acid 5 copolymer (manufactured by West German Rohm Pharma, Eudragit L30D) Carbonate ingredients Sodium bicarbonate 3°Copper sulfate pentahydrate 0.2 Carboxymethyl cellulose 8 Sodium implementation f! In the same manner as for jII, each component was coated using a 6% ethanol solution of acrylic acid ethyl-tacrylic acid copolymer and a 4% ethanol solution of sodium carboxymethylcellulose, and mixed to form tablets of 1 g each. Wrap this in aluminum foil and use it for 30~!
Add 1 tablet to 00m12 of water and use in Kurashiki.

The packages of Examples 4 and 5 were placed at a relative humidity of 75% and a temperature of 4.
Although the tablets were stored at 0°C for one month, no major changes were observed in the ascorbic acid content, tablet properties, appearance, effervescence, and bactericidal activity compared to immediately after manufacture.

Effects of the Invention Using various polymeric substances as coating agents, their ascorbic acid stabilizing effects and foaming retention effects were tested.

(1) Test polymer substance (a) Acidic polymer substance carboxymethyl ethyl cellulose (hereinafter abbreviated as CMEC) Hydroxypropyl methyl cellulose phthalate (HP55 and HP50 manufactured by Shin-Etsu Chemical Co., Ltd., hereinafter referred to as HPMC)
(abbreviated as HP55 and HP50) Methyl methacrylate-methacrylic acid copolymer (Eudragit Shi 100 manufactured by West German Rohm Pharma, hereinafter abbreviated as Lloo) Ethyl acrylate-methacrylic acid copolymer (Eudragit L30D, hereinafter abbreviated as L30D) Cellulose acetate phthalate (hereinafter abbreviated as CAP), starch acetate phthalate (hereinafter abbreviated as SAP), methyl methacrylate-methacrylic acid copolymer (Eudragit 5too, hereinafter abbreviated as 5100). It is shown in Table 1.

Table 1 (b) Neutral water-soluble polymer substances Hydroxypropyl cellulose (hereinafter abbreviated as HPC) Hydroxyethyl cellulose (hereinafter abbreviated as HEC) Sodium carboxymethyl cellulose (hereinafter abbreviated as CMC)
-Na) (C) Basic polymeric substance dimethylaminoethyl methacrylate-methyl methacrylate copolymer (Eudragit E100, hereinafter referred to as Eloo
(abbreviated as ) (2) Test method 120 g of ascorbic acid and 80 g of lactose were mixed and fluidized bed coated with an ethanol solution of each polymer substance so that 15 g of the polymer substance h (15 g) was coated. Similarly, 57 g of sodium bicarbonate was added. 6g.

140.4 g of lactose and, in the case of a fungicide, 1 g of copper sulfate pentahydrate were mixed and similarly coated with 15 g of a polymeric substance. Mixing each coating component in a weight ratio of l:l;
The mixture was compressed into tablets of tg each.

Each tablet was wrapped in aluminum foil at a relative humidity of 75% and a temperature of 40%.
The sample was left in an atmosphere at .degree. C. for one month, and gas generation during the time, residual rate of ascorbic acid after the time, discoloration, foaming time, presence or absence of insoluble matter, and antibacterial activity were measured and evaluated as follows.

(a) Generation of gas during storage The degree of expansion of the aluminum foil packaging during storage was determined according to the following criteria.

12 No expansion at all, ±: No problem, but a little expansion, +
: Swelling, ++: Significant swelling (b) Residual rate of ascorbic acid After standing, the residual amount of ascorbic acid was measured by the indophenol method, and the ratio (%) to the content immediately after tablet preparation was calculated.

(c) Discoloration The state of discoloration after standing was judged visually according to the following criteria.

12 No discoloration at all, ±: Slight discoloration that is not noticeable, +: Discoloration, ±: Significant discoloration (d) After leaving for foaming time, put 1 tablet in 10mQ of water and measure the time until foaming ends and dissolution. The average of the 10 measurement results was taken as the foaming time (seconds).

(e) Presence or absence of insoluble matter The presence (+) or absence (-) of insoluble matter was determined visually after measuring the foaming time.

(f) For the antibacterial active copper sulfate formulation, using a solution whose foaming time was measured, Staphylococcus aureus (Staphylococcus aureus)
ococcus aureus) was tested and evaluated according to the criteria of the following.

+: antibacterial activity (no colony formation), ±: weak antibacterial activity - (growth limit), -2: no antibacterial activity, many colonies formed) The results are shown in Table 2.

As is clear from Table 2, the ascorbic acid component is an acidic polymeric substance, especially one that has an ether or one type of ester group, is soluble in water at pH 5 or higher, and has a carboxyl group content of 10% or higher. Only when coating with an acidic polymeric substance and coating the carbonate compounded component with a neutral water-soluble polymeric substance, it is possible to specifically stabilize ascorbic acid, maintain foaming properties, and maintain antibacterial activity.

Claims (7)

[Claims] (1) Ascorbic acid-containing foaming product characterized by being composed of a mixture of an ascorbic acid component coated with a polymeric substance having an acidic group and a carbonate component coated with a neutral water-soluble polymeric substance. Solid composition. (2) The composition according to item (1) above, wherein the polymeric substance having an acidic group has an ether or one type of ester group and is soluble in water at a pH of 5 or more. (3) The composition according to item (2) above, wherein the polymeric substance having acidic groups is a cellulose-based or acrylic acid-based polymeric substance. (4) The polymer substance having an acidic group has a molecular weight of 10
% or more of the composition according to item (3) above. (5) The composition according to item (4) above, wherein the polymeric substance having an acidic group is hydroxypropylmethylcellulose phthalate, carboxymethylethylcellulose, methyl methacrylate-methacrylic acid copolymer, or ethyl acrylate-methacrylic acid copolymer. . (6) The coating amount of each component is 2 based on its weight.
~20% of the composition of any one of items (1) to (5) above. (7) The composition according to any one of items (1) to (6) above, wherein a copper ion source is added to the carbonate compounding component.