JPH025726B2 - - Google Patents

Description

[Detailed description of the invention]

Industrial Application Field The present invention relates to an ascorbic acid-containing foamable solid composition, more specifically, a foamable solid composition containing ascorbic acid, which generates carbon dioxide and foams when mixed with water, stably contains ascorbic acid, and is useful as a pharmaceutical, cosmetic, or food product. The present invention relates to a foamable solid composition. BACKGROUND ART 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 tartaric 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 has high hygroscopicity and the organic acid and carbonate are in a state where it is very easy to react, so it is possible to obtain a composition that can maintain commercial value for a long period of time while maintaining good foaming properties. This is quite difficult. Therefore, various methods have been proposed for maintaining the foamability of such compositions stably for a long period of time. For example, storing the composition at low temperatures or coating the carbonate with a gum (U.S. Patent No.
3,082,091) and coating the organic acid with a hydrophobic substance (US Pat. No. 2,956,926) to delay the reaction between the organic acid and carbonate. In addition, addition of dimethylpolysiloxane (Unexamined Japanese Patent Publication No. 1983-
56434), 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 various pharmaceuticals, cosmetics, and foods due to its reducing action.Furthermore, when it comes into contact with a small amount of copper ions in the presence of water, it has antifungal and antibacterial properties. It is also known that it exhibits antimicrobial effects such as antiviral effects and can be used as a disinfectant and cleaning agent (US Pat. No. 3,065,139). but,
Ascorbic acid is an unstable substance, especially in the presence of water, and reacts with other formulation ingredients, causing it to lose its original action or produce color. Various methods of stabilization have been attempted when using acids; for example, a method of stabilizing ascorbic acid by coating it with a polymeric substance containing polyethylene glycol is known (Japanese Patent Publication No. 1074/1974). . Problems to be Solved by the Invention When ascorbic acid is reacted with carbonate in water, it generates carbon dioxide and foams like organic acids. Therefore, if ascorbic acid and carbonate, as well as copper ions, can be stably blended with them, new foaming products can be created for pharmaceuticals, cosmetics, foods, etc. containing ascorbic acid, including disinfectants and detergents. It is possible to add value and make the efficacy of ascorbic acid more effective. 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 we use the above-mentioned conventional method of maintaining the foamability of foamable solid compositions stably for a long period of time, or even if we use the known ascorbic acid stabilization method, it is difficult to combine 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 ascorbic acid containing a mixture of an ascorbic acid compounding component coated with a polymeric substance having an acidic group 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 foaming properties are well maintained, and ascorbic acid itself is extremely stable due to the coating with a polymeric substance having acidic groups. has been made into In addition, when mixed with water, the carbonate coated with a neutral water-soluble polymer substance quickly dissolves to form a basic solution.
Then, as a result of this action, ascorbic acid coated with a polymeric material having acidic groups dissolves and immediately reacts with the carbonate to generate carbon dioxide, thereby delaying dissolution as in conventional foamable solid compositions. It exhibits good foaming properties without problems such as loss of foaming power or formation of insolubility, and at the same time exhibits the excellent efficacy of ascorbic acid. Furthermore, when a copper ion source is added to the carbonate compound, excellent antimicrobial effects are exhibited through reaction with ascorbic acid. 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 component. 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, polymeric substances having carboxyl groups corresponding to 10% or more of the molecular weight are preferred. Examples of such polymeric substances include hydroxypropyl methyl cellulose phthalate, carboxymethyl ethyl cellulose, methyl methacrylate-methacrylic acid copolymer, and ethyl acrylate-methacrylic acid copolymer. Ascorbic acid compounding ingredient may be just ascorbic acid itself, and ascorbic acid and
Organic acids such as tartaric acid and citric acid, and excipients such as lactose may be combined as appropriate. 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-containing components can be carried out according to a conventional method, for example, using an ethanol or aqueous ethanol solution of the above-mentioned acidic polymer substance, using a fluidized bed method, a spouted bed method, a transport bed method, etc. can. Further, the coating can be applied to a powdered ascorbic acid compound component or to an ascorbic acid compound component that has 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 carboxymethylcellulose, polyvinylpyrrolidone, vinylpyrrolidone- Examples include vinyl acetate copolymer, polyvinyl alcohol, sodium polyacrylate, and hydroxypropyl methylcellulose. The carbonates used include potassium carbonate, sodium carbonate, ammonium carbonate, potassium bicarbonate,
Examples include sodium bicarbonate and sodium sesquicarbonate. In the present invention, these carbonates alone may be used as the carbonate compounding component, and in order to further exhibit an antimicrobial effect, cupric chloride, cupric chloride,
Copper ion sources such as 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 foamable solid composition of the present invention can be prepared by mixing the coated ascorbic acid component and the carbonate component in a conventional manner, and if desired, further granulating and tableting in a conventional manner. It is a solid composition in the form of powder, fine granules, granules, tablets, capsules, etc. obtained by encapsulation. The mixing ratio of the coated ascorbic acid component and the carbonate component can be selected as appropriate, but usually,
Based on the total composition, the content of ascorbic acid (as free acid) is 5-30%, the content of carbonate is 10-30%
60%, and when using a copper ion source, it is preferable that the content of the copper ion source is 0.05 to 0.3%. If desired, additives such as excipients, sweeteners, flavorings, and colorants, as well as 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 enjoy the effervescence by putting it directly in your mouth, or drink it by dissolving it in water. It can be used as an agent. In addition, when a copper ion source is added, it can be used as a disinfectant cleaner for contact lenses and dentures,
It can also be used to sterilize water in toilets and bathtubs, and as a disinfectant. Examples Next, the present invention will be explained in more detail with reference to examples. Example 1 Effervescent bath agent Ingredients % Ascorbic acid ingredients Ascorbic acid 20 Tartaric acid 10 Lactose 10 Hydroxypropyl methyl 5 Cellulose phthalate carbonate ingredients Sodium bicarbonate 45 Colors and fragrances 2 Hydroxypropyl cellulose 8 Ascorbic acid, tartaric acid and lactose mix,
The mixture was coated with a 7% ethanol solution of hydroxypropyl methyl cellulose phthalate in a fluidized bed coating machine and dried (40°C) to obtain a coated ascorbic acid compound. Similarly, a 4% ethanol solution of hydroxypropylcellulose 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 solvent. When taking a bath, add an appropriate number of tablets to the hot water in the bathtub. Example 2 Sparkling powdered drink Ingredients % Ascorbic acid ingredients Ascorbic acid 20 Citric acid 15 Powdered sugar 37 Flavoring 2 Carboxymethylethyl cellulose 6 Carbonate ingredients Sodium bicarbonate 13 Coloring matter 1 Hydroxyethylcellulose 6 Ascorbic acid, citric acid, Mix powdered sugar and flavoring, add 7 ml of carboxymethylethyl cellulose
% ethanol solution, the mixture was coated while granulating with a fluidized bed coating machine, dried, and sized to obtain coated ascorbic acid compounded granules with a particle size of 80 mesh or more. Similarly, 4% of hydroxyethyl cellulose
Using an ethanol solution, coated carbonate compounded granules with a particle size of 80 mesh or more were obtained. The coated ascorbic acid compounding component granules and carbonate compounding component granules were mixed at a weight ratio of 80:20, and 1.5 g each was packed in stakes. This one
Add the bag to a regular glass 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 tablet Ingredients % Ascorbic acid component Ascorbic acid 30 Lactose 20 Methyl methacrylate-methacrylic acid 7 Copolymer (Eudragit L100, manufactured by Rohm Pharma, West Germany) Carbonate component Sodium bicarbonate 14 Copper sulfate pentahydrate 0.1 Sodium chloride 0.6 Neutralizing agent Appropriate amount Hydroxypropyl cellulose 5 Lactose Adjusted to 100% Similarly to Example 1, a 6% ethanol solution of methyl methacrylate-methacrylic acid copolymer and hydroxypropyl cellulose were added. Each component was coated using a 4% ethanol solution and mixed to form tablets of 100 mg each. Bottle this. Dissolve 1 tablet in 10ml of water and use to sterilize and clean contact lenses. Example 5 Effervescent gargle tablet Ingredients % Ascorbic acid ingredients Ascorbic acid 30 Malic acid 20 Powdered sugar 5 Flavor 1.8 Ethyl acrylate-methacrylic acid 5 Copolymer (manufactured by Rohm Pharma, West Germany, Eudragit L30D) Carbonate ingredients Bicarbonate Sodium 30 Copper sulfate pentahydrate 0.2 Sodium carboxymethylcellulose 8 In the same manner as in Example 1, each component was prepared using a 6% ethanol solution of ethyl acrylate-methacrylic acid copolymer and a 4% ethanol solution of sodium carboxymethylcellulose. coating,
The mixture was mixed to form tablets of 1 g each. This is wrapped in aluminum foil, and when used, one tablet is added to 30 to 100 ml of water and used for gargling. The packages of Examples 4 and 5 were subjected to relative humidity of 75%,
Although the tablets were stored at a temperature of 40°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 Various polymeric substances were used as coating agents to test their ascorbic acid stabilizing effects and foaming retention effects. (1) Test polymer substance (a) Acidic polymer substance carboxymethylethylcellulose (hereinafter referred to as
(abbreviated as CMEC) Hydroxypropyl methylcellulose phthalate (HP55 and HP50 manufactured by Shin-Etsu Chemical Co., Ltd., hereinafter referred to as
HPMCP (abbreviated as HP55 and HP50) Methyl methacrylate-methacrylic acid copolymer (Eudragit L100, manufactured by Rohm Pharma, West Germany)
(hereinafter abbreviated as L100) 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 S100, hereinafter abbreviated as S100) The properties of these acidic polymer substances are shown in Table 1.

【table】

[Table] (b) Neutral water-soluble polymer substance Hydroxypropyl cellulose (hereinafter referred to as HPC)
) Hydroxyethylcellulose (hereinafter abbreviated as HEC) Sodium carboxymethylcellulose (hereinafter abbreviated as CMC-Na) (c) Basic polymeric substances Dimethylaminoethyl methacrylate-methyl methacrylate copolymer (Eudragit E100, hereinafter abbreviated as CMC-Na) (abbreviated as E100) (2) Test method Mix 120g of ascorbic acid and 80g of lactose,
In the ethanol solution of each polymer substance, 15
Fluidized bed coating was carried out so that g coating was applied. Similarly, 57.6g of sodium bicarbonate, lactose
140.4 g and 1 g of copper sulfate pentahydrate in the case of a fungicide were mixed and similarly coated with 15 g of a polymeric substance. Each coating component was mixed at a weight ratio of 1:1 and compressed to prepare 1 g tablets each. Each tablet was packaged in aluminum foil at a relative humidity of 75% and a temperature of 40%.
The sample was left in an atmosphere at ℃ for one month, and the gas generation during the standing, residual rate of ascorbic acid after the standing, discoloration, foaming time, presence or absence of insoluble matter, and antibacterial activity were measured and evaluated as follows. (a) Gas generation during storage The degree of expansion of aluminum foil packaging during storage was judged according to the following criteria. −: No swelling at all, ±: No problem, but slightly swollen, +: Swelling, ++: Significant swelling (b) Residual rate of ascorbic acid After standing, the remaining amount of ascorbic acid was measured by the indophenol method, and the tablet The ratio (%) to the content immediately after preparation was calculated. (c) Discoloration The state of discoloration after standing was judged visually according to the following criteria. -: No discoloration at all, ±: Slight discoloration that is not noticeable, +: Discoloration, ±: Significant discoloration (d) Foaming time After standing, put one tablet in 10ml 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) Antibacterial activity The effect of the copper sulfate formulation on the growth of Staphylococcus aureus was tested using a solution whose foaming time was measured, and evaluated according to the following criteria. +: Antibacterial activity (no colony formation), ±:
Although weak, antibacterial activity is observed (growth limit), -:
No antibacterial activity (formation of many colonies) The results are shown in Table 2.

[Table] 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 and is soluble in water at a pH of 5 or higher, with a carboxyl group content of 10 Ascorbic acid can be specifically stabilized, foamed, and antibacterial activity maintained only when the carbonate component is coated with an acidic polymeric material of % or more, and the carbonate component is coated with a neutral water-soluble polymeric material.

Claims (1)

[Scope of Claims] 1. Ascorbic acid comprising 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. Acid-containing effervescent 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. Polymer substances with acidic groups have a molecular weight of
The composition according to item 3 above, which is a substance containing 10% or more of carboxyl groups. 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 composition according to any one of Items 1 to 5 above, wherein the coating amount of each component is 2 to 20% based on its weight. 7. The composition according to any one of Items 1 to 6 above, in which a copper ion source is added to the carbonate compounding component.