WO2001066083A1 - Gel preparations for oral administration having improved preservation properties - Google Patents

Abstract

Gel preparations for oral administration, which contain carrageen, a sugar alcohol and sorbic acid and have a pH value of from 4 to 9, show a sufficient preservation properties without any deterioration in the advantages of the conventional gel preparations (i.e., excellent administration properties, easiness in improving taste, molding properties into arbitrary shapes, portability without resort to water, etc.). Owing to these characteristics, these gel preparations are useful particularly for patients with poor deglutition (aged persons, infants, those with serious diseases, etc.), patients unwilling to take drugs (infants, etc.), patients being hardly able to take drugs together with water because of being out frequently, etc.

Description

 Description Oral gel formulation with improved antiseptic properties

 The present invention relates to an oral gel formulation, and more particularly, to an oral gel formulation having improved preservability while taking advantage of the gel formulation. Background art

 Since the gel preparation is excellent in ingestibility, it is suitably used as a preparation for elderly people, sick people, children and the like having a low swallowing ability. In addition, gel preparations can be easily colored and flavored to improve their visual and taste properties, and they can be taken without water, so they can be applied to products with excellent portability. There are various advantages. Various gelling agents such as agar and carrageenan are known as gelling agents used in such gel preparations. Among these gelling agents, carrageenan is most preferable in terms of water separation from the gel, ingestibility, and elution of the drug.

 In general, it is important to ensure the quality of pharmaceuticals and foods, and it is especially important to prevent corruption. To prevent spoilage, preservatives such as paraoxybenzoates are usually added.

 Conventionally, as gel preparations, the techniques described in JP-A-56-97220 and JP-A-6-256221 are known. The technology that focuses on is not known. Disclosure of the invention

Using carrageenan as a gelling agent, the present inventors adjusted pH to a range of 4 to 9, which is preferable for ensuring gel stability, blended sucrose to improve flavor, and added paraben as a preservative. Attempts to provide a gel formulation with a formulation based on drugs, the gel formulation has insufficient preservative effect, despite the fact that other dosage forms contain a sufficient amount of preservative to show a preservative effect I found something. The present inventors have conducted various studies to provide a gel preparation having a sufficient preservative effect without impairing the advantages of the gel preparation, and as a result, added sugar alcohol instead of sucrose used for flavor improvement, When the agent was changed to sorbic acid, it was found that a gel preparation having a sufficient preservative effect could be provided while maintaining the advantages of the gel preparation, and completed the present invention.

 That is, the present invention is an oral gel preparation containing carrageenan, sugar alcohol and sorbic acid, and having a pH in the range of 4 to 9. BEST MODE FOR CARRYING OUT THE INVENTION

 The amount of carrageenan used in the present invention is preferably from 0.01 to 20% by mass, more preferably from 0.5 to 10% by mass, from the viewpoint of the stability of the gel preparation. In the present invention, sugar alcohols include sorbitol, xylitol, erythritol, maltitol, etc., and xylitol or erythritol is preferred from the viewpoint of flavor and stability.

 The amount of the sugar alcohol varies depending on the type of the sugar alcohol, but is preferably from 10 to 50% by mass of the whole preparation from the viewpoint of flavor.

 As the sorbic acid used in the present invention, those usually used can be used, and salts thereof (eg, potassium salts) can also be used.

 The amount of sorbic acid is preferably from 0.01 to 0.8% by mass of the whole preparation from the viewpoint of preservability.

 In the present invention, the pH needs to be 4 to 9 from the viewpoint of stability of the gel, preferably 4 to 7 and more preferably 5 to 6. For adjusting pH, a commonly used pH adjuster can be used, but from the viewpoint of flavor, safety, preservation and the like, a combination of citric acid and sodium citrate is most preferred. The pH of the gel can be measured with a general pH meter.

In the present invention, the preservative effect can be further improved by adding a preservative effect enhancer. Here, the preservative effect enhancer is a component that helps the absorption of sorbic acid by spoilage sources such as mold, yeast, and bacteria. Specifically, menthol, limonene, Caprylic acid, capric acid, saponins and the like can be used. Of these, menthol is particularly preferred.

 The oral gel preparation of the present invention may optionally contain orally administrable pharmaceutical ingredients, nutritional ingredients, and the like.

 In the present invention, flavoring agents, flavors, emulsifiers, stabilizers, fillers, and the like, which can be incorporated in oral preparations, can be incorporated as additives. For example, sweeteners such as stevioside and thaumatin, flavoring agents such as cocoa powder, surfactants such as polyglycerin fatty acid ester and sucrose fatty acid ester, and fillers such as silicon dioxide, for example, Ezrol 200 (trade name), etc. Is raised. In addition to these additives, if necessary, components that can be blended with ordinary pharmaceuticals can be blended. In addition, it is preferable not to mix sucrose from the viewpoint of antiseptic properties, but it is possible to mix sucrose in a small amount that can ensure antiseptic properties from the viewpoint of improving flavor.

 The oral gel preparation of the present invention dissolves water, carrageenan, sugar alcohol, and other components, if necessary, adjusts the pH, mixes by heating, and then becomes a size and a shape easy for oral administration. As described above, it can be obtained by filling in an appropriate container and solidifying by cooling. Example

 Hereinafter, the present invention will be described in more detail with reference to Examples and Test Examples.

Example 1

 0.25 g of sodium picosulfate, 0.2 g of citrate, 4.8 g of sodium citrate, 12 g of menthol, and 1 g of potassium sorbate were dissolved in 729,83 g of purified water .

Separately, a powder mixture of 140 g of xylitol, 110 g of maltitol, and 14 g of carrageenan was added, and after sufficiently dispersing at room temperature, the mixture was dissolved by heating to 60 to 80, followed by quenching. After adjusting the pH to 6 by adding an appropriate amount of an acid, the mixture was filled in a predetermined container, and cooled and solidified to 30 or less to obtain a desired internal gel. Examples 2 to 5

 An oral gel preparation was prepared for the components shown in Table 1 in the same manner as in Example 1, Comparative Example 1

 Purify 0.25 g of sodium picosulfate, 0.2 g of citrate, 4.8 g of sodium citrate, 0.2 g of propylparaben, 0.07 g of butylparaben, and 3 g of sodium benzoate Dissolved in 727.683 g of water. Separately, powder mixed with 250 g of sugar and 14 g of carrageenan was added, dispersed sufficiently at room temperature, dissolved by heating to 60 to 80, and adjusted to pH 6 by adding an appropriate amount of citric acid. The mixture was filled in a predetermined container, and cooled and solidified in the following at 30 to obtain a target oral gel.

 table 1

Test example

The preservability of each Example and Comparative Example was evaluated by the preservative efficacy test described in Japanese Pharmacopoeia (13). Five strains (S. aureus C. albicans E. coli P. aeruginosa A.niger) were used for evaluation, and the results are shown in Tables 2 to 4 (the unit of number is log cfu / g).

 Table 2

表 3

Table 3

表 4

Table 4

その結果、 実施例 1の組成物では、 今回用いた 5菌株の増殖は認められなかつ た。 実施例 1の組成物は、 S. aureusにおいては比較例 1と同等の保存効力を示し, さらに比較例 1では効果のなかった P. aeruginosaや A.nigerに対しても効果が認 められた。 産業上の利用可能性

As a result, in the composition of Example 1, the growth of the five strains used in this experiment was not observed. The composition of Example 1 exhibited the same preservative efficacy in S. aureus as in Comparative Example 1, and was also effective against P. aeruginosa and A. niger, which had no effect in Comparative Example 1. . Industrial applicability

The gel preparation of the present invention has the advantages of conventionally known gel preparations (excellent ingestibility, ease of flavor improvement, moldability into free shapes, portability that can be taken without water). Having sufficient antiseptic properties without loss, patients with low swallowing ability (elderly, pediatric, severely ill, etc.), patients who do not like to take medicine (children, etc.) It has become possible to provide a particularly useful formulation for patients who are difficult to take.

Claims

The scope of the claims 1. An oral gel formulation containing carrageenan, sugar alcohol and sorbic acid and having a pH in the range of 4-9. 2. The oral gel preparation according to claim 1, wherein the amount of carrageenan is from 0.01 to 20% by mass of the whole preparation. 3. The oral gel preparation according to claim 1, wherein the sugar alcohol is xylitol or erythritol. 4. The oral gel preparation according to claim 1, wherein the content of the sugar alcohol is 10 to 50% by mass of the whole preparation. 5. The oral gel preparation according to claim 1, wherein the amount of sorbic acid is 0.01 to 0.8% by mass of the whole preparation. 6. The oral gel preparation according to claim 1, further comprising an antiseptic effect enhancer. 7. The oral gel preparation according to claim 6, wherein the preservative effect enhancer is menthol. 8. The oral gel preparation according to claim 1, wherein at least one of citrate and sodium citrate is combined as a pH regulator.