KR100718279B1 - Clear liquid formulation containing hedera extract - Google Patents

Abstract

The present invention relates to a clear liquid preparation containing Hedera extract, which contains a polyoxyethylene castor oil derivative, polyoxyethylene sorbitan monostearate, sodium lauryl sulfate or polyoxyethylene-polyoxypropylene polymer as a stability improver. The liquid formulation containing the Hedera extract of the present invention improves the stability and the taste of the formulation, thereby improving the adherence to medicines.

Hedera extract, liquid formulation, stability, sedimentation inhibition

Description

A clear liquid formulation containing hedera extract {

The present invention relates to a liquid formulation containing a herbal extract with improved stability during storage.

Hedera (Hedera) is a woody vine plant of sangrokseong the generic name of a plant belonging to Araliaceae (Araliaceae). Hedera canaiensis and Hedera Helix are the representative species. Their extracts lower the viscosity by the surfactant action and increase the mobility of the ciliate to rapidly remove the mucus, It has been known to treat bronchitis quickly with inhibitory action. For this reason, attempts have been made to utilize the extract of Hedera for medicines and the like, but due to the problems such as the solubility of the Hedera extract, the Hedera extract-containing liquid preparations have been limited to a suspension preparation such as an opaque syrup .

In general, a liquid preparation containing a plant extract has a problem in that the insoluble or poorly soluble component of the plant extract forms a precipitate with time to degrade the quality of the product visually. In order to improve the stability of the liquid formulation containing the plant extract, a method of adding an increasing agent such as gelatin, casein, carboxymethyl cellulose and gum arabic to the liquid formulation containing the plant extract has been proposed.

However, as a method for improving the stability using such a thickening agent, not only a sufficient effect of preventing precipitation can be secured during the use period of the liquid formulation containing the plant extract, but the difference in the components of the plant extract is very large depending on the type of plant to be extracted Simply increasing the viscosity can not increase the stability of all liquid formulations containing plant extracts. Further, even when a solubilizing agent is added to solubilize the active ingredient, there is a great difference in the effect of the solubilizing agent depending on the active ingredient. In particular, in the case of the plant extract, various ingredients are contained at the same time. Is not easy.

SUMMARY OF THE INVENTION Accordingly, the present invention has been made in view of the above problems, and an object of the present invention is to provide a transparent liquid preparation containing a hydratable extract having no sedimentation, that is, improved stability and improved taste.

In order to achieve the above-mentioned technical object, the present invention provides a composition for improving stability, which comprises a polyoxyethylene castor oil derivative, polyoxyethylene sorbitan monostearate, sodium lauryl sulfate, and polyoxyethylene-polyoxypropylene polymer A transparent liquid preparation containing the Hedera extract containing at least one of them is provided. More specifically, the present invention relates to a composition for improving stability, which comprises at least one selected from the group consisting of polyoxyethylene castor oil derivatives, polyoxyethylene sorbitan monostearate, sodium lauryl sulfate and polyoxyethylene-polyoxypropylene polymer, And 5 w / v% of the total amount of the herbal composition.

Hereinafter, the transparent liquid formulation containing the Hedera extract having improved stability of the present invention will be described in detail.

The present inventors have found that a variety of additives such as nonionic surfactants, ionic surfactants, thickeners, solubilizing agents, polysaccharides, water-soluble polymers, and the like can be used in order to find a stability improving agent capable of preventing the precipitation formation of a liquid formulation containing the Hadera extract. It has been found that when polyoxyethylene castor oil derivatives, polyoxyethylene sorbitan monostearate, sodium lauryl sulfate or polyoxyethylene-polyoxypropylene polymer is added to the liquid formulation containing the extract of Hetera, And found that the storage stability of the preparation is remarkably improved.

The present invention relates to a composition containing a hyderera extract containing at least one selected from the group consisting of a polyoxyethylene castor oil derivative, polyoxyethylene sorbitan monostearate, sodium lauryl sulfate and polyoxyethylene-polyoxypropylene polymer as the stability improver A transparent liquid preparation is provided. Considering the taste, ease of manufacture, etc. of liquid formulations prepared from polyoxyethylene castor oil derivatives, polyoxyethylene sorbitan monostearate, sodium lauryl sulfate or polyoxyethylene-polyoxypropylene polymer, polyoxyethylene castor oil Derivatives or sodium lauryl sulfate are more preferred.

Hedera Hedera extract of the present invention is a generic name of a vine plant of sangrokseong woody plant belonging to Araliaceae (Araliaceae). The extracts which can be used for the extract of Hedera of the present invention Representative species include Hedera canaiensis and Hedera Helix , but are not limited to these two species. Preferably, Hedera extract can be used as Hedera extract. Hedera Fluid Extract is generally known to have the effect of deep-sea gDNA, and a 70% ethanol extract of Hedera helix leaf ( Hedera helix folium 70% ethanol extract) may be used, but is not limited thereto. Therefore, the transparent liquid preparation containing the Haedera extract having improved stability according to the present invention can be used for the treatment of respiratory diseases, and its component, hederacoside C, may be used instead of the Haedera extract.

Various organic solvents can be extracted singly or in combination by methods well known in the art to obtain useful Hedera extract from Hedera. For example, a method of adding an extracting organic solvent of 2-15 times amount to Hedera, which is a starting material to be extracted, at a room temperature while stirring, and a method of extracting by heating reflux can be used. After the unnecessary substances are removed by centrifugation or filtration in the obtained extract, they may be used as they are or may be used after concentration. The present invention is not limited to the above extraction method and extraction conditions, and commercially available Hedera fluid X may be used.

In a preferred embodiment of the present invention, 1 ㎏ of Hedera leaf (Folia hedera helicis) was selected and used as 70% (w / w) ethanol according to Korean Pharmacopoeial Theory and Powdery Degree The mixture was extracted with percolation method at -80 ° C, filtered using a cotton filter, and concentrated under reduced pressure to obtain a solid content of 50%. 300 g of the obtained extract was dissolved in 700 g of 70% ethanol (1 g of Hedera fluid x) . Preferably, the Hedera extract contains not less than 2.0% as Hedera koceide C (C59H96O26: 1221.39).

The polyoxyethylene caster oil derivatives used in the present invention include polyoxyethylene glycolated natural castor oil or polyoxyethylene glycolated hydrogenated castor oil, preferably Cremophor ^TM , BASF) can be used. In the present invention, Cremophor RH40 ^TM , which is a polyoxyethylene 40 castor oil, is the most preferable in terms of stability.

The polyoxyethylene sorbitan monostearate used in the present invention refers to polyoxyethylene sorbitan monostearate having a plurality of ethylene oxides added to free hydroxyl groups present in sorbitan and partial esters of higher fatty acids, And is commonly referred to as tween or polysorbate. Depending on the kind of fatty acid residues, it is called with 20 (laurate), 40 (palmitate), 60 (stearate), 80 (oleate) and the like. Polysorbate 60 is most preferable in terms of stability.

The polyoxyethylene-polyoxypropylene polymer is generally referred to as Poloxamer in the field to which the present invention pertains, and various types exist depending on the degree of polymerization. Poloxamer 407 is the most preferable in terms of stability and production, although it is not limited to a certain poloxamer in the present invention.

The transparent liquid preparation containing the Hedera extract of the present invention may contain at least one selected from the group consisting of a polyoxyethylene castor oil derivative, polyoxyethylene sorbitan monostearate, sodium lauryl sulfate and polyoxyethylene-polyoxypropylene polymer to 0.1 -5 w / v%. The content of 0.1 w / v% or more is more preferable in terms of stability at the time of storage, and the content of 5 w / v% or less is more preferable in terms of overall quality such as taste and safety. Most preferably, the plant extract-containing transparent liquid formulation of the present invention contains 0.2-5 w / v% of a polyoxyethylene castor oil derivative, 0.2-5 w / v% of polyoxyethylene sorbitan monostearate, 2 w / v% or polyoxyethylene-polyoxypropylene polymer 0.1-5 w / v%.

The transparent liquid formulation containing the Hedera extract of the present invention may contain two or more stability improving agents selected from the group consisting of polyoxyethylene castor oil derivatives, polyoxyethylene sorbitan monostearate, sodium lauryl sulfate and polyoxyethylene-polyoxypropylene polymer . In a most preferred embodiment of the present invention, the transparent liquid formulation containing the Hedera extract contains a polyoxyethylene castor oil derivative and sodium lauryl sulfate together as a stability improver. The liquid preparation of the present invention, which contains a polyoxyethylene castor oil derivative and sodium lauryl sulfate together, is most preferred in terms of storage stability, product quality (taste, property, etc.) In this case, it is more preferable that the liquid preparation contains 0.2 to 0.9% by weight of a polyoxyethylene castor oil derivative and 0.005 to 0.03% by weight of sodium lauryl sulfate.

It is more preferable that the pH of the liquid preparation is 3 to 7 in order to allow oral administration and to exhibit an optimal surfactant effect. When the pH of the liquid preparation does not satisfy the above-mentioned pH range, it can be adjusted to the above-mentioned pH range using a pH adjusting agent. Examples of usable pH adjusting agents include acidic substances such as hydrochloric acid, phosphoric acid, citric acid, acetic acid, tartaric acid and malic acid, and alkaline substances such as potassium hydroxide, sodium citrate and ammonium hydroxide.

The transparent liquid preparation containing the Hedera extract of the present invention may contain other additives commonly used in the field of the present invention such as preservatives, chelating agents, acidifiers, sweeteners, colorants, Vitamins, amino acids, and the like.

The stability of the transparent liquid preparation containing the Hedera extract of the present invention can be evaluated using various methods. Although it can be evaluated while it is stored at the room temperature for the actual use period of the liquid formulation, it is preferable to increase the temperature and evaluate in a relatively short period under severe conditions. The clear liquid formulation containing the Hedera extract of the present invention has excellent storage stability at 40 占 폚 without precipitation over a period of 6 months or more.

Hereinafter, embodiments of the present invention will be described in more detail. However, the embodiments according to the present invention can be modified into various other forms, and the scope of the present invention should not be construed as being limited to the embodiments described below.

Production of Examples 1 to 4 and Comparative Examples 1 to 16

The amount of sorbitol solution (70%), white sugar, high fructose, citric acid, sodium citrate, and preservative were mixed by the amount shown in Table 1 below, and an appropriate amount of purified water was added thereto. 1. ≪ / RTI > Then, 70% Ethanol flow extract of Hedera was dissolved in the solution, and the flavoring agent was administered, and purified water was added thereto to make the total volume 100. The pH of the final liquid formulation after manufacture was measured to give a pH of 3-7.

Component (w / v%) Example Comparative Example One 2 3 4 One 2 3 4 5 6  Hedera Fluid X 2  Sorbitol solution (70%) 10  White sugar 10  High fructose 10  Polyoxyethylene castor oil derivative 0.2 - - - - - - - - -  Polyoxyethylene sorbitan monostearate - One - - - - - - - -  Sodium lauryl sulfate - - 0.5 - - - - - - -  Pollock Sommer - - - One - - - - - -  Xanthan gum - - - - - 0.2 - - - -  Hydroxyethylcellulose - - - - - - 0.1 - - -  Propylene glycol - - - - - - - 5 - -  Polyethylene glycol 400 - - - - - - - - 5 -  Xylitol - - - - - - - - - 5  Citric acid 0.009  Sodium citrate 0.008  Flavoring agent 0.1 0.1 0.2 0.2 0.1 0.1 0.1 0.2 0.2 0.2  Preservative 0.1  Purified water Suitable amount  The pH of the final liquid formulation 4.67 4.53 4.55 4.42 4.8 4.5 4.5 4.4 4.6 4.5

Component (w / v%) Comparative Example 7 8 9 10 11 12 13 14 15 16  Hedera Fluid X 2  Sorbitol solution (70%) 10  White sugar 10  High fructose 10  A mixture of microcrystalline cellulose and sodium carboxymethylcellulose 0.7 - - - - - - - - -  Sodium alginate - 0.005 - - - - - - - -  Carbomer 934 - - 0.001 - - - - - - -  Beta-cyclodextrin - - - 3 - - - - - -  Kaolin - - - - One - - - - -  Lecithin - - - - - 0.85 - - - -  glycerin - - - - - - 5 - - -  Sorbitol - - - - - - - 5 - -  Arasel 60 (Arlacel 60) - - - - - - - - 0.04 -  Hydroxypropylcellulose - - - - - - - - - 0.1  Citric acid 0.009  Sodium citrate 0.008  Flavoring agent 0.1 0.1 0.1 0.1 0.1 0.2 0.2 0.2 0.2 0.2  Preservative 0.1  Purified water Suitable amount  The pH of the final liquid formulation 4.6 4.5 4.6 4.5 4.5 4.5 4.5 4.7 4.5 4.5

Evaluation of the stability of Examples 1 to 4 and Comparative Examples 1 to 16

14 days, 1 month, 2 months, 3 months, 4 months, 5 months and 6 months after storage of the previously prepared Examples 1 to 4 and Comparative Examples 1 to 6 in a stability tester After the elapse of time, the presence or absence of the precipitate was visually observed to evaluate the stability. The results are shown in Table 2.

Time of evaluation Example 1 Example 2 Example 3 Example 4 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 Comparative Example 6 7 days Transparency Transparency Transparency Transparency Transparency Transparency Transparency Transparency Transparency Transparency 14 days Transparency Transparency Transparency Transparency Transparency Transparency Transparency Transparency Transparency Transparency 1 month Transparency Transparency Transparency Transparency Sedimentation Sedimentation Sedimentation Sedimentation Sedimentation Transparency 2 months Transparency Transparency Transparency Transparency Sedimentation 3 months Transparency Transparency Transparency Transparency 4 months Transparency Transparency Transparency Transparency 5 months Transparency Transparency Transparency Transparency 6 months Transparency Transparency Transparency Transparency

Time of evaluation Comparative Example 7 Comparative Example 8 Comparative Example 9 Comparative Example 10 Comparative Example 11 Comparative Example 12 Comparative Example 13 Comparative Example 14 Comparative Example 15 Comparative Example 16 7 days Transparency Transparency Transparency Transparency Transparency Transparency Transparency Transparency Transparency Transparency 14 days Transparency Transparency Transparency Transparency Transparency Transparency Transparency Transparency Transparency Transparency 1 month Sedimentation Sedimentation Sedimentation Sedimentation Sedimentation Transparency Sedimentation Sedimentation Sedimentation Transparency 2 months Sedimentation Sedimentation 3 months 4 months 5 months 6 months

As can be seen from the results in Table 2, the transparent liquid formulation containing the Hedera extract of the present invention was excellent in storage stability so as to maintain a transparent liquid form without sedimentation in a stability tester for 6 months, And it was unstable to such an extent that a visible precipitate was formed within a month.

Evaluation of tastes of Examples 1 to 4 and Comparative Examples 1 and 10

The flavors of the liquid preparations containing the Hedera extract prepared in Examples 1 to 4 and Comparative Examples 1 and 10 were evaluated for one month during the stability test period. It is an average value of 5 points (when the taste is very good) and 0 point (when the taste is bad).

Example 1 Example 2 Example 3 Example 4 Comparative Example 1 Comparative Example 2 Immediately after manufacture 4.2 4.0 3.9 3.6 3.7 3.8 7 days 4.3 3.7 4.0 3.5 3.5 3.9 14 days 4.0 3.8 4.2 3.4 3.6 3.7 1 month 4.1 3.8 4.1 3.3 3.8 3.8

As shown in Table 3, the taste of Example 1 using a polyoxyethylene castor oil derivative and Example 3 using sodium lauryl sulfate was the best.

INDUSTRIAL APPLICABILITY As described above, the transparent liquid preparation containing the extract of Hedera extract according to the present invention ensures stability during storage and does not cause precipitation. Therefore, the transparent liquid preparation containing the Hedera extract according to the present invention can reduce the rejection feeling when the patient is taking it, thereby enhancing the compliance with the medication. Further, the transparent liquid preparation containing the Hedera extract according to the present invention has a good taste and is easy to take.

Claims (6)

A liquid formulation containing the Hedera extract containing at least one selected from the group consisting of a polyoxyethylene castor oil derivative and sodium lauryl sulfate as a stability improving agent. The liquid formulation according to claim 1, wherein the liquid preparation is transparent. [3] The liquid formulation according to claim 1, wherein the Hetera extract is an extract of 70% (w / w) ethanol of Hedera helix leaf. delete The liquid formulation according to claim 1, wherein the liquid preparation contains 0.1-5 w / v% of the stability improving agent. The liquid formulation according to claim 1, wherein the pH of the liquid preparation is from 3 to 7.