WO2007125653A1

WO2007125653A1 - Oral liquid composition containing crude drug

Info

Publication number: WO2007125653A1
Application number: PCT/JP2007/000460
Authority: WO
Inventors: Toshiki Usui; Yasuhiro Shinkawa
Original assignee: Kowa Co., Ltd.
Priority date: 2006-04-27
Filing date: 2007-04-25
Publication date: 2007-11-08
Also published as: JPWO2007125653A1; KR20080111085A

Abstract

The object is to provide an oral liquid preparation containing a crude drug, which is stable under lower temperature conditions and higher temperature conditions. Disclosed is an oral liquid composition comprising the following components (A) to (D): (A) one or more crude drugs selected from ginseng, ginger, jujube, peony root, acutiloba and cinnamon bark; (B) a sucrose fatty acid ester; (C)a monoglycerin fatty acid ester; and (D) glycyrrhizic acid or a salt thereof.

Description

Specification

Herbal medicine-containing oral solution composition

Technical field

[0001] The present invention relates to a herbal medicine-containing oral liquid composition having good stability under low and high temperature conditions.

Background art

[0002] Herbal medicines such as carrots and peonies are widely used as drinks, for example, because they have nourishment and tonic effects. However, crude drugs contain many components that are poorly soluble in water, causing problems such as precipitation. In order to solve this problem, a technique for blending a solubilizer represented by a nonionic surfactant has been reported. For example, in Patent Document 1, a liquid composition containing polyfluorolin can be stabilized for a long period of time by adding polyoxyethylene hydrogenated castor oil, polyoxyethylene polyoxypropylene glycol, and polyethylene glycol fatty acid ester. Are listed. Patent Document 2 describes that a combination power of a polyglycerin fatty acid ester, a polyoxyethylene nonionic surfactant and an oil component is good for solubilizing ginsenosides. In Patent Document 3, a polyglycerin fatty acid ester, a polyoxyethylene nonionic surfactant and an oil component are blended into a crude drug extract, and the blending amount of the polyoxyethylene nonionic surfactant is A solubilized liquid composition having 1/6 parts by weight to 1 part by weight of glycerin fatty acid ester is described. Patent Document 4 describes blending a polyoxyethylene hydrogenated castor oil and a polyoxyethylene polyoxypropylene condensate with a crude drug extract.

Patent Document 1: Japanese Patent Laid-Open No. 2 00 _ 2 4 7 8 90

Patent Document 2: Japanese Patent Laid-Open No. 2 0 0 2 _ 1 9 3 8 2 5

Patent Document 3: Japanese Patent Laid-Open No. 2 0 0 2 _ 1 2 8 7 0 3

Patent Document 4: Japanese Patent Publication No. 5-9 4 0 8 Disclosure of the invention

Problems to be solved by the invention

[0003] However, the storage stability of the herbal medicine component-containing liquid preparation differs greatly depending on the herbal ingredients to be blended, as described in Patent Documents 1 and 2, and particularly the stabilization of the oral liquid medicine containing a plurality of herbal medicine ingredients. It is difficult. Also, during the distribution process, it can be as high as 40 ° C or higher, and as low as 5 ° C, so it can be stored under either low or high temperature conditions. However, it was desired to develop a stable oral solution that does not cause precipitation.

Accordingly, it is an object of the present invention to provide a crude drug-containing oral solution composition having good stability under low and high temperature conditions.

Means for solving the problem

[0004] Therefore, the present inventor has examined the stability of a liquid preparation containing a crude drug component. If the sucrose fatty acid ester, monoglycerin fatty acid ester, and glycyrrhizic acid or a salt thereof are combined in combination, The present invention was completed by finding that a stable oral solution can be obtained without precipitation for a long period of time not only under high temperature conditions but also under low temperature conditions.

That is, the present invention provides the following components (A) to (D):

(A) One or more herbal medicines selected from carrots, ginseng, taisou, peony, toki, and keihi

(B) Sucrose fatty acid ester

(C) Monoglycerin fatty acid ester

(D) Glycyrrhizic acid or a salt thereof

It is intended to provide an oral liquid composition characterized by containing.

The invention's effect

[0006] The oral liquid composition of the present invention is stable without precipitation for a long period of time at both low and high temperature conditions. Therefore, the oral liquid composition of the present invention can be circulated stably in both summer and winter. BEST MODE FOR CARRYING OUT THE INVENTION

[0007] The herbal medicine component (A) used in the present invention is one or more selected from carrots, ginseng, taisaw, peonies, toki, and keihi. Here, ginseng root extract of Panax ginseng is used as carrot. As the ginger, a ginger rhizome extract is used. For Taisou, the extract of jujube fruit from the family Aceraceae is used. As the peonies, the extract of the roots of Peonies is used. As the touki, an extract of the roots of the celery family is used. As the key, an extract of the bark of the cinnamon cassia of the camphor family is used. It is preferable to use an extract as the crude drug component (A). The form of the extract is not particularly limited, and examples thereof include a dry extract, a flow extract, and a soft extract. In the present invention, it is preferable to use a flow extract or a soft extract. Examples of the extraction solvent for obtaining these extracts include water and ethanol.

[0008] These herbal ingredients (A) can be blended in the oral liquid composition of the present invention in one kind or two or more kinds. It is preferable to mix herbal medicine ingredients, and further, it is preferable to mix ginseng and cypress, and if necessary, one or more selected from taiso, peony, toki and keihi.

[0009] The total content of these crude drug ingredients (A) as a raw drug equivalent value is not particularly limited, but from the viewpoint of pharmacological effects, it is 5 to 5 in the oral liquid composition of the present invention. It is preferably 25 mass%, more preferably 10 to 25 mass ⁰ / o, and particularly preferably 15 to 25 mass ⁰ / o.

[0010] The sucrose fatty acid ester (B) used in the present invention includes sucrose.

C,, -C, ₈ fatty acid esters are preferred. Commercially available sucrose fatty acid esters include DK ester SS (Daiichi Kogyo). The relative mass ratio of the content of the herbal medicine component (A) and the sucrose fatty acid ester (B) in the oral liquid composition of the present invention is not particularly limited. From the above, when the content of the crude drug component (A) in the oral liquid composition of the present invention is 1 (concentration value of the crude drug), the content of the sucrose fatty acid ester (B) is set to 0.0 0004-0. It is preferable to be within the range of 02. In addition, the content of the sucrose fatty acid ester (B) is not particularly limited. However, from the viewpoint of preventing the precipitation of the crude drug component, 0.001 to 0.1 in the oral liquid composition of the present invention. % By mass, more preferably 0.005 to 0.04% by mass, and particularly preferably 0.01 to 0.02 mass ⁰ / o.

As the monoglycerol fatty acid ester (C) used in the present invention, monoglycerol C ₁₄ -C ₁₈ fatty acid ester is preferable. As a commercial product of monoglycerin fatty acid ester, Poem M_100 (manufactured by Riken Vitamin) can be mentioned. The relative mass ratio of the content of the crude drug component (A) and the monoglycerin fatty acid ester (C) in the oral liquid composition of the present invention is not particularly limited, but from the viewpoint of preventing precipitation of the crude drug component, The content of the monoglycerin fatty acid ester (C) is from 0.00004 to 0.02 when the content of the crude drug component (A) in the oral liquid composition of the invention is 1 (concentration value of the crude drug). It is preferable to be within the range. In addition, the content of the monoglycerin fatty acid ester (C) is not particularly limited. However, from the viewpoint of preventing the precipitation of the crude drug component, 0.001 to 0.1 mass in the oral liquid composition of the present invention. %, More preferably 0.005 to 0.04 mass ⁰ / o, and particularly preferably 0.01 to 0.02 mass ⁰ / o.

In the present invention, glycyrrhizic acid or a salt thereof (D) includes not only glycyrrhizic acid itself but also a pharmaceutically acceptable salt thereof. Examples of the salt include alkali metal salts, alkyl earth metals, and the like. Salt, ammonium salt. Examples of glycyrrhizic acid or a salt thereof (D) include dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, ninatrium glycyrrhizinate, and trisodium glycyrrhizinate. In the present invention, nitric acid glycyrrhizinate is preferable from the viewpoint of the precipitation preventing effect. Glycyrrhizic acid or its salt can be combined with sucrose fatty acid ester and monoglycerin fatty acid ester to prevent precipitation under low temperature conditions. Play. The relative mass ratio of the content of the herbal component (A) and the glycyrrhizic acid or its salt (D) in the oral liquid composition of the present invention is not particularly limited, but from the viewpoint of preventing precipitation of the herbal component. When the content of the crude drug component (A) in the oral liquid composition of the present invention is 1 (concentration value of the crude drug), the content of glycyrrhizic acid or a salt thereof (D) is from 0.0004 to It is preferable to be within the range of 0.02. In addition, the content of glycyrrhizic acid or a salt thereof (D) is not particularly limited. However, from the viewpoint of preventing precipitation of crude drug components, 0.001 to 0.000 in the oral liquid composition of the present invention. It is preferably 1% by mass, more preferably 0.005 to 0.04 mass ⁰ / o, and particularly preferably 0.01 to 0.02 mass ⁰ / o.

[0013] The relative mass ratio of the content of each component in the oral liquid composition of the present invention is not particularly limited, but from the viewpoint of preventing precipitation of crude drug components, The content of sucrose fatty acid ester (B), monoglycerin fatty acid ester (C) and glycyrrhizic acid (D) is 0 for each content of crude drug component (A) in It is preferable to be within the range of 00004 to 0.02.

[0014] The oral liquid composition of the present invention may further contain other medicinal ingredients, sweeteners, pH adjusters, antioxidants, coloring agents, flavoring agents, flavoring agents, preservatives, water and the like. The

Other medicinal ingredients include aloe, wiki, turmeric, turquoise, engakusaku, age, ougi, ousei, onji, guarana, kukosi, jio, tochi yu, amarogentin, ougon, oubak, gauld Cascarilla, power mushroom grass, power wax, kikiyou, pheasant, kiyonin, yellowfin, wolfberry, kujin, keyai, kemameshi, kengoshi, gentiana, gennoshouko, kojin, kobushi, kopoku, goo, gosh, trash, goshbo, trash Conzu Lango, Psycho, San Sissi, Saffron, Sansho, Sandscon, Zhi, Sikon, Jishu, Sisoshi, Shazen (Obaco), Jia Incense, Shouma, Sehi, Sekishokon, Senega, Senkiyu, Senkou, Centaurium grass, Senpri, Senbo , Senso, senna, sojujuku, sohakuhi, soyou, daiou, captain, chimo, chiletta grass, chimpi, spruce, tonin, tokon, nibaki, peony cricket, peacock jutsu, belladonnakon, henopoi oil, yakuchi, yumotan, yomotan Gibyo, Nigamomogi, Bitter tincture, Hop, Homika, Bowie, Maou, Moku, Mokko, Yokuinin, Ryutan, Gentian, Luzon power, Forsythia, Rogiyo, and Royal jelly.

Sweeteners include sucrose, lactose, fructose, glucose, honey, sorbitol, and multi! 1, Erythr I 1, Xyliri 1 1, Trehalose, Saccharin and its salts, Aspartame, Acesulfame K, and Subaru extract.

Examples of the ρ soot adjusting agent include those capable of adjusting 1 to 1 to 4 to 7, particularly 5 to 6.

Examples of the antioxidant include ascorbic acid and its salt, erythorbic acid and its salt, edetic acid and its salt, sodium bisulfite, gallic acid propylene and the like.

Examples of the colorant include tar pigments, iron sesquioxide, and caramel.

As a fragrance | flavor, for example, a waffle frame / kuichi etc. are mentioned.

Examples of the corrigent include citrate and its salt, L_glutamic acid and its salt, povidone, I_menthol and the like.

Examples of preservatives include benzoic acid and its salts, parabens and the like.

[001 5] The oral liquid composition of the present invention can be produced by mixing the aforementioned raw materials into an aqueous solution form. The liquid composition obtained by the present invention can be used, for example, as an oral liquid composition for nourishing tonics due to the pharmacological action of a herbal medicine or the like to be blended.

[001 6] Next, the present invention will be described in detail with reference to Examples and Comparative Examples, but the present invention is not limited to these. [0017] Example 1

In 20 mL of purified water, ginseng extract (carrot extract ■ made in Japan powder) 450 mg (powder equivalent value 3000 mg), peonies extract (plum extract 1 A ■ powdered noodles made in Japan) 1 25 mg (powder equivalent value 500 mg), toki extract (toki soft) Extract ■ Alps Yakuhin) 1 51. 5mg (Drug substance equivalent value 500mg), Shokiyo extract (Shokiyo style extract ■ Japan powder type) 0.5mL (Drug substance equivalent value 50 Oing), Taisou extract (Taisou style extract ■ Japan powder 1) OmL (powder equivalent value 1 OOOmg), Keihi extract (Keihi style extract ■ made in Japan powder) 0.5mL (powder equivalent value 50 Omg), sucrose fatty acid ester (Eszure ■ Daiichi Kogyo ) 5. Omg, monoglycerin fatty acid ester (Poem M-1100-manufactured by Riken Vitamin) 5. Omg, dipotassium glycyrrhizinate (dipotassium glycyrrhizinate ■ Alps) 5. Omg, Que Acid 3 Omg, and the mixture was stirred to dissolve. Sodium citrate was added to adjust the pH to 5.5, and an appropriate amount of purified water (room temperature) was added to produce an oral solution with a total volume of 3 OmL (specific gravity: 1.05).

[0018] Comparative Example 1

According to the formulation in Table 1, an oral solution was prepared in the same manner as in Example 1 except that no monoglycerin fatty acid ester was added.

[0019] Comparative Example 2

According to the formulation in Table 1, an oral solution was prepared in the same manner as in Example 1 except that sucrose fatty acid ester was not added.

[0020] Comparative Example 3

According to the formulation in Table 1, an oral solution was prepared in the same manner as in Example 1 except that dipotassium glycyrrhizinate was not added.

[0021] Comparative Example 4

According to the formulation in Table 1, an oral solution was prepared in the same manner as in Example 1 except that polyethylene glycol fatty acid ester was added instead of monoglycerin fatty acid ester and sucrose fatty acid ester. [0022] Test example

The oral solutions obtained in Example 1 and Comparative Examples 1 to 4 were stored in the dark immediately after production and at 5 ° C and 60 ° C for 1 month, and then the visual stability of each oral solution was evaluated visually. Appearance stability is indicated by ○ when no precipitation occurred and by X when precipitation occurred. The results are shown in Table 1.

[0023] [Table 1] Content ίΐΐκ)

[0024] In oral liquids containing herbal medicines such as ginseng and peonies that contain sucrose fatty acid ester, monoglycerin fatty acid ester and glycyrrhizinate disulfuric acid (Example 1), 5 ° C for 1 month and 60 ° C for 1 month No precipitation was observed on both sides, and appearance stability was good. On the other hand, in Example 1, the oral solution containing monoglycerin fatty acid ester (Comparative Example 1), sucrose fatty acid ester (Comparative Example 2) and dipotassium glycyrrhizinate (Comparative Example 3) precipitates at 5 ° C for 1 month. Admitted. In Comparative Examples 1 and 2, precipitation was observed even at 60 ° C for 1 month. Further, in the oral liquid preparation (Comparative Example 4) containing polyethylene glycol fatty acid ester instead of sucrose fatty acid ester and monoglycerin fatty acid ester, precipitation was observed at 5 ° C for 1 month.

[0025] Based on the above, sucrose fatty acids were added to oral liquids containing herbal medicines such as carrots and peonies. By blending esters, monoglycerin fatty acid esters and glycyrrhizic acids, it was possible to obtain a herbal medicine-containing oral solution with good appearance stability under both low and high temperature conditions.

Claims

The scope of the claims

[1] The following ingredients (A) to (D):

(A) One or more herbal medicines selected from carrots, ginsengs, taisou, peonies, toki, and keihi

(B) Sucrose fatty acid ester

(C) Monoglycerin fatty acid ester

(D) Glycyrrhizic acid or a salt thereof

An oral liquid composition comprising:

[2] The content of component (B), component (C), and component (D) when the content of component (A) as an active ingredient equivalent is 1 is 0.00000 to 0.02. 2. The oral liquid composition according to claim 1, which is within the range.

[3] The content of component (A) as a value for a drug substance is 5 to 25% by mass,

The content of (B) is 0.001 to 0.1% by mass, and the content of component (C) is

0. 001 -0. 1% by mass and component (D) content is 0.001 to 0.

The oral liquid composition according to claim 1 or 2, which is 1% by mass.