JPS61254521A - Stable fenbufen suspended syrup free of irritant taste - Google Patents

Abstract

PURPOSE:The titled stable syrup free of irritant taste obtained by incorporating fenbufen which is an anti-inflammatory and analgesic agent with crystalline cellulose, magnesium aluminate metasilicate and cycloeextrin in a specific proportion and having no irritant taste. CONSTITUTION:A stable fenbufen suspended syrup containing (A) 0.1-5wt./vol% fenbufen [chemical name; 4-(4-biphenylyol)-4-oxobutyric acid], (B) 0.5-5wt./vol% crystalline cellulose and/or CMC-Na, (C) 0.01-15wt./vol% magnesium aluminate metasilicate and (D) 0.01-15wt./vol% cyclodextrin. The syrup becomes a uniform suspension by the action of the suspending agent of the component (B), and irritant taste is eliminated by the component (C). The coagulation of particles can be prevented by the component (D). Thus, the titled suspended syrup is stable even to high-temperature sterilization and the irritant taste can be reduced without causing coagulation even in preservation for a long period. The syrup can be readily administered even to infants.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to a suspension syrup of fenbufen, and more specifically, fenbufen, an antipyretic, analgesic, and antiinflammatory agent that is sparingly soluble in water and has a pungent taste, is suspended; This invention relates to a suspension syrup that can be taken with reduced irritation and is also stable in terms of physical properties.

[Conventional technology]

Fenbufen [4-(4-biphenylyl)-4-oxobutyric acid] is a nonsteroidal anti-inflammatory, analgesic, and antipyretic glodrug that shows almost no physiological activity on its own, but its metabolite, biphenylylacetic acid, has strong medicinal effects. be.

Therefore, it is an excellent drug that has strong anti-inflammatory, anti-rheumatic and analgesic and antipyretic effects, and has fewer side effects of gastrointestinal disorders, which are generally associated with non-steroidal anti-inflammatory, analgesic and antipyretic drugs.

Conventionally, fenbufen has been formulated as tablets, granules, and capsules, but liquid preparations have not yet been provided on the market because they are very difficult to dissolve in water and have a pungent taste.

[Problem that the invention seeks to solve]

Therefore, in order to make fenbufen, which has excellent medicinal efficacy and few side effects, easily administrable to infants, it is desired to develop a stable syrup that can disperse fenbufen uniformly in water, reduce the irritating taste, and make it easier to administer to infants. was.

[Means for solving problems]

As a method to reduce the pungent taste of fenbufen, (1)
Possible factors include pH adjustment and (2) clathrate formation.

Therefore, the present inventor attempted to reduce the solubility of fenbufen by lowering the pH of (11) to 4.00, but
No effect was observed, and aggregation occurred and physical properties were unstable. In addition, (2) was also unsuitable as a suspending agent because a large amount of host molecules was required to form an clathrate compound.

Furthermore, as a result of intensive research into liquid preparations of fenbufen, the present inventors found that a uniform suspension of fenbufen can be obtained by adding a specific suspending agent to the solution and dispersing it. The addition of cyclodextrin eliminates the irritating taste, and the addition of cyclodextrin prevents the coagulation of particles caused by the addition of magnesium aluminate metasilicate, resulting in a suspension syrup that is stable over time. They discovered this and completed the present invention.

That is, the present invention uses the following four components (A), (n), (C
) and (D) (A) 0.1-5 w/v% fenbufen, (B) 0
．． 5-5% w/v of crystalline cellulose and/or sodium carboxymethyl cellulose, (C) 0.01-15% w/v of magne metasilicate aluminate 1. ．． 1 um, (D)0. A suspension syrup containing OL-15 w/v% nocyclotextrin is provided.

As the crystalline cellulose of component (B), for example, one commercially available under the trade name of Avicel J RC (Asahi Kasei Industries, Ltd.) can be used. [Avicel J RC has five grades, any of which can be used, but [Avicel J RC-591NF is particularly preferred].

Component (C), magnesium aluminate metasilicate, is frequently used as an antacid and has excellent moisture absorption and adsorption ability, so it can be used as a separating agent for hygroscopic, sticky, and oil-containing powders and granules, and for maintaining fluidity. It is a safe additive that is widely used as a dispersion aid for agents or suspensions, and as a molding binder for granules and tablets. For example, it is commercially available under the trade name Neusilin (Fuji Chemical Co., Ltd.) Things can be used.

Component (D) cyclodextrin is a non-reducing maltooligosaccharide in which glucose molecules produced from starch are connected in a cyclic manner. There are three types of cyclodextrin, cyclodextrin and γ-cyclodextrin, and all are safe substances that are quickly metabolized in the body like starch and sucrose. In the present invention, any α-1β-1γ-cyclodextrin can be used, but β-cyclodextrin is particularly preferred, and is commercially available, for example, under the trade name of Celldex (Nihon Shokuhin Kako Co., Ltd.).

The suspension syrup of 7-embufene of the present invention contains component (A) in an amount of 0.1 to 5 w/v% (preferably 1.0 to 2%) based on the total amount and 0.5 to 5 W/1. % (preferably 1.2 to 2 w/v%) of component (B) and 0.0 l-1
5W/V% (preferably 0.02-5 w/v%)
component (C) and 0901 to 15 W/m% (preferably 0605 to 1).

It is prepared by adding and blending component (D) of W/ma%).

Furthermore, in addition to the above-mentioned components, the fenbufen suspension syrup of the present invention may contain active agents, antifoaming agents, sweeteners, preservatives, fragrances, and the like, if necessary.

[Action and effect of invention]

The fenbufen suspension syrup of the present invention is stable under high-temperature sterilization, does not cause sedimentation, syneresis, aggregation, or coagulation even when stored for a long period of time, and can also reduce the irritant taste characteristic of fenbufen, making it suitable for infants and children. Easy to administer.

〔Example〕

Next, the present invention will be explained in detail with reference to Examples and Test Examples.

Example 1 Avicel RC-59INF 1.52 was added to 25 mm of distilled water with gradual stirring on a 50° C. water bath and dispersed to form a suspension. Next, after dissolving 30 f of D-sorbitol solution and 15 f of refined sucrose, they were separately dissolved in distilled water, 30 g of 9-lyoxyethylene hydrogenated castor oil, and 2 g of β-cyclodextrin. Dissolve Of, Fenbufen 2.0tz Magnesium Metasilicate Aluminate 1. Add and disperse Of,
Stir 100% with distilled water to make a homogeneous suspension. 200m
Sieve through an esh sieve and fill in a 100-yen brown bottle.
It was sterilized at 5°C for 20 minutes.

Additionally, magnesium aluminate metasilicate and/or β
- Suspensions of Comparative Examples 1 to 3 were obtained in the same manner as above except that cyclodextrin was not blended. Their compositions are shown in Table 1.

The following margins are Test Example 1 Regarding the suspending agents of Example 1 and Comparative Examples 1 to 3 in Table 1 3
The suspension stability after standing for 0 days and the presence or absence of coagulation after one week at 70°C were observed by passing through a 200 mesh sieve.

The results are shown in Table 2.

Table 2 + indicates that syneresis, sedimentation, flocculation or coagulation has occurred; -
indicates that these did not occur.

Test Example 2 A sensory taste test was conducted on the suspension agents of Example 1 and Comparative Examples 1 to 3 by five No9ners. 3rd result of 7th
Shown in the table.

Table 3 ○: Stimulating taste is improved compared to Comparative Example 1 Δ: Compared to Comparative Example 1, the medium 1 intense flavor is slightly improved. ×: Stimulating taste is not improved compared to Comparative Example 1 that's all

Claims (1)

[Claims] 1 (A) 0.1 to 5 w/v% fenbufen, (B
) 0.5-5% w/v of crystalline cellulose and/or sodium carboxymethyl cellulose, (C) 0.01-15% w/v of magnesium aluminate metasilicate, and (D) 0.01-15% of w/v. Suspension syrup containing cyclodextrin.