JPH09301859A - Liquid medicine combined with ethenzamide - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a continuously stable liquid medicine combined with ethenzamide and including the solubilized ethenzamide by blending a tannin and a crude medicine containing the tannin with the ethenzamide and further optionally heating the one with a nonionic surfactant. SOLUTION: This liquid medicine combined with ethenzamide is obtained by blending (A) one or two kinds selected from a crude medicine containing a tannin [preferably, SYAKUYAKU (Paeonia albiflora), BOTANNPI (Paeonia moutan), KEIHI (Cinnamomi Cortex), CHOUJI (Caryophylli Flos), OUREN (Coptis japonica), OUBAKU (phellodendron amurense) or KAMITSURE (Matricaria chamomilla)] and the tannin and (B) ethenzamide. If necessary, (C) a nonionic surfactant (preferably a polyglycerol fatty acid ester) is blended therewith. The liquid medicine is preferably obtained by blending the components A with B and optionally C at 50-95 deg.C. Moreover, the blending ratio of component B is preferably 0.08-5.0wt.%. Further, the component A is blended >=20mg in terms of the tannin based on 1g component B.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a liquid preparation in which etenzamid is solubilized and stabilized.

[0002]

2. Description of the Related Art Ethenzamide can be solubilized by increasing the concentration of a solubilizing solvent such as ethanol, but it has a high alcohol concentration and is not suitable for liquid pharmaceutical products. In addition, it is difficult to solubilize with a synthetic surfactant that can be usually compounded in a pharmaceutical product, and as a product, only a suspension in a syrup is known. When adding etenzamid to a liquid agent, a suspension stabilizer such as a surfactant is added to stabilize it as suspended particles. In this case, high temperature sterilization operation such as plate sterilization is performed to solubilize it. The subsequent cooling caused fibrous crystal precipitation, which was a big problem in terms of ingestability and formulation.

[0003]

SUMMARY OF THE INVENTION An object of the present invention is to provide a liquid preparation which solubilizes etenzamid and is stable over time.

[0004]

Means for Solving the Problems As a result of intensive studies for solubilizing etenzamid, the present inventors have blended one or two kinds selected from the group consisting of tannin-containing crude drugs and tannin with etenzamid. Further, they have found that a stable etenzamid liquid preparation can be prepared by further heating with a nonionic surfactant as necessary, and completed the present invention. That is, the present invention is a liquid preparation containing one or two kinds selected from the group consisting of a herbal medicine containing tannin and tannin, and ethenamide.

In the present invention, the blending amount of ethenamide is 0.08 to 5.0% by weight.

The tannin used in the present invention may be either a gallotannin or a catechin, and examples of the tannin-containing crude drug include peony, button pipi, cinnamon sardine, clove, laurel, psyllium, chamomile and the like. The form is dry powder of crude drug, an extract extracted with a solvent containing water, and the like. Tannin (tannin-containing crude drug converted to tannin content) is 1 g of etenzamid
In contrast, 20 mg or more is blended.

The nonionic surfactant used in the present invention is not particularly limited as long as the object of the present invention can be achieved, and may be any one that can be used as a pharmaceutical additive. Particularly, a nonionic surfactant having an HLB value of 3 or more is preferable, and examples thereof include polyoxyethylene hydrogenated castor oil, polyoxyethylene polyoxypropylene glycol, sucrose fatty acid ester, glycerin fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid. Examples thereof include esters, polyglycerin fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene sorbit fatty acid esters, polyoxyethylene glycerin fatty acid esters, polyethylene glycol fatty acid esters, and polyoxyethylene castor oil. Among these nonionic surfactants, polyglycerin fatty acid ester, polyoxyethylene hydrogenated castor oil, and polyoxyethylene polyoxypropylene glycol are particularly preferable.

The concentration of the nonionic surfactant is 0.00
1 to 1.0% by weight, more preferably 0.01 to 0.5
% By weight. As other medicinal components, antipyretic analgesics, muscle relaxants, anticonvulsants, antihistamines, sympathomimetics and the like other than the above can be mixed.

The composition of the present invention may contain substances commonly used in the pharmaceutical art, such as pharmacologically acceptable sweeteners, pH adjusters, preservatives, flavors and colorants.

Examples of sweeteners include lactose, sucrose,
Fructose, glucose, sorbitol, mannitol, erythritol, xylitol, trehalose, stevia extract and the like can be mentioned.

Examples of the pH adjusting agent include lactic acid, citric acid, malic acid, succinic acid, fumaric acid, tartaric acid, phosphoric acid and salts thereof.

Examples of preservatives include parabens such as nipamethyi, nipaethi, nipapro and nipabuti, benzoic acid or salts thereof.

As the fragrance, orange, grapefruit, apple, lemon, lime, tangerine, yuzu,
Unshu mandarin oranges, nuts mandarin oranges, grapes, strawberries, pineapples, bananas, peaches, melons, watermelons, plums, cherries, pairs, apricots, currants, plums, mango, mangosteen, guava, raspberries, blueberries, and other fruit flavors, green tea, tea, Flavors such as cocoa, chocolate, coffee, almonds, maple, vanilla, whiskey, brandy, rum, wine, liqueur, cocktails, mint and the like can be mentioned, and these can be used alone or in a mixed flavor of two or more kinds.

[0014]

INDUSTRIAL APPLICABILITY In the present invention, one or two kinds selected from the group consisting of tannin and a herbal medicine containing tannin and, if necessary, a nonionic surfactant are blended, so that etenzamid can be stabilized. It was solubilized, and even after cooling, etenzamid did not precipitate as crystals, and an etenzamid-containing liquid preparation having good stability over time could be prepared.

Furthermore, since it is stably solubilized, high temperature sterilization operations such as plate sterilization can be performed, and it is not necessary to add special manufacturing conditions.

[0016]

EXAMPLES Next, the present invention will be described in more detail with reference to Examples, Comparative Examples and Test Examples, but the present invention is not limited to these descriptions. (Test Example) Ethenzamide, "substance selected from the group consisting of tannin and tannin-containing crude drug" and polyglycerin fatty acid ester were added in the amounts shown in Table 1, and 80 to 95
A composition was prepared by heating and melting at 0 ° C. 1 at 5 ℃
After storage for a week, crystal precipitation of ethenzamide was observed. As a result, in the liquid preparations prepared in Examples, ethenzamide was solubilized stably, crystal precipitation did not occur even at low temperature, and it was stable over time.

[0017]

[Table 1]

(Example 13) Ethenzamide, peony extract, polyglycerin fatty acid ester, glycerin,
After adding water and heating at 85 ° C to dissolve, cool to room temperature, add ibuprofen, anhydrous caffeine, xanthan gum, acidulant, adjust to pH 3 to 4.5, stir with a homomixer, and solubilize etenzamid ibuprofen A suspension was obtained. (30 ml) Ethenzamide 84 mg Peony extract 500 mg Ibuprofen 144 mg Anhydrous caffeine 15 mg Xanthan gum 60 mg Polyglycerin fatty acid ester 25 mg Glycerin 60 mg Sweetener 10000 mg Acidulant proper amount Preservative proper amount Purified water proper amount.

(Example 14) Ethenzamide, cinnamon syrup extract, polyglycerin fatty acid ester, glycerin, and water were added, and the mixture was heated and dissolved at 85 ° C and then cooled, and acetaminophen, chlorpheniramine maleate, methylephedrine hydrochloride, and sweetness were added. An agent, an acidulant, and a preservative were added, and the total amount was adjusted to 100% with purified water to obtain an etenzamid-solubilized liquid agent. (30 ml) Ethenzamide 100 mg Keihi flow extract 600 mg Acetaminophen 200 mg Chlorpheniramine maleate 2 mg Methylephedrine hydrochloride 20 mg Polyglycerin fatty acid ester 25 mg Glycerin 60 mg Sweetener 10000 mg Acidulant proper amount Purified water proper amount.

(Example 15) In the same manner as in Example 14, an etenzamid solubilizing liquid preparation containing the following components was obtained. (30 ml) Ethenzamide 100 mg Chamomile extract 1000 mg Dihydrocodeine phosphate 8 mg Bromhexine hydrochloride 12 mg Chlorpheniramine maleate 2 mg dl-Methylephedrine hydrochloride 20 mg Lysozyme chloride 30 mg Polyglycerin fatty acid ester 25 mg Glycerin 60 mg Sweetener Water-proofing agent Acid amount

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical display location A61K 35/78 A61K 35/78 X AAG AAGF (72) Inventor Toshiaki Nakajima 3 Takada, Toshima-ku, Tokyo No. 24-1 Taisho Pharmaceutical Co., Ltd. (72) Inventor Ichiro Okuhira 3-24-1, Takada, Toshima-ku, Tokyo Taisho Pharmaceutical Co., Ltd. (72) Kenji Tsunoda 3-24 Takada, Toshima-ku, Tokyo No. 1 within Taisho Pharmaceutical Co., Ltd.

Claims (6)

[Claims] 1. A liquid preparation containing one or two kinds selected from the group consisting of a herbal medicine containing tannin and tannin, and ethenamide. 2. A liquid preparation containing one or two kinds selected from the group consisting of a crude drug containing tannin and tannin, a nonionic surfactant and etenzamid. 3. The liquid preparation according to claim 1, wherein the herbal medicine containing tannin is peony, potanpi, cinnamon sardine, clove, oren, oat, and chamomile. 4. The liquid preparation according to claim 2, wherein the nonionic surfactant is a polyglycerin fatty acid ester. 5. A method for producing a liquid preparation, which comprises heating one or two kinds selected from the group consisting of a tannin-containing crude drug and tannin, and ethenamide to 50 to 95 ° C. 6. One or two selected from the group consisting of a tannin-containing crude drug and a tannin, a nonionic surfactant and etenzamid are blended in a state of being heated to 50 to 95 ° C. Manufacturing method of liquid agent.