JP-7857359-B2 - Oral pharmaceutical composition containing loxoprofen or a salt thereof and valerian.

Inventors

• 松田 一成
• 田中 美希

Assignees

• 第一三共ヘルスケア株式会社

Dates

Publication Date

20260512

Application Date

20240823

Priority Date

20190611

Claims (5)

1. An oral pharmaceutical composition containing valerian to alleviate gastric mucosal damage, The aforementioned gastric mucosal damage is gastric mucosal damage caused by loxoprofen. The mixture is formulated such that, per 1 part by weight of loxoprofen or its salt, valerian is present in an amount equivalent to at least 1 part by weight of crude drug. The oral pharmaceutical composition.
2. Furthermore, the oral pharmaceutical composition according to claim 1 comprises one or more selected from cough suppressants/expectorants, antihistamines, anti-inflammatory agents, gastrointestinal drug components, antacids, anticholinergics, sedatives, vitamins, and xanthine derivatives.
3. An oral pharmaceutical composition according to claim 1 or 2, which is a tablet, granule, capsule, or liquid.
4. An oral pharmaceutical composition according to claim 2, comprising an antacid, wherein the antacid is one or more selected from magnesium silicate, magnesium aluminosilicate, magnesium aluminum silicate, magnesium oxide, magnesium hydroxide, magnesium hydroxide, coprecipitation product of magnesium hydroxide and potassium aluminum sulfate, magnesium carbonate, synthetic hydrotalcite, magnesium aluminometasilicate, dried aluminum hydroxide gel, synthetic aluminum silicate, magnesium aluminum hydroxide, aluminum hydroxide gel, coprecipitation product of aluminum hydroxide and sodium bicarbonate, mixed dried gel of aluminum hydroxide and magnesium carbonate, coprecipitation product of aluminum hydroxide, magnesium carbonate and calcium carbonate, bentonite, calcium silicate, calcium carbonate, precipitated calcium carbonate, calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate, dried sodium carbonate, sodium hydroxide, sodium bicarbonate, sodium carbonate hydrate, sodium hydrogen phosphate hydrate, anhydrous monohydrogen phosphate, potassium hydroxide, potassium bicarbonate, potassium carbonate, oyster shell, and glycine.
5. The oral pharmaceutical composition according to claim 2, comprising a sedative, wherein the sedative is one or two selected from bromovalerylurea and allyl isopropylacetylurea.

Description

This invention relates to an oral pharmaceutical composition for antipyretic, analgesic, and anti-inflammatory purposes that reduces gastric mucosal damage caused by loxoprofen or its salts. More specifically, it relates to an oral pharmaceutical composition that reduces gastric mucosal damage by containing loxoprofen or its salts and valerian. Loxoprofen, a propionic acid-based nonsteroidal anti-inflammatory drug (NSAID), is known to have antipyretic, analgesic, and anti-inflammatory effects based on its prostaglandin biosynthesis inhibitory action, similar to other NSAIDs. Loxoprofen is a prodrug that, after oral administration, is absorbed from the gastrointestinal tract unchanged with minimal gastric mucosal irritation and becomes active in the body. Therefore, it is known to cause less gastric mucosal damage compared to other NSAIDs (see, for example, Non-Patent Document 1). Techniques for further suppressing gastric mucosal damage by oral administration of loxoprofen or its salts in combination with other active ingredients have been disclosed, including techniques for incorporating specific sugars (lactose, sucrose, maltitol, fructose, xylitol, or lactitol) into loxoprofen (see Patent Document 1), techniques for incorporating antacids (magnesium oxide) (see Patent Document 2), and techniques for incorporating the anti-plasmin drug tranexamic acid (see Patent Document 3). On the other hand, valerian (Valeriana fauriei Briquet) is a crude drug obtained from the roots and rhizomes of the plant. Dichlormethane extract of valerian and kesoglycol diacetate, one of its main components, exhibit sedative effects in mice when administered orally, including hexobarbital-induced sleep prolongation, suppression of spontaneous behavior in open-field tests, suppression of passive avoidance responses, and suppression of fight-or-flight responses (see Non-Patent Literature 2). As mentioned above, studies have investigated the effects of combining loxoprofen or its salts with other active ingredients. However, it is unknown how the combined oral administration of loxoprofen or its salts with valerian (Valeriana officinalis) affects the inhibitory effect on gastric mucosal damage. To date, reports have indicated that valerian has effects such as sedation, choleretic activity, and blood pressure reduction, as well as preventing or improving wrinkles by inhibiting heparanase activity (see Patent Document 4). It has also been reported that when combined with acetaminophen, ethenzamide, and allyl isopropylacetylurea, it has pain-relieving and insomnia-improving effects (Patent Document 5). Furthermore, a 50% ethanol extract of valerian showed anti-stress gastric ulcer activity in mice (Non-Patent Document 2). However, there are no reports investigating how gastric mucosal damage caused by loxoprofen or its salts, which differs from stress gastric ulcers in its cause and location, is affected by the sedative effects of valerian. Additionally, no oral compositions containing loxoprofen and valerian are known, and therefore, their combined effects remain unknown. Patent No. 4585220Patent No. 6106727Patent No. 5835865Japanese Patent Publication No. 2016-169238Japanese Patent Publication No. 2015-189733 Pharmacology and Therapeutics Vol.16 No.2 1988 pp.611-619The Seventeenth Revised Japanese Pharmacopoeia Commentary (Hirokawa Shoten) Figure 1 shows the results of an investigation into the effects of loxoprofen sodium dihydrate alone and loxoprofen sodium dihydrate in combination with valerian on gastric mucosal damage. In the figure, ** indicates that the group receiving loxoprofen sodium dihydrate and valerian showed a statistically significant difference compared to the group receiving loxoprofen sodium dihydrate alone (p < 0.01).Figure 2 shows the results of an investigation into the analgesic effects of the medium, loxoprofen sodium dihydrate alone, and loxoprofen sodium dihydrate in combination with valerian. In the figure, ** indicates that the group receiving loxoprofen sodium dihydrate and valerian showed a statistically significant difference compared to the group receiving loxoprofen sodium dihydrate alone (p < 0.01). In this invention, "loxoprofen or its salt" refers to loxoprofen or its salt (including hydrated salt), preferably loxoprofen sodium, and more preferably loxoprofen sodium dihydrate. The loxoprofen or its salt used in this invention, loxoprofen sodium hydrate, is listed in the 17th edition of the Japanese Pharmacopoeia together with valerian. In the present invention, the "Valeriana officinalis" can preferably be the one listed in the 17th edition of the Japanese Pharmacopoeia. Other varieties of valerian are also commercially available and can be easily obtained. Valerian used in this invention has been used medicinally since ancient times, either as a single ingredient or in herbal formulas. The crude drug powder or extract obtained according to conventional methods can be used as is. The form of the c