JP5519890B2 - Oral ibuprofen formulation - Google Patents

Description

  The present invention relates to an oral ibuprofen preparation having a highly immediate antipyretic analgesic effect on fever and pain among various symptoms of body fever, pain and cold.

  For the symptoms of fever and pain in the body, antipyretic analgesics are used alone, and cold medicine is used when caused by a cold. In both cases, ibuprofen, acetaminophen and the like are used as antipyretic analgesic components, and in particular, those containing ibuprofen have recently been frequently used.

Problems to be solved by the invention

However, fever and pain are uncomfortable for the patient, and it is desirable to remove it as soon as possible, especially in the case of pain. As a solution to this, it is conceivable to increase the absorption rate of the antipyretic analgesic component and to increase the blending amount in order to increase the blood concentration. As a method of increasing the absorption rate, there is a method of already adding magnesium hydroxide. Pertti J. Neuvonen et al. Announced that this method is not approved by the Ministry of Health and Welfare for the manufacture and import of antipyretic analgesics and common cold drugs. Since it is not listed, it was extremely difficult to apply to over-the-counter drugs. In addition, increasing the amount of ibuprofen has a problem in that the side effect of gastrointestinal disorders tends to occur.
Accordingly, an object of the present invention is to provide an oral ibuprofen preparation with high immediate effect on fever and pain.

Means for solving the problem

  Therefore, as a result of various investigations, the present inventors have formulated a specific amount of magnesium oxide listed in the above-mentioned pharmaceutical manufacturing (import) approval standards in oral preparations such as antipyretic analgesics and cold medicines containing ibuprofen. For example, when the pH in the stomach rises rapidly and becomes alkaline, the solubility of ibuprofen, an acidic substance, increases, the absorption rate of ibuprofen from the stomach and small intestine increases, and the plasma concentration decreases in a short time. As a result of the increase, it was found that the immediate effect was higher than that of the conventional one, and that the compounding amount of the magnesium oxide was higher than that of magnesium hydroxide, and a high immediate effect was obtained at a low dose, and the present invention was completed. It came to do.

  That is, this invention provides the oral ibuprofen formulation which contains 50-150 weight part of magnesium oxide with respect to 100 weight part of ibuprofen.

  In the oral ibuprofen preparation of the present invention, the daily dose for an adult of ibuprofen used as an antipyretic analgesic component or an anti-inflammatory component is preferably 400 to 600 mg.

  Magnesium oxide used in the oral ibuprofen preparation of the present invention is classified into heavy magnesium oxide and light magnesium oxide, and heavy magnesium oxide having a specific volume of 2 to 4 mL / g, particularly 3 to 4 mL / g is preferred.

  Magnesium oxide is required to contain 50 to 150 parts by weight with respect to 100 parts by weight of ibuprofen in the oral ibuprofen preparation of the present invention, and particularly 60 to 120 parts by weight. preferable. If it is less than 50 parts by weight, the increase in plasma concentration in a short time is not recognized and the immediate effect is inferior.

In the oral ibuprofen preparation of the present invention, it is preferable to further use allylisopropylacetylurea and / or caffeine in order to further improve the immediate effect.
The content of allyl isopropyl acetyl urea is preferably 20 to 50 parts by weight, particularly 30 to 40 parts by weight with respect to 100 parts by weight of ibuprofen.
Caffeine includes anhydrous caffeine and caffeine, with anhydrous caffeine being preferred. The content of caffeine is preferably 10 to 70 parts by weight, particularly 30 to 55 parts by weight, with respect to 100 parts by weight of ibuprofen.

  When using allyl isopropyl acetyl urea and / or caffeine together, the daily dose for an adult is preferably 90 to 180 mg for allyl isopropyl acetyl urea and 50 to 250 mg for caffeine.

  The oral ibuprofen preparation of the present invention is used as an antipyretic analgesic, a cold medicine and the like.

  The oral ibuprofen preparation of the present invention can be converted into oral dosage forms such as tablets, granules, fine granules, powders, capsules, chewable preparations, effervescent agents, mouth solubilizers, dry syrups, and oral liquids by conventional methods. Prepared.

  When the form is a solid preparation such as a tablet or granule, the carrier is a sugar such as lactose, sucrose, glucose or mannitol, an excipient such as crystalline cellulose; gelatin, sodium alginate, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone Binders such as carboxymethylcellulose; disintegrants such as carboxymethylcellulose calcium, low-substituted hydroxypropylcellulose, calcium carbonate; hydrogenated vegetable oils such as magnesium stearate and hydrogenated castor oil; and lubricants such as talc. A solubilizing agent, a buffering agent, a preservative, a fragrance, a pigment, a corrigent and the like can be used as necessary.

Example 1
Oral ibuprofen tablets having the composition shown in Table 1 were produced according to a conventional method.

Plasma ibuprofen concentration was measured by the following test method.
(1) Experimental animals 6 male dogs (beagle) aged 6 to 7 months (2 groups, 3 groups)
(2) Test method The test was carried out in a crossover of 3 preparations in 3 stages. The drug withdrawal period was 1 week.
(3) Administration method One tablet of each test drug was orally administered, and 30 mL of water was immediately administered using a sonde. In addition, although fasted during the test, water was ad libitum.
(4) Blood collection method About 1 mL of blood was collected from the forearm mesenteric vein at 0.25, 0.5, 1 and 2 hours after administration. The collected blood was transferred to a heparin sodium-added vacuum blood collection tube, centrifuged (3000 rpm, 10 minutes), plasma was collected, frozen at 20 ° C. or lower, and stored.
(5) Measurement method Frozen blood was thawed, extracted with a mixed solution of hexane and diethyl ether, and the concentration of ibuprofen in plasma was measured by liquid chromatography (calibration curve method using an internal standard substance).

  The measurement results are shown in Table 1. The product 1 of the present invention had a high concentration of ibuprofen in plasma after 0.25 to 1 hour and high immediate effect.

Example 2
Table 3 shows the results of studies on the oral ibuprofen tablets shown in Table 2 in the same manner as in Example 1.

  Inventive products 2 and 3 were higher in ibuprofen concentration in plasma after 0.25 to 1 hour and superior in immediate effect than Comparative product 2. Further, the products 2 and 3 of the present invention were excellent in sedation and drowsiness prevention effects.

Effect of the invention

  The oral ibuprofen preparation of the present invention has a highly immediate antipyretic analgesic effect on fever and pain, and is useful as an antipyretic analgesic and a cold medicine.

Claims (4)

Absorption of ibuprofen , which is an agent for increasing the absorption rate of ibuprofen in an oral ibuprofen preparation, containing magnesium oxide as an active ingredient , wherein magnesium oxide is blended in an amount of 50 to 150 parts by weight with respect to 100 parts by weight of ibuprofen. Speed increasing agent .
Oral ibuprofen formulations, further absorption rate increasing agent according to claim 1, containing caffeine selected allylisopropylacetylurea, and / or caffeine and anhydrous caffeine.
The absorption rate increasing agent according to claim 1 or 2, wherein the oral ibuprofen preparation is an antipyretic analgesic.
The absorption rate increasing agent according to claim 1 or 2, wherein the oral ibuprofen preparation is a cold medicine.