JP2021107330A - Oral pharmaceutical composition - Google Patents

Abstract

To provide an oral pharmaceutical composition having enhanced analgesic action of nabumetone.SOLUTION: In an oral pharmaceutical composition, nabumetone is used in combination with synthetic hydrotalcite, magnesium carbonate, aldioxa, cinnamon bark, and/or cinnamon bark extract, which can result in dramatically enhanced analgesic action of nabumetone.SELECTED DRAWING: None

Description

The present invention relates to an orally administered pharmaceutical composition containing nabumetone. More specifically, the present invention relates to an orally administered pharmaceutical composition in which the analgesic effect of nabumetone is enhanced.

Non-steroidal anti-inflammatory drugs such as nabumetone, diclofenac sodium, ibuprofen, and loxoprofen sodium have less concern about serious side effects as seen with steroidal anti-inflammatory drugs, and there are few restrictions on the amount and duration of use. It is widely used in oral pharmaceutical compositions for the purpose of analgesia, fever reduction, anti-inflammatory and the like. Among the non-steroidal anti-inflammatory drugs, nabumetone is metabolized in the liver and converted to the active form 6-methoxy-2-naphthylacetic acid, and the activated form has a higher inhibitory effect on cyclooxygenase 2 than cyclooxygenase 1. It is a steroidal anti-inflammatory drug. Among the non-steroidal anti-inflammatory drugs, nabumetone is known to be taken less frequently and have relatively few side effects.

Conventionally, various studies have been conducted on pharmaceutical formulations having enhanced analgesic action of steroidal anti-inflammatory agents. For example, Patent Document 1 discloses that the anti-inflammatory analgesic effect is enhanced by using menthols in combination with a phenylacetic acid derivative or salt such as nabumetone or diclofenac. Further, Patent Document 2 discloses that the analgesic effect is enhanced by the combined use of a propionic acid-based analgesic such as ibuprofen and two or more kinds of B vitamins. Has not been considered.

Japanese Unexamined Patent Publication No. 2003-286161 Japanese Unexamined Patent Publication No. 2008-247822

In recent years, there has been an increasing demand for enhanced drug efficacy in the pharmaceutical field, and there is a demand for the development of a technique for enhancing the analgesic action of nabumetone by a new formulation technology. Therefore, an object of the present invention is to provide an oral pharmaceutical composition having an enhanced analgesic effect of nabumetone.

As a result of diligent studies to solve the above problems, the present inventor has determined that synthetic hydrotalcite, magnesium carbonate, aldioxa, keihi, and / or keihi extract are used in combination with nabumetone in an oral pharmaceutical composition. , Found that the analgesic effect of nabumetone can be dramatically enhanced. The present invention has been completed by further studies based on such findings.

That is, the present invention provides the inventions of the following aspects.
Item 1. An oral pharmaceutical composition containing (A) nabumetone and (B) at least one selected from the group consisting of synthetic hydrotalcite, magnesium carbonate, aldioxa, cinnamon, and cinnamon extract.
Item 2. Item 1 contains 0.1 to 6000 parts by weight of the component (B) per 100 parts by weight of the component (A) in total amount (however, if the component (B) is cinnamon and cinnamon extract, the amount converted to crude drug). The pharmaceutical composition for internal use according to.
Item 3. Item 2. The pharmaceutical composition for internal use according to Item 1 or 2, wherein the component (B) is synthetic hydrotalcite.
Item 4. Item 4. The pharmaceutical composition for internal use according to any one of Items 1 to 3, which is used for analgesic use.
Item 5. A way to enhance the analgesic effect of nabumetone
A method for enhancing analgesic activity, wherein a pharmaceutical composition for internal use is blended with nabumetone at least one selected from the group consisting of synthetic hydrotalcite, magnesium carbonate, aldioxa, cinnamon, and cinnamon extract.

According to the pharmaceutical composition for internal use of the present invention, the analgesic effect of nabumetone is dramatically enhanced by the combined use of nabumetone with synthetic hydrotalcite, magnesium carbonate, aldioxa, cinnamon, and / or cinnamon extract. Can be done.

It is a figure which shows the result of having evaluated the analgesic effect by the acetic acid rising method in Test Example 1. It is a figure which shows the result of having evaluated the analgesic effect by the acetic acid rising method in Reference Test Example 1.

1. 1. Oral Pharmaceutical Composition The internal pharmaceutical composition of the present invention is composed of nabumetone (hereinafter, sometimes referred to as "(A) component"), synthetic hydrotalcite, magnesium carbonate, aldioxa, cinnamon, and cinnamon extract. It is characterized by containing at least one selected from the group (hereinafter, may be referred to as “component (B)”). Hereinafter, the pharmaceutical composition for internal use of the present invention will be described in detail.

[(A) component]
The pharmaceutical composition for internal use of the present invention contains nabumetone as an analgesic ingredient. Nabumetone is a known non-steroidal anti-inflammatory drug also called 4- (6-methoxynaphthalene-2-yl) -2-butanone.

The content of the component (A) in the oral pharmaceutical composition of the present invention may be appropriately set according to the dosage form, dosage and the like, and is, for example, 1 to 90% by weight, preferably 5 to 80% by weight. Can be mentioned.

[(B) component]
The oral pharmaceutical composition of the present invention contains at least one selected from the group consisting of synthetic hydrotalcite, magnesium carbonate, aldioxa, cinnamon, and cinnamon extract as a component that enhances the analgesic effect of nabumetone. By using these components (B) in combination with nabumetone, the analgesic effect of nabumetone can be dramatically enhanced.

Among the components (B), synthetic hydrotalcite and magnesium carbonate are known inorganic compounds used as antacids and the like in the pharmaceutical field.

Among the components (B), aldioxa is a known inorganic compound used as a gastric mucosa protective agent or the like in the pharmaceutical field.

Among the components (B), cinnamon tree is a dried bark of Lauraceae cinnamon tree and other plants of the same genus, and is a known component used as a crude drug. The cinnamon used in the present invention may be a crushed product, a shredded product, a powder product, or a dried product thereof, but a powder product (cinnamon powder) is preferable.

Among the components (B), cinnamon extract is an extract obtained by performing an extraction treatment using cinnamon as an extraction raw material, and can be obtained by an extraction treatment by a known method. Examples of the extraction solvent used for the extraction treatment of Keihi extract include water (including hot water); lower alcohols such as ethanol; polyhydric alcohols such as 1,3-butylene glycol; and polar solvents such as a mixture of these. These are preferably water, ethanol, 1,3-butylene glycol, or a mixed solvent thereof. The extraction method adopted in the production of the cinnamon extract is not particularly limited, and any general extraction method used in the production of the crude drug extract may be used. For example, a method of immersing the crude drug in an extraction solvent by cold immersion, warm immersion, or the like and stirring as necessary; a percolation method; a steam distillation method or the like can be mentioned. The crude drug extract can be recovered by removing solids from the obtained extract by filtration or centrifugation, if necessary. As the cinnamon extract, the liquid extract obtained by the above extraction treatment may be used as it is, but if necessary, a concentrated solution (soft extract) or a dried product (dried extract) is obtained by removing a part or all of the solvent. ) May be used. Further, these concentrated liquids (soft extracts) or dried products (dried extracts) may be further subjected to a purification treatment, and these may be further dissolved or suspended in an appropriate solvent for use.

These (B) components may be used alone or in combination of two or more.

Further, in the pharmaceutical composition for internal use of the present invention, the ratio of the component (A) to the component (B) is, for example, 0.1 to 6000 weight by weight of the total amount of the component (B) per 100 parts by weight of the component (A). The department is mentioned. When the component (B) is cinnamon and / or cinnamon extract, the ratio is a value calculated based on the crude drug equivalent amount of cinnamon and / or cinnamon extract. The "crude drug equivalent amount" is the weight (dry weight) of the crude drug required to obtain the amount of the component. In the case of cinnamon itself, the weight of cinnamon to be blended is the crude drug equivalent, and in the case of cinnamon extract, the dry weight of cinnamon required to obtain the amount of cinnamon extract to be blended is the crude drug equivalent. become.

From the viewpoint of further enhancing the analgesic effect of nabumetone, the preferable ratio of the component (A) to the component (B) for each type of the component (B) is as follows.
When the component (B) is synthetic hydrotalcite : Synthetic hydrotalcite is preferably 0.1 to 6000 parts by weight, more preferably 1 to 3000 parts by weight, still more preferably 10 to 1000 parts by weight per 100 parts by weight of nabumetone. Weight part.
When the component (B) is magnesium carbonate : Magnesium carbonate is preferably 0.1 to 3000 parts by weight, more preferably 1 to 1000 parts by weight, and further preferably 10 to 500 parts by weight per 100 parts by weight of nabumetone.
When the component (B) is aldioxa : per 100 parts by weight of nabumetone, aldioxa is preferably 0.1 to 1000 parts by weight, more preferably 1 to 500 parts by weight, still more preferably 1 to 100 parts by weight.
(B) When the component is cinnamon and / or cinnamon extract : per 100 parts by weight of nabumetone, cinnamon and / or cinnamon extract is preferably 0.1 to 6000 parts by weight, more preferably 1 to 1 by weight in terms of crude drug equivalent. 3000 parts by weight, more preferably 30 to 1000 parts by weight.

Regarding the content of the component (B) in the pharmaceutical composition for internal use of the present invention, the type and dosage form of the component (B) to be used within the range corresponding to the ratio of the component (A) and the component (B) described above. , And may be appropriately set according to the dose and the like, and examples thereof include 0.1 to 95% by weight.

The suitable contents of the component (A) and the component (B) for each type of the component (B) are as follows.
When the component (B) is synthetic hydrotalcite : the component (A) is 5 to 99% by weight and the synthetic hydrotalcite is 1 to 95% by weight, preferably the component (A) is 10 to 50% by weight and synthetic hydro. 50-90% by weight of talcite, more preferably 15-30% by weight of component (A) and 70-85% by weight of synthetic hydrotalcite.
When the component (B) is magnesium carbonate : the component (A) is 5 to 99% by weight and magnesium carbonate is 1 to 95% by weight, preferably the component (A) is 20 to 70% by weight and magnesium carbonate is 30 to 80% by weight. By weight%, more preferably, the component (A) is 25 to 35% by weight and magnesium carbonate is 65 to 75% by weight.
When the component (B) is aldioxa : the component (A) is 5 to 99% by weight and the aldioxa is 1 to 95% by weight, preferably the component (A) is 50 to 95% by weight and the aldioxa is 5 to 50% by weight. More preferably, the component (A) is 60 to 70% by weight and the aldioxa is 30 to 40% by weight.
When the component (B) is cinnamon and / or cinnamon extract : component (A) is 5 to 95% by weight and cinnamon and / or cinnamon extract is 5 to 95% by weight in terms of crude drug, preferably component (A). 13-65% by weight and cinnamon and / or cinnamon extract is 35 to 87% by weight in terms of crude drug, more preferably component (A) is 10 to 20% by weight and cinnamon and / or cinnamon extract is in terms of crude drug. 80-90% by weight.

[Other ingredients]
The pharmaceutical composition for internal use of the present invention may contain other pharmacological components in addition to the above-mentioned components, if necessary. The types of such pharmacological components are not particularly limited, but are, for example, vitamins, anti-inflammatory analgesics other than nabmeton, intestinal motility improving agents, digestive agents, antispasmodics, mucosal repair agents, astringents, antiemetics, antitussives, and sputum. Agents, anti-inflammatory enzyme agents, analgesic hypnotics, antihistamines, cardiotonic diuretics, antibacterial agents, vasoconstrictors, vasodilators, local anesthetics, proton pump inhibitors, crude drugs, crude drug extracts, caffeines, menthols, polyphenols, etc. Can be mentioned. These pharmacological components may be used alone or in combination of two or more. The content of these pharmacological components may be appropriately set according to the type of the pharmacological component used, the dosage form of the pharmaceutical composition for internal use, and the like.

The pharmaceutical composition of the present invention may contain a pharmaceutically acceptable base, additives and the like, if necessary, in order to prepare a desired dosage form. Such bases and additives include, for example, excipients, binders, disintegrants, lubricants, isotonic agents, plasticizers, dispersants, emulsifiers, solubilizers, wetting agents, stabilizers. Agents, suspending agents, pressure-sensitive agents, coating agents, brighteners, water, fats and oils, waxes, hydrocarbons, fatty acids, higher alcohols, esters, water-soluble polymers, surfactants, lower alcohols Types, polyhydric alcohols, pH adjusters, buffers, antioxidants, UV inhibitors, preservatives, flavoring agents, fragrances, powders, thickeners, pigments, chelating agents and the like. These bases and additives may be used alone or in combination of two or more. The content of these bases and additives may be appropriately set according to the type of additive component to be used, the dosage form of the pharmaceutical composition for internal use, and the like.

[Dosage form]
The dosage form of the pharmaceutical composition for internal use of the present invention is not particularly limited, and may be any of a solid-state preparation, a semi-solid-state preparation, and a liquid-state preparation.

Specific examples of the solid-state preparation include tablets, pills, capsules (soft capsules, hard capsules), powders, granules (including dry syrup) and the like. Specific examples of the semi-solid preparation include a jelly agent and the like. Specific examples of the liquid preparation include liquid preparations, suspension preparations, syrup preparations and the like.

Among these dosage forms, a solid-state preparation is preferable.

In order to prepare the pharmaceutical composition for internal use of the present invention in the above-mentioned dosage form, the component (A), the component (B), and other pharmacological components, the base, and the additive added as needed are used. , It may be formulated according to the usual formulation method adopted in the pharmaceutical field.

[Dosage and administration]
The oral pharmaceutical composition of the present invention has an enhanced analgesic effect and can exert an excellent analgesic effect. Therefore, for example, headache, menstrual pain (physiological pain) / arthralgia, pain after tooth extraction, sore throat, low back pain, etc. It can be used for the purpose of relieving joint pain, nerve pain, muscle pain, stiff shoulder pain, ear pain, bruising pain, fracture pain, dysmenorrhea, traumatic pain, etc .; ..

The dose of the pharmaceutical composition for internal use of the present invention may be appropriately set according to the degree of symptoms, the age of the user, and the like. For example, the daily dose of nabumetone is about 200 to 1600 mg, preferably 400. The dose may be about 1000 mg once a day, and may be divided into a plurality of doses depending on the age and symptoms.

2. Method for enhancing analgesic action The present invention is a method for further enhancing the analgesic action of nabumetone, which comprises a pharmaceutical composition for internal use, together with nabumetone, synthetic hydrotalcite, magnesium carbonate, aldioxa, keihi, and keihi extract. Provided is a method for enhancing analgesic action, which comprises blending at least one selected from the group.

The types of ingredients used in the method for enhancing the analgesic action, the blending amount, the dosage form of the pharmaceutical composition for internal use, and the like are as described in the column of "1. Pharmaceutical composition for internal use".

Hereinafter, the present invention will be specifically described with reference to Examples, but the present invention is not limited to these Examples.

Test Example 1: Evaluation test of analgesic effect 6-week-old male mice (Slc: ddy, Nippon SLC Co., Ltd.) were used in 6 groups (per group) of a control group and a test group (Examples 1 to 4 and Comparative Example 1). It was divided into 7 to 11 animals). After the mice in each group were bred for 1 week and acclimatized, the test was conducted under the following conditions.

-Control group After fasting for about 16 hours, an aqueous solution (control solution) containing 0.1% by weight of carboxymethyl cellulose was orally administered so as to be 10 ml / kg (mouse body weight). Fifty minutes after the administration of the control solution, a 0.6 wt% acetic acid aqueous solution was intraperitoneally administered to 20 ml / kg (mouse body weight). The number of mouse rising behaviors (exercises to stretch the hind limbs) for 10 minutes after 10 minutes of administration of the acetic acid aqueous solution was measured.

-After fasting for about 16 hours in the test group, the test solution in which the components shown in Table 1 were added to the control solution at a predetermined dose was orally administered at a rate of 10 ml / kg (mouse body weight). Fifty minutes after the administration of the test solution, a 0.6 wt% acetic acid aqueous solution was intraperitoneally administered to 20 ml / kg (mouse body weight). The number of mouse rising behaviors (exercises to stretch the hind limbs) for 10 minutes after 10 minutes of administration of the acetic acid aqueous solution was measured.

The results are shown in FIG. As a result, when nabumetone was used in combination with magnesium carbonate, aldioxa, synthetic hydrotalcite, or kehi powder (Examples 1 to 4), the number of rising actions was higher than that of nabumetone alone (Comparative Example 1). Was significantly reduced, confirming that the analgesic effect of nabumetone was significantly enhanced.

Reference Test Example 1: Evaluation of analgesic action As a test group, a test was conducted in the same manner as in Test Example 1 except that the components shown in Table 2 were administered at a predetermined dose, and the rising behavior was determined. I asked for the number of times. Diclofenac sodium is the same phenylacetic acid non-steroidal anti-inflammatory drug as nabumetone.

The results are shown in FIG. As a result, when diclofenac sodium was used in combination with magnesium carbonate, aldioxa, synthetic hydrotalcite, or cinnamon powder (Reference Examples 2 to 5), the rising behavior was higher than that of diclofenac sodium alone (Reference Example 1). There was a tendency for the number of times to be equal or higher. That is, from the results of this test, the enhancement of analgesic effect by using diclofenac sodium and magnesium carbonate, aldioxa, synthetic hydrotalcite, or Keihi powder is observed when nabumetone is selected as a non-steroidal anti-inflammatory drug. It was confirmed that it was a peculiar effect.

Examples of pharmaceuticals Tablets having the compositions shown in Tables 3 to 5 were prepared. In Tables 3 to 5, the unit of the content of each component is the daily dose (mg). These tablets can be expected to dramatically improve the analgesic effect of nabumetone.

Claims (5)

An oral pharmaceutical composition containing (A) nabumetone and (B) at least one selected from the group consisting of synthetic hydrotalcite, magnesium carbonate, aldioxa, cinnamon, and cinnamon extract. Claim that per 100 parts by weight of the component (A), the total amount of the component (B) (however, if the component (B) is cinnamon and cinnamon extract, the amount converted to crude drug) is 0.1 to 6000 parts by weight. The pharmaceutical composition for internal use according to 1. The pharmaceutical composition for internal use according to claim 1 or 2, wherein the component (B) is synthetic hydrotalcite. The pharmaceutical composition for internal use according to any one of claims 1 to 3, which is used for analgesic use. A way to enhance the analgesic effect of nabumetone
A method for enhancing analgesic activity, wherein a pharmaceutical composition for internal use is blended with nabumetone at least one selected from the group consisting of synthetic hydrotalcite, magnesium carbonate, aldioxa, cinnamon, and cinnamon extract.

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