Oral pharmaceutical composition

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

[Technical Field]

[0001] The present invention relates to an oral pharmaceutical composition containing nabumetone. More specifically, the present invention relates to an oral pharmaceutical composition in which the analgesic effect of nabumetone is enhanced. [Background technology]

[0002] Nonsteroidal anti-inflammatory drugs such as nabumetone, diclofenac sodium, ibuprofen, and loxoprofen sodium are less likely to cause serious side effects as seen with steroidal anti-inflammatory drugs, and there are fewer restrictions on the dosage and duration of use, so they are widely used in oral pharmaceutical compositions for the purposes of analgesia, antipyresis, anti-inflammation, etc. Among nonsteroidal anti-inflammatory drugs, nabumetone is metabolized in the liver and converted to its active form, 6-methoxy-2-naphthylacetic acid, and this activated form is a nonsteroidal anti-inflammatory drug with a stronger inhibitory effect on cyclooxygenase 2 than on cyclooxygenase 1. Among nonsteroidal anti-inflammatory drugs, nabumetone is known to require less administration and to have relatively few side effects.

[0003] Various studies have been conducted on pharmaceutical formulations that enhance the analgesic effect of steroidal anti-inflammatory agents. For example, Patent Document 1 discloses that the anti-inflammatory and analgesic effect is enhanced by combining a phenylacetic acid derivative or salt such as nabumetone or diclofenac with a menthol. Furthermore, Patent Document 2 discloses that the analgesic effect is enhanced by combining a propionic acid analgesic such as ibuprofen with two or more types of vitamin B, but does not specifically study formulations containing nabumetone. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2003-286161 [Patent Document 1] Japanese Patent Application Laid-Open No. 2008-247822 Summary of the Invention [Problem to be solved by the invention]

[0005] In recent years, there has been an increasing demand in the pharmaceutical field for enhanced efficacy, and there is a need for the development of a technology for enhancing the analgesic effect of nabumetone using 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. [Means for solving the problem]

[0006] The present inventors have conducted extensive research to solve the above-mentioned problems and have found that the analgesic effect of nabumetone can be dramatically enhanced by using nabumetone in combination with synthetic hydrotalcite, magnesium carbonate, aldioxa, cinnamon bark, and / or cinnamon bark extract in an oral pharmaceutical composition. Based on this finding, the present invention has been completed through further research.

[0007] That is, the present invention provides the following aspects. Item 1. A pharmaceutical composition for oral administration comprising (A) nabumetone and (B) at least one member selected from the group consisting of synthetic hydrotalcite, magnesium carbonate, aldioxa, cinnamon bark, and cinnamon bark extract. Item 2. The pharmaceutical composition for internal use according to Item 1, comprising 0.1 to 6,000 parts by weight of the total amount of the component (B) per 100 parts by weight of the component (A) (provided that, when the component (B) is cinnamon bark or cinnamon bark extract, the amount is calculated as the crude drug). Item 3. The oral pharmaceutical composition according to Item 1 or 2, wherein the component (B) is synthetic hydrotalcite. Item 4. The oral pharmaceutical composition according to any one of Items 1 to 3, which is used for analgesic purposes. Item 5. A method for enhancing the analgesic effect of nabumetone, comprising: A method for enhancing analgesic effect, comprising blending nabumetone with at least one member selected from the group consisting of synthetic hydrotalcite, magnesium carbonate, aldioxa, cinnamon, and cinnamon extract into an oral pharmaceutical composition. [Effects of the Invention]

[0008] According to the oral pharmaceutical composition of the present invention, the analgesic effect of nabumetone can be dramatically enhanced by using nabumetone in combination with synthetic hydrotalcite, magnesium carbonate, aldioxa, cinnamon, and / or cinnamon extract. [Brief explanation of the drawings]

[0009] [Figure 1] FIG. 1 shows the results of evaluation of analgesic action by the acetic acid writhing method in Test Example 1. [Figure 2] FIG. 1 shows the results of evaluation of analgesic action by the acetic acid writhing method in Reference Test Example 1. DETAILED DESCRIPTION OF THE INVENTION

[0010] 1. Oral pharmaceutical composition The oral pharmaceutical composition of the present invention is characterized by containing nabumetone (hereinafter sometimes referred to as "ingredient (A)") and at least one selected from the group consisting of synthetic hydrotalcite, magnesium carbonate, aldioxa, cinnamon, and cinnamon extract (hereinafter sometimes referred to as "ingredient (B)"). The oral pharmaceutical composition of the present invention is described in detail below.

[0011] [Component (A)] The oral pharmaceutical composition of the present invention contains nabumetone as an analgesic ingredient. Nabumetone is a known non-steroidal anti-inflammatory agent also known as 4-(6-methoxynaphthalen-2-yl)-2-butanone.

[0012] The content of component (A) in the internal pharmaceutical composition of the present invention may be appropriately determined depending on the dosage form, dosage amount, etc., and may be, for example, 1 to 90% by weight, preferably 5 to 80% by weight.

[0013] [(B) Component] The oral pharmaceutical composition of the present invention contains at least one component selected from the group consisting of synthetic hydrotalcite, magnesium carbonate, aldioxa, cinnamon, and cinnamon extract as an ingredient 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.

[0014] Of the components (B), synthetic hydrotalcite and magnesium carbonate are known inorganic compounds used as antacids and the like in the pharmaceutical field.

[0015] Among the components (B), aldioxa is a known inorganic compound that is used in the pharmaceutical field as a gastric mucosa protecting agent, etc.

[0016] Among the components (B), cinnamon is the dried bark of Cinnamon Bark of the Lauraceae family and other plants of the same genus, and is a well-known component used as a herbal medicine. The cinnamon used in the present invention may be in the form of pulverized material, shredded material, powder, or dried form thereof, but is preferably in the form of powder (cinnamon powder).

[0017] Among the components (B), cinnamon extract is an extract obtained by extracting cinnamon bark as an extraction raw material and can be obtained by known extraction methods. Examples of extraction solvents used in the extraction process for cinnamon bark extract include polar solvents such as water (including hot water); lower alcohols such as ethanol; polyhydric alcohols such as 1,3-butylene glycol; and mixtures thereof. Water, ethanol, 1,3-butylene glycol, or a mixture thereof is preferred. The extraction method used in the production of cinnamon bark extract is not particularly limited and may be any common extraction method used in the production of herbal extracts. Examples include a method in which the raw herbal medicine is immersed in the extraction solvent by cold or hot infusion, with stirring as needed; percolation; and steam distillation. The resulting extract can be filtered or centrifuged to remove solids, if necessary, to recover the herbal extract. The liquid extract obtained by the extraction process may be used as is, or, if necessary, a concentrated liquid (soft extract) or a dried product (dry extract) may be obtained by removing some or all of the solvent. Furthermore, these concentrated liquids (soft extracts) or dried products (dry extracts) may be further subjected to a purification treatment, and these may also be used by dissolving or suspending them in an appropriate solvent.

[0018] These components (B) may be used alone or in combination of two or more.

[0019] In the oral pharmaceutical composition of the present invention, the ratio of component (A) to component (B) can be, for example, 0.1 to 6,000 parts by weight of the total amount of component (B) per 100 parts by weight of component (A). When component (B) is cinnamon bark and / or cinnamon bark extract, the ratio is calculated based on the amount of cinnamon bark and / or cinnamon bark extract equivalent to the crude drug. The "equivalent amount of crude drug" refers to the weight (dry weight) of the crude drug required to obtain the amount of the ingredient. In the case of cinnamon itself, the weight of the cinnamon bark to be blended is the equivalent amount of crude drug, and in the case of cinnamon extract, the dry weight of the cinnamon bark required to obtain the amount of cinnamon extract to be blended is the equivalent amount of crude drug.

[0020] From the viewpoint of further enhancing the analgesic effect of nabumetone, the preferred ratio of component (A) to component (B) for each type of component (B) is as follows. (B) When component is synthetic hydrotalcite The amount of synthetic hydrotalcite per 100 parts by weight of nabumetone is preferably 0.1 to 6000 parts by weight, more preferably 1 to 3000 parts by weight, and even more preferably 10 to 1000 parts by weight. (B) When the component is magnesium carbonate Magnesium carbonate is preferably 0.1 to 3000 parts by weight, more preferably 1 to 1000 parts by weight, and even more preferably 10 to 500 parts by weight per 100 parts by weight of nabumetone. (B) When the component is aldioxa The amount of aldioxa per 100 parts by weight of nabumetone is preferably 0.1 to 1000 parts by weight, more preferably 1 to 500 parts by weight, and even more preferably 1 to 100 parts by weight. (B) When the ingredient is cinnamon and / or cinnamon extract The amount of cinnamon and / or cinnamon extract, calculated as the crude drug, per 100 parts by weight of nabumetone is preferably 0.1 to 6000 parts by weight, more preferably 1 to 3000 parts by weight, and even more preferably 30 to 1000 parts by weight.

[0021] The content of component (B) in the oral pharmaceutical composition of the present invention may be appropriately set within the range corresponding to the ratio of component (A) to component (B) described above, depending on the type, dosage form, dosage amount, etc. of component (B) used, and may be, for example, 0.1 to 95% by weight.

[0022] The preferred contents of components (A) and (B) for each type of component (B) are as follows: (B) When component is synthetic hydrotalcite : 5 to 99% by weight of component (A) and 1 to 95% by weight of synthetic hydrotalcite, preferably 10 to 50% by weight of component (A) and 50 to 90% by weight of synthetic hydrotalcite, more preferably 15 to 30% by weight of component (A) and 70 to 85% by weight of synthetic hydrotalcite. (B) When the component is magnesium carbonate: 5 to 99% by weight of component (A) and 1 to 95% by weight of magnesium carbonate, preferably 20 to 70% by weight of component (A) and 30 to 80% by weight of magnesium carbonate, more preferably 25 to 35% by weight of component (A) and 65 to 75% by weight of magnesium carbonate. (B) When the component is aldioxa : 5 to 99% by weight of component (A) and 1 to 95% by weight of aldioxa, preferably 50 to 95% by weight of component (A) and 5 to 50% by weight of aldioxa, more preferably 60 to 70% by weight of component (A) and 30 to 40% by weight of aldioxa. (B) When the ingredient is cinnamon and / or cinnamon extract : 5 to 95% by weight of component (A) and 5 to 95% by weight of cinnamon bark and / or cinnamon bark extract in terms of the amount of crude drug, preferably 13 to 65% by weight of component (A) and 35 to 87% by weight of cinnamon bark and / or cinnamon bark extract in terms of the amount of crude drug, more preferably 10 to 20% by weight of component (A) and 80 to 90% by weight of cinnamon bark and / or cinnamon bark extract in terms of the amount of crude drug.

[0023] [Other ingredients] The oral pharmaceutical composition of the present invention may contain other pharmacological ingredients, if necessary, in addition to the above-mentioned ingredients. The types of such pharmacological ingredients are not particularly limited, and examples include vitamins, anti-inflammatory analgesics other than nabumetone, intestinal motility improvers, digestive aids, antispasmodics, mucosal repair agents, astringents, antiemetics, antitussives, expectorants, anti-inflammatory enzymes, sedatives and hypnotics, antihistamines, cardiac diuretics, antibacterial agents, vasoconstrictors, vasodilators, local anesthetics, proton pump inhibitors, herbal medicines, herbal extracts, caffeines, menthols, polyphenols, and the like. These pharmacological ingredients may be used alone or in combination of two or more. The content of these pharmacological ingredients may be appropriately determined depending on the type of pharmacological ingredient used, the dosage form of the oral pharmaceutical composition, and the like.

[0024] The pharmaceutical composition of the present invention may contain pharmaceutically acceptable bases and additives, as necessary, to prepare it into the desired dosage form. Examples of such bases and additives include excipients, binders, disintegrants, lubricants, isotonicity agents, plasticizers, dispersants, emulsifiers, solubilizers, wetting agents, stabilizers, suspending agents, adhesives, coating agents, glossing agents, water, oils and fats, waxes, hydrocarbons, fatty acids, higher alcohols, esters, water-soluble polymers, surfactants, lower alcohols, polyhydric alcohols, pH adjusters, buffers, antioxidants, UV protection agents, preservatives, flavoring agents, fragrances, powders, thickeners, dyes, and chelating agents. 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 determined depending on the type of added ingredient used and the dosage form of the oral pharmaceutical composition.

[0025] [Dosage form] The dosage form of the oral pharmaceutical composition of the present invention is not particularly limited, and may be any of a solid preparation, a semi-solid preparation, or a liquid preparation.

[0026] Specific examples of solid preparations include tablets, pills, capsules (soft capsules, hard capsules), powders, granules (including dry syrups), etc. Specific examples of semi-solid preparations include jellies, etc. Specific examples of liquid preparations include solutions, suspensions, syrups, etc.

[0027] Among these dosage forms, solid preparations are preferred.

[0028] To prepare the oral pharmaceutical composition of the present invention into the above dosage form, the composition may be formulated using component (A), component (B), and other pharmacological ingredients, bases, and additives that are added as needed, according to conventional formulation techniques used in the pharmaceutical field.

[0029] [Dosage and administration] The oral pharmaceutical composition of the present invention has an enhanced analgesic effect and can exert an excellent analgesic effect, and can therefore be used for purposes such as relieving pain from headache, menstrual pain (period pain), toothache, pain after tooth extraction, sore throat, lower back pain, joint pain, neuralgia, muscle pain, stiff shoulder pain, earache, pain from bruises, bone fractures, sprains, pain from trauma, etc.; reducing fever during chills and fever; and alleviating cold symptoms.

[0030] The dosage of the oral pharmaceutical composition of the present invention may be appropriately determined depending on the severity of symptoms, the age of the user, etc. For example, the dosage of nabumetone per day is about 200 to 1600 mg, preferably about 400 to 1000 mg, and may be taken once a day, or may be taken in multiple divided doses depending on the user's age and symptoms.

[0031] 2. Methods for enhancing analgesic effects The present invention further provides a method for enhancing the analgesic effect of nabumetone, which comprises blending nabumetone and at least one selected from the group consisting of synthetic hydrotalcite, magnesium carbonate, aldioxa, cinnamon, and cinnamon extract into an oral pharmaceutical composition.

[0032] In the method for enhancing analgesic effect, the types of ingredients used, the amounts blended, the dosage form of the oral pharmaceutical composition, etc. are as described in the section "1. Oral pharmaceutical composition" above. [Example]

[0033] The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.

[0034] Test Example 1: Evaluation test of analgesic effect Six-week-old male mice (Slc:ddy, Japan SLC Co., Ltd.) were divided into six groups (7 to 11 mice per group): a control group and test groups (Examples 1 to 4 and Comparative Example 1). Mice in each group were kept for one week to allow them to acclimate, and then tested under the following conditions.

[0035] Control group After fasting for approximately 16 hours, mice were orally administered 10 ml / kg (mouse body weight) of an aqueous solution containing 0.1 wt% carboxymethylcellulose (control solution). 50 minutes after administration of the control solution, 20 ml / kg (mouse body weight) of a 0.6 wt% aqueous acetic acid solution was intraperitoneally administered. The number of times the mice writhed (stretched their hind limbs) for 10 minutes after administration of the acetic acid solution was counted.

[0036] Test group After fasting for approximately 16 hours, the mice were orally administered a test solution containing the components shown in Table 1 added to the control solution at the prescribed doses at 10 ml / kg (mouse body weight). 50 minutes after administration of the test solution, a 0.6 wt % aqueous acetic acid solution was intraperitoneally administered at 20 ml / kg (mouse body weight). The number of times the mice writhed (stretched their hind limbs) for 10 minutes starting 10 minutes after administration of the aqueous acetic acid solution was counted.

[0037] [Table 1]

[0038] The results are shown in Figure 1. As a result, when nabumetone was used in combination with magnesium carbonate, aldioxa, synthetic hydrotalcite, or cinnamon powder (Examples 1 to 4), the number of writhing behaviors was significantly reduced compared to when nabumetone was used alone (Comparative Example 1), confirming that the analgesic effect of nabumetone was significantly enhanced.

[0039] Reference test example 1: Evaluation test of analgesic effect The test was conducted in the same manner as in Test Example 1, except that the test group was administered the prescribed doses of the ingredients shown in Table 2, and the number of writhing behaviors was determined. Diclofenac sodium is a phenylacetic acid-based nonsteroidal anti-inflammatory drug, the same as nabumetone.

[0040] [Table 2]

[0041] The results are shown in Figure 2. 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 number of writhing behaviors tended to be equal to or greater than that when diclofenac sodium was used alone (Reference Example 1). In other words, the results of this test confirmed that the enhancement of the analgesic effect by using diclofenac sodium in combination with magnesium carbonate, aldioxa, synthetic hydrotalcite, or cinnamon powder is a unique effect observed when nabumetone is selected as the nonsteroidal anti-inflammatory agent.

[0042] Formulation example Tablets were prepared with the compositions shown in Tables 3 to 5. In Tables 3 to 5, the content of each ingredient is expressed in units of the daily dose (mg). These tablets are expected to dramatically improve the analgesic effect of nabumetone.

[0043] [Table 3]

[0044] [Table 4]

[0045] [Table 5]

Claims

1. An oral pharmaceutical composition containing (A) nabumetone and (B) aldioxa.

2. 2. The pharmaceutical composition for oral administration according to claim 1, comprising a total amount of 0.1 to 6,000 parts by weight of component (B) per 100 parts by weight of component (A).

3. 3. The oral pharmaceutical composition according to claim 1 or 2, which is used for analgesic purposes.

4. 1. A method for enhancing the analgesic effect of nabumetone, comprising: A method for enhancing analgesic effect by incorporating aldioxa together with nabumetone into an oral pharmaceutical composition.

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