JP6949645B2 - Pharmaceutical composition - Google Patents

Description

The present invention relates to a pharmaceutical composition capable of suppressing the unpleasant odor of peony and / or its extract.

Peony and its extracts are known to have muscle tone-relieving effects, vasodilatory, anti-inflammatory, sedative, and analgesic effects, and their application to pharmaceuticals is being investigated. For example, in Patent Document 1, an oral liquid composition containing shakuyaku, sucrose fatty acid ester, monoglycerin fatty acid ester, glycyrrhizinic acid or a salt thereof, polyoxyethylene hydrogenated castor oil, and polyvinylpyrrolidone can be stored at a low temperature. It is disclosed that the formation of precipitation and cloudiness can be suppressed, and the properties can be stably maintained for a long period of time. Further, in Patent Document 2, a pharmaceutical composition containing a phenylpropionic acid-based anti-inflammatory analgesic, a specific amount of shakyaku extract, and a specific amount of an antacid is a gastric mucosal disorder which is a side effect of the phenylpropionic acid-based anti-inflammatory analgesic. It is disclosed that can be reduced. However, peony and its extract have a peculiar unpleasant odor, and a preparation containing peony and / or its extract has a drawback that the unpleasant odor caused by peony and / or its extract increases with time. Since such an unpleasant odor causes deterioration of the feeling of taking the drug and deterioration of compliance with the drug, development of a formulation technique is required to suppress the unpleasant odor of peony and / or its extract.

Conventionally, it has been known that an unpleasant odor can be masked by formulating a component with an unpleasant odor into a coated tablet or a sugar-coated tablet. However, when it is formulated as a coated tablet or a sugar-coated tablet, it has a drawback that the production time and cost are increased.

Further, in Patent Document 3, regarding the kakkonto solution containing peony, (a) sucrose, honey and / or isomerized sugar, (b) sucralose, stevia and / or thaumatin, and (c) specific fruit flavors. It is disclosed that a kakkonto liquid composition containing a specific amount of ginger flavor and / or peony flavor and having a sugar content of 2 to 20 can suppress an unpleasant odor derived from the kakkonto liquid. However, Patent Document 3 has not verified the inhibitory effect of peony and / or its extract itself on unpleasant odors. In addition, the technique of Patent Document 3 is applied only to liquid preparations, and since it is indispensable to mix a plurality of sweeteners, there are many restrictions on the formulation and formulation, and there are cases where it is not possible to cope with the diversifying formulation and formulation in recent years. be. Therefore, it is desired to develop a new pharmaceutical technology capable of suppressing the unpleasant odor of peony and / or its extract.

On the other hand, nabumetone is a crystalline or crystalline powder exhibiting a white to yellowish white color, and is a component that is hardly soluble in water and does not show a taste by itself. In addition, nabumetone has a long-acting analgesic effect and is known to be suitable for relieving repeated pain without recurring. However, conventionally, a formulation in which nabumetone is blended with peony and / or its extract has not been reported, and the effect of nabumetone on the unpleasant odor of peony and / or its extract has not been clarified at all.

International Publication No. 2007/135 774 Japanese Unexamined Patent Publication No. 2014-070024 Japanese Unexamined Patent Publication No. 2012-193178

An object of the present invention is to provide a formulation technique for suppressing an unpleasant odor of peony and / or an extract thereof in a pharmaceutical composition containing peony and / or an extract thereof.

As a result of diligent studies to solve the above problems, the present inventor has found that a pharmaceutical composition containing nabumetone together with peony and / or its extract can suppress the unpleasant odor of peony and / or its extract. In addition, the present inventor has obtained a new finding that when peony and / or its extract is formulated and stored, the unpleasant odor of peony and / or its extract increases with time. It was also found that when a predetermined amount of nabumetone is blended together, the unpleasant odor that increases with time can be suppressed more effectively. The present invention has been completed by further studies based on these findings.

That is, the present invention provides the inventions of the following aspects.
Item 1. A pharmaceutical composition containing peony and / or an extract thereof, and nabumetone.
Item 2. Item 2. The pharmaceutical composition according to Item 1, which contains 1 to 100,000 parts by weight of nabumetone per 100 parts by weight of the total amount of peony and / or its extract in terms of crude drug.
Item 3. Item 3. The pharmaceutical composition according to Item 1 or 2, which contains 0.01 to 95% by weight of peony, or 0.01 to 950 parts by weight of peony extract in terms of crude drug equivalent per 100 parts by weight of the pharmaceutical composition.
Item 4. Item 6. The pharmaceutical composition according to any one of Items 1 to 3, which contains 5 to 99.9% by weight of nabumetone.
Item 5. Item 8. The pharmaceutical composition according to any one of Items 1 to 4, which is a solid preparation.
Item 6. An unpleasant odor suppressant for peony and / or its extract containing nabumetone as an active ingredient.
Item 7. A method for reducing an unpleasant odor of peony and / or an extract thereof, in which nabumetone is blended with a peony and / or an extract thereof in a pharmaceutical composition.

According to the present invention, the unpleasant odor of peony and / or its extract contained in a pharmaceutical composition can be suppressed. In particular, in a preferred embodiment of the present invention, the unpleasant odor of peony and / or its extract, which increases with time, can be suppressed even more effectively. Therefore, according to the present invention, it is possible to facilitate taking a pharmaceutical composition containing peony and / or an extract thereof, and to enhance medication compliance.

1. 1. Pharmaceutical Composition The pharmaceutical composition of the present invention is characterized by containing peony and / or an extract thereof, and nabumetone. Hereinafter, the pharmaceutical composition of the present invention will be described in detail.

Peony and / or an extract thereof The pharmaceutical composition of the present invention contains a peony and / or an extract thereof. Peony and / or its extract has an unpleasant odor, but in the present invention, by using nabumetone, such a drawback can be overcome and the unpleasant odor of peony and / or its extract can be suppressed.

Peony (peony) is the root of the peony Paeonia lactiflora Pallas or other closely related plants of the Peony family (Peonyaceae), and is a known ingredient used as a crude drug (Japanese Pharmacopoeia). The peony used in the present invention may be a crushed product, a shredded product, or a dried product thereof.

In addition, peony extract is a known component described in the quasi-drug raw material standard, and can be obtained by extracting the roots of peony or other closely related plants with an extraction solvent.

Examples of the extraction solvent used for the extraction treatment of the shakuyaku extract include water; lower alcohols such as ethanol; polyhydric alcohols such as 1,3-butylene glycol; and polar solvents such as a mixture thereof, which are preferable. Water, ethanol, 1,3-butylene glycol, or a mixed solvent thereof.

The extraction method used in the production of peony extract is not particularly limited, and any general extraction method used in the production of plant extracts may be used. For example, a method of immersing Shakuyaku in an extraction solvent by cold immersion, warm immersion, or the like and stirring it as necessary; a percolation method; a steam distillation method or the like can be mentioned. The peony extract can be recovered by removing solids from the obtained extract by filtration or centrifugation, if necessary. In the pharmaceutical composition of the present invention, the liquid extract obtained by the above extraction treatment may be used as it is, but if necessary, a concentrated solution or a dried product (extract powder) is obtained by removing a part or all of the solvent. , Dry extract). Further, these concentrates or dried products may be further subjected to a purification treatment, and these may be further dissolved or suspended in an appropriate solvent for use.

Since peony and its extract are commercially available, commercially available ones may be used in the present invention.

In the pharmaceutical composition of the present invention, either peony or an extract thereof may be used alone, or these may be used in combination. In particular, the peony extract is preferably used in the present invention because the active ingredient is concentrated, the amount of the peony extract can be reduced, and the peony extract can be easily formulated into a desired dosage form.

In the pharmaceutical composition of the present invention, the content of peony and / or its extract may be appropriately set according to the dosage form, use, daily dose, etc., but for example, when peony itself is used. If there is, the content of peony is 0.01 to 95% by weight, preferably 0.1 to 95% by weight, more preferably 1 to 95% by weight, particularly preferably 10 to 90% by weight, and more preferably 15 to 95% by weight. 80% by weight, particularly preferably 15 to 70% by weight, and even more preferably 15 to 60% by weight. When the extract of Shakuyaku is used, the amount of Shakuyaku extract is 0.01 to 950 parts by weight, preferably 0.1 to 670 parts by weight, per 100 parts by weight of the total amount of the pharmaceutical composition of the present invention. Parts, more preferably 1 to 670 parts, particularly preferably 10 to 630 parts by weight, more preferably 10 to 400 parts by weight, particularly preferably 10 to 300 parts by weight, still more preferably 15 to 200 parts by weight.

In the present specification, the "herbal medicine equivalent amount" is the weight (dry weight) of the crude drug required to obtain the amount of the component thereof. In the case of peony itself, the weight of the herbal medicine to be mixed is the amount converted to the crude drug, and in the case of the peony extract, the dry weight of the crude drug (peony) required to obtain the amount of the peony extract to be mixed is It becomes the equivalent amount of crude drug.

In the pharmaceutical composition of the present invention, the daily dose of peony and / or its extract may be appropriately set according to the dosage form, use, administration form, etc., but for example, 1 to 1 in terms of crude drug equivalent. 9000 mg / day, preferably 10 to 6000 mg / day, more preferably 30 to 6000 mg / day, and particularly preferably 60 to 5500 mg / day.

Nabumetone The pharmaceutical composition of the present invention contains nabumetone in order to suppress the unpleasant odor of peony and / or its extract.

Nabumetone is a known compound also called 4- (6-methoxynaphthalene-2-yl) -2-butanone.

Further, in the pharmaceutical composition of the present invention, the content of nabumetone may be appropriately set according to the dosage form and the like, and is, for example, 5 to 99.9% by weight, preferably 10 to 95% by weight, more preferably. Is 20 to 90% by weight. Further, as shown in the test example described later, it has been confirmed that the unpleasant odor of peony and / or its extract increases with time, but the content of nabumetone is 30 to 85% by weight, particularly 40 to 85% by weight. In the case of%, the unpleasant odor of peony and / or its extract, which increases with time, can be suppressed more effectively. Therefore, a particularly preferred range of nabumetone content in the pharmaceutical composition of the present invention is 30-85% by weight, especially 40-85% by weight.

In the pharmaceutical composition of the present invention, the ratio of nabmeton to shakyaku and / or its extract is determined according to the content of both components, but it is said that the unpleasant odor of shakyak and / or its extract is suppressed more effectively. From the viewpoint, nabumeton is 1 to 100,000 parts by weight, preferably 3 to 9000 parts by weight, more preferably 5 to 3000 parts by weight, and more preferably 10 per 100 parts by weight of the total amount of the crude drug equivalent of the sardine and / or its extract. The ratio is ~ 1500 parts by weight, particularly preferably 10 to 200 parts by weight, and most preferably 30 to 200 parts by weight.

In the pharmaceutical composition of the present invention, the daily dose of nabumetone is not particularly limited, but is, for example, 100 to 1000 mg / day, preferably 200 to 900 mg / day, more preferably 400 to 900 mg / day, and particularly preferably. Is 600 to 800 mg / day.

Other Ingredients In addition to peony and / or its extract and nabumetone, the pharmaceutical composition of the present invention may contain other pharmacological ingredients, if necessary. The types of such pharmacological components are not particularly limited, but for example, analgesics other than nabmeton, intestinal motility improving agents, antioxidants, stomachic agents, digestive agents, intestinal regulators, antispasmodics, mucosal repair agents, anti-inflammatory agents, and astringents. Agents, antiemetics, antitussives, sputum, anti-inflammatory enzyme agents, sedative hypnotics, antihistamines, cardiotonic diuretics, antibacterial agents, vasoconstrictors, vasodilators, local anesthetics, crude drugs other than menthol, crude drug extracts other than menthol extract Examples include powders, vitamins, caffeines, menthols, polyphenols and the like. 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, 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 the 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, adhesives, coating agents, brighteners, water, fats and oils, waxes, hydrocarbons, fatty acids, higher alcohols, esters, water-soluble polymers, surfactants, metal soaps , Lower alcohols, polyhydric alcohols, pH adjusters, buffers, antioxidants, UV inhibitors, preservatives, flavoring agents, fragrances, powders, thickeners, pigments, chelating agents, etc. 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, and the like.

Dosage Form / Dosage Form The dosage form of the pharmaceutical composition of the present invention may be solid, semi-solid, or liquid.

Specific examples of the dosage form of the pharmaceutical composition of the present invention include solid preparations such as tablets, pills, capsules (soft capsules and hard capsules), powders and granules (including dry syrup); jelly agents. , Semi-solid preparations such as foams, ointments, creams and gels; liquid preparations such as liquids, capsules, syrups, lotions, sprays, aerosols and emulsions. Among these dosage forms, the solid-state preparation is a dosage form in which the unpleasant odor of peony and / or its extract is easily perceived and its suppression is strongly required, and is suitable as the dosage form of the pharmaceutical composition of the present invention. Is.

In order to prepare the pharmaceutical composition of the present invention into the above-mentioned dosage form, the pharmaceutical field uses peony and / or an extract thereof, nabumetone, and other pharmacological components, bases, and additives added as needed. It may be formulated according to the usual formulation method adopted in.

The administration form of the pharmaceutical composition of the present invention is not particularly limited, and may be oral administration, transdermal administration, enteral administration, transmucosal administration, intravascular (arterial or intravenous) administration, or the like. However, oral administration is preferable.

Uses The pharmaceutical composition of the present invention can exert an action of relaxing muscle tension, vasodilation, anti-inflammatory, sedation, analgesia, etc. by shakyaku and / or its extract, and can exert an analgesic action by nabumetone, for example, headache.・ Menstrual pain (physiological pain) ・ Tooth pain ・ Pain after tooth extraction ・ Sore throat ・ Low back pain ・ Joint pain ・ Nervous pain ・ Muscle pain ・ Stiff shoulder pain ・ Ear pain -Can be used for the purpose of relieving heat when heat is generated.

2. An unpleasant odor suppressant for peony and / or its extract, and a method for reducing an unpleasant odor of peony and / or its extract As described above, nabumetone can suppress an unpleasant odor of peony and / or its extract. Therefore, the present invention further provides an unpleasant odor suppressant for peony and / or an extract thereof containing nabumetone as an active ingredient. The present invention also provides a method for reducing an unpleasant odor of peony and / or an extract thereof, in which nabumetone is blended with a peony and / or an extract thereof in a pharmaceutical composition.

The unpleasant odor suppressant is used as an additive of nabumetone, and the unpleasant odor reducing method is a method of suppressing unpleasant odor of a pharmaceutical composition containing peony and / or an extract thereof by utilizing nabumetone. be.

The types and amounts of the components used in the unpleasant odor suppressant and the unpleasant odor reducing method, the form of the pharmaceutical composition, and the like are as shown in the column of "1. Pharmaceutical composition".

Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited thereto.

Test Example 1
Tablets having the compositions shown in Table 1 (300 mg per tablet, 6 tablets per day) were prepared according to a conventional method. Immediately after production, 10 tablets of each were placed in an aluminum laminated bag, sealed by heat sealing, and stored at 60 ° C. for 2 weeks.

The aluminum laminate bag was opened before storage, and the unpleasant odor was evaluated by gradually scoring according to the strength of the odor, with 0 points for odorless cases and 15 points for strong odors. .. Further, after storage, the product temperature was returned to room temperature, the aluminum laminated bag was opened, and the unpleasant odor was evaluated in the same manner. In addition, in this evaluation method, when it is judged that the score is 9 points or less, it indicates that the odor has a level that does not cause any problem in terms of the feeling of taking.

The results obtained are shown in Table 1. The tablets containing the peony extract alone (Comparative Examples 1 to 3) had a strong unpleasant odor before storage, and the unpleasant odor increased after storage. On the other hand, the tablets containing peony extract and nabumetone (Examples 1 to 8) were able to effectively reduce the unpleasant odor before and after storage as compared with the tablets of Comparative Example. In particular, the tablets containing 44% by weight of nabumetone together with the peony extract (Examples 1 to 5) can sufficiently suppress the unpleasant odor before storage and remarkably suppress the unpleasant odor after storage. rice field.

Formulation Examples Tablets having the compositions shown in Tables 2 to 9 (300 mg per tablet, daily dose of 6 tablets) were prepared. In the tablets shown in Tables 2 to 9, the peony extract used is the extract powder of a 7-fold concentrated product. All of the obtained tablets were able to suppress the unpleasant odor of the peony extract.

Claims (7)

A pharmaceutical composition containing peony and / or an extract thereof, and nabumetone. The pharmaceutical composition according to claim 1, which contains 1 to 100,000 parts by weight of nabumetone per 100 parts by weight of the total amount of peony and / or its extract in terms of crude drug. The pharmaceutical composition according to claim 1 or 2, which contains 0.01 to 95% by weight of peony, or 0.01 to 950 parts by weight of peony extract in terms of crude drug equivalent per 100 parts by weight of the pharmaceutical composition. The pharmaceutical composition according to any one of claims 1 to 3, which comprises 5 to 99.9% by weight of nabumetone. The pharmaceutical composition according to any one of claims 1 to 4, which is a solid preparation. An unpleasant odor suppressant for peony and / or its extract containing nabumetone as an active ingredient. A method for reducing an unpleasant odor of peony and / or an extract thereof, in which nabumetone is blended with a peony and / or an extract thereof in a pharmaceutical composition.