JP2020002087A - Pharmaceutical composition for internal use - Google Patents
Pharmaceutical composition for internal use Download PDFInfo
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- JP2020002087A JP2020002087A JP2018124494A JP2018124494A JP2020002087A JP 2020002087 A JP2020002087 A JP 2020002087A JP 2018124494 A JP2018124494 A JP 2018124494A JP 2018124494 A JP2018124494 A JP 2018124494A JP 2020002087 A JP2020002087 A JP 2020002087A
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- nabumetone
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 43
- 239000000284 extract Substances 0.000 claims abstract description 38
- BLXXJMDCKKHMKV-UHFFFAOYSA-N Nabumetone Chemical compound C1=C(CCC(C)=O)C=CC2=CC(OC)=CC=C21 BLXXJMDCKKHMKV-UHFFFAOYSA-N 0.000 claims abstract description 37
- 229960004270 nabumetone Drugs 0.000 claims abstract description 36
- 230000003110 anti-inflammatory effect Effects 0.000 claims abstract description 33
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 claims abstract description 14
- 235000006886 Zingiber officinale Nutrition 0.000 claims abstract description 8
- 235000008397 ginger Nutrition 0.000 claims abstract description 8
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- YMBXTVYHTMGZDW-UHFFFAOYSA-N loxoprofen Chemical compound C1=CC(C(C(O)=O)C)=CC=C1CC1C(=O)CCC1 YMBXTVYHTMGZDW-UHFFFAOYSA-N 0.000 description 3
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- LOWWSYWGAKCKLG-UHFFFAOYSA-N 2-(6-methoxynaphthalen-1-yl)acetic acid Chemical compound OC(=O)CC1=CC=CC2=CC(OC)=CC=C21 LOWWSYWGAKCKLG-UHFFFAOYSA-N 0.000 description 1
- CMCCHHWTTBEZNM-UHFFFAOYSA-N 2-bromo-N-carbamoyl-3-methylbutanamide Chemical compound CC(C)C(Br)C(=O)NC(N)=O CMCCHHWTTBEZNM-UHFFFAOYSA-N 0.000 description 1
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- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
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- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
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- KSUUMAWCGDNLFK-UHFFFAOYSA-N apronal Chemical compound C=CCC(C(C)C)C(=O)NC(N)=O KSUUMAWCGDNLFK-UHFFFAOYSA-N 0.000 description 1
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- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines Containing Plant Substances (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
本発明は、ナブメトンを含む内服用医薬組成物に関する。より詳細には、本発明は、ナブメトンの抗炎症作用が向上されている内服用医薬組成物に関する。 The present invention relates to a pharmaceutical composition for internal use containing nabumetone. More specifically, the present invention relates to a pharmaceutical composition for internal use in which nabumetone has an improved anti-inflammatory effect.
ナブメトン、ジクロフェナクナトリウム、イブプロフェン、ロキソプロフェンナトリウム等の非ステロイド性抗炎症剤は、ステロイド性抗炎症剤で見られるような重篤な副作用の懸念が少なく、使用量や使用期間等の制約も少ないため、解熱、鎮痛、消炎等を目的とした内服用医薬組成物において汎用されている。 Non-steroidal anti-inflammatory drugs such as nabumetone, diclofenac sodium, ibuprofen, and loxoprofen sodium have few concerns about serious side effects such as those seen with steroidal anti-inflammatory drugs, and there are few restrictions on the amount or period of use. It is widely used in internal medicine compositions for antipyretic, analgesic, anti-inflammatory, and the like.
一方、近年、医薬分野において薬効の向上に対する要望があり、非ステロイド性抗炎症剤を利用した医薬組成物でも抗炎症作用を向上させることが求められている。非ステロイド性抗炎症剤の用量を増大させると、抗炎症作用の向上につながるが、非ステロイド性抗炎症剤では、胃粘膜障害等の副作用を伴うものがあり、用量の増大が必ずしも有効になるとは限らない。 On the other hand, in recent years, there has been a demand in the pharmaceutical field for improvement of drug efficacy, and there has been a demand for a pharmaceutical composition using a non-steroidal anti-inflammatory agent to improve the anti-inflammatory effect. Increasing the dose of a non-steroidal anti-inflammatory drug leads to an improvement in anti-inflammatory action.However, some non-steroidal anti-inflammatory drugs have side effects such as gastric mucosal damage, and it is not always effective to increase the dose. Not necessarily.
そこで、従来、ステロイド性抗炎症剤の抗炎症作用自体を増強した製剤処方について種々検討が行われている。例えば、特許文献１には、ロキソプロフェン類と、カフェイン類、アリルイソプロピルアセチル尿素、ブロムワレリル尿素、アセトアミノフェン類及び／又はエテンザミドとを併用することによって、ロキソプロフェン類の抗炎症作用が増強されることが報告されている。しかしながら、特許文献１が開示する製剤技術は、その他の非ステロイド性抗炎症剤に適用可能なものでない。 Therefore, various studies have been made on pharmaceutical formulations in which the anti-inflammatory action of the steroidal anti-inflammatory agent itself is enhanced. For example, Patent Literature 1 discloses that the anti-inflammatory effect of loxoprofen is enhanced by using loxoprofen in combination with caffeine, allylisopropylacetyl urea, bromvalerylurea, acetaminophen and / or etensamide. Have been reported. However, the formulation technology disclosed in Patent Document 1 is not applicable to other non-steroidal anti-inflammatory agents.
一方、ナブメトンは、肝臓で代謝されて活性体である6-メトキシ-2-ナフチル酢酸に変換され、当該活性化体がシクロオキシゲナーゼ１よりもシクロオキシゲナーゼ２に対する阻害作用が高い非ステロイド性抗炎症剤である。非ステロイド性抗炎症剤の中でも、ナブメトンは、服用回数が少なく、更に副作用が比較的少ないことが知られており、ナブメトンを配合した内服用医薬組成物が実用化されている。しかしながら、ナブメトンの抗炎症作用を向上させ得る製剤技術については、依然として十分な検討が行われていない。 On the other hand, nabumetone is a non-steroidal anti-inflammatory drug that is metabolized in the liver and converted into the active form 6-methoxy-2-naphthylacetic acid, and the activated form has a higher inhibitory effect on cyclooxygenase 2 than cyclooxygenase 1 . Among the non-steroidal anti-inflammatory agents, nabumetone is known to be taken less frequently and to have relatively few side effects, and a pharmaceutical composition for internal use containing nabumetone has been put to practical use. However, a formulation technique capable of improving the anti-inflammatory effect of nabumetone has not yet been sufficiently studied.
本発明は、ナブメトンの抗炎症作用を向上させた内服用医薬組成物を提供することを目的とする。 An object of the present invention is to provide a pharmaceutical composition for internal use in which the anti-inflammatory effect of nabumetone is improved.
本発明者は、前記課題を解決すべく鋭意検討を行ったところ、内服用医薬組成物において、ナブメトンと共に、カンゾウ、ケイヒ、ボタンピ、カノコソウ、サンショウ、ショウキョウ、ジリュウ、アカメガシワ、エンゴサク及び／又はこれらのエキスを組み合わせて使用すると、ナブメトンの抗炎症作用が飛躍的に向上し得ることを見出した。本発明は、かかる知見に基づいて、更に検討を重ねることにより完成したものである。 Means for Solving the Problems The present inventors conducted intensive studies to solve the above-mentioned problems. It has been found that when these extracts are used in combination, the anti-inflammatory effect of nabumetone can be dramatically improved. The present invention has been completed by further study based on such knowledge.
即ち、本発明は、下記に掲げる態様の発明を提供する。
項１． (A)ナブメトン、並びに、
(B)カンゾウ、ケイヒ、ボタンピ、カノコソウ、サンショウ、ショウキョウ、ジリュウ、アカメガシワ、エンゴサク及びこれらのエキスよりなる群から選択される少なくとも１種、
を含有する、内服用医薬組成物。
項２． 前記(A)成分を１〜９０重量％含む、項１に記載の内服用医薬組成物。
項３． 前記(B)成分を原生薬量換算で１日服用量が４００〜１２０００ｍｇとなる量を含む、項１又は２に記載の内服用医薬組成物。
項４． 前記(A)成分１００重量部当たり、前記(B)成分を原生薬量換算で１〜６０００重量部含む、項１〜３のいずれかに記載の内服用医薬組成物。
項５． 前記(B)成分が、カンゾウ及び／又はカンゾウエキスである、項１〜４のいずれかに記載の内服用医薬組成物。
項６． ナブメトンの抗炎症作用を増強する方法であって、
内服用医薬組成物に、ナブメトンと共に、カンゾウ、ケイヒ、ボタンピ、カノコソウ、サンショウ、ショウキョウ、ジリュウ、アカメガシワ、エンゴサク及びこれらのエキスよりなる群から選択される少なくとも１種を配合する、抗炎症作用増強方法。
That is, the present invention provides the following aspects of the invention.
Item 1. (A) Nabumetone, and
(B) at least one selected from the group consisting of liquorice, calyx, buttonpi, valerian foliage, salamander, ginger, giraffe, akamegawiwa, engosaku and their extracts,
A pharmaceutical composition for internal use, comprising:
Item 2. Item 2. The pharmaceutical composition for internal use according to Item 1, comprising the component (A) in an amount of 1 to 90% by weight.
Item 3. Item 3. The pharmaceutical composition for internal use according to Item 1 or 2, which comprises the component (B) in an amount such that the daily dose is 400 to 12000 mg in terms of the amount of the crude drug.
Item 4. Item 4. The pharmaceutical composition for internal use according to any one of Items 1 to 3, wherein the component (B) is contained in an amount of 1 to 6000 parts by weight in terms of the amount of the crude drug per 100 parts by weight of the component (A).
Item 5. Item 6. The pharmaceutical composition for internal use according to any one of Items 1 to 4, wherein the component (B) is licorice and / or licorice extract.
Item 6. A method for enhancing the anti-inflammatory effect of nabumetone,
An anti-inflammatory effect comprising, in combination with nabumetone, at least one selected from the group consisting of liquorice, cauliflower, buttonpi, valerian, sansho, ginger, giraffe, red pike, engosaku and these extracts, together with nabumetone. How to augment.
本発明の内服用医薬組成物によれば、ナブメトンと、カンゾウ等の特定の生薬及び／又はそのエキスとを併用することによって、ナブメトンの抗炎症作用が飛躍的に向上しており、優れた消炎鎮痛作用を発揮することができる。従って、本発明の内服用医薬組成物は、鎮痛、解熱；感冒症状の緩和等に卓効を示すことができる。 ADVANTAGE OF THE INVENTION According to the pharmaceutical composition for internal use of this invention, the anti-inflammatory effect of nabumetone is improved remarkably by using nabumetone and the specific crude drug, such as licorice, and / or its extract in combination, and the excellent anti-inflammatory It can exert an analgesic effect. Therefore, the pharmaceutical composition for internal use of the present invention can exhibit excellent effects on analgesia, antipyretic, alleviation of cold symptoms and the like.
１．内服用医薬組成物
本発明の内服用医薬組成物は、ナブメトン（以下、「(A)成分」と表記することもある）と、カンゾウ、ケイヒ、ボタンピ、カノコソウ、サンショウ、ショウキョウ、ジリュウ、アカメガシワ、エンゴサク及びこれらのエキスよりなる群から選択される少なくとも１種（以下、「(B)成分」と表記することもある）を含有することを特徴とする。以下、本発明の内服用医薬組成物について詳述する。
1. Pharmaceutical composition for internal use The pharmaceutical composition for internal use according to the present invention comprises nabumetone (hereinafter, sometimes referred to as "component (A)"), liquorice, cauliflower, buttonpi, kanokoso, sansho, shokyo, ziryu, It is characterized by containing at least one selected from the group consisting of red wrinkles, red sorghum, and extracts thereof (hereinafter, sometimes referred to as “component (B)”). Hereinafter, the pharmaceutical composition for internal use of the present invention will be described in detail.
［(A)成分］
本発明の内服用医薬組成物は、消炎鎮痛成分として、ナブメトンを含有する。ナブメトンとは、４−（６−メトキシナフタレン−２−イル）−２−ブタノンとも称される公知の非ステロイド性抗炎症剤である。
[(A) component]
The pharmaceutical composition for internal use of the present invention contains nabumetone as an anti-inflammatory analgesic component. Nabumetone is a known non-steroidal anti-inflammatory drug also called 4- (6-methoxynaphthalen-2-yl) -2-butanone.
本発明の外用医薬組成物における(A)成分の含有量については、剤型、投与量等に応じて適宜設定すればよいが、例えば、１〜９０重量％、好ましくは１．５〜９０重量％、更に好ましくは８〜７０重量％が挙げられる。 The content of the component (A) in the pharmaceutical composition for external use of the present invention may be appropriately set according to the dosage form, the dosage, and the like, and is, for example, 1 to 90% by weight, preferably 1.5 to 90% by weight. %, More preferably 8 to 70% by weight.
［(B)成分］
本発明の内服用医薬組成物は、抗炎症作用を増強させる成分として、カンゾウ、ケイヒ、ボタンピ、カノコソウ、サンショウ、ショウキョウ、ジリュウ、アカメガシワ、エンゴサク、及びこれらのエキスよりなる群から選択される少なくとも１種を含有する。これらの(B)成分をナブメトンと併用することによって、ナブメトンの抗炎症作用を飛躍的に向上させることができる。
[(B) component]
The pharmaceutical composition for internal use according to the present invention is selected from the group consisting of liquorice, cauliflower, buttonpi, valerian, salamander, ginger, giraffe, akamegashiwa, engosaku, and extracts thereof as components that enhance the anti-inflammatory action. Contains at least one. By using these components (B) in combination with nabumetone, the anti-inflammatory effect of nabumetone can be dramatically improved.
カンゾウは、マメ科カンゾウ属植物の根及び／又は根茎であり、生薬として使用されている公知の成分である。本発明に使用されるカンゾウは、粉砕物、細切物、及びこれらの乾燥物のいずれであってもよい。 Licorice is a root and / or rhizome of a leguminous plant of the family Leguminosae, and is a known component used as a crude drug. The liquorice used in the present invention may be any of a pulverized product, a finely chopped product, and a dried product thereof.
ケイヒは、クスノキ科トンキンニッケイやその他同属植物の樹皮を乾燥したものであり、生薬として使用されている公知の成分である。本発明に使用されるケイヒは、粉砕物、細切物、及びこれらの乾燥物のいずれであってもよい。 Caffeine is a well-known component that is obtained by drying the bark of Tonkin Nikko and other congeners of the family Camphoraceae, and is used as a crude drug. The cabbage used in the present invention may be a pulverized product, a finely chopped product, or a dried product thereof.
ボタンピは、ボタン科ボタンの根の皮であり、生薬として使用されている公知の成分である。本発明に使用されるボタンピは、粉砕物、細切物、及びこれらの乾燥物のいずれであってもよい。 Button boar is the root bark of the button family, and is a known component used as a crude drug. The buttoned pig used in the present invention may be a crushed material, a finely chopped material, or a dried product thereof.
カノコソウは、オミナエシ科カノコソウの根であり、生薬として使用されている公知の成分である。本発明に使用されるカノコソウは、粉砕物、細切物、及びこれらの乾燥物のいずれであってもよい。 Valeriana is the root of Valerianaceae, and is a known ingredient used as a crude drug. Valerium used in the present invention may be a pulverized product, a finely chopped product, or a dried product thereof.
サンショウは、ミカン科サンショウの果皮であり、生薬として使用されている公知の成分である。本発明に使用されるサンショウは、粉砕物、細切物、及びこれらの乾燥物のいずれであってもよい。 Salamander is the pericarp of the Rutaceae salamander, and is a known component used as a crude drug. The salmon used in the present invention may be a pulverized material, a finely chopped material, or a dried product thereof.
ショウキョウは、ショウガ科ショウガの根茎であり、生薬として使用されている公知の成分である。本発明に使用されるショウキョウは、粉砕物、細切物、及びこれらの乾燥物のいずれであってもよい。 Ginger is the rhizome of the ginger family Ginger, and is a known component used as a crude drug. The ginger used in the present invention may be a pulverized product, a finely chopped product, or a dried product thereof.
ジリュウは、フトミミズ科Pheretima aspergillum Perrier又はその他近縁動物の全体又は内部を除いたものであり、生薬として使用されている公知の成分である。本発明に使用されるジリュウは、粉砕物、細切物、及びこれらの乾燥物のいずれであってもよい。 Ziryu is a well-known component used as a crude drug, excluding the whole or the inside of Pheretima aspergillum Perrier or other closely related animals. The ziryu used in the present invention may be any of a pulverized product, a finely chopped product, and a dried product thereof.
アカメガシワは、トウダイグサ科アカメガシワの樹皮であり、生薬として使用されている公知の成分である。本発明に使用されるアカメガシワは、粉砕物、細切物、及びこれらの乾燥物のいずれであってもよい。 The red oak wrinkle is the bark of the red spurge, which is a known ingredient used as a crude drug. The red wrinkle used in the present invention may be a crushed product, a finely cut product, or a dried product thereof.
エンゴサクは、ケマンソウ科エンゴサクの塊茎であり、生薬として使用されている公知の成分である。本発明に使用されるエンゴサクは、粉砕物、細切物、及びこれらの乾燥物のいずれであってもよい。 Engosaku is a tuber of Egosacaceae and is a known component used as a crude drug. Engosaku used in the present invention may be a pulverized product, a finely chopped product, or a dried product thereof.
これらの生薬を原料とする生薬エキスは、公知の手法で抽出処理することにより得ることができる。 Crude drug extracts using these crude drugs as raw materials can be obtained by performing an extraction treatment by a known method.
これらの生薬エキスの抽出処理に使用される抽出溶媒としては、例えば、水(熱水含む)；エタノール等の低級アルコール；１，３−ブチレングリコール等の多価アルコール；これらの混合液等の極性溶媒が挙げられ、好ましくは水、エタノール、１，３−ブチレングリコール、又はこれらの混合溶媒である。 Examples of the extraction solvent used for the extraction treatment of these crude drug extracts include water (including hot water); lower alcohols such as ethanol; polyhydric alcohols such as 1,3-butylene glycol; Examples of the solvent include water, ethanol, 1,3-butylene glycol, and a mixed solvent thereof.
これらの生薬エキスの製造において採用される抽出方法については、特に制限されず、生薬エキスの製造に使用される一般的な抽出手法であればよい。例えば抽出溶媒中に原生薬を冷浸、温浸等によって浸漬し、必要に応じて撹拌する方法；パーコレーション法；水蒸気蒸留法等を挙げることができる。得られた抽出液を、必要に応じてろ過または遠心分離によって固形物を除去することにより、生薬エキスを回収できる。 The extraction method used in the production of these crude drug extracts is not particularly limited, and may be any general extraction method used for producing crude drug extracts. For example, a method in which a crude drug is immersed in an extraction solvent by cold immersion, hot immersion, or the like, and agitated as necessary; a percolation method; a steam distillation method; A crude drug extract can be collected by removing a solid substance from the obtained extract by filtration or centrifugation as needed.
本発明の内服用医薬組成物では、上記抽出処理により得られた液状のエキスをそのまま使用してもよいが、必要に応じて、一部又は全ての溶媒を除去して濃縮液（軟エキス）若しくは乾燥物（乾燥エキス）として使用してもよい。また、これらの濃縮液（軟エキス）若しくは乾燥物（乾燥エキス）を更に精製処理に供してもよく、更にこれらを適当な溶剤に溶解若しくは懸濁して用いることもできる。 In the pharmaceutical composition for internal use of the present invention, the liquid extract obtained by the above-mentioned extraction treatment may be used as it is, but if necessary, a part or all of the solvent is removed to obtain a concentrated liquid (soft extract). Alternatively, it may be used as a dried product (dry extract). Further, these concentrated liquids (soft extracts) or dried products (dry extracts) may be further subjected to a purification treatment, and they may be used by dissolving or suspending them in an appropriate solvent.
(B)成分の中でも、生薬エキス（特に乾燥エキス）は、有効成分が濃縮されており、製剤量を減じることができ、所望の剤型への製剤化も容易であるため、好適に使用される。 Among the components (B), crude drug extracts (especially dry extracts) are preferably used because the active ingredient is concentrated, the amount of the preparation can be reduced, and the preparation into a desired dosage form is easy. You.
本発明の内服用医薬組成物において、(B)成分として、カンゾウ、ケイヒ、ボタンピ、カノコソウ、サンショウ、ショウキョウ、ジリュウ、アカメガシワ、エンゴサク及びこれらのエキスの中から１種を選択して単独で使用してもよく、またこれらの中から２種以上を組み合わせて使用してもよい。 In the pharmaceutical composition for internal use according to the present invention, as the component (B), one selected from the following: They may be used, or two or more of these may be used in combination.
これらの(B)成分の中でも、ナブメトンの抗炎症作用を向上させるという観点から、好ましくは、カンゾウ、及びカンゾウエキスが挙げられる。 Among these components (B), from the viewpoint of improving the anti-inflammatory effect of nabumetone, preferably, licorice and licorice extract are used.
本発明の内服用医薬組成物における(B)成分の含有量については、使用する(B)成分の種類、１日当たりの服用量、剤型、投与量等に応じて適宜設定すればよい。1日当りの服用量としては、原生薬換算量で４００〜１２０００ｍｇ、好ましくは１０００〜１００００ｍｇが挙げられる。 The content of the component (B) in the pharmaceutical composition for internal use according to the present invention may be appropriately set according to the type of the component (B) to be used, daily dose, dosage form, dosage, and the like. The daily dose may be 400 to 12000 mg, preferably 1000 to 10000 mg in terms of a crude drug equivalent.
なお、本発明において、「原生薬換算量」とは、その成分量を得るために必要な生薬の重量（乾燥重量）である。生薬自体の場合であれば配合する生薬の重量が原生薬換算量になり、生薬エキスの場合であれば、配合される生薬エキスの量を得るために必要な生薬の乾燥重量が原生薬換算量になる。 In the present invention, the “equivalent amount of crude drug” is the weight (dry weight) of the crude drug necessary to obtain the amount of the component. In the case of crude drugs themselves, the weight of the crude drug to be combined is the crude drug equivalent amount, and in the case of crude drug extracts, the dry weight of the crude drug required to obtain the amount of the crude drug extract to be combined is the crude drug equivalent amount become.
また、本発明の内服用医薬組成物において、(A)成分と(B)成分の比率については、前記各含有量に応じた範囲内であればよく、特に制限されないが、例えば、(A)成分１００重量部当たり、(B)成分が原生薬換算量で１〜６０００重量部、好ましくは２〜６０００重量部が挙げられる。 Further, in the pharmaceutical composition for internal use of the present invention, the ratio of the component (A) and the component (B) is not particularly limited as long as it is within the range according to each of the above-mentioned contents, but, for example, (A) The component (B) is used in an amount of 1 to 6000 parts by weight, preferably 2 to 6000 parts by weight in terms of a crude drug, per 100 parts by weight of the component.
［その他の含有成分］
本発明の内服用医薬組成物には、前述する成分以外に、必要に応じて、他の薬理成分を含んでいてもよい。このような薬理成分の種類については、特に制限されないが、例えば、ビタミン類、ナブメトン以外の消炎鎮痛剤、腸管運動改善剤、制酸剤、胃粘膜保護剤、消化剤、鎮痙剤、粘膜修復剤、収れん剤、鎮吐剤、鎮咳剤、去痰剤、消炎酵素剤、鎮静催眠剤、抗ヒスタミン剤、強心利尿剤、抗菌剤、血管収縮剤、血管拡張剤、局所麻酔剤、プロトンポンプ阻害剤、カフェイン類、メントール類、ポリフェノール等が挙げられる。これらの薬理成分は、１種単独で使用してもよく、また２種以上を組み合わせて使用してもよい。また、これらの薬理成分の含有量については、使用する薬理成分の種類や内服用医薬組成物の剤型等に応じて適宜設定すればよい。
[Other components]
The pharmaceutical composition for internal use of the present invention may contain other pharmacological components, if necessary, in addition to the components described above. The type of such a pharmacological component is not particularly limited, for example, vitamins, anti-inflammatory analgesics other than nabumetone, intestinal motility improving agents, antacids, gastric mucosal protective agents, digestive agents, antispasmodics, mucosal repair agents, Astringent, antiemetic, antitussive, expectorant, anti-inflammatory enzyme, sedative-hypnotic, antihistamine, inotropic diuretic, antibacterial, vasoconstrictor, vasodilator, local anesthetic, proton pump inhibitor, caffeine, menthol And polyphenols. These pharmacological components may be used alone or in a combination of two or more. In addition, the content of these pharmacological components may be appropriately set according to the type of the pharmacological components used, the dosage form of the pharmaceutical composition for internal use, and the like.
本発明の医薬組成物には、所望の剤型に調製するために、必要に応じて、薬学的に許容される基剤や添加剤等が含まれていてもよい。このような基剤及び添加剤としては、例えば、賦形剤、結合剤、崩壊剤、滑沢剤、等張化剤、可塑剤、分散剤、乳化剤、溶解補助剤、湿潤化剤、安定化剤、懸濁化剤、粘着剤、コーティング剤、光沢化剤、水、油脂類、ロウ類、炭化水素類、脂肪酸類、高級アルコール類、エステル類、水溶性高分子、界面活性剤、低級アルコール類、多価アルコール、ｐＨ調整剤、緩衝剤、酸化防止剤、紫外線防止剤、防腐剤、矯味剤、香料、粉体、増粘剤、色素、キレート剤等が挙げられる。これらの基剤や添加剤は、１種単独で使用してもよく、また２種以上を組み合わせて使用してもよい。また、これらの基剤や添加剤の含有量については、使用する添加成分の種類や内服用医薬組成物の剤型等に応じて適宜設定すればよい。 The pharmaceutical composition of the present invention may contain a pharmaceutically acceptable base or additive, if necessary, in order to prepare a desired dosage form. Such bases and additives include, for example, excipients, binders, disintegrants, lubricants, tonicity agents, plasticizers, dispersants, emulsifiers, solubilizing agents, wetting agents, stabilizing agents. Agents, suspending agents, adhesives, coating agents, brighteners, water, oils and fats, waxes, hydrocarbons, fatty acids, higher alcohols, esters, water-soluble polymers, surfactants, lower alcohols , Polyhydric alcohols, pH adjusters, buffers, antioxidants, UV inhibitors, preservatives, corrigents, fragrances, powders, thickeners, pigments, chelating agents and the like. These bases and additives may be used alone or in a combination of two or more. In addition, the content of these bases and additives may be appropriately set according to the type of additive component used, the dosage form of the pharmaceutical composition for internal use, and the like.
［剤型］
本発明の内服用医薬組成物の剤型については、特に制限されず、固体状製剤、半固体状製剤、又は液体状製剤のいずれであってもよい。
[Formulation]
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 preparation, a semi-solid preparation, and a liquid preparation.
固体状製剤としては、具体的には、錠剤、丸剤、カプセル剤（軟カプセル剤、硬カプセル剤）、散剤、顆粒剤（ドライシロップを含む）等が挙げられる。半固体状製剤としては、具体的には、ゼリー剤等が挙げられる。液体状製剤としては、具体的には、液剤、懸濁剤、シロップ剤等が挙げられる。 Specific examples of the solid preparation include tablets, pills, capsules (soft capsules and hard capsules), powders, granules (including dry syrup), and the like. Specific examples of the semi-solid preparation include a jelly preparation. Specific examples of the liquid preparation include liquid preparations, suspensions, syrups and the like.
これらの剤型の中でも、好ましくは固体状製剤が挙げられる。 Among these dosage forms, a solid preparation is preferable.
本発明の内服用医薬組成物を前記剤型に調製するには、(A)成分、(B)成分、及び必要に応じて添加される他の薬理成分、基剤、及び添加剤を用いて、医薬分野で採用されている通常の製剤化手法に従って製剤化すればよい。 To prepare the pharmaceutical composition for internal use of the present invention in the above dosage form, using the (A) component, the (B) component, and other pharmacological components, bases, and additives that are added as necessary. The preparation may be made according to a usual preparation technique employed in the field of medicine.
［用法・用量］
本発明の内服用医薬組成物は、抗炎症作用が向上しており、優れた消炎鎮痛効果を奏し得るので、例えば、頭痛、月経痛（生理痛）・歯痛、抜歯後の疼痛、咽喉痛、腰痛、関節痛、神経痛、筋肉痛、肩こり痛、耳痛、打撲痛、骨折痛、ねんざ痛、外傷痛等の鎮痛；悪寒・発熱時の解熱；感冒症状の緩和等の目的で使用することができる。
[Dosage and administration]
The pharmaceutical composition for internal use according to the present invention has an improved anti-inflammatory effect and can exhibit an excellent anti-inflammatory and analgesic effect. For example, headache, menstrual pain (menstrual pain) / tooth pain, pain after tooth extraction, sore throat, Back pain, joint pain, neuralgia, muscle pain, stiff shoulder, ear pain, bruise, fracture pain, sprain pain, trauma pain, etc .; relieving fever during chills / fever; relieving cold symptoms Can be.
本発明の内服用医薬組成物の服用量については、症状の程度、服用者の年齢等に応じて適宜設定すればよいが、例えば、１日当たりのナブメトン服用量が２００〜１６００ｍｇ程度、好ましくは４００〜１０００ｍｇ程度となる量で、１日当たり１回服用すればよく、年齢、症状によっては複数回に分けて服用してもよい。 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 about 400 mg. The dose may be about once to about 1000 mg once a day, or may be divided into a plurality of doses depending on age and symptoms.
２．抗炎症作用の増強方法
本発明は、更に、ナブメトンの抗炎症作用を増強する方法であって内服用医薬組成物に、ナブメトンと共に、カンゾウ、ケイヒ、ボタンピ、カノコソウ、サンショウ、ショウキョウ、ジリュウ、アカメガシワ、エンゴサク及びそれらのエキスよりなる群から選択される少なくとも１種を配合することを特徴とする抗炎症作用増強方法を提供する。
2. The present invention further relates to a method for enhancing the anti-inflammatory effect of nabumetone, which is a method for enhancing the anti-inflammatory effect of nabumetone, in a pharmaceutical composition for internal use, along with nabumetone, licorice, cauliflower, buttonpi, kanokoso, sansho, shokyo, ziryu, Provided is a method for enhancing an anti-inflammatory action, characterized by comprising at least one selected from the group consisting of red wrinkles, engosaku, and extracts thereof.
当該抗炎症作用増強方法において、使用される成分の種類、配合量、内服用医薬組成物の剤型等については、前記「１．内服用医薬組成物」の欄に記載の通りである。 In the method for enhancing anti-inflammatory action, the type and amount of the components used, the dosage form of the pharmaceutical composition for internal use, and the like are as described in the above section “1. Pharmaceutical composition for internal use”.
以下、本発明を実施例により具体的に説明するが、本発明はこれらの実施例に限定されるものではない。 Hereinafter, the present invention will be described specifically with reference to Examples, but the present invention is not limited to these Examples.
試験例１：抗炎症作用の評価試験
５週齢の雄性ラット（Slc:Wister(SPF)、日本エスエルシー株式会社）をノーマル群、コントロール群、及び試験群（実施例１及び比較例１）の４群（１群当たり６匹）に分けた。各群のラットを１週間飼育して馴化させた後に、以下の条件で試験を行った。
Test Example 1: Evaluation test of anti-inflammatory action Five-week-old male rats (Slc: Wister (SPF), Japan SLC Co., Ltd.) were subjected to a normal group, a control group, and a test group (Example 1 and Comparative Example 1). The animals were divided into four groups (six per group). After the rats in each group were bred for one week to acclimate, the test was performed under the following conditions.
・ノーマル群
試験開始（-1 hr）時に注射用水（蒸留水）を１０ｍｌ／ｋｇ（ラット体重）となるように経口投与し、その後、カラゲニンの投与を行わなかった。試験開始時（-1 hr）（注射用水の投与前）に後肢足蹠容積を測定し、更に試験開始２時間後（1 hr）から６時間後（5 hrs）まで１時間毎に後肢足蹠容積を測定した。
-At the start of the normal group test (-1 hr), water for injection (distilled water) was orally administered so as to be 10 ml / kg (rat weight), and then carrageenan was not administered. At the start of the test (-1 hr) (before administration of water for injection), the volume of the hind footpad was measured, and from 2 hours (1 hr) to 6 hours (5 hrs) after the start of the test, the hind footpad was changed every hour. The volume was measured.
・コントロール群
試験開始（-1 hr）時に注射用水（蒸留水）を１０ｍｌ／ｋｇ（ラット体重）となるように経口投与した。試験開始から１時間後（0 hr）に、カラゲニン１重量％を含む生理食塩水を０．１ｍｌ／ｈｅａｄとなるようにラットの後肢足蹠に皮下投与し、炎症による浮腫を惹起させた。試験開始時（-1 hr）（注射用水の投与前）に後肢足蹠容積を測定し、更にカラゲニン投与の１時間後（1 hr）から５時間後（5 hrs）まで１時間毎に後肢足蹠容積を測定した。
Control group At the start of the test (-1 hr), water for injection (distilled water) was orally administered so as to be 10 ml / kg (rat body weight). One hour (0 hr) after the start of the test, physiological saline containing 1% by weight of carrageenin was subcutaneously administered to the hind footpad of the rat at a concentration of 0.1 ml / head to induce edema due to inflammation. At the beginning of the test (-1 hr) (before administration of water for injection), the volume of the hind footpad was measured, and after 1 hour (1 hr) to 5 hours (5 hrs) after carrageenin administration, the hind limb foot was increased every hour. The pad volume was measured.
・試験群
試験開始（-1 hr）時に、表１に示す成分を所定の投与量となるように注射用水（蒸留水）に添加した試験液を１０ｍｌ／ｋｇ（ラット体重）となる用量でラットに経口投与した。試験開始から１時間後（0 hr）に、カラゲニン１重量％を含む生理食塩水を０．１ｍｌ／ｈｅａｄとなるようにラットの後肢足蹠に皮下投与した。試験開始時（-1 hr）（試験液の投与前）に後肢足蹠容積を測定し、更にカラゲニン投与の１時間後（1 hr）から５時間後（5 hrs）まで１時間毎に後肢足蹠容積を測定した。
-Test group At the start of the test (-1 hr), rats were given a test solution in which the components shown in Table 1 were added to water for injection (distilled water) so as to give a prescribed dose, at a dose of 10 ml / kg (rat weight). Was orally administered. One hour (0 hr) after the start of the test, physiological saline containing 1% by weight of carrageenan was subcutaneously administered to the hind footpad of the rat at a concentration of 0.1 ml / head. At the start of the test (-1 hr) (before administration of the test solution), the volume of the hind footpad was measured, and the hind foot paws were hourly from 1 hour (1 hr) to 5 hours (5 hrs) after carrageenin administration. The pad volume was measured.
ラットの後肢足蹠容積の測定は、水を用いたデジタル肢容積測定装置（「Digital Plethysmometer ＬＥ7500」、Panlab, S.L.U.）を用いて行った。測定した後肢足蹠容積から、以下の式に従って、浮腫率（％）、及びＡＵＣ（浮腫率の総和）（％・時間）を算出した。なお、浮腫率及びＡＵＣは、個体毎に算出し、各群での平均値を求めた。
結果を表２に示す。コントロール群では、浮腫率及びＡＵＣが高く、カラゲニン投与によって炎症が惹起されていた。ナブメトン単独の投与した場合（比較例１）では、コントロール群に比べて浮腫率及びＡＵＣをある程度低減できていた。これに対して、ナブメトンと共に、カンゾウエキスを投与した場合（実施例１）では、コントロール群に比べて、浮腫率及びＡＵＣが格段に低くなっており、抗炎症作用が飛躍的に向上していた。 Table 2 shows the results. In the control group, the edema rate and AUC were high and inflammation was induced by carrageenan administration. When nabumetone was administered alone (Comparative Example 1), the edema rate and AUC could be reduced to some extent as compared with the control group. In contrast, when licorice extract was administered together with nabumetone (Example 1), the edema rate and AUC were significantly lower than those of the control group, and the anti-inflammatory effect was dramatically improved. .
参考試験例１：抗炎症作用の評価試験
試験群として、表３に示す成分を所定の投与量となるように投与したこと以外は、前記試験例１と同様の方法で試験を行い、浮腫率及びＡＵＣを求めた。ジクロフェナクナトリウムは、ナブメトンと同じフェニル酢酸系非ステロイド抗炎症剤である。
Reference Test Example 1: Evaluation test of anti-inflammatory action As a test group, the test was conducted in the same manner as in Test Example 1 except that the components shown in Table 3 were administered so as to have a predetermined dose. And AUC were determined. Diclofenac sodium is the same phenylacetic acid non-steroidal anti-inflammatory drug as nabumetone.
結果を表４に示す。この結果、ジクロフェナクナトリウムと、カンゾウエキスを併用した場合（参考例２）では、ジクロフェナクナトリウム単独の場合（参考例１）に比べて浮腫率が高くなる傾向があり、ＡＵＣが上昇していた。つまり、抗炎症作用は低下した。即ち、本試験結果から、カンゾウエキスを使用することによる抗炎症作用の向上は、非ステロイド性抗炎症剤としてナブメトンを選択した場合に認められる特有の効果であることが確認された。 Table 4 shows the results. As a result, in the case of using diclofenac sodium and licorice extract together (Reference Example 2), the edema rate tended to be higher than that in the case of using diclofenac sodium alone (Reference Example 1), and the AUC was increased. That is, the anti-inflammatory effect was reduced. That is, from the present test results, it was confirmed that the improvement of the anti-inflammatory effect by using licorice extract is a unique effect observed when nabumetone was selected as a nonsteroidal anti-inflammatory agent.
製剤例
表５及び６に示す組成の顆粒剤（処方例１〜４、及び８〜１０）、及び錠剤（処方例５〜７、及び１１〜３０）を調製した。表５及び６において各含有成分の含有量の単位は、１日当たりの服用量（ｍｇ）である。これらの顆粒剤及び錠剤は、ナブメトンの抗炎症作用の飛躍的な向上が期待できる。
Formulation Examples Granules (Formulation Examples 1 to 4 and 8 to 10) and tablets (Formulation Examples 5 to 7 and 11 to 30) having the compositions shown in Tables 5 and 6 were prepared. In Tables 5 and 6, the unit of the content of each component is the daily dose (mg). These granules and tablets can be expected to dramatically improve the anti-inflammatory effect of nabumetone.
なお、表５及び６に示す生薬に関する剤形等は以下の通りである。
・カンゾウ末：粉末状の生薬末
・ケイヒ末：粉末状の生薬末
・ボタンピ末：粉末状の生薬末
・カノコソウ末：粉末状の生薬末
・サンショウ末：粉末状の生薬末
・ショウキョウ末粉末状の：生薬末
・ジリュウ末：粉末状の生薬末
・アカメガシワ末：粉末状の生薬末
・エンゴサク末：粉末状の生薬末
・カンゾウエキス末：乾燥エキス、抽出溶媒は水、原生薬換算で５倍濃縮エキス
・ケイヒエキス末：乾燥エキス、抽出溶媒は水、原生薬換算で２２倍濃縮エキス
・ショウキョウエキス末：乾燥エキス、原生薬換算で５倍濃縮エキス
・ジリュウエキス末：乾燥エキス、抽出溶媒は３０％エタノール水溶液、原生薬換算で５倍濃縮エキス
・アカメガシワエキス末：乾燥エキス、抽出溶媒は水、原生薬換算で１０倍濃縮エキス
The dosage forms of crude drugs shown in Tables 5 and 6 are as follows.
-Licorice powder : powdered crude drug powder
・ Kaihi powder : powdered herbal powder
・ Potato powder : powdered herbal powder
-Valerian powder : powdered herbal powder
・ Fish powder : powdered crude drug powder
・ Gallery powder powder: Crude drug powder
・ Giryu powder: powdered crude drug powder
・ Akamega wrinkle powder : powdered crude drug powder
・ Engosaku powder : powdered crude drug powder
-Licorice extract powder : dry extract, extraction solvent is water, extract 5 times concentrated in terms of crude drug
・ Keihi extract powder : dried extract, extraction solvent is water, extract 22 times concentrated in terms of crude drug
-Ginger extract powder : dried extract, 5-fold concentrated extract in crude drug equivalent
・ Grill extract powder : Dried extract, extraction solvent is 30% ethanol aqueous solution, extract 5 times concentrated in terms of crude drug
・ Akamega wrinkle extract powder : dried extract, extraction solvent is water, 10 times concentrated extract in terms of crude drug
Claims (6)
(B)カンゾウ、ケイヒ、ボタンピ、カノコソウ、サンショウ、ショウキョウ、ジリュウ、アカメガシワ、エンゴサク及びこれらのエキスよりなる群から選択される少なくとも１種、
を含有する、内服用医薬組成物。 (A) Nabumetone, and
(B) at least one selected from the group consisting of liquorice, calyx, buttonpi, valerian foliage, salamander, ginger, giraffe, akamegawiwa, engosaku and their extracts,
A pharmaceutical composition for internal use, comprising:
内服用医薬組成物に、ナブメトンと共に、カンゾウ、ケイヒ、ボタンピ、カノコソウ、サンショウ、ショウキョウ、ジリュウ、アカメガシワ、エンゴサク及びこれらのエキスよりなる群から選択される少なくとも１種を配合する、抗炎症作用増強方法。 A method for enhancing the anti-inflammatory effect of nabumetone,
An anti-inflammatory effect comprising, in combination with nabumetone, at least one selected from the group consisting of liquorice, cauliflower, buttonpi, valerian, sansho, ginger, giraffe, red pike, engosaku, and these extracts, in a pharmaceutical composition for internal use. How to augment.
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