JP2012077003A - Combination preparation of extracts of radix angelicae tuhuo and puerariae radix decoction - Google Patents
Combination preparation of extracts of radix angelicae tuhuo and puerariae radix decoction Download PDFInfo
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- JP2012077003A JP2012077003A JP2010220551A JP2010220551A JP2012077003A JP 2012077003 A JP2012077003 A JP 2012077003A JP 2010220551 A JP2010220551 A JP 2010220551A JP 2010220551 A JP2010220551 A JP 2010220551A JP 2012077003 A JP2012077003 A JP 2012077003A
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- extract
- glycyrrhizic acid
- paeoniflorin
- kakkonto
- salt
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Abstract
Description
本発明は、独活葛根湯エキス配合剤に関する。本発明は、特に、グリチルリチン酸及びその塩の総量に対してペオニフロリンを一定以上の割合で含有する独活葛根湯エキス配合剤に関する。 The present invention relates to an independent kakkonto extract compounding agent. In particular, the present invention relates to an independent kakkonto extract compound containing paeoniflorin at a certain ratio or more with respect to the total amount of glycyrrhizic acid and salts thereof.
日常生活の中でしばしば経験する症状に、肩こり、寝違え、四十肩、五十肩等がある。例えば、近年の高度情報化社会では、コンピュータを使用する業務が増加している。このような職場環境では、長時間VDT(Visual Display Terminal)に向う仕事などによって肩に負担がかかりやすく、従って、肩こりなどの愁訴が問題となっている。また、寝違えは、ひどい痛みを伴う場合があり、早急に痛みを軽減乃至解消することが求められている。このように、肩こり、寝違え、四十肩、五十肩等の症状は、患者に痛み、不快感、倦怠感などの肉体的苦痛及び精神的苦痛を与え、従って、生活の質(Quality of Life)を低下させることから、これらの症状の効果的な改善方法が強く求められている。 Symptoms often experienced in daily life include stiff shoulders, falling asleep, forty shoulders and fifty shoulders. For example, in the recent advanced information society, operations using computers are increasing. In such a work environment, it is easy to put a burden on the shoulder due to work directed to VDT (Visual Display Terminal) for a long time, and therefore, complaints such as stiff shoulders are a problem. In addition, sleeping mistakes may be accompanied by severe pain, and it is required to quickly reduce or eliminate the pain. In this way, symptoms such as stiff shoulders, sleeping mistakes, forty shoulders, fifty shoulders, etc. cause physical and mental pain such as pain, discomfort, fatigue, and thus quality of life. Therefore, there is a strong demand for an effective method for improving these symptoms.
これらの症状の改善方法の一つとして、症状に応じた薬物が用いられている。例えば、いわゆる「こり感」を伴う場合には非ステロイド性消炎鎮痛剤、筋の緊張が高い場合や硬結が触知される場合には筋弛緩剤、漢方薬では独活葛根湯などが使用されている。 As one of the methods for improving these symptoms, drugs corresponding to the symptoms are used. For example, non-steroidal anti-inflammatory analgesics when so-called “stiffness” is used, muscle relaxants are used when muscle tension is high or induration is palpated, and Kokukokuto is used as a traditional Chinese medicine. .
独活葛根湯は、抗酸化作用、抗炎症作用、鎮痛作用、血行促進作用のある漢方薬であり(例えば特許文献1、非特許文献1及び2)、肩こりをはじめとする肩背の症状に広く適用されている。しかしながら、独活葛根湯の従来の適用対象は症状が軽いものに限られ、すなわち、独活葛根湯の効果が不十分であるとの問題点があった。 Dokatsu Kakkonto is a Chinese herbal medicine that has antioxidant, anti-inflammatory, analgesic, and blood circulation promoting effects (eg, Patent Document 1, Non-Patent Documents 1 and 2), and is widely applied to shoulder and back symptoms including shoulder stiffness Has been. However, the conventional application target of Kokukatsu Kakkento is limited to those with mild symptoms, that is, there is a problem that the effect of Kokukokukokuto is insufficient.
また、漢方の分野においては、原料となる生薬の配合割合については規定があるものの、最終的に得られる漢方製剤に含有される各有効成分の量については明確な規定がない。従って、産地や収穫時期等によって原料となる生薬自体の品質にバラツキがあり、このため調製される漢方製剤中の有効成分の量も一定に保持されていないことが多い。また、抽出条件等によっても抽出される有効成分の量は大きく変動し、また、抽出条件等は調合者の裁量に委ねられていることから、漢方製剤の品質が調合者によって異なることも問題となっている(例えば非特許文献3及び4参照)。 Moreover, in the field of Kampo, there is a provision about the blending ratio of the crude drug used as a raw material, but there is no clear provision about the amount of each active ingredient contained in the Kampo preparation finally obtained. Therefore, the quality of the crude drug itself used as a raw material varies depending on the production area, harvest time, and the like, and the amount of active ingredients in the Kampo preparations thus prepared is often not kept constant. In addition, the amount of active ingredient to be extracted varies greatly depending on the extraction conditions, etc., and the extraction conditions are left to the discretion of the formulator. (For example, see Non-Patent Documents 3 and 4).
また、独活葛根湯などの甘草を含有する漢方薬において、その有効性を高めるために、甘草中の成分であるグリチルリチン酸の抽出効率を上げる試みがしばしば行われている。しかしながら、漢方製剤中のグリチルリチン酸の含有量を高めると、グリチルリチン酸の過剰摂取による偽アルドステロン症の発症といった副作用を引き起こすことも問題となっている(例えば非特許文献5及び6参照)。 In addition, in Chinese medicines containing licorice such as Tokatsu Kakkonto, attempts are often made to increase the extraction efficiency of glycyrrhizic acid, which is a component in licorice, in order to increase its effectiveness. However, when the content of glycyrrhizic acid in a Chinese medicine preparation is increased, it causes a side effect such as the onset of pseudoaldosteronism due to excessive intake of glycyrrhizic acid (see, for example, Non-Patent Documents 5 and 6).
これらの背景から、抗酸化作用、抗炎症作用、鎮痛作用が高く、且つ安全性が高い漢方製剤が求められていた。 From these backgrounds, a Kampo preparation with high antioxidative action, anti-inflammatory action and analgesic action and high safety has been demanded.
そこで、本発明は、抗酸化作用、抗炎症作用、鎮痛作用が高く、且つ安全性が高い独活葛根湯エキス配合剤を提供することを目的とする。 Therefore, an object of the present invention is to provide an independent kakkonto extract compounding agent having high antioxidant action, anti-inflammatory action, analgesic action and high safety.
本発明者らは、上記課題を解決すべく鋭意検討を重ねていたところ、独活葛根湯エキスに含まれるグリチルリチン酸とペオニフロリンを一定の比率に調整することにより、驚くべきことに、グリチルリチン酸の抗酸化作用、抗炎症作用、鎮痛作用が顕著に増強することを見出した。本願発明は、かかる知見に基づいて完成したものであり、次の実施態様を包含するものである。
項1.グリチルリチン酸及びその塩の総量1重量部に対して、ペオニフロリンを0.5重量部以上含有する独活葛根湯エキス配合剤。
項2.グリチルリチン酸及びその塩の総量1重量部に対して、ペオニフロリンを0.5〜50重量部含有する、項1に記載の独活葛根湯エキス配合剤。
項3.グリチルリチン酸及びその塩の総量1重量部に対して、ペオニフロリンを0.5〜10重量部含有する、項1又は2に記載の独活葛根湯エキス配合剤。
項4.グリチルリチン酸及びその塩の総量1重量部に対して、ペオニフロリンを3〜5重量部含有する、項1〜3のいずれかに記載の独活葛根湯エキス配合剤。
項5.1日投与単位あたりグリチルリチン酸及びその塩の総量を5〜15mg含有する、項1〜4のいずれかに記載の独活葛根湯エキス配合剤。
The inventors of the present invention have made extensive studies in order to solve the above problems, and surprisingly, by adjusting the ratio of glycyrrhizic acid and paeoniflorin contained in Sotsukatsu Kakkonto extract to a certain ratio, It was found that the oxidative action, anti-inflammatory action and analgesic action are remarkably enhanced. The present invention has been completed based on such knowledge and includes the following embodiments.
Item 1. An independent kakkonto extract compounding agent containing 0.5 parts by weight or more of paeoniflorin with respect to 1 part by weight of the total amount of glycyrrhizic acid and its salt.
Item 2. The independent kakkonto extract compounding agent of claim | item 1 containing 0.5-50 weight part of paeoniflorins with respect to 1 weight part of total amounts of glycyrrhizic acid and its salt.
Item 3. The independent kakkonto extract compounding agent of claim | item 1 or 2 containing 0.5-10 weight part of paeoniflorin with respect to 1 weight part of total amounts of glycyrrhizic acid and its salt.
Item 4. The independent kakkonto extract compounding agent in any one of claim | item 1-3 which contains 3-5 weight part of paeoniflorins with respect to 1 weight part of total amounts of glycyrrhizic acid and its salt.
Item 5. The independent kakkonto extract combination preparation according to any one of Items 1 to 4, comprising 5 to 15 mg of a total amount of glycyrrhizic acid and a salt thereof per daily dosage unit.
本発明の独活葛根湯エキス配合剤は、グリチルリチン酸及びその塩の総量に対してペオニフロリンが一定以上の割合で含有されていることから、グリチルリチン酸に由来する抗酸化作用、抗炎症作用、鎮痛作用が顕著に高められている。 The sole active kakkonto extract combination agent of the present invention contains paeoniflorin at a certain ratio or more with respect to the total amount of glycyrrhizic acid and its salt, so that it has an antioxidant action, an anti-inflammatory action and an analgesic action derived from glycyrrhizic acid. Is significantly increased.
従来、グリチルリチン酸における抗酸化作用等は知られているが、本発明の独活葛根湯エキス配合剤では、ペオニフロリンによって、グリチルリチン酸及びその塩の抗酸化作用、抗炎症作用、鎮痛作用が相乗的に高められている。 Conventionally, the antioxidant action and the like in glycyrrhizic acid are known, but in the independent kakkonto extract combination agent of the present invention, the antioxidant action, anti-inflammatory action, and analgesic action of glycyrrhizic acid and its salt are synergistic by paeoniflorin. Has been enhanced.
このため、本発明の独活葛根湯エキス配合剤を摂取又は服用することにより、肩こり、四十肩、五十肩等の疾患を、従来と比較して迅速且つ効率よく軽減乃至解消することが可能である。また、寝違えは、肩こりよりも炎症の程度が高いが、本発明の独活葛根湯エキス配合剤によれば、このように炎症の程度の高い寝違えなどに対しても、これまでにない顕著に優れた軽減乃至解消効果を発揮でき且つ即効性を備えている。 For this reason, it is possible to reduce or eliminate diseases such as stiff shoulders, forty shoulders, fifty shoulders and the like quickly and efficiently by ingesting or taking the self-existing kakkonto extract compound of the present invention. . In addition, although the degree of inflammation is higher than that of the stiff shoulder, according to the composition of the independent kakkonto extract of the present invention, it is remarkably superior to that of such a high level of inflammation. It can be used for reducing or eliminating effects and has immediate effect.
また、本発明の独活葛根湯エキス配合剤では、グリチルリチン酸及びその塩の抗酸化作用、抗炎症作用、鎮痛作用が相乗的に高められていることから、グリチルリチン酸の過剰摂取による偽アルドステロン症の発症等の副作用を効果的に防止しながら、グリチルリチン酸に由来する抗酸化作用等を有意に発揮させることが可能である。 In addition, in the composition of the independent kakkonto extract of the present invention, the antioxidative action, anti-inflammatory action, and analgesic action of glycyrrhizic acid and its salts are synergistically enhanced, so that pseudoaldosteronism caused by excessive intake of glycyrrhizic acid can be prevented. While effectively preventing side effects such as onset, it is possible to significantly exert an antioxidant action and the like derived from glycyrrhizic acid.
本発明の独活葛根湯エキス配合剤は、グリチルリチン酸及びその塩の総量に対してペオニフロリンが一定以上の割合で含有されていることを特徴とする。以下、本発明について更に詳細に説明する。
(1)独活葛根湯エキス
独活葛根湯は従来知られた漢方薬である。本発明において独活葛根湯は、従来知られたものを使用できる。
The sole active kakkonto extract compounding agent of the present invention is characterized in that paeoniflorin is contained at a certain ratio or more with respect to the total amount of glycyrrhizic acid and its salt. Hereinafter, the present invention will be described in more detail.
(1) Tokatsu Kakkonto Extract Tokoku Kakkonto is a traditional Chinese medicine. In the present invention, conventionally known Kakkonto can be used.
独活葛根湯は、原料の生薬として具体的には、通常、カッコン(Pueraria lobata Ohwi)、ケイヒ(Cinnamomum cassia Blume)、シャクヤク(Paeonia lactiflora Pallas)、マオウ(Ephedra sinica Stapf,Ephedra intermedia Schrenk et C.A. Meyer,Ephedra equisetina Bunge)、ドクカツ(Aralia Rhizome)、ショウキョウ(Zingiber officinale Roscoe)、ジオウ(Rehmannnia glutinosa Liboschitz var,purpurea Makino,Rehmannia glutinosa Liboschitz)、タイソウ(Zizypus jujube Miller var. inermis Rehder)、カンゾウ(Glycyrrhiza uralensis Fischer,Glycyrrhiza glabra Linne)からなる。これらの原料は、日本薬局方に準じて使用部位が規定されており、本発明においてはこれに従う。 Tokutsu Kakkonto is specifically used as a crude drug for raw materials, and is usually used in cucumber (Pueraria lobata Ohwi), keihi (Cinnamomum cassia Blume), peonies (Paeonia lactiflora Pallas), maou (Ephedra sinica Stapf, Ephedra intermedia Schrenk et CA Meyer, Ephedra equisetina Bunge, Aralia Rhizome, Zingiber officinale Roscoe, Rehmannnia glutinosa Liboschitz var, purpurea Makino, Rehmannia glutinosa Liboschitz, Zizypus jujube Miller der. , Glycyrrhiza glabra Linne). These raw materials are used in accordance with the Japanese Pharmacopoeia, and the site of use is defined in the present invention.
独活葛根湯の調製は、「改訂 一般用漢方処方の手引き」(日本公定書協会監修、日本漢方生薬製剤協会編集、薬業時報社発行)や「漢方製剤の基本的取扱い方針」等に記載されている規定に従い行えばよい。書簡によっては、成分比等が多少異なるものもあるが、これらの差異は特に制限されず、いずれも上記独活葛根湯として包含される。 The preparation of Dokatsu Kakkonto is described in the “Revised General Kampo Prescription Guide” (supervised by the Japan Association of Official Medicines, edited by the Japanese Herbal Medicines Association, published by Yakuho Jihosha) and the “Basic Handling Policy of Kampo Preparations”. You can follow the rules. Depending on the letter, the component ratio and the like may be slightly different, but these differences are not particularly limited, and any of them are included as the above-mentioned Kokukoku-to.
制限されないが、例えば、独活葛根湯は、原料となる生薬の乾燥重量に換算して、カッコン2.5、ケイヒ1.5、シャクヤク1.5、マオウ1、ドクカツ1、ショウキョウ0.5、ジオウ2.0、タイソウ0.5、カンゾウ0.5とすることができる。 Although not limited, for example, Kokukatsu Kakkonto is converted into the dry weight of the crude drug used as a raw material, and is 2.5, Keihi 1.5, Peonies 1.5, Maow 1, Dokkatsu 1, Shokyo 0.5, It can be set to Zio 2.0, Tiso 0.5, and Licorice 0.5.
本発明において独活葛根湯エキスは、独活葛根湯の前記原料生薬の混合物から得られる抽出エキスである。独活葛根湯エキスは、例えば、前記生薬の混合物に対して、約10〜20倍量の水を加え、80〜100℃程度で1〜3時間程度撹拌抽出し、遠心分離又はろ過して抽出液を得ることにより取得できる。得られた独活葛根湯エキスは、液状であってもよく、濃縮又は希釈してもよく、スプレードライ処理や凍結乾燥処理など公知の方法により乾燥してもよく、また、必要に応じて乾燥後粉砕することにより粉状としてもよく、その形態は使用態様に応じて適宜決定すればよく、制限されない。 In the present invention, Kokukoku-to extract is an extract obtained from a mixture of the raw herbal medicines of Kokukoku-koku-to. For example, Tokatsu Kakkonto extract is about 10 to 20 times the amount of water added to the herbal medicine mixture, stirred and extracted at about 80 to 100 ° C. for about 1 to 3 hours, centrifuged or filtered, and extracted. Can be obtained by obtaining The resulting Kokukokuto extract may be liquid, may be concentrated or diluted, may be dried by a known method such as spray-drying treatment or freeze-drying treatment, and if necessary after drying It is good also as a powder form by grind | pulverizing, The form should just be determined suitably according to a use aspect, and is not restrict | limited.
独活葛根湯エキスは、より詳細には、限定されないが、例えば、前記生薬の混合物に対して、約10倍量の水を加え、95〜100℃程度で1時間程度撹拌抽出し、抽出物について100〜200メッシュに相当するろ過(遠心分離又は自然ろ過)をしたのち、ろ液を60〜70℃以下で減圧濃縮後、スプレードライすることにより得ることができる。 Tokutsu Kakkonto extract is not limited in more detail. For example, about 10 times the amount of water is added to the herbal medicine mixture, and the mixture is stirred and extracted at about 95 to 100 ° C. for about 1 hour. After filtration (centrifugation or natural filtration) corresponding to 100 to 200 mesh, the filtrate is concentrated under reduced pressure at 60 to 70 ° C. or less and then spray-dried.
独活葛根湯の原料となる各生薬は、生薬の産地や収穫時期等によって品質にバラツキがある。また、独活葛根湯の原料となる各生薬の配合比率によっても、エキスに含まれる有効成分量は変化する。このため、前記独活葛根湯エキスの取得は、使用される生薬の品質や各生薬の配合比率に応じて適宜微調整して実施される。該微調整は、当業者であれば当然に行い得る。また、例えば、グリチルリチン酸はカンゾウなどに含まれており、ペオニフロリンはシャクヤクなどに含まれているため、具体的には、カンゾウ及びシャクヤクの剪断方法を調整する(細かく又は粗く刻む)、カンゾウ及びシャクヤクの産地や収穫時期を選別する、抽出溶媒を調整する、抽出温度を調整する、抽出時間を調整する、抽出回数を増減させる、濃縮方法、乾燥方法を選択する等の方法が例示される。これらの方法によって、グリチルリチン酸、その塩及びペオニフロリンの収率や含有量が調整され、得られた独活葛根湯エキス中のこれらの成分の含有量を確認して、本発明の配合剤を調製することができる。 Each herbal medicine, which is the raw material for Kokukatsu Kakkonto, varies in quality depending on the production area and harvest time of the herbal medicine. Moreover, the amount of active ingredients contained in the extract also changes depending on the blending ratio of each herbal medicine used as a raw material for Kokukatsu Kakkonto. For this reason, acquisition of the above-mentioned Kokusai Kakkonto extract is performed by appropriately fine-tuning according to the quality of the herbal medicine used and the blending ratio of each herbal medicine. The fine adjustment can be naturally performed by those skilled in the art. In addition, for example, glycyrrhizic acid is contained in licorice and paeoniflorin is contained in peony and the like. Specifically, the shearing method of licorice and peony is adjusted (finely or roughly chopped), licorice and peony. Examples include selecting the production area and harvest time, adjusting the extraction solvent, adjusting the extraction temperature, adjusting the extraction time, increasing or decreasing the number of extractions, selecting a concentration method, and a drying method. By these methods, the yield and content of glycyrrhizic acid, its salt, and paeoniflorin are adjusted, and the content of these components in the resulting sotsukatsu kakkonto extract is confirmed to prepare the compounding agent of the present invention. be able to.
このようにして独活葛根湯エキスを得ることにより、グリチルリチン酸及びその塩の総量に対してペオニフロリンを次の割合で含有する独活葛根湯エキスを得ることができる。 Thus, by obtaining Kokukokuto extract, Kokuketsuto extract containing paeoniflorin in the following ratio with respect to the total amount of glycyrrhizic acid and its salt can be obtained.
すなわち、得られた独活葛根湯エキスには、グリチルリチン酸及びその塩の総量に対して、ペオニフロリンが一定以上の割合で含有されていることが重要である。具体的には、該独活葛根湯エキスは、グリチルリチン酸及びその塩の総量1重量部に対して、ペオニフロリンを0.5重量部以上で含有する。また、該独活葛根湯エキスは、グリチルリチン酸及びその塩の総量1重量部に対して、ペオニフロリンを、好ましくは0.5〜50重量部で含有し、更に好ましくは0.5〜10重量部で含有し、特に好ましくは3〜5重量部で含有する。この範囲内であれば、独活葛根湯エキスの抗酸化作用、抗炎症作用、鎮痛作用が相乗的に高められるとともに、副作用の原因となるグリチルリチン酸及びその塩の含有量を低くすることができる。 That is, it is important that the obtained Kokukokuto extract obtained contains paeoniflorin at a certain ratio or more with respect to the total amount of glycyrrhizic acid and its salt. Specifically, the self-existing Kakkonto extract contains 0.5 parts by weight or more of paeoniflorin with respect to 1 part by weight of the total amount of glycyrrhizic acid and its salt. In addition, the sole active kakkonto extract preferably contains 0.5 to 50 parts by weight of paoniflorin, more preferably 0.5 to 10 parts by weight with respect to 1 part by weight of the total amount of glycyrrhizic acid and its salt. Contained, particularly preferably 3 to 5 parts by weight. Within this range, the antioxidant, anti-inflammatory and analgesic effects of Kokukokukokuto extract can be synergistically increased, and the content of glycyrrhizic acid and salts thereof that cause side effects can be reduced.
ここで、グリチルリチン酸の塩としては、ナトリウムやカリウム等のアルカリ金属との塩;アンモニウム塩等が挙げられる。具体的にはグリチルリチン酸二ナトリウム、グリチルリチン酸三ナトリウム、グリチルリチン酸二カリウム、グリチルリチン酸三カリウム等のアルカリ金属との塩;グリチルリチン酸モノアンモニウム等のアンモニウム塩等が例示される。これらの中でも、好ましくはアルカリ金属との塩であり、より好ましくはグリチルリチン酸二カリウムが例示される。これらのグリチルリチン酸の塩は、1種単独で使用してもよく、また2種以上を任意に組み合わせて使用してもよい。 Here, examples of the salt of glycyrrhizic acid include salts with alkali metals such as sodium and potassium; ammonium salts and the like. Specific examples include salts with alkali metals such as disodium glycyrrhizinate, trisodium glycyrrhizinate, dipotassium glycyrrhizinate and tripotassium glycyrrhizinate; and ammonium salts such as monoammonium glycyrrhizinate. Among these, Preferably it is a salt with an alkali metal, More preferably, dipotassium glycyrrhizinate is illustrated. These glycyrrhizic acid salts may be used alone or in any combination of two or more.
独活葛根湯エキス中のグリチルリチン酸及びその塩、ならびにペオニフロリンの含有量は、以下の方法により測定される。
<グリチルリチン酸及びその塩の定量方法>
The content of glycyrrhizic acid and its salt, and paeoniflorin in Tokatsu Kakkonto extract is measured by the following method.
<Quantitative method of glycyrrhizic acid and its salt>
独活葛根湯エキス0.6gをメタノールで十分に抽出したのち、第十五改正日本薬局方解説書(生薬等)D−142−D−151頁「カンゾウ」の定量法に従い定量する。カラムはCOSMOSIL「5C18−MS−II」(内径4.6×150mm)を使用する。カラム温度20℃にて、移動相に、蒸留水とアセトニトリルとリン酸が850:150:1となる混合液を用い、紫外吸光光度計により232nmにおける吸光度を測定する。
<ペオニフロリンの定量方法>
After sufficiently extracting 0.6 g of Tokatsu Kakkonto extract with methanol, it is quantified according to the quantification method described in the 15th revised Japanese Pharmacopoeia Manual (herbal medicine, etc.), pages D-142 to D-151 “kanzo”. The column uses COSMOSIL “5C18-MS-II” (inner diameter 4.6 × 150 mm). At a column temperature of 20 ° C., the absorbance at 232 nm is measured with an ultraviolet absorptiometer using a mixture of distilled water, acetonitrile and phosphoric acid at 850: 150: 1 as the mobile phase.
<Quantification method of paeoniflorin>
独活葛根湯エキス0.6gをメタノールで十分に抽出したのち、第十五改正日本薬局方解説書(生薬等)D−324−D−329頁「シャクヤク」の定量法に従い定量する。カラムはCOSMOSIL「5C18−MS−II」(内径4.6×150mm)を使用する。カラム温度20℃にて、移動相に、蒸留水で15倍に希釈した酢酸とアセトニトリルが3:2となる混合液を用い、紫外吸光光度計により254nmにおける吸光度を測定する。 After sufficiently extracting 0.6 g of Dokatsu Kakkonto extract with methanol, it is quantified according to the quantification method described in the 15th revision Japanese Pharmacopoeia Manual (herbal medicine, etc.) D-324-D-329 “Rakuyaku”. The column uses COSMOSIL “5C18-MS-II” (inner diameter 4.6 × 150 mm). At a column temperature of 20 ° C., the absorbance at 254 nm is measured with an ultraviolet absorptiometer using a mixed solution of acetic acid and acetonitrile diluted 15-fold with distilled water as a mobile phase at a column temperature of 20 ° C.
該測定により、得られた独活葛根湯エキス中のグリチルリチン酸及びその塩の量、ならびにペオニフロリンの量を定量することができる。
(2)独活葛根湯エキス配合剤
本発明の独活葛根湯エキス配合剤は、独活葛根湯エキスを含有するものであって、グリチルリチン酸及びその塩の総量に対してペオニフロリンが一定以上の割合で含有されていることを特徴とする。
By this measurement, the amount of glycyrrhizic acid and its salt and the amount of paeoniflorin in the obtained Kokukokuto extract can be quantified.
(2) Dokatsu Kakkonto extract combination agent The Dokoku Kakkonto extract combination agent of the present invention contains Dokatsu Kakkonto extract, which contains paeoniflorin at a certain ratio or more with respect to the total amount of glycyrrhizic acid and its salt. It is characterized by being.
具体的には、本発明の独活葛根湯エキス配合剤は、グリチルリチン酸及びその塩の総量1重量部に対して、ペオニフロリンを0.5重量部以上で含有することを特徴とする。また、本発明の独活葛根湯エキス配合剤は、グリチルリチン酸及びその塩の総量1重量部に対して、ペオニフロリンを、好ましくは0.5〜50重量部含有し、より好ましくは0.5〜10重量部含有し、更に好ましくは3〜5重量部含有することを特徴とする。 Specifically, the sole active kakkonto extract compounding agent of the present invention is characterized by containing 0.5 parts by weight or more of paeoniflorin with respect to 1 part by weight of the total amount of glycyrrhizic acid and its salt. Moreover, the sole active kakkonto extract compounding agent of the present invention preferably contains 0.5-50 parts by weight of paeoniflorin, more preferably 0.5-10 parts per 1 part by weight of the total amount of glycyrrhizic acid and its salt. It is characterized by containing 3 parts by weight, more preferably 3-5 parts by weight.
グリチルリチン酸の塩としては、前述のものが挙げられる。また、独活葛根湯エキス配合剤中のグリチルリチン酸及びその塩の定量、ならびにペオニフロリンの定量は、前述の定量方法に従い、同様に実施される。 Examples of the glycyrrhizic acid salt include those described above. In addition, the quantification of glycyrrhizic acid and its salt and the quantification of paeoniflorin in Dokatsu Kakkonto extract compounding agent are carried out in the same manner according to the aforementioned quantification method.
本発明の独活葛根湯エキス配合剤に含まれるグリチルリチン酸及びその塩、ならびにペオニフロリンは、独活葛根湯エキスに含まれるもののみから構成されていてもよく、独活葛根湯エキスだけではグリチルリチン酸及びその塩、ならびにペオニフロリンの含有量が前述の一定以上の比率を充足していない場合、グリチルリチン酸及びその塩ならびにペオニフロリンを外添する等して、所定の配合比率となるように適宜調整すればよい。例えば、外添可能なものとして、グリチルリチン酸(和光純薬工業株式会社製)、グリチルチリン酸二カリウム(丸善製薬株式会社製)、ペオニフロリン(和光純薬工業株式会社製)などが商業的に入手可能である。 Glycyrrhizic acid and its salt, and paeoniflorin contained in the composition of the sole active kakkonto extract of the present invention, may be composed only of those contained in the sole active kakkonto extract. In addition, when the content of paeoniflorin does not satisfy the above-mentioned ratio, the glycyrrhizic acid and its salt and paeoniflorin may be appropriately adjusted so as to obtain a predetermined blending ratio. For example, glycyrrhizic acid (manufactured by Wako Pure Chemical Industries, Ltd.), dipotassium glycyrrhizinate (manufactured by Maruzen Pharmaceutical Co., Ltd.), paeoniflorin (manufactured by Wako Pure Chemical Industries, Ltd.), etc. are commercially available as those that can be externally added. It is.
好ましくは、本発明の独活葛根湯エキス配合剤におけるグリチルリチン酸やペオニフロリンは、独活葛根湯エキスに含まれるもののみで構成されており、より好ましくは、前記「(1)独活葛根湯エキス」に記載の独活葛根湯エキスに含まれるもののみで構成されている。 Preferably, glycyrrhizic acid and paeoniflorin in the combination agent of the Kokukokuto extract of the present invention are composed only of those contained in the Kakkonto extract, more preferably, described in the above “(1) Kakkonto extract”. It is composed only of those contained in the Kokukokuto extract.
本発明の独活葛根湯エキス配合剤における独活葛根湯エキスの配合量は、グリチルリチン酸及びその塩の総量ならびにペオニフロリンの量が、前記比率を充足することを限度として制限されない。 The blending amount of the sotsukatsu kekkonto extract in the soot kakkonto extract composition of the present invention is not limited as long as the total amount of glycyrrhizic acid and its salt and the amount of paeoniflorin satisfy the above ratio.
例えば、本発明の独活葛根湯エキス配合剤におけるグリチルリチン酸及びその塩の総量ならびにペオニフロリンが、前記「(1)独活葛根湯エキス」に記載の独活葛根湯エキスに含まれるもののみで構成される場合、該独活葛根湯エキスの配合割合は、本発明の効果が発揮されることを限度として制限されないが、例えば、配合剤中に、エキスの乾燥重量総量で10〜90重量%程度、好ましくは30〜80重量%程度、より好ましくは50〜70重量%程度が挙げられる。 For example, in the case where the total amount of glycyrrhizic acid and its salt and paeoniflorin in the combination agent of the sole active kakkonto extract of the present invention are composed only of those contained in the above-mentioned self-existing kakkonto extract described in “(1) the sole active kakkonto extract” The blending ratio of the self-existing kakkonto extract is not limited as long as the effect of the present invention is exerted. For example, the total dry weight of the extract in the compounding agent is about 10 to 90% by weight, preferably 30%. About 80 to 80 weight%, More preferably, about 50 to 70 weight% is mentioned.
また、例えば、独活葛根湯エキス配合剤中に、グリチルリチン酸及びその塩の乾燥重量総量で0.01〜10重量%程度、好ましくは0.1〜1重量%程度、より好ましくは0.1〜0.5重量%程度が挙げられる。 In addition, for example, in the Kokukatsu-Kento extract compounding agent, the total dry weight of glycyrrhizic acid and its salt is about 0.01 to 10% by weight, preferably about 0.1 to 1% by weight, more preferably 0.1 to 0.1% by weight. About 0.5% by weight can be mentioned.
また、本発明の独活葛根湯エキス配合剤におけるグリチルリチン酸及びその塩は、前述と同様に制限されないが、例えば大人一人(体重60kg)に対する投与量は、1日投与単位あたり、通常、乾燥重量換算で、例えば5〜15mg、好ましくは5〜10mg、より好ましくは7〜10mgが挙げられる。本発明によれば、この程度にまでグリチルリチン酸及びその塩の含有量を抑えることができるため、優れた抗酸化作用、抗炎症作用、鎮痛作用を有するだけでなく、グリチルリチン酸及びその塩に起因する副作用の少ない独活葛根湯エキス配合剤とすることができる。 In addition, glycyrrhizic acid and its salt in the combination composition of Kokukokuto extract of the present invention are not limited in the same manner as described above. For example, the dose for one adult (body weight 60 kg) is usually converted into dry weight per daily dosage unit. And, for example, 5 to 15 mg, preferably 5 to 10 mg, more preferably 7 to 10 mg. According to the present invention, since the content of glycyrrhizic acid and its salt can be suppressed to this extent, it not only has excellent antioxidant action, anti-inflammatory action and analgesic action, but also originates from glycyrrhizic acid and its salt Can be used as a combination agent of Kakkonto extract with less side effects.
本発明の独活葛根湯エキス配合剤の投与方法も前述と同様に制限されないが、通常一日2〜3回に分けて経口投与の形態で用いられる。服用時刻も特に制限されないが、食前または食間が好ましい。 The administration method of the sole active kakkonto extract combination agent of the present invention is not limited as described above, but it is usually used in the form of oral administration divided into 2 to 3 times a day. The dose time is not particularly limited, but is preferably before or between meals.
当然のことながら、本発明の独活葛根湯エキス配合剤における独活葛根湯エキスやグリチルリチン酸等の配合割合、投与量等は、後述する配合剤の投与形態、対象者への投与時間、個体差等に応じて、更に適宜設定することが可能である。 As a matter of course, the blending ratio, dosage, etc. of the solitary kakkonto extract, glycyrrhizic acid, etc. in the solitary kakkonto extract combination agent of the present invention are the dosage form of the compounding agent described later, the administration time to the subject, individual differences, etc. Further, it can be set as appropriate according to the above.
本発明の独活葛根湯エキス配合剤におけるグリチルリチン酸等が、前記「(1)独活葛根湯エキス」に記載の独活葛根湯エキス以外のものにも由来する場合、該配合剤は、前述の説明に基づき調製すればよい。該調製は、当業者であれば前述の説明に基づき当然に行い得る。 When the glycyrrhizic acid or the like in the composition of the sole active kakkonto extract of the present invention is derived from something other than the sole active kakkonto extract described in the above-mentioned “(1) the sole active kakkonto extract”, the combination agent is as described above. It may be prepared based on this. This preparation can be naturally performed by those skilled in the art based on the above description.
本発明の独活葛根湯エキス配合剤は、その形態は特に制限されず、経口投与可能な形態であれば制限されない。経口投与可能な形態としては、慣用の形態がいずれも含まれ、特に制限されない。このような形態として、例えば、錠剤、丸剤、散剤、細粒剤、顆粒剤、錠剤、カプセル剤(ソフトカプセルを含む)等の固形製剤;液剤(シロップ等を含む)等の液状製剤(懸濁剤含む)が例示される。好ましくは、本発明の独活葛根湯エキス配合剤は、摂取又は服用のしやすさの点から、固形製剤である。各種形態にある独活葛根湯エキス配合剤は、通常の方法に従い、製造される。 The form of the kokukokuto extract combination agent of the present invention is not particularly limited, and is not limited as long as it can be administered orally. The form that can be administered orally includes any conventional form and is not particularly limited. Examples of such forms include solid preparations such as tablets, pills, powders, fine granules, granules, tablets, capsules (including soft capsules); liquid preparations (suspensions) such as liquids (including syrups) Including the agent). Preferably, the sole active kakkonto extract combination agent of the present invention is a solid preparation from the viewpoint of ease of ingestion or taking. Independent Kakkonto extract compounding agents in various forms are produced according to ordinary methods.
本発明の独活葛根湯エキス配合剤が錠剤である場合、前述の独活葛根湯エキスとともに、薬学的に許容される担体として当該分野で従来公知のものを広く使用することができる。このような担体としては、例えば乳糖、白糖、塩化ナトリウム、ブドウ糖、尿素、デンプン、炭酸カルシウム、カオリン、ケイ酸、含水二酸化ケイ素等の賦形剤;水、エタノール、プロパノール、単シロップ、ブドウ糖液、デンプン液、ゼラチン溶液、カルボキシメチルセルロース、セラック、メチルセルロース、リン酸カリウム、ポリビニルピロリドン、結晶セルロース、ヒドロキシプロピルセルロース、ヒプロメロース、カルメロースカルシウム、アルギン酸ナトリウム等の結合剤;乾燥デンプン、カンテン末、ラミナラン末、炭酸水素ナトリウム、ポリオキシエチレンソルビタン脂肪酸エステル類、ラウリル硫酸ナトリウム、ステアリン酸モノグリセリド、デンプン、クロスポビドン、ポビドン、低置換度ヒドロキシプロピルセルロース等の崩壊剤;ステアリン、カカオバター、水素添加油等の崩壊抑制剤;第4級アンモニウム塩、ラウリル硫酸ナトリウム等の吸収促進剤;グリセリン等の保湿剤;デンプン、乳糖、カオリン、ベントナイト、コロイド状ケイ酸等の吸着剤;精製タルク、ステアリン酸マグネシウム、ステアリン酸塩、ホウ酸末、ポリエチレングリコール等の滑沢剤等を使用できる。 In the case where the solitary kakkonto extract compounding agent of the present invention is a tablet, a well-known carrier in the art can be widely used as a pharmaceutically acceptable carrier together with the above-described solitary kakkonto extract. Examples of such carriers include excipients such as lactose, sucrose, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, silicic acid, hydrous silicon dioxide; water, ethanol, propanol, simple syrup, glucose solution, Binders such as starch solution, gelatin solution, carboxymethylcellulose, shellac, methylcellulose, potassium phosphate, polyvinylpyrrolidone, crystalline cellulose, hydroxypropylcellulose, hypromellose, carmellose calcium, sodium alginate; dry starch, kanteng powder, laminaran powder, carbonic acid Sodium hydrogen, polyoxyethylene sorbitan fatty acid esters, sodium lauryl sulfate, monoglyceride stearate, starch, crospovidone, povidone, low substituted hydroxypropyl cellulose Disintegrating agents such as stearin, cocoa butter, hydrogenated oil, etc .; absorption accelerators such as quaternary ammonium salts and sodium lauryl sulfate; humectants such as glycerin; starch, lactose, kaolin, bentonite, colloidal Adsorbents such as silicic acid; lubricants such as purified talc, magnesium stearate, stearate, boric acid powder, and polyethylene glycol can be used.
さらに錠剤は、必要に応じ通常の剤皮を施した錠剤、例えば糖衣錠、ゼラチン被包錠、腸溶被錠、フィルムコーティング錠あるいは二重錠、多層錠とすることができる。 Further, the tablets can be made into tablets with ordinary coatings as necessary, for example, sugar-coated tablets, gelatin-encapsulated tablets, enteric-coated tablets, film-coated tablets, double tablets, and multilayer tablets.
また、本発明の独活葛根湯エキス配合剤を丸剤とする場合も、薬学的に許容される担体として当該分野で従来公知のものを広く使用できる。このような担体としては、例えばブドウ糖、乳糖、デンプン、カカオ脂、硬化植物油、カオリン、タルク等の賦形剤、アラビアゴム末、トラガント末、ゼラチン、エタノール等の結合剤、ラミナラン、カンテン等の崩壊剤等を使用できる。 Moreover, also when using the independent active kakkonto extract compounding agent of this invention as a pill, a conventionally well-known thing can be widely used in the said field | area as a pharmaceutically acceptable carrier. Examples of such carriers include glucose, lactose, starch, cacao butter, hydrogenated vegetable oil, kaolin, talc and other excipients, gum arabic powder, tragacanth powder, gelatin, ethanol and other binders, laminaran, agar, etc. Agents can be used.
また、上記以外に、添加剤として、例えば、薬学的に許容される界面活性剤、吸収促進剤、吸着剤、充填剤、防腐剤、安定剤、乳化剤、可溶化剤、浸透圧を調節する塩を、調製する形態に応じて適宜選択し使用することができる。 In addition to the above, as additives, for example, pharmaceutically acceptable surfactants, absorption promoters, adsorbents, fillers, preservatives, stabilizers, emulsifiers, solubilizers, salts that regulate osmotic pressure Can be appropriately selected and used depending on the form to be prepared.
また、前述の独活葛根湯エキスと前述の薬学的に許容される担体を、さらにゼラチン、プルラン、デンプン、アラビアガム、ヒプロメロース等を原料とする従来公知のカプセルに充填して、カプセル剤とすることができる。 Moreover, the above-mentioned Kokukokuto extract and the above-mentioned pharmaceutically acceptable carrier are further filled into a conventionally known capsule made of gelatin, pullulan, starch, gum arabic, hypromellose, etc., to form a capsule. Can do.
更に、本発明の独活葛根湯エキス配合剤には、上記以外にアミノ酸、ビタミン類、無機塩類等の他の活性成分を含有させることができる。他の活性成分としては、例えば、バリン、ロイシン、イソロイシン、トレオニン、メチオニン、フェニルアラニン、トリプトファン、リジン、グリシン、アラニン、アスパラギン、グルタミン、セリン、システイン、シスチン、チロシン、プロリン、ヒドロキシプロリン、アスパラギン酸、グルタミン酸、ヒドロキシリジン、アルギニン、オルニチン、ヒスチジン等のアミノ酸;ビタミンA1、ビタミンA2、カロチン、リコピン(プロビタミンA)、ビタミンB6、ビタミンB1、ビタミンB2、アスコルビン酸、ニコチン酸アミド、ビオチン等のビタミン類;塩化ナトリウム、塩化カリウム等のアルカリ金属塩や、クエン酸塩、酢酸塩、リン酸塩等の無機塩類が例示される。 Furthermore, in addition to the above, other active ingredients such as amino acids, vitamins, inorganic salts and the like can be contained in the composition of the independent kakkonto extract of the present invention. Examples of other active ingredients include valine, leucine, isoleucine, threonine, methionine, phenylalanine, tryptophan, lysine, glycine, alanine, asparagine, glutamine, serine, cysteine, cystine, tyrosine, proline, hydroxyproline, aspartic acid, glutamic acid , Amino acids such as hydroxylysine, arginine, ornithine, histidine; vitamins such as vitamin A1, vitamin A2, carotene, lycopene (provitamin A), vitamin B6, vitamin B1, vitamin B2, ascorbic acid, nicotinamide, biotin; Examples thereof include alkali metal salts such as sodium chloride and potassium chloride, and inorganic salts such as citrate, acetate and phosphate.
本発明の独活葛根湯エキス配合剤においては、グリチルリチン酸及びその塩が有する抗酸化作用、抗炎症作用、鎮痛作用が相乗的に高められている。このため、本発明の独活葛根湯エキス配合剤を投与(摂取)することにより、顕著に効率よく、肩こり、寝違え、四十肩、五十肩等の疾患を迅速且つ効果的に軽減乃至解消することができる。特に、寝違えは、通常の肩こり等に比べて炎症の程度が高いが、本発明の独活葛根湯エキス配合剤は、このような高度な炎症の軽減乃至解消に対しても十分に有効であり、更に即効性を備えている。 In the independent kakkonto extract combination agent of the present invention, the antioxidant action, anti-inflammatory action and analgesic action of glycyrrhizic acid and its salts are synergistically enhanced. For this reason, administration (ingestion) of the self-existing Kakkonto extract combination agent of the present invention can remarkably and efficiently reduce or eliminate diseases such as stiff shoulders, falling asleep, forty shoulders and fifty shoulders. it can. In particular, while lying down has a high degree of inflammation compared to normal shoulder stiffness etc., the self-existing kakkonto extract combination agent of the present invention is sufficiently effective for reducing or eliminating such advanced inflammation, Furthermore, it has immediate effect.
従って、本発明の独活葛根湯エキス配合剤は、肩こり、寝違え、四十肩、五十肩等の疾患を患っている患者に好適に適用でき、従来公知の製剤等より有効である。 Therefore, the independent kakkonto extract combination agent of the present invention can be suitably applied to patients suffering from diseases such as stiff shoulders, falling asleep, forty shoulders and fifty shoulders, and is more effective than conventionally known preparations.
また、本発明の独活葛根湯エキス配合剤では、グリチルリチン酸及びその塩の抗酸化作用、抗炎症作用、鎮痛作用が相乗的に高められていることから、グリチルリチン酸の過剰摂取による副作用を効果的に防止することができ、すなわち安全性が高い。 In addition, the combination drug of Kakkonto extract of the present invention synergistically enhances the antioxidant action, anti-inflammatory action, and analgesic action of glycyrrhizic acid and its salts, so that side effects due to excessive intake of glycyrrhizic acid are effective. Can be prevented, that is, the safety is high.
以下、実施例を挙げて本発明を説明するが、本発明はこれに限定されるものではない。
実施例:独活葛根湯エキス配合剤
本実施例において使用する独活葛根湯エキス配合剤を以下のようにして製造した。
EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated, this invention is not limited to this.
Example: Independent Kakkonto extract combination agent The Independent Kakkonto extract combination agent used in this example was produced as follows.
1.独活葛根湯エキス
本実施例において、原料乾燥重量に換算して、カッコン2.5(重量部、以下同じ)、ケイヒ1.5、シャクヤク1.5、マオウ1.0、ドクカツ1.0、ショウキョウ0.5、ジオウ2.0、タイソウ0.5、カンゾウ0.5を、水10倍量を用いて約100℃で1時間抽出し、遠心分離して抽出液を得た。得られた抽出液をろ過(150メッシュ)した後、65℃の減圧下で濃縮後、スプレードライを用いて乾燥し、「独活葛根湯エキス」を取得した。
1. Independence kakkonto extract In this example, in terms of the raw material dry weight, Kakonkon 2.5 (parts by weight, the same applies hereinafter), Keihi 1.5, Peonies 1.5, Maow 1.0, Dokkatsu 1.0, Show Kyo 0.5, Zhi 2.0, Tiso 0.5, and Liquorice 0.5 were extracted with 10 times the amount of water at about 100 ° C. for 1 hour, and centrifuged to obtain an extract. The obtained extract was filtered (150 mesh), concentrated under reduced pressure at 65 ° C., and then dried using spray drying to obtain “Kokukatsu Kakkonto extract”.
2.独活葛根湯エキス中のグリチルリチン酸及びペオニフロリンの含有量
得られた独活葛根湯エキスに含まれるグリチルリチン酸及びその塩とペオニフロリンの量を以下の方法に従い測定した。
<グリチルリチン酸及びその塩の定量方法>
2. Content of glycyrrhizic acid and paeoniflorin in Tokatsu Kakkonto extract The amounts of glycyrrhizic acid, its salt and paeoniflorin contained in the souped Kakkonto extract obtained were measured according to the following method.
<Quantitative method of glycyrrhizic acid and its salt>
得られた独活葛根湯エキス0.6gをメタノールで十分に抽出したのち、第十五改正日本薬局方解説書(生薬等)D−142−D−151頁「カンゾウ」の定量法に従い定量した。 After sufficiently extracting 0.6 g of the resulting Kokuketsuto extract with methanol, it was quantified according to the quantification method described in the 15th revised Japanese Pharmacopoeia Manual (herbal medicines, etc.) D-142-D-151 “kanzo”.
カラムはCOSMOSIL「5C18−MS−II」(内径4.6×150mm)(ナカライテスク株式会社製)を使用した。 As the column, COSMOSIL “5C18-MS-II” (inner diameter 4.6 × 150 mm) (manufactured by Nacalai Tesque Co., Ltd.) was used.
カラム温度20℃にて、移動相に、蒸留水とアセトニトリル(和光純薬工業株式会社製)とリン酸(和光純薬工業株式会社製)が850:150:1となる混合液を用い、紫外吸光光度計(株式会社島津製作所製)により232nmにおける吸光度を測定した。
<ペオニフロリンの定量方法>
得られた独活葛根湯エキス0.6gをメタノールで十分に抽出したのち、第十五改正日本薬局方解説書(生薬等)D−324−D−329頁「シャクヤク」の定量法に従い定量した。
At a column temperature of 20 ° C., a mixed liquid in which distilled water, acetonitrile (manufactured by Wako Pure Chemical Industries, Ltd.) and phosphoric acid (manufactured by Wako Pure Chemical Industries, Ltd.) are 850: 150: 1 is used as the mobile phase, and ultraviolet rays are used. Absorbance at 232 nm was measured with an absorptiometer (manufactured by Shimadzu Corporation).
<Quantification method of paeoniflorin>
After 0.6 g of the obtained Kokukokuto extract obtained was sufficiently extracted with methanol, it was quantified according to the quantification method described in the 15th revised Japanese Pharmacopoeia Manual (herbal medicine, etc.) D-324-D-329 “Rakuyaku”.
カラムはCOSMOSIL「5C18−MS−II」(内径4.6×150mm)(ナカライテスク株式会社製)を使用した。 As the column, COSMOSIL “5C18-MS-II” (inner diameter 4.6 × 150 mm) (manufactured by Nacalai Tesque Co., Ltd.) was used.
カラム温度20℃にて、移動相に、蒸留水で15倍に希釈した酢酸(和光純薬工業株式会社製)とアセトニトリル(和光純薬工業株式会社製)が3:2となる混合液を用い、紫外吸光光度計(株式会社島津製作所製)により254nmにおける吸光度を測定した。
<グリチルリチン酸及びその塩及びペオニフロリンの含有量の調整>
At a column temperature of 20 ° C., a mixed solution in which acetic acid (manufactured by Wako Pure Chemical Industries, Ltd.) and acetonitrile (manufactured by Wako Pure Chemical Industries, Ltd.) diluted 15 times with distilled water is used as the mobile phase is 3: 2. The absorbance at 254 nm was measured with an ultraviolet absorptiometer (manufactured by Shimadzu Corporation).
<Adjustment of content of glycyrrhizic acid and its salt and paeoniflorin>
得られた独活葛根湯エキス中のグリチルリチン酸及びその塩並びにペオニフロリンを上述の方法で定量したうえで、抽出量が少ない場合には細かく刻み、また抽出量が多い場合には粗く刻むなどして目的とする含有量を得た。
3.独活葛根湯エキス配合剤
ここでは、錠剤の形態の独活葛根湯エキス配合剤を製造した。
After quantifying glycyrrhizic acid and its salt and paeoniflorin in the resulting Kokuketsu-to extract by the above method, finely chop when the extraction amount is small, or chop coarsely when the extraction amount is large Was obtained.
3. Tokatsu Kakkonto extract combination agent Here, a kokukokuto extract combination agent in the form of a tablet was produced.
具体的には、前述のようにして得た独活葛根湯エキス、含水二酸化ケイ素(カープレックス、DSL.ジャパン株式会社製)、カルメロースカルシウム(E.C.G-505、父リン化学工業株式会社製)、タルク(タルク原末「マルイシ」、丸石製薬(株))、ステアリン酸マグネシウム(日本薬局方 ステアリン酸マグネシウム、太平化学産業株式会社製)、結晶セルロース(セオラス、旭化成ケミカルズ株式会社製)を混合することにより、混合物を得た。このようにして得た混合物を油圧打錠機を用いて打錠して、錠剤の形態の独活葛根湯エキス配合剤を得た。
試験例1:抗酸化能測定試験
本試験例では、グリチルリチン酸及びペオニフロリンの抗酸化効果を評価した。
Specifically, the self-existing Kakkonto extract obtained as described above, hydrous silicon dioxide (Carplex, manufactured by DSL Japan Co., Ltd.), carmellose calcium (ECG-505, manufactured by Father Lin Chemical Industry Co., Ltd.), talc (By mixing talc raw powder “Marushi”, Maruishi Pharmaceutical Co., Ltd.), magnesium stearate (Japanese Pharmacopoeia Magnesium Stearate, Taihei Chemical Sangyo Co., Ltd.), crystalline cellulose (Theolas, Asahi Kasei Chemicals Co., Ltd.) A mixture was obtained. The mixture thus obtained was tableted using a hydraulic tableting machine to obtain an independent kakkonto extract formulation in tablet form.
Test Example 1: Antioxidant Capacity Measurement Test In this test example, the antioxidant effect of glycyrrhizic acid and paeoniflorin was evaluated.
グリチルリチン酸及びペオニフロリンとして、それぞれ日本薬局方標準品であるグルチルリチン酸標準品とペオニフロリン標準品を使用した。また、抗酸化の測定には、抗酸化測定TAS(Total Antioxidant Status)キット(Randox Laboratories Ltd製)を用いた。測定は、当該キットに含まれるマニュアルに従い行った。 As glycyrrhizic acid and paeoniflorin, a Japanese pharmacopoeia standard product, a glycyrrhizic acid standard product and a paeoniflorin standard product were used, respectively. For the measurement of antioxidant, an antioxidant measurement TAS (Total Antioxidant Status) kit (manufactured by Randox Laboratories Ltd) was used. The measurement was performed according to the manual included in the kit.
具体的には、下記の表1に示す量のグリチルリチン酸及びペロニフロリンを含有するように調製した20μlの水溶液(サンプル)をクロモゲン1mlに混合し、37℃でインキュベートし、初期吸光度A1を測定した。その後、当該キットに含まれる基質溶液200μLを添加し、よく混合し、3分後に吸光度A2を測定した。 Specifically, 20 μl of an aqueous solution (sample) prepared so as to contain the amounts of glycyrrhizic acid and peroniflorin shown in Table 1 below was mixed with 1 ml of chromogen, incubated at 37 ° C., and the initial absorbance A1 was measured. Thereafter, 200 μL of the substrate solution contained in the kit was added, mixed well, and the absorbance A2 was measured after 3 minutes.
ブランク及びスタンダードにおける測定は、それぞれ、サンプルに代えて、キットに含まれるブランク試薬又はスタンダードを使用する以外は、前述と同様の手順で行った。 Measurements in the blank and standard were performed in the same procedure as described above, except that the blank reagent or standard included in the kit was used instead of the sample.
抗酸化能は以下の式に従って算出した。
A2−A1=△A (ブランク/スタンダード/サンプル)
The antioxidant capacity was calculated according to the following formula.
A2-A1 = ΔA (Blank / Standard / Sample)
mmol/l=Factor×(△Aブランク−△Aサンプル)
また、「抗酸化効果」は以下の式に従って算出した。
mmol / l = Factor × (ΔA blank−ΔA sample)
The “antioxidant effect” was calculated according to the following formula.
また、「ペオニフロリンの配合量当たりの抗酸化効果」を、以下の式に従って算出した。 The “antioxidant effect per blended amount of paeoniflorin” was calculated according to the following formula.
結果を以下の表1に示す。 The results are shown in Table 1 below.
この結果から明らかなように、抗酸化作用を備えているグリチルリチン酸に(比較例1)、抗酸化作用を殆ど備えていないペオニフロリン(比較例2)を組み合わせることにより、驚くべきことに、その抗酸化効果が相乗的に高まった。 As is clear from this result, surprisingly, by combining peonyflorin (Comparative Example 2) having almost no antioxidant action with glycyrrhizic acid having an antioxidant action (Comparative Example 1) The oxidation effect increased synergistically.
具体的には、グリチルリチン酸とペオニフロリンとの配合比率が重量換算で1:0.5以上において抗酸化効果が効率よく増強されており、1:50であっても効率よく増強されていることがわかった(実施例1〜9)。 Specifically, the antioxidant effect is efficiently enhanced when the blending ratio of glycyrrhizic acid and paeoniflorin is 1: 0.5 or more in terms of weight, and even when it is 1:50, it is efficiently enhanced. Okay (Examples 1-9).
また、抗酸化効果を一層効率よく相乗的に増強できる点で、グリチルリチン酸とペオニフロリンの配合比率は、好ましくは1:0.5〜1:10であり(実施例1〜7)、より好ましくは1:3〜1:5であることがわかった(実施例4〜6)。
試験例2:鎮痛試験(酢酸ライジング試験:炎症性疼痛モデル)
本試験例では、鎮痛試験(酢酸ライジング試験)を行った。
In addition, the blending ratio of glycyrrhizic acid and paeoniflorin is preferably 1: 0.5 to 1:10 (Examples 1 to 7), more preferably, in that the antioxidant effect can be enhanced more efficiently and synergistically. It was found to be 1: 3 to 1: 5 (Examples 4 to 6).
Test Example 2: Analgesia test (acetic acid rising test: inflammatory pain model)
In this test example, an analgesic test (acetic acid rising test) was performed.
モデルとして、5週齢の雄性ddyマウス(日本エスエルシー株式会社より購入)を使用した。試験には、18時間絶食させたマウス(6週齢)を1群6匹として用いた。 As a model, a 5-week-old male ddy mouse (purchased from Nippon SLC Co., Ltd.) was used. In the test, mice (6 weeks old) fasted for 18 hours were used as 6 mice per group.
具体的には、グリチルリチン酸とペオニフロリンとが、下記表2における実施例又は比較例に示す比率(1:0.48、1:2.1及び1:4.3)になるように調製した独活葛根湯エキス配合剤を前述の通りにして得た。得られた配合剤(サンプル)をすり潰し、蒸留水1mlに混合し、前記マウスに胃ゾンデを用いて経口投与した(投与量は表2に記載のとおりであり、マウスの体重に基づいて算出した)。経口投与の45分後に、0.7%の酢酸水溶液を腹腔内投与し、5分間放置した。その後、15分間中に観察されたライジングの数を測定した。サンプルに代えて蒸留水のみを与えたマウスを無処理(参考例1)とした。 Specifically, the sole activity prepared such that glycyrrhizic acid and paeoniflorin are in the ratios (1: 0.48, 1: 2.1 and 1: 4.3) shown in the Examples or Comparative Examples in Table 2 below. The kakkonto extract compounding agent was obtained as described above. The obtained compounding agent (sample) was crushed, mixed with 1 ml of distilled water, and orally administered to the mouse using a stomach tube (the dose was as shown in Table 2 and calculated based on the body weight of the mouse). ). 45 minutes after oral administration, 0.7% acetic acid aqueous solution was intraperitoneally administered and left for 5 minutes. The number of risings observed during 15 minutes was then measured. Mice that received only distilled water instead of the sample were not treated (Reference Example 1).
鎮痛効果は以下の式に従って算出した。 The analgesic effect was calculated according to the following formula.
結果を表2に示す。 The results are shown in Table 2.
本試験例では、前記試験例1における実施例1〜9のグリチルリチン酸とペオニフロリンとの配合比率の代表例として、グリチルリチン酸とペオニフロリンとの配合比率が実施例10及び11になるように調製した独活葛根湯エキス配合剤のサンプルを使用した。 In this test example, as a representative example of the blending ratio of glycyrrhizic acid and paeoniflorin of Examples 1 to 9 in Test Example 1, the sole activity prepared so that the blending ratio of glycyrrhizic acid and paeoniflorin was Examples 10 and 11 A sample of Kakkonto extract formulation was used.
この結果から、グリチルリチン酸に対してペオニフロリンを一定以上の比率で含有する実施例10及び実施例11では、無処理群(参考例1)及び該比率を充足しない比較例3と比較して、ライジング回数が顕著に低減されたことがわかった。すなわち、グリチルリチン酸に対してペオニフロリンを一定以上の割合で組み合わせて使用することにより、その鎮痛効果が相乗的に増強されていることがわかった。また、その効果の即効性も確認された。 From these results, in Example 10 and Example 11 containing paeoniflorin in a ratio of a certain amount or more with respect to glycyrrhizic acid, as compared with the untreated group (Reference Example 1) and Comparative Example 3 which does not satisfy the ratio, Rising It was found that the number of times was significantly reduced. That is, it was found that the analgesic effect was synergistically enhanced by using paeoniflorin in combination with a certain ratio or more with respect to glycyrrhizic acid. Moreover, the immediate effect of the effect was confirmed.
通常、炎症の増幅は、細胞内の転写因子が、過剰の活性酸素種によるシグナルで活性化され、炎症性サイトカインのmRNAの発現が増大することにより生じる。本試験例では、グリチルリチン酸に対してペオニフロリンを一定以上の割合で含有させることに起因する、グリチルリチン酸及びペオニフロリンによる抗酸化作用の相乗的な増強により、抗炎症作用及び鎮痛作用が顕著に増強されていることが確認できた。
試験例3:自覚症状試験
本試験例では、自覚症状の改善について評価した。
Inflammation amplification usually occurs when intracellular transcription factors are activated by signals from excess reactive oxygen species, resulting in increased expression of inflammatory cytokine mRNA. In this test example, the anti-inflammatory action and analgesic action were remarkably enhanced by the synergistic enhancement of the antioxidant action by glycyrrhizic acid and paeoniflorin resulting from the inclusion of paeoniflorin at a certain ratio or more with respect to glycyrrhizic acid. It was confirmed that
Test Example 3: Subjective Symptom Test In this test example, improvement of subjective symptoms was evaluated.
本試験例では、寝違えによる痛みを有する患者12名を被験者とした。該被験者を6名ずつの2群に分け、一方の群を独活葛根湯エキス配合剤(サンプル)を投与する「サンプル投与群」、他方の群をサンプルを投与しない「サンプル非投与群」とした。 In this test example, 12 patients who had pain due to falling asleep were used as subjects. The test subjects were divided into two groups of 6 persons, one group being a “sample administration group” in which the independent kakkonto extract formulation (sample) was administered, and the other group being a “sample non-administration group” in which no sample was administered. .
サンプルとして、グリチルリチン酸とペオニフロリンとが下記表3の実施例12に示す比率(1:4.3)になるように調製した独活葛根湯エキス配合剤を前述の通りにして得た。 As a sample, an independent kakkonto extract compounding agent prepared so that glycyrrhizic acid and paeoniflorin had a ratio (1: 4.3) shown in Example 12 of Table 3 below was obtained as described above.
サンプルにおけるグリチルリチン酸及びペオニフロリンの1日投与量は、表3の実施例12に示す通りであり、具体的には、1日分のサンプル12錠を3回に分けて、食間に服用させる方法で行った(1回4錠投与した)。 The daily doses of glycyrrhizic acid and paeoniflorin in the sample are as shown in Example 12 of Table 3. Specifically, the daily sample of 12 tablets is divided into three times and taken between meals. (4 tablets were administered once).
サンプル投与群では、疼痛の程度を、サンプル服用前及び服用開始から24時間後に検査した。サンプル非投与群では、疼痛の程度を、サンプル投与群の測定時にあわせて検査した。 In the sample administration group, the degree of pain was examined before taking the sample and 24 hours after the start of taking the sample. In the sample non-administered group, the degree of pain was examined together with the measurement of the sample administered group.
疼痛の程度は、服用前の疼痛を10として、VisualAnalogueScale(以下VASと記載する)アンケートに記入させることにより検査した。 The degree of pain was examined by filling in a Visual Analogue Scale (hereinafter referred to as VAS) questionnaire with 10 as the pain before taking.
結果を以下の表3に示す。 The results are shown in Table 3 below.
本試験例においても、前記試験例1における実施例1〜9のグリチルリチン酸とペオニフロリンとの配合比率の代表例として、グリチルリチン酸とペオニフロリンとの配合比率が実施例12になるように調製した独活葛根湯エキス配合剤のサンプルを使用した。 Also in this test example, as a representative example of the blending ratio of glycyrrhizic acid and paeoniflorin of Examples 1 to 9 in Test Example 1, the independent kuzukuri prepared so that the blending ratio of glycyrrhizic acid and paeoniflorin becomes Example 12. A sample of hot water extract formulation was used.
この結果から、実施例12に記載のサンプルを服用させることにより、顕著に優れた疼痛軽減効果が確認された。また、その効果の即効性も確認された。 From this result, by taking the sample described in Example 12, a markedly excellent pain reduction effect was confirmed. Moreover, the immediate effect of the effect was confirmed.
このように、肩こりよりも炎症の程度が高い寝違えにおいても疼痛の軽減が確認できたことから、グリチルリチン酸に対してペオニフロリンを一定以上の割合で組み合わせた場合には、これまでにない顕著に優れた抗炎症作用及び鎮痛効果が発揮されることが分かった。
処方例
下記表4〜7に処方例1〜28を示す。各処方例における独活葛根湯エキス配合剤の製造は以下の通りである。
In this way, it was confirmed that pain was reduced even when sleeping with a higher degree of inflammation than stiff shoulders, so when paeoniflorin was combined with glycyrrhizic acid at a certain ratio or more, it was significantly better than ever It was found that anti-inflammatory action and analgesic effect were exhibited.
Formulation Examples Formulation Examples 1 to 28 are shown in Tables 4 to 7 below. Manufacture of Kokukokuto extract formulation in each formulation example is as follows.
グリチルリチン酸及びペオニフロリンが以下の含有量である独活葛根湯エキスを前述の通りにして得た。得られたエキス(a)〜(g)を用いて、常法により、処方例1〜14で錠剤、処方例15〜28で顆粒剤を製した。これらの製剤についても試験例3と同様の試験を実施したところ、優れた疼痛軽減効果が確認された。また、その効果の即効性も確認された。 An independent Kakkonto extract having the following contents of glycyrrhizic acid and paeoniflorin was obtained as described above. Using the obtained extracts (a) to (g), tablets were prepared according to Formulation Examples 1 to 14 and granules were prepared according to Formulation Examples 15 to 28 by a conventional method. When these preparations were also tested in the same manner as in Test Example 3, an excellent pain reduction effect was confirmed. Moreover, the immediate effect of the effect was confirmed.
エキス(a) グリチルリチン酸:5.0mg/g
ペオニフロリン :5.0mg/g
エキス(b) グリチルリチン酸:5.0mg/g
ペオニフロリン:10.0mg/g
エキス(c) グリチルリチン酸:5.0mg/g
ペオニフロリン:15.0mg/g
エキス(d) グリチルリチン酸:5.0mg/g
ペオニフロリン:20.0mg/g
エキス(e) グリチルリチン酸:5.0mg/g
ペオニフロリン:25.0mg/g
エキス(f) グリチルリチン酸:5.0mg/g
ペオニフロリン:35.0mg/g
エキス(g) グリチルリチン酸:5.0mg/g
ペオニフロリン:50.0mg/g
Extract (a) Glycyrrhizic acid: 5.0 mg / g
Paeoniflorin: 5.0mg / g
Extract (b) Glycyrrhizic acid: 5.0 mg / g
Paeoniflorin: 10.0mg / g
Extract (c) Glycyrrhizic acid: 5.0 mg / g
Paeoniflorin: 15.0mg / g
Extract (d) Glycyrrhizic acid: 5.0 mg / g
Paeoniflorin: 20.0mg / g
Extract (e) Glycyrrhizic acid: 5.0 mg / g
Paeoniflorin: 25.0mg / g
Extract (f) Glycyrrhizic acid: 5.0 mg / g
Paeoniflorin: 35.0mg / g
Extract (g) Glycyrrhizic acid: 5.0 mg / g
Paeoniflorin: 50.0mg / g
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CN103494900A (en) * | 2013-10-17 | 2014-01-08 | 刘运波 | Traditional Chinese medicine for treating stiff neck |
JP2019006697A (en) * | 2017-06-22 | 2019-01-17 | 小林製薬株式会社 | Active oxygen scavenger |
US11291624B2 (en) | 2018-07-30 | 2022-04-05 | Conopco, Inc. | Compositions comprising active botanical ingredients |
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
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CN103494900A (en) * | 2013-10-17 | 2014-01-08 | 刘运波 | Traditional Chinese medicine for treating stiff neck |
JP2019006697A (en) * | 2017-06-22 | 2019-01-17 | 小林製薬株式会社 | Active oxygen scavenger |
US11291624B2 (en) | 2018-07-30 | 2022-04-05 | Conopco, Inc. | Compositions comprising active botanical ingredients |
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