JP6008466B2 - Mood disorder improving agent - Google Patents
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Description
本発明は、ハマウツボ科のオニクの抽出物を含有する気分障害改善剤に関する。 [Technical Field] The present invention relates to a mood disorder ameliorating agent containing an extract of a crocodile family onyc.
近年、気分障害に悩む人の数が増加している。また、仮面うつ病とも呼ばれる精神症状が表に出ないものまで含めると、その患者数は非常に多く、日本人の5人に一人は一生のうちで一度は気分障害を経験すると言われている。 In recent years, the number of people suffering from mood disorders has increased. In addition, the number of patients with psychological symptoms, also known as masked depression, is very large, and it is said that one out of five Japanese people will experience mood disorders once in their lifetime. .
気分障害の一つとしてうつ病があり、その原因は様々ではっきりとわかっていないのが現状である。生物学的要因、性格的要因に限らず、現代の社会環境の激しい変化、弱者切捨ての社会構造、少子高齢化などによる家庭環境の変化もうつ病患者増加と無縁ではないと考えられる。 Depression is one of the mood disorders, and the causes are various and are not clearly understood. It is not limited to biological factors and personality factors, but changes in the modern social environment, the social structure of cutting down the weak, and changes in the home environment due to the declining birthrate and aging, etc.
うつ病の治療としては、まず休養が勧められ、次いで薬物治療が併用されることが一般的である。しかしながら、現実には十分な休養等をとることが難しく、抗うつ薬などの薬物治療のみに頼ってしまうことが少なくない。 As a treatment for depression, rest is generally recommended, followed by drug therapy. However, in reality, it is difficult to take sufficient rest, and it is often the case that only pharmacotherapy such as antidepressants is used.
抗うつ薬は、うつ病を中心とした気分障害の治療を目的として、使用される頻度の高い薬剤である。三環系抗うつ薬や四環系抗うつ薬に比べれば適用が広く、安全性も高いという理由からSSRI(選択的セロトニン再取り込み阻害薬)やSNRI(セロトニン・ノルアドレナリン再取り込み阻害薬)が多く用いられているが、頭痛、下痢、口渇、排尿困難や血圧低下などの副作用が依然として報告されており、より副作用が少なく安全性の高い抗うつ剤の開発が期待されている。 Antidepressants are drugs that are frequently used for the treatment of mood disorders centered on depression. There are many SSRIs (selective serotonin reuptake inhibitors) and SNRIs (serotonin / noradrenaline reuptake inhibitors) because they are more applicable and safer than tricyclic antidepressants and tetracyclic antidepressants Although it has been used, side effects such as headache, diarrhea, dry mouth, difficulty in urinating and lowering blood pressure are still reported, and development of safer antidepressants with fewer side effects is expected.
一方、天然物の抽出物を用いてストレス負荷した動物の肉体的機能亢進を明らかにした報告は多い。例えば、ストレス負荷したマウスでは、性行動と学習記憶行動が低下することが認められている。そこで、ハマウツボ科のニクジュヨウ(別名:ホンオニク、学名:Cistanche salsa)から抽出した抽出物をストレス負荷したマウスに投与すると、これらの機能が改善することが明らかになっている(特許文献1及び2)。しかし、これらの実験結果は明らかな肉体疲労に起因する行動障害の改善を見たものであり、自発運動や探索運動の低下を引き起こす気分障害(精神疲労)の改善は評価されていない。 On the other hand, there have been many reports that have revealed physical enhancement of animals stressed using natural product extracts. For example, it is recognized that sexual behavior and learning / memory behavior decline in a stress-loaded mouse. Thus, it has been clarified that these functions are improved when an extract extracted from the crested crabs (aka Honku, scientific name: Cistanche salsa) is administered to a stress-loaded mouse (Patent Documents 1 and 2). . However, these experimental results look at the improvement of behavioral disorder caused by obvious physical fatigue, and the improvement of mood disorder (mental fatigue) that causes a decrease in spontaneous movement and exploratory movement has not been evaluated.
また、ハマウツボ科のオニク(学名:Boschniakia rossica)は、ニクジュヨウの代用品として、肉体疲労の改善や滋養強壮を目的に使用されてきた。しかし、これまでに気分障害(精神疲労)の改善や抗うつ作用を目的に研究開発されたことはなかった。 In addition, Onyaku (Boschniakia rossica) of the Amaranthaceae family has been used for the purpose of improving physical fatigue and nourishing tonic as a substitute for Japanese horsetail. However, there has never been research and development aimed at improving mood disorders (mental fatigue) or antidepressant action.
本発明は、うつ状態(抑うつ気分)の改善作用を有する気分障害改善剤を提供することを目的とする。 An object of this invention is to provide the mood disorder improving agent which has the effect | action of a depression state (depressed mood).
本発明者らは、鋭意検討した結果、マウスに絶望感を与えて不動時間を指標とし、自発運動や探索運動の低下状態の改善を評価する試験において、ハマウツボ科のオニク(Boschniakia rossica)の抽出物にその改善効果(気分障害改善作用、抗うつ作用)を見出した。 As a result of intensive studies, the present inventors extracted Boschniakia rossica in a test for giving an impression of despair to mice and using immobility time as an index to evaluate the improvement of the reduced state of spontaneous movement and exploratory movement. The improvement effect (feeling disorder improvement action, antidepressant action) was found to the thing.
すなわち、本発明は、以下の通りである。
1.ハマウツボ科のオニク(Boschniakia rossica)の抽出物を含有する気分障害改善剤。
2.抑うつ気分改善剤である、前記項1の気分障害改善剤。
That is, the present invention is as follows.
1. A mood disorder improving agent containing an extract of Boschniakia rossica.
2. The mood disorder improving agent according to Item 1, which is an agent for improving depression.
本発明の気分障害改善剤は、気分障害において、とりわけ抑うつ気分を改善することができる。 The mood disorder improving agent of the present invention can particularly improve depressed mood in mood disorders.
以下、本発明について説明する。
(1)気分障害
気分障害とは、躁鬱病及び感情障害等と呼ばれる一群の精神疾患である。
The present invention will be described below.
(1) Mood disorders Mood disorders are a group of mental disorders called manic depression and emotional disorders.
本発明における気分障害とは、特に、ある程度の期間にわたって持続する気分(感情)の変調により、苦痛を感じたり、日常生活に何らかの支障をきたしたりする状態のことをいう。その気分障害の症状としては、例えば、喜怒哀楽の感情表出の異常;憂鬱感、悲壮感、罪責感及び絶望感等の抑うつ気分;精神運動制止;不安焦燥感;並びに、睡眠障害、食欲不振、***減退、便秘、口渇及び頭痛等の身体症状等が挙げられる。 The mood disorder in the present invention refers to a state of feeling pain or causing some trouble in daily life due to mood modulation that lasts for a certain period of time. Symptoms of mood disorders include, for example, abnormal emotional expression of emotions; depression, feelings of melancholy, tragedy, guilt and despair; psychomotor restraint; feeling of anxiety; and sleep disorders, appetite Physical symptoms such as poorness, decreased libido, constipation, thirst and headache are included.
本発明は、その様な気分障害を改善することにより、これらの症状を改善することができる。本発明の気分障害改善剤は、とりわけ、抑うつ気分の改善に資する剤である。 The present invention can improve these symptoms by improving such mood disorders. The mood disorder improving agent of the present invention is an agent that contributes particularly to the improvement of depressed mood.
ここで、肉体疲労及び精神疲労(気分障害)について説明する。日本疲労学会の抗疲労臨床評価ガイドラインによれば、肉体疲労は、「病的疲労を伴わない健常者において身体に運動などの負荷が生じた際に発現する短期的な疲労を指す。」と定義される。また、精神疲労は、「中枢神経系を活発に使うことによって起こる機能低下。考えたり気力を出したりすることが困難になる。」と定義される。そして、一般的に、休むことによって肉体疲労は回復するものの、精神疲労は回復し難いものである。 Here, physical fatigue and mental fatigue (mood disorder) will be described. According to the Japanese Society for Fatigue Anti-fatigue Clinical Evaluation Guidelines, physical fatigue is defined as “short-term fatigue that occurs when the body is subjected to exercise or other stress in healthy individuals without morbid fatigue”. Is done. Also, mental fatigue is defined as "function deterioration caused by active use of the central nervous system. It becomes difficult to think and to give energy." In general, physical fatigue is recovered by resting, but mental fatigue is difficult to recover.
(2)オニクの抽出物
オニク(学名:Boschniakia rossica)は、ハマウツボ科の植物であり、別名、クサジュヨウ(草じゅ蓉)、キムラタケ又はワニクジュヨウ(和肉じゅ蓉)とも呼ばれる。オニクは、亜高山〜高山に生える1年草であり、葉緑素のない寄生植物で、ミヤマハンノキの根に寄生する。
(2) Onyx extract Onyk (scientific name: Boschniakia rossica) is a plant of the genus Oleoptera, also known as Kusajuyo, Kimuratake or crocodile jujube. Onyx is an annual plant that grows in sub-alpine to alpine, and is a parasitic plant without chlorophyll.
植物体の抽出する部位は限定されないが、例えば、植物の全体を用いるほか、花、葉(及び葉柄)、茎(及び肉質茎)、根(根及び気根)、果実、果穂、果皮及び種子等の部位を用いることができる。原料収量と抽出効率の点から、植物の全体を用いることが好ましい。 The part to be extracted from the plant body is not limited. For example, in addition to using the whole plant, flowers, leaves (and petiole), stems (and fleshy stems), roots (roots and aerial roots), fruits, fruit ears, pericarps and seeds, etc. These sites can be used. It is preferable to use the whole plant from the viewpoint of raw material yield and extraction efficiency.
抽出する植物体は、葉、果実、種子、幹若しくは根を生の状態のもの(未乾燥物)、乾燥させた後適切な大きさに細砕し粉末化したもの(乾燥物)、若しくは、凍結したもの(凍結物)を用いることができる。 Plants to be extracted are leaves, fruits, seeds, trunks or roots in a raw state (undried matter), dried and then pulverized to an appropriate size and pulverized (dried matter), or A frozen product (frozen product) can be used.
本発明に関する植物体の抽出物を作製する方法としては、抽出工程及び分離工程を組み合わせる方法、上記方法に更に分画工程を組み合わせる方法等があげられるが、これらに限定されない。 Examples of a method for producing an extract of a plant body relating to the present invention include a method of combining an extraction step and a separation step, a method of further combining a fractionation step with the above method, and the like, but is not limited thereto.
抽出工程は、植物体から抽出溶媒を用いて、抽出物として必要な成分を取り出す工程であり、抽出方法や抽出条件は特に限定されない。 An extraction process is a process of taking out a component required as an extract from a plant body using an extraction solvent, and an extraction method and extraction conditions are not specifically limited.
抽出溶媒の種類は特に限定されないが、水、有機溶媒及びこれらを混合した混合溶媒等があげられる。上記の水としては、冷水、常温水、温水、熱水及び水蒸気等の全ての温度における水の状態があげられ、また、殺菌処理、イオン交換処理、浸透圧調整又は緩衝化されていてもよい。有機溶媒としては、親水性有機溶媒が好ましく、例えば、炭素数1〜5の1価アルコール(エタノール、メタノール、プロパノール及びイソプロパノール等)、炭素数2〜5の多価アルコール(グリセリン、イソプロピレングリコール、プロピレングリコール及びブチレングリコール等)、エステル(酢酸メチル等)及びケトン(アセトン等)等を用いることができる。これらの親水性有機溶媒は、1種のみを用いても、或いは2種以上を併用してもよい。本発明では、安全性及び有効成分の抽出効率の点からエタノール又は含水エタノールを用いることが好ましい。 Although the kind of extraction solvent is not specifically limited, Water, an organic solvent, the mixed solvent which mixed these, etc. are mention | raise | lifted. Examples of the water include water at all temperatures such as cold water, room temperature water, hot water, hot water and water vapor, and may be sterilized, ion exchanged, osmotic pressure adjusted or buffered. . As an organic solvent, a hydrophilic organic solvent is preferable, for example, C1-C5 monohydric alcohol (ethanol, methanol, propanol, isopropanol, etc.), C2-C5 polyhydric alcohol (glycerin, isopropylene glycol, Propylene glycol, butylene glycol, etc.), esters (methyl acetate, etc.), ketones (acetone, etc.) and the like can be used. These hydrophilic organic solvents may be used alone or in combination of two or more. In the present invention, ethanol or hydrous ethanol is preferably used from the viewpoints of safety and extraction efficiency of active ingredients.
抽出手法としては、浸漬抽出、攪拌抽出、還流抽出、振とう抽出及び超音波抽出があげられ、抽出条件としては、室温抽出、加熱抽出(加温抽出ともいう)、加圧抽出、超臨界抽出等があげられるが、好ましくは、加温抽出である。抽出温度は抽出溶媒の種類等により適宜決定できる。本発明の抽出を加温抽出で行う場合の具体的な抽出条件としては、30〜100℃程度で良く、沸騰状態で行っても良い。抽出時間は特に限定されないが、例えば、5分〜6時間程度で良く、より好ましくは10分〜3時間程度である。また、pH調整してもよい。上記抽出操作は1回でもよく、抽出操作を行った後に得られる抽出残渣を再度抽出することを複数回数繰り返すことにより複数回行ってもよい。さらに、工程の前後に、必要に応じて濾過等の処理を行ってもよい。 Examples of extraction methods include immersion extraction, stirring extraction, reflux extraction, shaking extraction, and ultrasonic extraction. Extraction conditions include room temperature extraction, heat extraction (also called warm extraction), pressure extraction, and supercritical extraction. Among them, warm extraction is preferable. The extraction temperature can be appropriately determined depending on the type of extraction solvent. Specific extraction conditions when performing the extraction of the present invention by warm extraction may be about 30 to 100 ° C., and may be performed in a boiling state. Although extraction time is not specifically limited, For example, about 5 minutes-6 hours may be sufficient, More preferably, it is about 10 minutes-3 hours. Moreover, you may adjust pH. The extraction operation may be performed once, or may be performed a plurality of times by repeating extraction of the extraction residue obtained after the extraction operation a plurality of times. Furthermore, you may perform processes, such as filtration, before and after a process as needed.
分離工程は、上記で得られた抽出物から、抽出残渣である不溶物と抽出物を分離する方法であり、例えば、遠心分離、フィルタプレス、濾過(加圧、常圧)及びクロマトグラフィー等の吸着剤・吸収剤を用いた抽出分離等による方法があげられる。抽出液から分取された抽出物はそのまま用いてもよく、さらに、分画等により精製してもよい。 The separation step is a method for separating the insoluble matter and the extract as the extraction residue from the extract obtained above. For example, centrifugation, filter press, filtration (pressurization, normal pressure), chromatography, etc. Examples thereof include extraction and separation using an adsorbent / absorbent. The extract collected from the extract may be used as it is, and further purified by fractionation or the like.
分画工程は、上記で得られた分離物から必要な成分を分画して精製及び濃縮する方法である。分画工程に用いられる方法としては、担体として陰イオン交換樹脂、陽イオン交換樹脂、シリカゲル、芳香族化合物を吸着するポリスチレン系の樹脂などを用いるクロマトグラフィー、透析、分子ふるいや減圧濃縮、凍結乾燥等の方法があげられるがこれらに限定されない。さらに、本工程後に、必要に応じて遠心分離等により上清を回収する工程を行ってもよい。なお、上記各工程の前後に、必要に応じて濾過等の処理を行ってもよい。濾過には、ガーゼや濾過フィルター、市販の濾過器等を用いることができる。また、必要に応じて、滅菌処理等を施すことができる。 The fractionation step is a method of fractionating and purifying and concentrating necessary components from the isolate obtained above. As a method used in the fractionation step, chromatography using anion exchange resin, cation exchange resin, silica gel, polystyrene resin that adsorbs aromatic compounds as a carrier, dialysis, molecular sieving, vacuum concentration, lyophilization, etc. However, it is not limited to these methods. Furthermore, you may perform the process of collect | recovering supernatants by centrifugation etc. as needed after this process. In addition, you may perform processes, such as filtration, before and after each said process as needed. A gauze, a filtration filter, a commercially available filter, etc. can be used for filtration. Moreover, a sterilization process etc. can be given as needed.
上記方法により、本発明の抽出物を得ることができる。得られた抽出物は、噴霧乾燥、真空乾燥、凍結乾燥等の乾燥工程により粉末化することもできる。 By the above method, the extract of the present invention can be obtained. The obtained extract can also be pulverized by a drying process such as spray drying, vacuum drying, freeze drying and the like.
(3)気分障害改善剤
本発明の気分障害改善剤は、前記オニクの抽出物を含有する。
(3) Mood disorder improving agent The mood disorder improving agent of the present invention contains the extract of Onyx.
本発明の気分障害改善剤(医薬品の形態)の投与方法は特に限定されるものではないが、経口投与可能な剤形が好ましい。例えば、経口投与のためには、錠剤、カプセル剤、散剤、顆粒剤、丸剤、液剤、乳剤、懸濁剤、溶液剤、酒精剤、シロップ剤、エキス剤及びエリキシル剤とすることができるが、経口摂取可能な形態であれば良く、特に限定されない。 The method for administering the mood disorder-improving agent (pharmaceutical form) of the present invention is not particularly limited, but an orally administrable dosage form is preferred. For example, for oral administration, it can be tablets, capsules, powders, granules, pills, solutions, emulsions, suspensions, solutions, spirits, syrups, extracts and elixirs. Any form that can be taken orally is acceptable and is not particularly limited.
非経口投与としては、静脈内投与、筋肉内投与、皮下投与、経皮投与、関節内投与及び膣内投与等が挙げられ、その場合は、丸剤、軟膏、ゲル、ペースト、クリーム、噴霧剤、溶液剤及び懸濁液剤等とすることができる。また、注射により投与する場合、局所注入、腹腔内投与、選択的静脈注入、静脈注射、皮下注射、臓器灌流液注入等の方法が選択することができる。 Parenteral administration includes intravenous administration, intramuscular administration, subcutaneous administration, transdermal administration, intraarticular administration, intravaginal administration, etc. In this case, pills, ointments, gels, pastes, creams, sprays, etc. , Solutions and suspensions. When administering by injection, methods such as local injection, intraperitoneal administration, selective intravenous injection, intravenous injection, subcutaneous injection, organ perfusate injection and the like can be selected.
製剤には薬剤的に許容できる種々の担体を加えることができる。例えば、賦形剤、結合剤、崩壊剤、滑沢剤、着香剤、着色剤、甘味剤、矯味剤、溶解補助剤、懸濁化剤、乳化剤、コーティング剤、ビタミンC及び抗酸化剤を含むことができるが、これらに限定されない。 Various pharmaceutically acceptable carriers can be added to the formulation. For example, excipients, binders, disintegrants, lubricants, flavoring agents, coloring agents, sweeteners, corrigents, solubilizers, suspending agents, emulsifiers, coating agents, vitamin C and antioxidants It can include but is not limited to these.
本発明の気分障害改善剤の投与量は、気分障害を改善できる効果を発揮する量であれば良く、一般的には、オニク抽出物に換算して、成人1日用量として、好ましくは2.5〜50g(50〜1000mg/kg体重)、より好ましくは5.0〜25g(100〜500mg/kg体重)を使用する。もちろん個別的に、投与されるヒトの年齢、体重、症状、投与経路、投与期間及び治療経過等に応じて変化させることもできる。1日あたりの量を数回に分けて投与することもできる。また、他の抗うつ剤や治療法と組み合わせて投与することもできる。 The dosage of the mood ameliorating agent of the present invention may be an amount that exhibits an effect of improving mood disorders, and is generally preferably used as an adult daily dose in terms of an onyc extract, preferably 2. 5 to 50 g (50 to 1000 mg / kg body weight), more preferably 5.0 to 25 g (100 to 500 mg / kg body weight) is used. Of course, it can be changed individually according to the age, weight, symptoms, administration route, administration period, course of treatment, etc. of the administered human. The daily dose can be administered in several divided doses. It can also be administered in combination with other antidepressants and treatments.
また、本発明の気分障害改善剤は、一成分として食品に配合させることもできる。その場合は、本発明の気分障害改善剤を、例えば、食品添加物の形態とすることもできる。 Moreover, the mood disorder improving agent of this invention can also be mix | blended with foodstuffs as one component. In that case, the mood disorder improving agent of the present invention can be in the form of, for example, a food additive.
(4)気分障害改善効果の評価方法
オニク抽出物が有する気分障害改善効果(抑うつ気分改善効果)は、抗うつ効果を有する薬剤の代表的なスクリーニング方法であるマウス強制遊泳試験法により評価することができる。マウスをある逃れられない容器の中に水を満たして強制遊泳させると、一定時間後に不動状態が出現する。不動状態は動物が水から逃避を放棄した一種の絶望状態と考えられており、人間におけるうつ状態に近い状態にあると考えられているからである。
(4) Evaluation method of mood disorder improvement effect The mood disorder improvement effect (depressive mood improvement effect) of Onyx extract should be evaluated by mouse forced swimming test method, which is a representative screening method for drugs with antidepressant effect. Can do. When a mouse is forced to swim with water filled in an inescapable container, a fixed state appears after a certain time. This is because the immobility state is considered to be a kind of despair where the animal has abandoned escape from the water, and is considered to be close to depression in humans.
そして、気分障害改善効果は、Porsolt等の抗うつ病動物モデル試験法(Porsolt RD, Bertin A, Jalfre M. Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther. 1977,229(2):327-336.)に基づくマウス強制遊泳試験法により、その評価を行うことができる。 Furthermore, the effect of improving mood disorders is described in Porsolt RD, Bertin A, Jalfre M. Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther. 1977,229 (2 ): 327-336.) Can be evaluated by the mouse forced swimming test method.
以下、実施例により本発明をさらに詳細に説明するが、本発明は実施例によって限定されるものではない。 EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited by an Example.
(1)オニク抽出物の調製
良く乾燥したオニク(学名:Boschniakia rossica)を細かく刻み、その粉砕物に8倍量の75%エタノールを加えて、2時間沸騰状態を保ちながらエタノール抽出液を得た。そのエタノール抽出液をろ過し、エタノール抽出液中の残渣をろ別した。その残渣に対して、上記抽出操作を繰り返した。
(1) Preparation of onyx extract Finely dried onyk (scientific name: Boschniakia rossica) was finely chopped, and 8 times the amount of 75% ethanol was added to the pulverized product to obtain an ethanol extract while maintaining the boiling state for 2 hours. . The ethanol extract was filtered, and the residue in the ethanol extract was filtered off. The above extraction operation was repeated for the residue.
この様にして得られた2回分のエタノール抽出液を合わせて減圧濃縮した後、70℃にて減圧乾燥し、オニク抽出物を得た。 The two ethanol extracts thus obtained were combined and concentrated under reduced pressure, and then dried under reduced pressure at 70 ° C. to obtain an onyc extract.
(2)マウスを用いた強制遊泳試験法
本試験は、前述のPorsolt等抗うつ病動物モデル試験法に基づき行った。
(2−1)使用動物
早期老化マウスとして知られるSAM系統のマウスのうち、老化過程において抑うつ傾向を示すことを特徴とするSAMP10を用いた。6ヶ月齢SAMP10の雄を使用した。
(2) Forced swimming test method using mice This test was performed based on the aforementioned anti-depression animal model test method such as Porsolt.
(2-1) Animal used Among the mice of the SAM strain known as premature aging mice, SAMP10 characterized by showing a tendency to depression in the aging process was used. Six month old SAMP10 males were used.
ここで、SAM系統のマウスは、老化促進モデルマウス(senescence-accelerated mouse:SAM)と呼ばれる一群の関連近交系マウスであり、促進老化を具体的に示したモデル動物である(Takeda, T. et al. Mech. Ageing Dev., 17 183-194, 1981)。そして、SAMP10が加齢するに従い示す病態としては、学習・記憶能障害、抑うつ状態、嗅球・前頭部萎縮がある(細川昌則 「SAM系統マウスの老化の特性」 実験医学 Vol.16 No.18(増刊) 1998 p.86-90)。 Here, the mice of the SAM strain are a group of related inbred mice called senescence-accelerated mice (SAM), which are model animals specifically showing accelerated aging (Takeda, T. et al. et al. Mech. Aging Dev., 17 183-194, 1981). The pathological conditions that SAMP10 shows as it ages include learning / memory impairment, depression, and olfactory bulb / frontal atrophy (Masayoshi Hosokawa “Aging Characteristics of SAM Mice” Experimental Medicine Vol.16 No.18 (Extra edition) 1998 p.86-90).
(2−2)動物飼育
購入した動物を7日間馴化した。馴化期間中の体重及び一般状態の観察により異常のないことを確認し、健康な動物を用いた。飼育条件は、温度(24±2℃)と湿度(50±20%)とを保ち、1ケージ中に1個体の条件で、照明は12時間周期で点灯と消灯を繰り返した(明期:6:00〜18:00)。また、飼料(マウス繁殖用飼料1035、北京華阜康生物科技有限公司)と飲用水はともに自由摂取とした。
(2-2) Animal breeding The purchased animal was acclimatized for 7 days. It was confirmed that there was no abnormality by observing the body weight and general condition during the acclimation period, and healthy animals were used. The breeding conditions were temperature (24 ± 2 ° C.) and humidity (50 ± 20%), with one individual in one cage, and lighting was repeatedly turned on and off in a 12-hour cycle (light period: 6 : 00 to 18:00). In addition, both feed (mouse breeding feed 1035, Beijing Huafu Kang Biotechnology Co., Ltd.) and drinking water were freely ingested.
(2−3)試験例I
試験例Iでは、オニク抽出物の投与量の違いによる投与効果を確認した。
(2-3) Test Example I
In Test Example I, the administration effect due to the difference in the dose of Onyx extract was confirmed.
SAMP10の雄8匹を1群として、対照(0mg/kg)群、オニク抽出物100mg/kg群、同200mg/kg群及び同400mg/kg群の4群に群分けした。
Eight males of SAMP10 were grouped into four groups: a control (0 mg / kg) group, an
次に、オニク抽出物の投与用量を、夫々0mg/kg(対照群)、100mg/kg、200mg/kg及び400mg/kgとし、オニク抽出物を5%(W/W)アラビアゴム末水溶液に懸濁させ、固定時間(朝9時)に、一日1回10mL/kgの液量で強制経口投与した。薬物投与は連続で4週間行った。 Next, the doses of the onyx extract were 0 mg / kg (control group), 100 mg / kg, 200 mg / kg and 400 mg / kg, respectively, and the onyk extract was suspended in a 5% (W / W) gum arabic powder aqueous solution. The solution was made turbid and administered by oral gavage once a day at a liquid volume of 10 mL / kg at a fixed time (9:00 am). Drug administration was performed continuously for 4 weeks.
次に、薬物投与開始から4週間後、25℃の水を深さ15cmまで入れた円筒中で、7分間の強制遊泳試験を行い、上記各群のマウスを強制遊泳させた。上記各群のマウスに対して、初めの2分間強制遊泳した後、続く5分間に観察される不動時間の累積時間(累積不動時間)を測定した。 Next, 4 weeks after the start of the drug administration, a forced swimming test for 7 minutes was performed in a cylinder filled with water at 25 ° C. to a depth of 15 cm, and the mice of each group were forced to swim. For each group of mice, after the first 2 minutes of forced swimming, the cumulative immobility time (cumulative immobility time) observed over the next 5 minutes was measured.
数値(累積不動時間)は平均値±標準誤差で表し、対照群と被験物群の平均値の差の検定には、一元配置の分散分析後、ANOVAの統計学的処理方法を用いた。累積不動時間については有意差検定を行った。いずれの場合も危険率が5%未満(p<0.05)の場合を有意差ありと判定した。 The numerical value (cumulative immobility time) is expressed as an average value ± standard error, and the statistical processing method of ANOVA was used for the test of the difference between the average values of the control group and the test group after one-way analysis of variance. A significant difference test was performed for the cumulative immobility time. In any case, a case where the risk rate was less than 5% (p <0.05) was determined to be significant.
また、上記試験期間中、各群のマウスの体重は正常に推移した。 In addition, during the test period, the weight of each group of mice remained normal.
図1に、試験例Iにおける薬物投与4週間後の各群の累積不動時間(秒)の結果を示した。*はp<0.05を、**はp<0.01を示す。 FIG. 1 shows the results of cumulative immobility time (seconds) of each group 4 weeks after drug administration in Test Example I. * Indicates p <0.05, and ** indicates p <0.01.
(2−4)試験例II
試験例IIでは、オニク抽出物の投与効果の経時変化を確認した。
(2-4) Test Example II
In Test Example II, the change with time of the administration effect of Onyx extract was confirmed.
SAMP10の雄8匹を1群として、対照(0mg/kg)群及びオニク抽出物200mg/kgに群分けした。
Eight males of SAMP10 were grouped into a control (0 mg / kg) group and an
次に、オニク抽出物の投与用量を、夫々0mg/kg(対照群)及び200mg/kgとし、オニク抽出物を5%(W/W)アラビアゴム末水溶液に懸濁させ、固定時間(朝9時)に、一日1回10mL/kgの液量で強制経口投与した。薬物投与は連続で4週間行った。 Next, the doses of onyx extract were 0 mg / kg (control group) and 200 mg / kg, respectively, and the onyk extract was suspended in 5% (W / W) gum arabic powder aqueous solution for a fixed time (morning 9 ) By oral gavage once a day at a liquid volume of 10 mL / kg. Drug administration was performed continuously for 4 weeks.
次に、薬物投与(対照群は非投与)開始から毎週1回、25℃の水を深さ15cmまで入れた円筒中で、7分間の強制遊泳試験を行い、上記各群のマウスを強制遊泳させた。上記各群のマウスに対して、初めの2分間強制遊泳した後、続く5分間に観察される不動時間の累積時間(累積不動時間)を測定した。薬物投与(対照群は非投与)開始から、1、2、3及び4週目の各時点での累積不動時間を測定した。 Next, a 7-minute forced swimming test was conducted in a cylinder containing 25 ° C. water to a depth of 15 cm once a week from the start of drug administration (the control group was not administered), and the mice in each group were forced to swim. I let you. For each group of mice, after the first 2 minutes of forced swimming, the cumulative immobility time (cumulative immobility time) observed over the next 5 minutes was measured. From the start of drug administration (no administration in the control group), the cumulative immobility time at each time point of 1, 2, 3 and 4 weeks was measured.
数値(累積不動時間)は、試験例Iと同様に、ANOVAの統計学的処理方法を用いた。累積不動時間については有意差検定を行った。いずれの場合も危険率が5%未満(p<0.05)の場合を有意差ありと判定した。 As for the numerical value (cumulative immobility time), the statistical processing method of ANOVA was used as in Test Example I. A significant difference test was performed for the cumulative immobility time. In any case, a case where the risk rate was less than 5% (p <0.05) was determined to be significant.
また、上記試験期間中、各群のマウスの体重は正常に推移した。 In addition, during the test period, the weight of each group of mice remained normal.
図2に、試験例IIにおける毎週の各群の累積不動時間(秒)の結果を示した。*はp<0.05を示す。 FIG. 2 shows the results of the cumulative immobility time (seconds) of each group every week in Test Example II. * Indicates p <0.05.
(2−5)試験例III
試験例IIIでは、オニク抽出物と人参抽出物との投与効果の違いを確認した。
(2-5) Test Example III
In Test Example III, the difference in administration effect between the onyx extract and the carrot extract was confirmed.
SAMP10の雄8匹を1群として、A:対照(0mg/kg)群、B:人参抽出物200mg/kg群及びC:オニク抽出物200mg/kg群に群分けした。人参抽出物は白参軟エキス(天津中一製薬社製)を用いた。 Eight males of SAMP10 were grouped into A: control (0 mg / kg) group, B: carrot extract 200 mg / kg group, and C: onyc extract 200 mg / kg group. As a carrot extract, white ginseng soft extract (manufactured by Tianjin Nakaichi Pharmaceutical Co., Ltd.) was used.
次に、対照群Aは抽出物の投与無し、人参抽出物(B群)及びオニク抽出物(C群)の投与用量を、夫々200mg/kgとし、各抽出物を5%(W/W)アラビアゴム末水溶液に懸濁させ、固定時間(朝9時)に、一日1回10mL/kgの液量で強制経口投与した。薬物投与は連続で3週間行った。 Next, in the control group A, no extract was administered, and the doses of ginseng extract (group B) and onyx extract (group C) were 200 mg / kg, and each extract was 5% (W / W). It was suspended in an aqueous solution of gum arabic powder and administered by oral gavage once a day at a liquid volume of 10 mL / kg during a fixed time (9:00 am). Drug administration was performed continuously for 3 weeks.
次に、薬物投与開始から3週間後、25℃の水を深さ15cmまで入れた円筒中で、7分間の強制遊泳試験を行い、上記各群のマウスを強制遊泳させた。上記各群のマウスに対して、初めの2分間強制遊泳した後、続く5分間に観察される不動時間の累積時間(累積不動時間)を測定した。 Next, 3 weeks after the start of drug administration, a forced swimming test for 7 minutes was performed in a cylinder filled with water at 25 ° C. to a depth of 15 cm, and the mice in each group were forced to swim. For each group of mice, after the first 2 minutes of forced swimming, the cumulative immobility time (cumulative immobility time) observed over the next 5 minutes was measured.
数値(累積不動時間)は、試験例Iと同様に、ANOVAの統計学的処理方法を用いた。累積不動時間については有意差検定を行った。いずれの場合も危険率が5%未満(p<0.05)の場合を有意差ありと判定した。 As for the numerical value (cumulative immobility time), the statistical processing method of ANOVA was used as in Test Example I. A significant difference test was performed for the cumulative immobility time. In any case, a case where the risk rate was less than 5% (p <0.05) was determined to be significant.
また、上記試験期間中、各群のマウスの体重は正常に推移した。 In addition, during the test period, the weight of each group of mice remained normal.
図3に、試験例IIIにおける薬物投与3週間後の各群の累積不動時間(秒)の結果を示した。*はp<0.05を示す。 FIG. 3 shows the results of the cumulative immobility time (seconds) of each group 3 weeks after drug administration in Test Example III. * Indicates p <0.05.
4週間連続投与した結果の説明をする。 The results of continuous administration for 4 weeks will be explained.
試験例Iの結果から、オニク抽出物の投与用量100、200及び400mg/Kgの全てにおいて投与効果が確認され、オニク抽出物の至適投与用量は200mg/kgであることが明らかになった。また、試験例IIの結果において、投与開始1週目は対照群とオニク抽出物群に累積不動時間の有意差は見られず、2週目から投与効果が確認された。更に、3週目からオニク抽出物群の累積不動時間が、対照群のそれと比べて有意に短縮され、4週目も有意差がみられた。これらの結果から、オニク抽出物投与により老化マウスの気分障害(うつ状態)を改善することが明らかになった。 From the results of Test Example I, the effect of administration was confirmed at all doses of 100, 200, and 400 mg / Kg of onyc extract, and the optimum dose of onyc extract was found to be 200 mg / kg. Further, in the results of Test Example II, no significant difference in cumulative immobility time was observed between the control group and the onyc extract group in the first week of administration, and the administration effect was confirmed from the second week. Furthermore, the cumulative immobility time of the Onyk extract group was significantly shortened compared to that of the control group from the 3rd week, and a significant difference was also observed at the 4th week. From these results, it became clear that administration of Onyx extract improves mood disorders (depressed state) in aging mice.
この3週目からオニク抽出物投与効果が発現した効果を考察する。 The effect of the onyc extract administration effect will be considered from the third week.
この効果は、抗うつ作用の発現には1〜2週間の連続的な薬物投与が必要であるところ、殆どの抗うつ薬は、服薬を開始してから2週間程度は経たなければ本来の効果が発現しないとされている、ことに一致するものである(新田淳美 「うつ病の病態生理と抗うつ薬の薬理の理解を深めるキーワード」 薬局 2007, Vol.58, No.3 p.41-42)。これは、抗うつ薬の抗うつ作用は、神経間隙におけるモノアミン量を単純に増やすことによるものではなく、モノアミン量の変化によるシナプス後レセプターの密度や感受性の変化など、二次的なものが大きく関わっているからとも推測されている。 Although this effect requires continuous drug administration for 1 to 2 weeks for the development of antidepressant action, most antidepressants have their original effects unless they have been taken for about 2 weeks. (Satomi Nitta “Key words to deepen understanding of the pathophysiology of depression and pharmacology of antidepressants” Pharmacy 2007, Vol.58, No.3 p.41 -42). This is because the antidepressant action of antidepressants is not due to simply increasing the amount of monoamines in the nerve gap, but secondary factors such as changes in the density and sensitivity of post-synaptic receptors due to changes in the amount of monoamines. It is speculated that they are involved.
試験例IIIの結果から、オニク抽出物投与により、対照群と比較して有意に累積不動時間を短縮し、人参抽出物投与群よりも不動時間が短くなることが確認された。このことから、肉体疲労の改善や滋養強壮を目的に広く使用されている人参抽出物は、累積不動時間短縮に有意な効果を示さないことが明らかになった。 From the results of Test Example III, it was confirmed that administration of the onyc extract significantly shortened the accumulated immobility time compared to the control group, and the immobility time was shorter than that of the carrot extract administration group. From this, it became clear that the ginseng extract widely used for the purpose of improving physical fatigue and nourishing tonic does not show a significant effect on shortening the accumulated immobility time.
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JP4965132B2 (en) * | 2006-01-27 | 2012-07-04 | 森下仁丹株式会社 | Menopause disorder improving agent |
JP2008280310A (en) * | 2007-04-11 | 2008-11-20 | Oriza Yuka Kk | Promoter for forming and metabolizing testosterone |
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