JP6555738B2 - Preventive / ameliorating agent for diseases with fatigue - Google Patents
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Description
本発明は、疲労を伴う疾患の予防または改善に有用な、ウシ初乳酵素処理物を含んでなる予防改善剤に関する。 The present invention relates to a preventive / ameliorating agent comprising a bovine colostrum enzyme-treated product, which is useful for preventing or ameliorating a disease accompanied by fatigue.
疲労は、一般に疲労感、倦怠感を主症状とするが、その他睡眠障害や意欲低下など多彩な症状を伴う疾患である。疲労感や倦怠感は体の異常を知らせる重要なアラーム信号の一つであり、健常時でも激しい運動、長時間の労働を行った場合や過度のストレス状況におかれた場合などに、自覚するようになる。このような生理学的な疲労は通常、体を休めることにより元の正常な状態に回復し、長く続くことはない。１９８５年総理府の「健康に関する国民意識調査」では、約６割強の人が疲労を訴えているが、疲労を訴えている人の７割は「一晩の睡眠により疲労は回復する」と答えている。しかしながら、現代人は、長時間の労働や過度のストレス状況に置かれることが多く、また十分な休息を取るのが難しいため、疲労感や倦怠感の回復が困難になることもしばしばある。１９９９年厚生省疲労調査研究班が実施した疫学調査によると、疲労を自覚している人の割合は約６割と変わっていないが、このうちの６割もの人が６ヶ月以上にわたって疲れを感じていることが報告されている。すなわち、慢性的な疲労に悩む人が増加し、疲労の質が変化してきているのである（非特許文献１）。 In general, fatigue is a disease accompanied by various symptoms such as sleep disorder and decreased motivation, although fatigue and fatigue are the main symptoms. Fatigue and fatigue are one of the important alarm signals that inform you of abnormalities in your body, and you can be aware of such things as intense exercise at normal times, long working hours, and excessive stress. It becomes like this. Such physiological fatigue is usually restored to normal by resting and does not last long. In the 1985 “National Survey on Health,” about 60% of people complained of fatigue, but 70% of those complaining of fatigue replied that “overnight sleep recovers fatigue” ing. However, modern people are often placed in long working hours and excessive stress, and it is often difficult to recover from fatigue and fatigue because it is difficult to get enough rest. According to an epidemiological survey conducted by the 1999 Ministry of Health and Welfare Fatigue Research Group, the proportion of people who are aware of fatigue has not changed to about 60%, but 60% of those who have felt tired for over 6 months. It has been reported that That is, the number of people who suffer from chronic fatigue is increasing, and the quality of fatigue is changing (Non-Patent Document 1).
また、最近、慢性疲労症候群（Ｃｈｒｏｎｉｃ Ｆａｔｉｇｕｅ Ｓｙｎｄｒｏｍｅ；ＣＦＳ）なる疾患が難病の一つとして話題になっている。これは、日常生活に支障を来すほどの長期的な全身疲労感、倦怠感、微熱、リンパ節腫脹、筋肉痛、関節痛、精神神経症状などの基本的な症状を示す。他方、過労死が大きな社会問題となっている。過労死は、長時間の過密の働きすぎによる突然死であると定義されている。過労死の問題は、医学的、経済的、社会的に非常に重要であると認識されているものである。 Recently, a disease called Chronic Fatigue Syndrome (CFS) has become a hot topic as one of intractable diseases. This shows basic symptoms such as long-term general fatigue, fatigue, slight fever, lymphadenopathy, muscle pain, joint pain, and neuropsychiatric symptoms that hinder daily life. On the other hand, death from overwork is a major social problem. Overwork death is defined as sudden death due to excessive overwork for a long time. The problem of death from overwork is recognized as very important medically, economically and socially.
そこで、激しい運動、長時間の労働を行った場合や過度のストレス状況におかれた場合の疲労を軽減しうる物質、疲労から正常な状態への回復を早めることができる物質等のいわゆる「抗疲労物質」が提案されている。たとえば、ある種のアミノ酸組成物（特許文献１）や、Ｌ−カルニチンおよびヒスチジン関連ジペプチド（特許文献２）、サンザシ抽出物（特許文献３）などに体力増強作用があることが報告されている。また、運動等による体力の消耗や疲労時等における栄養補給を目的として、アスコルビン酸を含む栄養補給組成物が有用であることが示されている（特許文献４）。 Therefore, so-called anti-resisting substances such as substances that can reduce fatigue when strenuous exercise, long hours of work or excessive stress, and substances that can accelerate recovery from fatigue to normal conditions "Fatigue substances" have been proposed. For example, it has been reported that certain amino acid compositions (Patent Document 1), L-carnitine and histidine-related dipeptides (Patent Document 2), hawthorn extract (Patent Document 3) and the like have a physical strength enhancing action. Moreover, it has been shown that a nutritional supplement composition containing ascorbic acid is useful for the purpose of nutritional supplementation during exhaustion of physical strength or fatigue due to exercise (Patent Document 4).
ヒト血清の酵素処理物（β−ガラクトシダーゼ、または、β−ガラクトシダーゼとシアリダーゼ）がマクロファージ活性化作用を有することは、特許文献５に記載がある。 Patent Document 5 describes that an enzyme-treated product of human serum (β-galactosidase, or β-galactosidase and sialidase) has a macrophage activating action.
本発明は、疲労を伴う疾患の予防または改善に有用な、ウシ初乳酵素処理物を含んでなる予防改善剤、それを含んでなる飲食品および医薬品を提供しようとするものである。 The present invention is intended to provide a preventive / ameliorating agent comprising a bovine colostrum enzyme-treated product, a food and drink and a pharmaceutical comprising the same, which are useful for preventing or ameliorating a disease accompanied by fatigue.
本発明者は、鋭意検討した結果、ウシ初乳を特定の酵素、すなわち、β−ガラクトシダーゼ、または、β−ガラクトシダーゼおよびシアリダーゼと接触させる工程を含んでなる製造方法により得られるウシ初乳酵素処理物が、疲労を伴う疾患の予防、改善または治療に優れた効果を奏することを見出し、さらに検討を重ねて本発明を完成した。 As a result of intensive studies, the inventor has obtained a bovine colostrum enzyme-treated product obtained by a production method comprising a step of contacting bovine colostrum with a specific enzyme, that is, β-galactosidase, or β-galactosidase and sialidase. Has been found to have an excellent effect in the prevention, amelioration or treatment of a disease accompanied by fatigue, and the present invention has been completed through further studies.
すなわち、本発明は、
［１］疲労を伴う疾患の予防改善剤であって、
ウシ初乳をβ−ガラクトシダーゼと接触させる工程を含んでなる製造方法により得られるウシ初乳酵素処理物を含んでなる予防改善剤、
［２］ウシ初乳酵素処理物の製造方法が、シアリダーゼと接触させる工程をさらに含む上記［１］記載の予防改善剤、
［３］１回の投与用として、０．０２μｇ〜４０ｍｇの範囲の量のタンパク質を含む上記［１］または［２］記載の予防改善剤、
［４］消化管内から吸収させる剤形である上記［１］〜［３］のいずれかに記載の予防改善剤、
［５］疲労を伴う疾患が、慢性疲労症候群である上記［１］〜［４］のいずれかに記載の予防改善剤、
［６］疲労を伴う疾患の予防または改善のための飲食品であって、
上記［１］〜［５］のいずれかに記載の予防改善剤を含んでなる飲食品、
［７］疲労を伴う疾患の予防または治療のための医薬品であって、
上記［１］〜［５］のいずれかに記載の予防改善剤を含んでなる医薬品、
に関する。
That is, the present invention
[1] An agent for preventing and improving fatigue-related diseases,
A preventive / ameliorating agent comprising a bovine colostrum enzyme-treated product obtained by a production method comprising a step of contacting bovine colostrum with β-galactosidase,
[2] The preventive / ameliorating agent according to [1] above, wherein the method for producing an enzyme-treated bovine colostrum further comprises a step of contacting with sialidase,
[3] The preventive / ameliorating agent according to the above [1] or [2], comprising a protein in an amount in the range of 0.02 μg to 40 mg for single administration,
[4] The preventive / ameliorating agent according to any one of the above [1] to [3], which is a dosage form absorbed from the digestive tract,
[5] The preventive / ameliorating agent according to any one of the above [1] to [4], wherein the disease accompanied by fatigue is chronic fatigue syndrome,
[6] A food or drink for preventing or ameliorating a disease accompanied by fatigue,
A food or drink comprising the preventive / ameliorating agent according to any one of [1] to [5] above,
[7] A pharmaceutical product for preventing or treating a disease accompanied by fatigue,
A pharmaceutical comprising the preventive / ameliorating agent according to any one of [1] to [5] above,
About.
本発明に係るウシ初乳酵素処理物は、疲労を伴う疾患の予防、改善または治療に優れた効果を奏するので、当該疾患の予防、改善または治療に有用である。したがって、該ウシ初乳酵素処理物を用いれば、これら疾患の予防または改善に有用な飲食品、および、これら疾患の予防または治療に有用な医薬品を提供することができる。 Since the bovine colostrum enzyme-treated product according to the present invention has an excellent effect in the prevention, amelioration or treatment of a disease accompanied by fatigue, it is useful for the prevention, amelioration or treatment of the disease. Therefore, if the bovine colostrum enzyme-treated product is used, foods and drinks useful for the prevention or improvement of these diseases and pharmaceuticals useful for the prevention or treatment of these diseases can be provided.
さらに、本発明に係るウシ初乳酵素処理物は、ウシ初乳をβ−ガラクトシダーゼ、または、β−ガラクトシダーゼおよびシアリダーゼで処理することによって調製できるため、簡便かつ低コストであるという利点を有する。 Furthermore, since the bovine colostrum enzyme-treated product according to the present invention can be prepared by treating bovine colostrum with β-galactosidase, or β-galactosidase and sialidase, it has an advantage of being simple and low-cost.
＜ウシ初乳＞
本発明で使用するウシ初乳とは、子牛の分娩後、母牛が１０日目までに分泌する乳汁をいい、好ましくは７日目まで、より好ましくは５日目までに分泌する乳汁である。本発明において、ウシ初乳は、ホルスタイン種、黒毛和種などのウシの種類にかかわらず、いずれの種のものをも使用することができる。
<Bovine colostrum>
The bovine colostrum used in the present invention refers to milk secreted by calves by the 10th day after calf delivery, preferably by 7 days, more preferably by the 5th day. is there. In the present invention, any bovine colostrum can be used regardless of the type of cow such as Holstein and Japanese Black.
＜酵素＞
本発明で使用するβ−ガラクトシダーゼは、特に限定なく、周知のいずれの種類のものも使用することができる。そのようなものとしては、例えば、大腸菌（Escherichia coli）由来のもの、ウシ肝臓（bovine liver）由来のものなどが挙げられる。市販されたものとしては、例えば、和光純薬工業（株）のカタログＮｏ．０７２−０４１４１、ＳＩＧＭＡ−ＡＬＤＲＩＣＨ社のＧ１８７５などが挙げられる。本発明において、β−ガラクトシダーゼは、単独で用いてもよく、２種以上を組み合わせて用いてもよい。
<Enzyme>
The β-galactosidase used in the present invention is not particularly limited, and any known type can be used. Examples of such include those derived from Escherichia coli and bovine liver. Examples of commercially available products include catalog No. of Wako Pure Chemical Industries, Ltd. 072-04141, G1875 of SIGMA-ALDRICH, and the like. In the present invention, β-galactosidase may be used alone or in combination of two or more.
本発明で使用するシアリダーゼは、特に限定なく、周知のいずれの種類のものも使用することができる。そのようなものとしては、例えば、ウェルシュ菌（Clostridium perfringenes）由来のもの、レンサ球菌（Streptococcus 6646K）由来のもの、コレラ菌（Vibrio cholerae）由来のもの、アースロバクター・ウレアファシエンス（Arthrobacter ureafaciens）由来のものなどが挙げられる。市販されたものとしては、例えば、ＳＩＧＭＡ−ＡＬＤＲＩＣＨ社の製品番号（Sigma Prod. Nos.）Ｎ２８７６、Ｎ２１３３、Ｎ２９０４、Ｎ３００１、Ｎ５６３１、生化学バイオビジネス社のコード番号（Code Number）１２００５２、ＢｉｏＬａｂｓ社のカタログ番号（Catalog#）Ｐ０７２０Ｌ、Ｐ０７２０Ｓなどが挙げられる。本発明において、シアリダーゼは、単独で用いてもよく、２種以上を組み合わせて用いてもよい。 The sialidase used in the present invention is not particularly limited, and any known type can be used. As such, for example, those derived from Clostridium perfringenes, those derived from Streptococcus 6646K, those derived from Vibrio cholerae, Arthrobacter ureafaciens (Arthrobacter ureafaciens) The thing of origin etc. are mentioned. Examples of commercially available products include SIGMA-ALDRICH product numbers (Sigma Prod. Nos.) N2876, N2133, N2904, N3001, N5631, Biochemical Biobusiness Code Number 120052, BioLabs Catalog numbers (Catalog #) P0720L, P0720S, and the like. In the present invention, the sialidase may be used alone or in combination of two or more.
＜酵素処理＞
本発明において、ウシ初乳と、β−ガラクトシダーゼ若しくはシアリダーゼとの接触（酵素処理）は、それぞれ、十分な量の酵素を用いて十分な時間接触させることにより、それ以上実質的に酵素反応が進行しない程度まで行うのが好ましい。このような目的には、酵素の種類にもよるが、例えば、β−ガラクトシダーゼとして和光純薬工業（株）のカタログＮｏ．０７２−０４１４１を用いる場合、ウシ初乳１００μｌに対して、酵素を６５ｍＵ使用すれば十分である。また、例えば、シアリダーゼとしてＳＩＧＭＡ−ＡＬＤＲＩＣＨ社の製品番号（Ｎ２８７６）を用いる場合、ウシ初乳１００μｌに対して、酵素を６５ｍＵ使用すれば十分である。この場合の酵素処理の時間としては、３時間行えば十分である。
<Enzyme treatment>
In the present invention, the contact (enzyme treatment) of bovine colostrum with β-galactosidase or sialidase makes contact with a sufficient amount of enzyme for a sufficient time, so that the enzyme reaction further proceeds substantially. It is preferable to carry out to such an extent that it does not. For this purpose, although it depends on the kind of enzyme, for example, catalog No. of Wako Pure Chemical Industries, Ltd. as β-galactosidase. When using 072-04141, it is sufficient to use 65 mU of enzyme for 100 μl of bovine colostrum. For example, when using the product number (N2876) of SIGMA-ALDRICH as sialidase, it is sufficient to use 65 mU of enzyme for 100 μl of bovine colostrum. In this case, it is sufficient to perform the enzyme treatment for 3 hours.
酵素処理は、任意の容器中で、これら酵素を、ウシ初乳に添加して実施することができるが、所望により、ウシ初乳中の総タンパク質濃度を調整するために、この分野で通常用いられる緩衝液を加えてもよい。そのような緩衝液としては、生理食塩水、リン酸緩衝生理食塩水（ＳＰＢ）、リンゲル液などが挙げられる。酵素処理の温度は、酵素が活性を示す温度であれば特に限定はないが、通常酵素が高い活性を示す３７℃付近の温度である。 Enzymatic treatment can be carried out in any vessel by adding these enzymes to bovine colostrum, but is commonly used in this field to adjust the total protein concentration in bovine colostrum if desired. Buffer may be added. Examples of such a buffer include physiological saline, phosphate buffered saline (SPB), Ringer's solution, and the like. The temperature of the enzyme treatment is not particularly limited as long as the enzyme exhibits activity, but it is usually around 37 ° C. where the enzyme exhibits high activity.
酵素処理は、加熱（熱処理）により、酵素を失活させることにより終了する。かかる熱処理は、酵素を失活させることができる限り特に限定されないが、例えば、６０℃付近の温度で、約１０分間加熱することにより、実施することができる。熱処理後の検体は、所望により、濃縮してもよい。当該濃縮は、市販の機器、例えば遠心濃縮器（例えば、ＭＩＬＬＩＰＯＲＥ社製の１００００ＭＷＣＯ ＹＭ−１０）を用いて行うことができる。 The enzyme treatment is terminated by inactivating the enzyme by heating (heat treatment). Such heat treatment is not particularly limited as long as the enzyme can be inactivated. For example, the heat treatment can be performed by heating at a temperature around 60 ° C. for about 10 minutes. The specimen after the heat treatment may be concentrated if desired. The concentration can be performed using a commercially available device, for example, a centrifugal concentrator (for example, 10000MWCO YM-10 manufactured by MILLIPORE).
また、酵素処理は、固相に固定した酵素（固定化酵素）を用いて行うこともできる。酵素を固相に固定させる方法は、当業者に知られており、例えば、β−ガラクトシダーゼおよび／またはシアリダーゼを、シアンブロマイドの如きカップリング剤により、アガロースビーズに固定することができる。そのような固定化酵素としては、例えば、イモビライズド β−ガラクトシダーゼ Ｇ３Ｍ（Ｍｏ Ｂｉ Ｔｅｃ社、＃Ａ３１０２）、ノイラミニダーゼアガロース Ｃｌｏｓｔｒｉｄｉｕｍ ｐｅｒｆｒｉｎｇｅｎｓ（ウェルシュ菌）由来（ＳＩＧＭＡ−ＡＬＤＲＩＣＨ社製、製品番号（Product Number)：Ｎ５２５４）などが市販されている。固定化酵素を用いる利点は、酵素処理後、酵素を熱処理により失活させることなく回収することが可能なこと、および、そのような回収により夾雑物（熱処理により失活した酵素などのタンパク質等）の存在を減じることができることである。 The enzyme treatment can also be performed using an enzyme (immobilized enzyme) immobilized on a solid phase. A method for immobilizing an enzyme on a solid phase is known to those skilled in the art. For example, β-galactosidase and / or sialidase can be immobilized on agarose beads with a coupling agent such as cyanogen bromide. Examples of such immobilized enzymes include immobilized β-galactosidase G3M (Mo Bi Tec, # A3102), neuraminidase agarose Clostridium perfringens (manufactured by Welsh bacteria) (manufactured by SIGMA-ALDRICH, product number: N5254). ) Etc. are commercially available. The advantage of using an immobilized enzyme is that the enzyme can be recovered without being deactivated by heat treatment after the enzyme treatment, and foreign substances (proteins such as enzymes deactivated by heat treatment) by such recovery It is possible to reduce the existence of.
＜ウシ初乳酵素処理物＞
こうして得られる本発明のウシ初乳酵素処理物は、さらに、凍結乾燥して、固体ないし粉体状としてもよい。このようなウシ初乳酵素処理物は、疲労を伴う疾患の予防、改善または治療に有用な新規組成物である。
<Bovine colostrum enzyme-treated product>
The thus obtained bovine colostrum enzyme-treated product of the present invention may be further freeze-dried to form a solid or powder. Such a bovine colostrum enzyme-treated product is a novel composition useful for the prevention, amelioration or treatment of a disease accompanied by fatigue.
＜予防改善剤＞
該ウシ初乳酵素処理物は、食品分野または薬学分野で許容される補助剤（担体）を、所望により配合することにより、予防改善剤とすることができる。そして、該予防改善剤は、これを含んでなる飲食品または医薬品とすることができる。
<Prevention improving agent>
The bovine colostrum enzyme-treated product can be used as a preventive / ameliorating agent by blending an adjuvant (carrier) that is acceptable in the food or pharmaceutical field, if desired. And this prevention-improving agent can be made into the food-drinks or pharmaceutical which comprise this.
＜医薬品＞
本発明のウシ初乳酵素処理物は、そのまま、もしくは、適宜、薬学的に許容しうる補助剤（担体）を配合することにより、医薬組成物として調製することができる。このような薬学的に許容し得る補助剤としては、この分野で通常用いられるものをいずれも好適に使用することができ、具体例としては、例えば、希釈剤、安定剤、保存剤、緩衝剤、賦形剤、結合剤、防腐剤、崩壊剤、滑沢剤、矯味剤等が挙げられる。これら補助剤は、医薬組成物の剤型に応じて、適宜配合される。
<Pharmaceuticals>
The bovine colostrum enzyme-treated product of the present invention can be prepared as a pharmaceutical composition as it is or by appropriately blending a pharmaceutically acceptable adjuvant (carrier). As such pharmaceutically acceptable adjuvants, any of those commonly used in this field can be suitably used. Specific examples include diluents, stabilizers, preservatives, buffering agents. , Excipients, binders, preservatives, disintegrants, lubricants, flavoring agents and the like. These adjuvants are appropriately blended according to the dosage form of the pharmaceutical composition.
上記医薬組成物は、適当な剤型に製剤化して、医薬品とすることができる。本発明の医薬組成物や医薬品は、疲労を伴う疾患の予防、治療に効果を奏する。医薬品の剤型としては特に制限されず、経口製剤であっても非経口製剤であってもよい。非経口製剤としては、注射剤、輸液剤、点鼻剤、点耳剤、坐剤、経腸栄養剤などが挙げられる。例えば、注射剤としては、静脈内注射、皮下注射、皮内注射、筋肉内注射、腹腔内注射などの投与形態のものが挙げられ、このうち、筋肉内注射が好ましい。一方、経口製剤としては、散剤、顆粒剤、錠剤（舌下錠などを含む）、カプセル剤、丸剤、腸溶剤、内用液剤（懸濁剤、乳剤、シロップ剤などを含む）、吸入剤などが挙げられる。 The above-mentioned pharmaceutical composition can be formulated into an appropriate dosage form to make a pharmaceutical product. The pharmaceutical composition and pharmaceutical of the present invention are effective in preventing and treating diseases accompanied by fatigue. The dosage form of the pharmaceutical is not particularly limited, and may be an oral preparation or a parenteral preparation. Examples of parenteral preparations include injections, infusions, nasal drops, ear drops, suppositories, enteral nutrients and the like. For example, examples of the injection include those in administration forms such as intravenous injection, subcutaneous injection, intradermal injection, intramuscular injection, intraperitoneal injection, etc. Among them, intramuscular injection is preferable. On the other hand, as oral preparations, powders, granules, tablets (including sublingual tablets), capsules, pills, intestinal solvents, liquids for internal use (including suspensions, emulsions, syrups, etc.), inhalants Etc.
本発明に係るウシ初乳酵素処理物の投与量は、投与対象の年齢、性別、体重および症状、投与方法などにより異なるが、典型的な例としては、例えば、本ウシ初乳酵素処理物に含まれるタンパク質の総量として、成人に対し、１回の投与あたり、約０．０２μｇ以上、好ましくは約０．２μｇ以上、より好ましくは約２μｇ以上、より好ましくは約２０μｇ以上、より好ましくは約５０μｇ以上であり、かつ、約４０ｍｇ以下、好ましくは約２０ｍｇ以下、より好ましくは約１３ｍｇ以下、より好ましくは約１０ｍｇ以下、より好ましくは２ｍｇ以下である。好ましい投与量の範囲としては、例えば、約０．０２μｇ〜約４０ｍｇ、好ましくは約０．２μｇ〜約２０ｍｇ、より好ましくは約２μｇ〜約１３ｍｇ、より好ましくは約２０μｇ〜約１０ｍｇ、より好ましくは約５０μｇ〜約２ｍｇの範囲にあるのがよい。なお、本明細書において、タンパク質の量は、波長５７０ｎｍでの吸光度により決定したタンパク質濃度をもとに、算定するものである。 The dose of the bovine colostrum enzyme-treated product according to the present invention varies depending on the age, sex, body weight and symptoms, administration method, etc. of the subject of administration, but typical examples include, for example, this bovine colostrum enzyme-treated product. The total amount of protein contained in adults is about 0.02 μg or more, preferably about 0.2 μg or more, more preferably about 2 μg or more, more preferably about 20 μg or more, more preferably about 50 μg per administration per adult. And about 40 mg or less, preferably about 20 mg or less, more preferably about 13 mg or less, more preferably about 10 mg or less, more preferably 2 mg or less. A preferred dosage range is, for example, about 0.02 μg to about 40 mg, preferably about 0.2 μg to about 20 mg, more preferably about 2 μg to about 13 mg, more preferably about 20 μg to about 10 mg, more preferably about It may be in the range of 50 μg to about 2 mg. In the present specification, the amount of protein is calculated based on the protein concentration determined by the absorbance at a wavelength of 570 nm.
本発明に係るウシ初乳酵素処理物を、上記の如き１回あたりの投与量で投与する場合の、典型的な投与間隔および投与回数は、１〜２回／日である。なお、投与量および投与間隔は、医薬組成物中に含まれるタンパク質の総量を指標として、投与されるタンパク質の総量が同等となるような範囲内で、適宜変更することができる。また、予防目的での投与は、改善ないし治療目的の投与の場合と同じ投与量で行ってもよいし、あるいは、概ね半量程度を目安として行ってもよい。 When the bovine colostrum enzyme-treated product according to the present invention is administered at a dose per administration as described above, a typical administration interval and administration frequency are 1-2 times / day. The dose and the administration interval can be appropriately changed within a range in which the total amount of protein to be administered is equivalent with the total amount of protein contained in the pharmaceutical composition as an index. In addition, administration for prophylactic purposes may be performed at the same dose as that for improvement or therapeutic purposes, or approximately half the dose may be used as a guide.
本発明に係るウシ初乳酵素処理物は、他の疲労を伴う疾患の予防改善剤とともに併用することができる。併用する場合には、当該他の予防改善剤の効能、効果、投与量を考慮の上、本発明に係るウシ初乳酵素処理物の投与量を適宜調節する。 The bovine colostrum enzyme-treated product according to the present invention can be used in combination with other preventive / ameliorating agents for diseases associated with fatigue. When used in combination, the dose of the bovine colostrum enzyme-treated product according to the present invention is adjusted as appropriate in consideration of the efficacy, effect, and dose of the other preventive / ameliorating agent.
＜医薬部外品＞
本発明に係るウシ初乳酵素処理物は、必要に応じて、上記補助剤を配合することにより、医薬部外品用組成物とすることができ、さらには、該医薬部外品用組成物をさらに加工して、これを含んでなる医薬部外品とすることができる。該医薬部外品用組成物または医薬部外品は、溶液状、懸濁液状、シロップ状、顆粒状、クリーム状、ペースト状、ゼリー状等の種々の形態をとり得るものであり、必要に応じ、所望の形状に成形することもできる。医薬部外品用組成物および医薬部外品の調製はいずれも常法にのっとり実施することができる。本発明の医薬部外品用組成物または医薬部外品におけるウシ初乳酵素処理物の使用量は、特に限定されるものではないが、上記医薬品の場合の投与量と同じもの、あるいは、上記を参考にして適宜設定したものを採用することができる。
<Quasi-drug>
The bovine colostrum enzyme-treated product according to the present invention can be made into a quasi-drug composition by blending the auxiliary agent as necessary, and further, the quasi-drug composition. Can be further processed into a quasi-drug comprising the same. The quasi-drug composition or quasi-drug can take various forms such as solution, suspension, syrup, granule, cream, paste, jelly, etc. Accordingly, it can be formed into a desired shape. Both quasi-drug compositions and quasi-drugs can be prepared by conventional methods. The amount of bovine colostrum enzyme-treated product used in the quasi-drug composition or quasi-drug of the present invention is not particularly limited. Those appropriately set with reference to can be adopted.
＜飲食品＞
本発明に係るウシ初乳酵素処理物は、必要に応じて、上記補助剤や、甘味料、香辛料、調味料、防腐剤、保存料、殺菌剤、酸化防止剤などの飲食品に通常用いられる各種添加剤を適宜配合することにより飲食品用組成物とすることができ、さらには、該飲食品用組成物をさらに加工して、これを含んでなる飲食品とすることができる。該飲食品用組成物または飲食品は、溶液状、懸濁液状、シロップ状、顆粒状、クリーム状、ペースト状、ゼリー状等の種々の形態をとり得るものであり、必要に応じ、所望の形状に成形することもできる。また、該飲食品は、パン、麺、菓子、飲料、スープ、加工食品など様々な形態をとることができる。飲食品用組成物および飲食品の調製はいずれも常法にのっとり実施することができる。
<Food &Drink>
The bovine colostrum enzyme-treated product according to the present invention is usually used in foods and drinks such as the above-mentioned adjuvants, sweeteners, spices, seasonings, preservatives, preservatives, bactericides, and antioxidants as necessary. It can be set as the composition for food-drinks by mix | blending various additives suitably, Furthermore, this food-drinks composition can be further processed and it can be set as the food-drinks containing this. The composition for food or drink or food or drink can take various forms such as solution, suspension, syrup, granule, cream, paste, jelly, etc. It can also be formed into a shape. In addition, the food and drink can take various forms such as bread, noodles, confectionery, beverages, soups, and processed foods. Preparation of the composition for food / beverage products and food / beverage products can be carried out according to a conventional method.
本発明のウシ初乳酵素処理物は、上記疾患の予防、治療等に効果を奏するものであるので、本発明の飲食品用組成物や飲食品は、該疾患の予防、改善等に効果を奏する。この場合において、本発明の飲食品用組成物または飲食品におけるウシ初乳酵素処理物の使用量は、特に限定されるものではないが、上記医薬品の場合の投与量と同じもの、あるいは、上記を参考にして適宜設定したものを採用することができる。 Since the bovine colostrum enzyme-treated product of the present invention is effective for the prevention and treatment of the above diseases, the composition for food and beverage and the food and beverage of the present invention are effective for the prevention and improvement of the disease. Play. In this case, the amount of the bovine colostrum enzyme-treated product used in the composition for food or beverage of the present invention or food and beverage is not particularly limited, but is the same as the dose in the case of the above pharmaceutical product, or the above Those appropriately set with reference to can be adopted.
かかる本発明の飲食品は、いわゆる健康食品、健康飲料、機能性食品、栄養機能食品、健康補助食品、栄養補助食品（サプリメント）、特別用途食品、特定保健用食品等の経口投与可能なものであったり、その他ヒト以外の動物（作業用家畜、猟犬、競走馬、愛玩動物、その他の動物）に対する飼料であり得る。 Such foods and drinks of the present invention can be administered orally such as so-called health foods, health drinks, functional foods, functional nutritional foods, health supplements, nutritional supplements (supplements), special purpose foods, foods for specified health use, etc. Or other non-human animals (work livestock, hounds, racehorses, pets, other animals).
このような本発明の医薬品、医薬部外品、および飲食品は、活性成分であるウシ初乳酵素処理物を、消化管内、好ましくは口腔内または腸管内から吸収させる剤形（例えば、上述の舌下錠や腸溶剤の形態）であることが好ましい。 Such pharmaceuticals, quasi-drugs, and foods and drinks according to the present invention have a dosage form that absorbs bovine colostrum enzyme treated product, which is an active ingredient, from the digestive tract, preferably from the oral cavity or intestinal tract (for example, the above-mentioned It is preferably in the form of sublingual tablets or enteric solvents.
＜疲労＞
本発明において、疲労とは、身体的あるいは精神的負荷を連続して与えたときに一時的な身体的および／または精神的パフォーマンスの低下として現れる状態をいい、ここで、パフォーマンスの低下とは、身体的および／または精神的作業能力の質的あるいは量的な低下を意味する。また、本発明の「疲労」は、慢性的な疲労や、慢性疲労症候群における疲労または過労死をもたらす疲労をも包含するものとする。
<Fatigue>
In the present invention, fatigue refers to a state that appears as a temporary physical and / or mental performance degradation when a physical or mental load is continuously applied. Meaning a qualitative or quantitative decline in physical and / or mental work ability. In addition, “fatigue” of the present invention includes chronic fatigue, fatigue in chronic fatigue syndrome, or fatigue resulting in overwork death.
本発明における「疲労の改善ないし治療の効果」とは、上記疲労を減弱させる作用や疲労を回復させる作用をいい、具体的には、運動や作用した部位（脳を含む）の働きの持続時間を向上させること、および、同じ運動量や作用量での疲労物質の増加を抑制すること（持久力向上・体力増強）、運動や作用した部位が疲労していないにもかかわらず脳や神経などが疲労感知状態になっていることを改善すること、ならびに運動や作用した部位の疲労状態を通常状態に回復することを促進する効果をいう。また、本発明における「疲労の予防効果」とは、上記の如き疲労の状態に至ることを妨げる効果をいう。 The “improvement of fatigue or the effect of treatment” in the present invention refers to the above-described action of reducing fatigue and the action of recovering fatigue. Specifically, the duration of exercise and the action of the affected part (including the brain) To improve fatigue and to suppress the increase of fatigue substances with the same amount of exercise and action (improve endurance and physical fitness) This refers to the effect of improving the fatigue-sensing state and promoting the recovery of the fatigued state of the exercised or affected part to the normal state. In addition, the “prevention effect of fatigue” in the present invention refers to an effect of preventing the fatigue state as described above.
慢性疲労症候群とは、明確な定義が確立されている訳ではないが、持続性で日常生活に支障がある脱力感または疲労感の症候群で、６カ月以上続く非特異的身体症状を伴い、他の原因によらないものをいう（ステッドマン医学大辞典改訂第６版）。 Chronic fatigue syndrome is not a well-defined definition, but it is a syndrome of weakness or fatigue that is persistent and hinders daily life, with nonspecific physical symptoms that last for more than 6 months, and others This does not depend on the cause of the disease (Stedman Medical Dictionary Revision 6th Edition).
一方、過労死とは、重度の過労状態にあり、身体的活力を保つことができないにも関わらず、疲労を十分に感じることができなくなり、その結果、脳血管疾患や心疾患を発症して永久的労働不能や死亡に至った状態をいう。 On the other hand, death from overwork is a severe overworked state, and despite being unable to maintain physical vitality, he / she cannot fully feel fatigue, resulting in cerebrovascular disease or heart disease. A condition that results in permanent incapacity or death.
本発明に係るウシ初乳酵素処理物は、この慢性疲労症候群を処置すること、すなわち慢性疲労症候群各症状を緩和し、正常な状態に移行させることができ、また、過労死をも予防しうるものである。 The bovine colostrum enzyme-treated product according to the present invention can treat this chronic fatigue syndrome, that is, alleviate each symptom of chronic fatigue syndrome, shift to a normal state, and can prevent death from overwork. Is.
実施例にもとづいて本発明を詳細に説明するが、本発明はこれらのみに限定されるものではない。 The present invention will be described in detail based on examples, but the present invention is not limited to these examples.
＜ウシ初乳酵素処理物の調製＞
固体のウシ初乳（ｃｏｌｏｓｔｒｕＭｕｎｅ２５５０）１ｇを、１００ｍｌの５０ｍＭ ＳＰＢ（１５．６０１ｇのＮａＨ2ＰＯ4・２Ｈ2Ｏおよび３５．８１４ｇのＮａ2ＨＰＯ4・１２Ｈ2Ｏを、５００ｍｌの蒸留水に溶解して、２００ｍＭ ＳＰＢ（ｐＨ７．０）を調製し、これを希釈して、５０ｍＭ ＳＰＢとした。）で撹拌溶解し、１％溶液を調製した。その初乳液を８，０００ｒｐｍ、４℃で１時間遠心した。上清を、Ｇ２膜、８μｍ、５μｍ、１．２μｍ、０．２μｍ（ミリポア社、ニトロセルロースフィルター）で順次、ろ過処理した。ろ液を中空糸膜（旭化成ケミカルズ社、ペンシル型モジュールＳＥＰ−００１３）で透析処理した。
<Preparation of bovine colostrum enzyme-treated product>
1 g of solid bovine colostrum (colostru Mune 2550) was dissolved in 100 ml of 50 mM SPB (15.601 g NaH 2 PO 4 .2H 2 O and 35.814 g Na 2 HPO 4 · 12H 2 O in 500 ml distilled water. 200 mM SPB (pH 7.0) was prepared and diluted to 50 mM SPB. The colostrum was centrifuged at 8,000 rpm and 4 ° C. for 1 hour. The supernatant was sequentially filtered with G2 membrane, 8 μm, 5 μm, 1.2 μm, and 0.2 μm (Millipore, Nitrocellulose filter). The filtrate was dialyzed with a hollow fiber membrane (Asahi Kasei Chemicals Corporation, pencil type module SEP-0013).
初乳１ｍｇあたり、ホルミル樹脂（ＴＯＹＯＰＥＡＲＬ社、ＡＦ−Ｆｏｒｍｙ−６５０Ｍ）で固定化したβ−ガラクトシダーゼ（和光純薬工業（株）製、カタログＮｏ．０７２−０４１４１）を１Ｕ添加し、３７℃で１時間インキュベートした。インキュベート後、反応液をＧ２膜でろ過し、反応液中の固定化した酵素を除去した。ろ液は、０．２μｍでフィルター処理を行った。タンパク質濃度を、波長５７０ｎｍでの吸光度測定により決定したところ（ＢＳＡ（ｂｏｖｉｎｅ ｓｅｒｕｍ ａｌｂｕｍｉｎ、ＳＩＧＭＡ、Ａ４５０３）について作成した検量線を使用）、ウシ初乳１ｇから０．７４７ｇのタンパク質が回収されていた（検体１）。 1 mg of β-galactosidase (manufactured by Wako Pure Chemical Industries, Catalog No. 072-04141) immobilized with formyl resin (TOYOPEARL, AF-Formy-650M) was added per 1 mg of colostrum, and 1 at 37 ° C. Incubated for hours. After incubation, the reaction solution was filtered through a G2 membrane, and the immobilized enzyme in the reaction solution was removed. The filtrate was filtered at 0.2 μm. When the protein concentration was determined by measuring absorbance at a wavelength of 570 nm (using a calibration curve prepared for BSA (bovine serum albumin, SIGMA, A4503)), 0.747 g of protein was recovered from 1 g of bovine colostrum ( Sample 1).
かかる検体１を、冷却メタノールで急速凍結した後、−８０℃で静置して完全に凍結させた。これを真空乾燥して粉末化し、ウシ初乳酵素処理物とした。その一部を再溶解し、タンパク質濃度を、波長５７０ｎｍでの吸光度測定により決定したところ（ＢＳＡ（ｂｏｖｉｎｅ ｓｅｒｕｍ ａｌｂｕｍｉｎ、ＳＩＧＭＡ、Ａ４５０３）について作成した検量線を使用）、ウシ初乳１ｇから０．６２８ｇのタンパク質が回収されていた。 The specimen 1 was rapidly frozen with chilled methanol and then allowed to stand at −80 ° C. to be completely frozen. This was vacuum-dried to obtain a bovine colostrum enzyme-treated product. A part of the solution was redissolved and the protein concentration was determined by measuring absorbance at a wavelength of 570 nm (using a calibration curve prepared for BSA (bovine serum albumin, SIGMA, A4503)). From 1 g to 0.628 g of bovine colostrum Of protein was recovered.
＜試験例＞
上記で調製したウシ初乳酵素処理物を用いて、その中に含まれるタンパク質の量が１．０ｍｇとなるよう調整した腸溶性カプセルを、常法により調製した。該腸溶性カプセルを朝、晩の１日２回、被験者に投与した。結果を表１に示す。
<Test example>
Using the bovine colostrum enzyme-treated product prepared above, an enteric capsule adjusted so that the amount of protein contained therein was 1.0 mg was prepared by a conventional method. The enteric capsule was administered to the subject twice daily in the morning and evening. The results are shown in Table 1.
本発明によれば、疲労を伴う疾患の予防または改善に有用な、ウシ初乳酵素処理物を含んでなる予防改善剤、それを含んでなる飲食品および医薬品を提供することができる。 According to the present invention, it is possible to provide a preventive / ameliorating agent comprising a bovine colostrum enzyme-treated product, a food and drink and a pharmaceutical comprising the same, which are useful for preventing or ameliorating a disease accompanied by fatigue.
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