JP2017007947A - Body temperature reduction inhibitor - Google Patents
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Abstract
Description
本発明は、体温低下抑制剤に関する。より詳しくは、エネルギー代謝の低下に伴う体温低下の抑制剤及びエネルギー代謝低下の抑制剤に関する。 The present invention relates to a body temperature decrease inhibitor. More specifically, the present invention relates to an inhibitor of a decrease in body temperature accompanying a decrease in energy metabolism and an inhibitor of a decrease in energy metabolism.
一般的に加齢に伴い体温が下がることが知られており、近年では、子供や女性においても低体温の人が増加していることが提唱されている。低体温は、免疫力低下、冷え性、新陳代謝の低下など様々な不具合につながることが考えられ、体温を上昇させることは健康を維持するために重要であると考えられる。 In general, it is known that the body temperature decreases with aging. In recent years, it has been proposed that the number of hypothermia is increasing in children and women. Hypothermia may lead to various problems such as decreased immunity, coolness, and decreased metabolism, and raising body temperature is considered important for maintaining health.
非特許文献１において体温と腸内環境には関連があることが分かっており、腸内で作用する乳酸菌の中には体温を高める効果を有するものが知られている。特許文献１にはラクトバチラス・ブレビス ＳＢＣ８８０３が、非特許文献２にはラクトバチラス・パラカゼイ ＳＴ１１が、非特許文献３にはラクトバチラス・プランタラム Ｎｏ．１４がそれぞれ体温上昇効果を示すことが記載されている。 Non-Patent Document 1 shows that there is a relationship between body temperature and intestinal environment, and some lactic acid bacteria that act in the intestine have an effect of increasing body temperature. Patent Document 1 discloses Lactobacillus brevis SBC8803, Non-Patent Document 2 includes Lactobacillus paracasei ST11, Non-Patent Document 3 discloses Lactobacillus plantarum No. It is described that 14 shows the body temperature raising effect.
しかしながら、特許文献１に記載されている菌株は、体温上昇効果が認められているものの、その効果はストレス負荷による体温低下を抑制することで、正常時に近い体温を維持していることが分かる(特許文献１の図１)。よって、ストレス負荷が原因ではない体温低下に対しては、その効果は不明である。また、非特許文献２に記載されている菌株は摂取後２〜３時間において有意な体温上昇効果が認められ(非特許文献２の図１)、非特許文献３に記載されている菌株は摂取後１時間までの体温上昇効果が認められ(非特許文献３の図４)、いずれも一過性の効果として考えられる。 However, although the strain described in Patent Document 1 has an effect of increasing body temperature, it is understood that the effect maintains body temperature close to normal by suppressing body temperature decrease due to stress load ( FIG. 1 of Patent Document 1). Therefore, the effect is unclear for a decrease in body temperature that is not caused by a stress load. In addition, the strain described in Non-Patent Document 2 has a significant effect of increasing body temperature 2 to 3 hours after ingestion (FIG. 1 of Non-Patent Document 2), and the strain described in Non-Patent Document 3 is ingested. The effect of increasing body temperature up to 1 hour later was observed (FIG. 4 of Non-Patent Document 3), both of which are considered as transient effects.
本発明の課題は、エネルギー代謝の低下に伴う体温低下を継続して抑制する抑制剤を提供することにある。 The subject of this invention is providing the inhibitor which suppresses the body temperature fall accompanying the fall of energy metabolism continuously.
本発明者らが鋭意検討した結果、ラクトバチルス・ペントーサス ＴＵＡ４３３７Ｌを継続投与することにより、ストレス環境下に限定されず、また一過性の効果ではなく、体質を改善させることによって体温低下を抑制することを見出し、本発明を完成するに至った。 As a result of intensive studies by the present inventors, continuous administration of Lactobacillus pentosaus TUA4337L is not limited to a stress environment, and is not a transient effect, but suppresses a decrease in body temperature by improving the constitution. As a result, the present invention has been completed.
即ち、本発明は、下記〔１〕〜〔２〕に関する。
〔１〕 ラクトバチルス・ペントーサス ＴＵＡ４３３７Ｌ株（受託番号ＮＩＴＥ ＢＰ-１４７９）の菌体又はその処理物を有効成分とする、エネルギー代謝の低下に伴う体温低下の抑制剤。
〔２〕 ラクトバチルス・ペントーサス ＴＵＡ４３３７Ｌ株（受託番号ＮＩＴＥ ＢＰ-１４７９）の菌体又はその処理物を有効成分とする、エネルギー代謝低下の抑制剤。
That is, the present invention relates to the following [1] to [2].
[1] Lactobacillus pentosasus TUA4337L strain (Accession No. NITE BP-1479) or a processed product thereof as an active ingredient is an inhibitor of a decrease in body temperature accompanying a decrease in energy metabolism.
[2] Lactobacillus pentosasus TUA4337L strain (Accession number NITE BP-1479) or a processed product thereof as an active ingredient is an inhibitor of a decrease in energy metabolism.
本発明の体温低下の抑制剤は、エネルギー代謝そのものを亢進することで、体温低下を抑制することができるという優れたものである。 The body temperature decrease inhibitor of the present invention is excellent in that it can suppress the decrease in body temperature by enhancing energy metabolism itself.
従来、エネルギー代謝は、加齢、血行不良、運動不足、自立神経調節不足、栄養不足、エネルギー不足、筋肉量の減少等により低下し、ひいては体温も低下することが知られている。また、近年においては、高脂肪食を摂取し続けてもエネルギー代謝が徐々に低下して体温が低下することも分かってきた。このように体温が持続的に低温となる原因が様々に考えられるところ、本願発明においては、特定の乳酸菌をエネルギー代謝が低下した人に投与することで、エネルギー代謝が亢進して、体温の低下が抑制され、ひいては体温が上昇して低体温を改善することを見出した。即ち、本発明は、エネルギー代謝の低下に伴う体温低下を抑制するために、ラクトバチルス・ペントーサス ＴＵＡ４３３７Ｌ株の菌体又はその処理物を用いることを特徴とする。このような効果が奏される詳細なる理由は不明なるも、腸内で生体に直接作用する、もしくは腸内環境改善を介して間接的に作用すると推定される。ただし、これらの推測は、本発明を限定するものではない。なお、生体の体温は身体深部の温度を表す深部体温と体表面の温度を表す体表面温の二つに大別することができるが、本明細書における体温とはどちらかに限定したものではなく、例えば人の場合、腋下温、口腔（舌下）温、直腸温などを意味する。 Conventionally, it is known that energy metabolism decreases due to aging, poor circulation, lack of exercise, lack of independent nerve regulation, lack of nutrition, lack of energy, decrease in muscle mass and the like, and thus body temperature. In recent years, it has also been found that even if a high-fat diet is continued, energy metabolism gradually decreases and body temperature decreases. There are various reasons why the body temperature is continuously lowered. In the present invention, by administering a specific lactic acid bacterium to a person with reduced energy metabolism, energy metabolism is promoted and the body temperature is lowered. Was found to be suppressed, and as a result, the body temperature rose to improve hypothermia. That is, the present invention is characterized by using a cell of Lactobacillus pentosasus TUA4337L strain or a processed product thereof in order to suppress a decrease in body temperature accompanying a decrease in energy metabolism. Although the detailed reason for such an effect is unclear, it is presumed to act directly on the living body in the intestine or indirectly through improvement of the intestinal environment. However, these assumptions do not limit the present invention. The body temperature of a living body can be broadly divided into a deep body temperature that represents the temperature of the deep body and a body surface temperature that represents the temperature of the body surface, but the body temperature in this specification is not limited to either one. For example, in the case of human beings, it means armpit temperature, oral (sublingual) temperature, rectal temperature, and the like.
本発明におけるラクトバチルス・ペントーサス ＴＵＡ４３３７Ｌ株は、識別の表示ＮＲＩＣ ０８８３、受託番号ＮＩＴＥ ＢＰ−１４７９として、国際受託日２０１２年１２月１０日付で、独立行政法人 製品評価技術基盤機構 特許微生物寄託センター（日本国千葉県木更津市かずさ鎌足２−５−８）に寄託されたものである。以下、ラクトバチルス・ペントーサス ＴＵＡ４３３７Ｌ株のことを、ＴＵＡ４３３７Ｌ株と略記する。 The Lactobacillus pentosasus TUA4337L strain in the present invention has the identification NRIC 0883 and the accession number NITE BP-1479 as of December 10, 2012, and is incorporated by the National Institute of Technology and Evaluation, Japan It has been deposited with Kazusa Kamashima 2-5-8) in Kisarazu City, Chiba Prefecture. Hereinafter, Lactobacillus pentosasus TUA4337L strain is abbreviated as TUA4337L strain.
ＴＵＡ４３３７Ｌ株の菌体の形態としては、生菌及び死菌のいずれであってもよい。生菌は、例えば、当該乳酸菌株を培養することにより得ることができる。死菌は、例えば、生菌に対して加熱、紫外線照射、ホルマリン処理、酸処理などを行うことにより得ることができる。 The cell form of the TUA4337L strain may be either live or dead. Live bacteria can be obtained, for example, by culturing the lactic acid strain. Dead bacteria can be obtained, for example, by subjecting live bacteria to heating, ultraviolet irradiation, formalin treatment, acid treatment, and the like.
ＴＵＡ４３３７Ｌ株を培養するための培地としては、特に制限されず、通常の、炭素源、窒素源、無機塩類、有機栄養素などを含む培地が挙げられる。また、寒天培地や液体培地での培養も可能である。培養温度は、好ましくは１０〜４５℃、より好ましくは１５〜４２℃、さらに好ましくは２８〜３８℃、さらに好ましくは３５〜３７℃であり、増殖可能ｐＨは、好ましくはｐＨ３．０〜１２．５、より好ましくはｐＨ３．５〜１２．０である。 The medium for culturing the TUA4337L strain is not particularly limited, and examples thereof include a normal medium containing a carbon source, a nitrogen source, inorganic salts, organic nutrients, and the like. In addition, culture on an agar medium or liquid medium is also possible. The culture temperature is preferably 10 to 45 ° C., more preferably 15 to 42 ° C., further preferably 28 to 38 ° C., further preferably 35 to 37 ° C., and the proliferative pH is preferably pH 3.0 to 12. 5, more preferably pH 3.5 to 12.0.
また、菌体の処理物としては、得られた生菌、死菌に対して、磨砕や破砕等の公知の処理を行ったものが挙げられる。具体的には、磨砕物、破砕物、液状物（抽出液等）、濃縮物、ペースト化物、乾燥物（噴霧乾燥物、凍結乾燥物、真空乾燥物、ドラム乾燥物等）、希釈物等を挙げることができる。 Moreover, as a processed material of a microbial cell, what performed well-known processes, such as grinding and crushing, with respect to the obtained live microbe and dead microbe is mentioned. Specifically, ground, crushed, liquid (extracted liquid, etc.), concentrated, pasted, dried (spray dried, lyophilized, vacuum dried, drum dried, etc.), diluted, etc. Can be mentioned.
本発明の体温低下の抑制剤は、前記したＴＵＡ４３３７Ｌ株の菌体又はその処理物を有効成分として含有することで、エネルギー代謝の低下に伴う体温低下を抑制するために使用することができるが、その作用効果の関係からすると、ストレスが負荷された際に体温が低下するといった一過性の原因による体温低下を抑制するのではなく、持続的にエネルギー代謝を亢進して体温低下を抑制するものである。よって、本発明はまた、ＴＵＡ４３３７Ｌ株の菌体又はその処理物を有効成分とするエネルギー代謝低下の抑制剤を提供する。本発明の体温低下の抑制剤及び本発明のエネルギー代謝低下の抑制剤は、ストレス負荷に起因しない体温低下に対しても体温低下を抑制することができるという優れた効果を奏する。なお、以降、本発明の体温低下の抑制剤及び本発明のエネルギー代謝低下の抑制剤をまとめて、本発明の抑制剤と記載することがある。 The body temperature decrease inhibitor of the present invention can be used to suppress a decrease in body temperature associated with a decrease in energy metabolism by containing the above-described cells of TUA4337L strain or a processed product thereof as an active ingredient. In terms of the relationship between its effects, it does not suppress a decrease in body temperature due to a temporary cause such as a decrease in body temperature when stress is applied, but it continuously increases energy metabolism to suppress a decrease in body temperature. It is. Therefore, this invention also provides the inhibitor of the energy metabolism fall which uses the microbial cell of TUA4337L strain, or its processed material as an active ingredient. The body temperature lowering inhibitor of the present invention and the energy metabolism lowering inhibitor of the present invention have an excellent effect of being able to suppress a body temperature decrease even with respect to a body temperature decrease not caused by a stress load. Hereinafter, the body temperature decrease inhibitor of the present invention and the energy metabolism decrease inhibitor of the present invention may be collectively referred to as the inhibitor of the present invention.
本発明の抑制剤は、ＴＵＡ４３３７Ｌ株の菌体又はその処理物を含有するのであれば、その他の成分は特に限定されない。本発明の抑制剤におけるＴＵＡ４３３７Ｌ株の菌体又はその処理物の含有量としては通常０．００００１〜１００重量％程度である。また、菌体数としては、１．０×１０２〜１．０×１０１２個／ｇの範囲内であることが好ましく、１．０×１０６〜１．０×１０１２個／ｇの範囲内であることがより好ましい。上記「個／ｇ」は生菌又は死菌では「ＣＦＵ／ｇ」と表すことができる。 If the inhibitor of this invention contains the microbial cell of TUA4337L strain, or its processed material, another component will not be specifically limited. The content of the cells of TUA4337L strain or the processed product thereof in the inhibitor of the present invention is usually about 0.00001 to 100% by weight. In addition, the number of cells is preferably in the range of 1.0 × 10 2 to 1.0 × 10 12 cells / g, and is 1.0 × 10 6 to 1.0 × 10 12 cells / g. More preferably within the range. The above “number / g” can be expressed as “CFU / g” in live or dead bacteria.
また、本発明の抑制剤は、ＴＵＡ４３３７Ｌ株の菌体又はその処理物が経口投与できるのであれば、その形態は限定されない。例えば、ＴＵＡ４３３７Ｌ株の菌体又はその処理物に、所望により溶剤、分散剤、乳化剤、緩衝剤、安定剤、賦形剤、結合剤、崩壊剤、滑沢剤等を加えて、公知の方法に従って、錠剤、顆粒剤、散剤、粉末剤、カプセル剤等の固形剤や、通常液剤、懸濁剤、乳剤等の液剤等に製剤化することもできる。 In addition, the form of the inhibitor of the present invention is not limited as long as the cells of TUA4337L strain or a processed product thereof can be administered orally. For example, a solvent, a dispersant, an emulsifier, a buffer, a stabilizer, an excipient, a binder, a disintegrant, a lubricant, etc. are added to the cells of the TUA4337L strain or the treated product, if desired, and according to a known method. Further, it can be formulated into solid preparations such as tablets, granules, powders, powders and capsules, and liquid preparations such as normal solutions, suspensions and emulsions.
本発明の抑制剤の投与量は、その形態や投与目的、当該抑制剤の投与対象の種類、年齢、体重、症状によって適宜設定され一定ではない。例えば、本発明におけるＴＵＡ４３３７Ｌ株の菌体又はその処理物の有効ヒト投与量としては、菌体数として、体重５０ｋｇのヒトで１日当たり、好ましくは２．０×１０６個以上、より好ましくは２．０×１０７個以上、さらに好ましくは２．０×１０８個以上、さらに好ましくは１．０×１０９個以上であり、好ましくは２．０×１０１３個以下、より好ましくは２．０×１０１２個以下、さらに好ましくは２．０×１０１１個以下、さらに好ましくは５．０×１０９個以下である。また、乾燥重量としては、体重５０ｋｇのヒトで１日当たり、好ましくは２．８×１０−６ｇ以上、より好ましくは２．８×１０−５ｇ以上、さらに好ましくは２．８×１０−４ｇ以上、さらに好ましくは１．４×１０−３ｇ以上であり、好ましくは２．８×１０ｇ以下、より好ましくは２．８ｇ以下、さらに好ましくは２．８×１０−１ｇ以下、さらに好ましくは７．０×１０−３ｇ以下である。投与は、所望の投与量範囲内において、１日内において単回で又は数回に分けて行ってもよい。投与期間も任意である。本発明においては、前記有効量の範囲内において投与する場合に、投与時の呈味を邪魔することなく、より強力なエネルギー代謝の低下を抑制する作用を示し、かつ、その効果が投与期間中は投与する限り維持されるという優れた効果を奏するものである。 The dose of the inhibitor of the present invention is appropriately set according to the form and purpose of administration, the type of administration target of the inhibitor, age, weight, and symptoms, and is not constant. For example, the effective human dosage of the cells of TUA4337L strain or treated product thereof in the present invention is preferably 2.0 × 10 6 or more, more preferably 2 per day for a human body weight of 50 kg as the number of cells. 0.0 × 10 7 or more, more preferably 2.0 × 10 8 or more, further preferably 1.0 × 10 9 or more, preferably 2.0 × 10 13 or less, more preferably 2. 0 × 10 12 or less, more preferably 2.0 × 10 11 or less, and further preferably 5.0 × 10 9 or less. The dry weight is preferably 2.8 × 10 −6 g or more, more preferably 2.8 × 10 −5 g or more, and further preferably 2.8 × 10 −4 per day for a human with a body weight of 50 kg. g or more, more preferably 1.4 × 10 −3 g or more, preferably 2.8 × 10 g or less, more preferably 2.8 g or less, still more preferably 2.8 × 10 −1 g or less, further preferably Is 7.0 × 10 −3 g or less. Administration may be performed once or divided into several times within one day within a desired dose range. The administration period is also arbitrary. In the present invention, when administered within the range of the effective amount, without disturbing the taste at the time of administration, it exhibits the action of suppressing a more powerful decrease in energy metabolism, and the effect is during the administration period. Has an excellent effect of being maintained as long as it is administered.
本明細書中において本発明の抑制剤の投与対象とは、好ましくはエネルギー代謝の低下に伴う体温低下の抑制を必要とするヒトであるが、ウシ、ウマ、ヤギ等の家畜動物、イヌ、ネコ、ウサギ等のペット動物、又は、マウス、ラット、モルモット、サル等の実験動物であってもよい。また、投与対象として、エネルギー代謝の低下に伴う体温低下が認められる個体だけでなく、体温低下は認められないが、エネルギー代謝の低下が気になる個体、エネルギー代謝の低下を予防したい個体、脂肪の摂取量の多い個体、脂肪の摂取量が気になる個体など、エネルギー代謝の低下や改善を予防することを望む個体、ＴＵＡ４３３７Ｌ株の菌体又はその処理物が配合されている旨の表示を観て、健康に良いので服用したいと考える潜在的な個体も含まれる。またさらに、体温低下やエネルギー代謝の低下を抑制することにより治療効果がみられる疾患を有する対象でもよい。例えば、体脂肪蓄積、低血圧、内臓機能低下（便秘・下痢）、血行不良（冷え症・肩こり・腰痛・関節痛）、睡眠障害、うつ等の症状を有する対象が例示される。 In the present specification, the subject of administration of the inhibitor of the present invention is preferably a human who needs to suppress a decrease in body temperature accompanying a decrease in energy metabolism, but a domestic animal such as a cow, a horse, a goat, a dog, a cat, etc. It may be a pet animal such as a rabbit, or a laboratory animal such as a mouse, rat, guinea pig or monkey. In addition, not only individuals with a decrease in body temperature due to a decrease in energy metabolism but also individuals who are not concerned about a decrease in body temperature but are concerned about a decrease in energy metabolism, individuals who want to prevent a decrease in energy metabolism, fat Individuals who want to prevent the decrease or improvement of energy metabolism, such as individuals with a high intake of fat, individuals who are worried about the intake of fat, display that the cells of TUA4337L strain or its processed products are blended It also includes potential individuals who want to take it because they are healthy. Furthermore, it may be a subject having a disease that shows a therapeutic effect by suppressing a decrease in body temperature or a decrease in energy metabolism. For example, subjects having symptoms such as body fat accumulation, hypotension, visceral function decline (constipation / diarrhea), poor circulation (coldness / stiff shoulders / lumbar pain / joint pain), sleep disorder, depression and the like are exemplified.
以下、実施例を示して本発明を具体的に説明するが、本発明は下記実施例に制限されるものではない。 EXAMPLES Hereinafter, although an Example is shown and this invention is demonstrated concretely, this invention is not restrict | limited to the following Example.
試験例１
高脂肪食の摂取を続けることにより体重当りのエネルギー代謝が低下することが知られていることから、高脂肪食マウスを用いてＴＵＡ４３３７Ｌ株の菌体又はその処理物によるエネルギー代謝亢進作用を検討した。
Test example 1
Since it is known that energy metabolism per body weight decreases by continuing to ingest a high fat diet, the energy metabolism enhancing effect of cells of TUA4337L strain or its treated product was examined using high fat diet mice. .
具体的には、C57BL／6Jマウス（７週齢、雄）を１週間馴化させた後に、体重の平均値に差が出ないようコントロール群とＴＵＡ４３３７Ｌ群に群分けした（各ｎ＝４）。その後、エネルギー代謝測定装置（オキシマックス：バイオリサーチセンター）の代謝ケージにマウスを入れ、２日間環境に慣れさせた後に、コントロール群には高脂肪食（表１）を与え、ＴＵＡ４３３７Ｌ群には前記高脂肪食にＴＵＡ４３３７Ｌ株の凍結乾燥菌体（8.8×1011cells/g）が0.31％配合された組成物（マウスが１日あたり5.0×109億個(7.0×10-3g)の菌体数が投与できるように配合）を与え、それぞれ飼育した。各飼料は自由摂取させた。また代謝ケージにて飼育している最中では摂餌量を測ることが出来ないことから、代謝ケージでの飼育開始後から１４日目に代謝ケージから出して群飼を行い、３週目（１４〜２２日目）の摂餌量を算出した（図１）。 Specifically, after acclimating C57BL / 6J mice (7 weeks old, male) for 1 week, they were divided into a control group and a TUA4337L group so that there was no difference in the average body weight (each n = 4). Then, after putting the mouse in the metabolic cage of the energy metabolism measuring device (Oxymax: Bioresearch Center) and getting used to the environment for 2 days, the control group was given a high fat diet (Table 1), and the TUA4337L group was Composition containing 0.31% lyophilized cells of TUA4337L strain (8.8 × 10 11 cells / g) in a high fat diet (5.0 × 10 9 billion mice (7.0 × 10 −3 g) per day) Formulated so that the number of animals can be administered, and each was raised. Each feed was ad libitum. In addition, during feeding in metabolic cages, food intake cannot be measured, so the animals were taken out of the metabolic cages on the 14th day after the start of feeding in the metabolic cages, and the groups were kept in the 3rd week ( The amount of food intake on day 14-22) was calculated (FIG. 1).
図１から摂餌量は各群で差はなく、ＴＵＡ４３３７Ｌ株の菌体又はその処理物を配合することや投与することが摂餌量に影響を与えないことが示唆された。 From FIG. 1, there was no difference in the amount of food intake in each group, and it was suggested that blending and administration of the cells of TUA4337L strain or its treated product did not affect the food intake.
また、飼育期間中の酸素消費量（VO2(mL/kg/hr)）及び排出二酸化炭素排出量(VCO2(mL/kg/hr))から、下式に基づいて、１週目（２〜５日目）、２週目（７〜１３日目）、４週目（２３〜２８日目）の消費カロリーの平均値を算出した。結果を図２に示す。
消費カロリー：VO2×（ＲＥＲ×1.232＋3.815）／1000
呼吸商（ＲＥＲ）：VCO2／VO2
In addition, from the oxygen consumption during the breeding period (VO 2 (mL / kg / hr)) and the discharged carbon dioxide emissions (VCO 2 (mL / kg / hr)), the first week (2 ˜5 days) The average value of calories burned in the 2nd week (7th to 13th day) and 4th week (23th to 28th day) was calculated. The results are shown in FIG.
Calories burned: VO 2 × (RER × 1.232 + 3.815) / 1000
Respiratory quotient (RER): VCO 2 / VO 2
図２から、２週目において、ＴＵＡ４３３７Ｌ群で有意に消費カロリーが上昇していた。よって、ＴＵＡ４３３７Ｌ株の菌体を投与することによってエネルギー代謝が亢進されることが示された。 From FIG. 2, the calorie consumption increased significantly in the TUA4337L group at the second week. Therefore, it was shown that energy metabolism is promoted by administering the cells of the TUA4337L strain.
試験例２
ＴＵＡ４３３７Ｌ株の菌体又はその処理物による体温低下抑制作用の用量依存性を検討した。
Test example 2
The dose dependency of the body temperature decrease-inhibiting action of the TUA4337L strain or its treated product was examined.
具体的には、ICRマウス（８週齢、雄）を１週間馴化させた後に、体重の平均値に差が出ないようコントロール群、ＴＵＡ４３３７Ｌ低用量群、ＴＵＡ４３３７Ｌ高用量群に群分けした（各ｎ＝８）。その後、餌を高脂肪食（表１）に切り替え、コントロール群にはＰＢＳ（−）を２５０μＬ、ＴＵＡ４３３７Ｌ低用量群にはＴＵＡ４３３７Ｌ株の凍結乾燥菌体（１回あたり1.0×109個(1.4×10-3g)の菌体数）をＰＢＳに分散させたもの２５０μＬ、ＴＵＡ４３３７Ｌ高用量群にはＴＵＡ４３３７Ｌ株の凍結乾燥菌体（１回あたり５.0×109個(7.0×10-3g)の菌体数）をＰＢＳに分散させたもの２５０μＬ、それぞれ１日１回経口投与を行った。経口投与を４週間連続し、最後の投与（午前中）を実施してから４時間以上経過した時点で体温（直腸温）を専用プローブにて測定した。結果を図３に示す。 Specifically, after ICR mice (8 weeks old, male) were acclimatized for 1 week, they were grouped into a control group, a TUA4337L low-dose group, and a TUA4337L high-dose group so that there was no difference in the average body weight (each n = 8). Thereafter, the diet was switched to a high fat diet (Table 1), 250 μL of PBS (−) was used for the control group, and TUA4337L lyophilized cells (1.0 × 10 9 cells per time (1.4 ×) were used for the TUA4337L low dose group. 10 −3 g)) dispersed in PBS, 250 μL, TUA4337L high-dose group, freeze-dried cells of TUA4337L strain (5.0 × 10 9 cells per time (7.0 × 10 −3 g) ) Was dispersed orally in PBS, and each was orally administered once a day. Oral administration was continued for 4 weeks, and body temperature (rectal temperature) was measured with a dedicated probe when 4 hours or more had passed since the last administration (in the morning). The results are shown in FIG.
図３から、コントロール群と比較してＴＵＡ４３３７Ｌの低用量群、高用量群ともに効果が認められ、特に高用量群で有意な体温上昇が認められた（＊＊：p<0.01 Dunnett’s test）。よって、ＴＵＡ４３３７Ｌ株の投与菌体数が多い程、その効果が顕著となることが示された。また、最後の投与後４時間経過した時点で測定したものであることを考慮すると、ＴＵＡ４３３７Ｌ株の菌体又はその処理物の効果は一過性ではないことも分かる。 As shown in FIG. 3, the effects of both the low dose group and the high dose group of TUA4337L were observed compared to the control group, and a significant increase in body temperature was observed particularly in the high dose group (**: p <0.01 Dunnett's test). Therefore, it was shown that the effect becomes remarkable, so that there are many administration cells of TUA4337L strain. Moreover, when it considers that it measured when 4 hours passed after the last administration, it turns out that the effect of the microbial cell of TUA4337L strain or its processed material is not transient.
本発明の体温低下の抑制剤は、エネルギー代謝そのものを亢進することで、体温低下を抑制することができることから、例えば、体脂肪蓄積、低血圧、内臓機能低下（便秘・下痢）、血行不良（冷え症・肩こり・腰痛・関節痛）、睡眠障害、うつ等の症状等の予防又は改善に有用である。 Since the body temperature decrease inhibitor of the present invention can suppress body temperature decrease by enhancing energy metabolism itself, for example, body fat accumulation, hypotension, visceral function decrease (constipation / diarrhea), poor circulation ( It is useful for the prevention or improvement of symptoms such as coldness, stiff shoulders, low back pain, and joint pain), sleep disorders, and depression.
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| JP2019218324A (en) * | 2018-06-22 | 2019-12-26 | 花王株式会社 | Agent for improving hypothermia |
| CN114410547A (en) * | 2022-02-25 | 2022-04-29 | 西南大学 | Lactobacillus pentosus LPQ1 capable of promoting secretion of 5-HTP and relieving depression and application thereof |
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| JP2019083713A (en) * | 2017-11-02 | 2019-06-06 | 大塚食品株式会社 | Beverage food product composition for remedying cold body |
| JP7027126B2 (en) | 2017-11-02 | 2022-03-01 | 大塚食品株式会社 | Food and beverage composition for improving coldness of the body |
| JP2019218324A (en) * | 2018-06-22 | 2019-12-26 | 花王株式会社 | Agent for improving hypothermia |
| CN114410547A (en) * | 2022-02-25 | 2022-04-29 | 西南大学 | Lactobacillus pentosus LPQ1 capable of promoting secretion of 5-HTP and relieving depression and application thereof |
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