WO2004047565A1 - Agent for foods, drinks or medical uses containing body temperature-elevating amino acid - Google Patents

Agent for foods, drinks or medical uses containing body temperature-elevating amino acid Download PDF

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Publication number
WO2004047565A1
WO2004047565A1 PCT/JP2003/014740 JP0314740W WO2004047565A1 WO 2004047565 A1 WO2004047565 A1 WO 2004047565A1 JP 0314740 W JP0314740 W JP 0314740W WO 2004047565 A1 WO2004047565 A1 WO 2004047565A1
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Prior art keywords
amino acid
tyrosine
body temperature
agent
amino acids
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PCT/JP2003/014740
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French (fr)
Japanese (ja)
Inventor
Hajime Tsunoo
Masayuki Uchida
Takae Wakabayashi
Yasuko Sawai
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Meiji Dairies Corporation
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Priority to AU2003302374A priority Critical patent/AU2003302374A1/en
Publication of WO2004047565A1 publication Critical patent/WO2004047565A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/195Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
    • A61K31/198Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17Amino acids, peptides or proteins
    • A23L33/175Amino acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/06Antihyperlipidemics
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention relates to a food or drink or medical agent effective for increasing body temperature. More specifically, the agent of the present invention comprises a specific amino acid, particularly tyrosine, as an active ingredient. It has an excellent physiological effect, especially an excellent body temperature increasing effect. Further, the agent according to the present invention promotes metabolism in the body by the action of increasing body temperature, thereby improving basal metabolism, further reducing body fat accumulation, improving coldness, and as a means for warming a body cooled in a cold region. Is also effective. Conventional technology
  • Patent Document 1 Japanese Patent Application Laid-Open No. 2000-20089
  • Cabsaicins which are said to have a body temperature increasing effect, are pungent components contained in pepper. If you add a large amount of capsaicin, you will feel strong spiciness. Had restrictions. In order to warm the body, a method of ingesting warm food and drink and taking in heat into the body can be considered, but this has a temporary effect. Therefore, a composition having an effect of improving energy and metabolism is required to be able to obtain the effect promptly, to continue its action after that, and to have good palatability when taken orally. Means for solving the problem
  • the present inventors have focused on a large number of amino acid compositions as a result of studies from various directions.
  • a very large number of amino acid compositions were prepared by changing the types of amino acids, their combinations, and the amounts thereof, and the physiological effects of these amino acid compositions were thoroughly examined.
  • they found for the first time an amino acid composition of a specific composition that raises basal body temperature and lasts for a long time, and as a result of further study of these amino acid group compositions, a composition with a high content of tyrosine was found.
  • the present inventors conducted a study focusing on this tyrosine, identified it as an amino acid that increased body temperature, confirmed the effect of increasing the body temperature of tyrosine only by this amino acid by an in vivo test, and conducted further studies. Finally, the present invention has been completed.
  • the present inventors have also confirmed for the first time that, in the course of the above method, when tyrosine was used in combination with aspartic acid, glutamic acid, and alanine, only these four amino acids exhibited an excellent body temperature increasing effect. As a result of further research, the present invention has finally been completed.
  • 4 is a graph showing the average of the maximum basal body temperature increase when rats were administered tyrosine at each dose.
  • 1 is a graph showing the average of the highest basal body temperature increase when the amino acid composition (four amino acids) according to the present invention is administered to rats.
  • the present invention has been made for the first time to determine that the body of the body temperature increasing amino acid is tyrosine, wherein the active ingredient of the agent according to the present invention is tyrosine.
  • the active ingredient of the agent according to the present invention is tyrosine.
  • the above-mentioned four kinds of amino acids (four kinds of amino acids) containing tyrosine (one kind of amino acids) also have an excellent body temperature increasing effect, and can be used as an active ingredient of the agent according to the present invention.
  • various amino acids can be used, both natural products (including those produced by fermentation) and synthetic products.
  • the L-form is preferable to the D-form, but the racemic form can also be used. is there. Therefore, in the agent according to the present invention containing only tyrosine as the active ingredient as the active ingredient, the active ingredient is only tyrosine, and in addition to tyrosine, other amino acids, peptides, foods and other body temperature increasing ingredients as active ingredients It does not refer to the combination of. The same applies to the case of four amino acids.
  • the agent according to the present invention contains tyrosine alone or only four amino acids of tyrosine, aspartic acid, glutamic acid, and alanine as active ingredients.
  • the active ingredient of the agent according to the present invention is as follows: 1 and 2.
  • the mixing ratio (% by weight) of each amino acid can be, for example, as follows.
  • the agent according to the present invention contains tyrosine as an active ingredient.
  • Tyrosine may be used alone or may coexist with other amino acids to form an amino acid group (four amino acids).
  • Each amino acid is preferably contained in a specific composition ratio, and is shown below. That is, each amino acid is tyrosine 0.5 to 15 mol or more, aspartic acid 0.02 to 0.4 mol, gnoretamic acid 0.3 to 7 monole, and aranine 0.7 to 1
  • tyrosine-containing amino acids four amino acids (4AA) constituting the active ingredient of the agent according to the present invention are shown in Table 1 below.
  • T yr% 38.8 51.2 The food, drink, or medical agent related to the present study that has increased body temperature and contains only tyrosine or only four amino acids containing tyrosine as an amino acid is a component or an active ingredient.
  • the active ingredient alone may be orally ingested in the form of a powder or an aqueous solution without or without mixing, but the contained or active ingredient may be liquid or solid and taste If it is not good, or if it is difficult to swallow, use the contained or active ingredients and additives that are commonly used for eating and drinking or medical use to improve the taste It is better to make it easier to drink or to make the whole biscuit easier to eat.
  • the drinks can be made easier only by adding a souring agent such as citric acid or a sweetener such as sugar to the aqueous liquid containing or containing the active ingredient.
  • a souring agent such as citric acid or a sweetener such as sugar
  • a sweetener such as sugar
  • Addition of purified starch, etc. to the active ingredient in a powder-mixed state, mixing, baking, and biscuit form makes it possible to eat deliciously.
  • the food or drink or medical agent for increasing body temperature may be ingested as a powder or may be dissolved in water and ingested as an aqueous solution or the like.
  • the ingestion method may be oral administration, rectal administration, intravenous injection, intravenous drip, and other general administration routes.
  • oral administration in addition to making it easy to drink and eat for eating and drinking, it is mixed with pharmaceutically acceptable carriers, excipients and diluents, and powders, granules, tablets, forcepsels, It may be used as a mouthpiece.
  • solid powders and tablets may require time for absorption, so it is preferable to administer the active ingredient orally.
  • it may be administered as a solution as described above together with a suitable additive, for example, a salt such as sodium chloride, a pH adjusting agent, and a chelating agent.
  • a suitable additive for example, a salt such as sodium chloride, a pH adjusting agent, and a chelating agent.
  • an appropriate buffer and isotonic agent may be added and dissolved in sterile distilled water.
  • tyrosine as an active ingredient so as to contain at least 25 mg, preferably at least 250 mg, more preferably at least 2.5 g per 2 OO m1 of the drink. is there.
  • the dosage of the food or drink or medical agent of the present invention can be set in a wide range,
  • 0.1 to 5 g of active ingredient is usually administered at a time depending on the method and purpose of use.
  • When administered or ingested as a solution is 10 to once as a solution of about 0.05 to 10 wt ° / 0 1000 m l, preferably 100 to 500 meters l administration or once a 1-4 wt ° / 0 Ingest.
  • the food or drink or medical agent according to the present invention has an excellent basal body temperature-increasing action, increases basal metabolism, and consumes energy in daily life. As a result, body fat is burned, and as a result, it is also effective in reducing body fat accumulation and improving coldness. Therefore, various pharmaceuticals such as a body temperature increasing agent and an anti-chilling agent can be prepared by formulating the active ingredient as a medicament.
  • the food or drink or medical agent according to the present invention has an extremely effective effect of increasing body temperature, and when used, it may be used as a powder.
  • the composition of the present invention may be dissolved directly in water to prepare a solution, or each amino acid may be separately dissolved in water to realize the above-described composition in the solution.
  • amino acids tyrosine, aspartic acid, glutamic acid, alanine
  • amino acid tyrosine
  • the mixing ratio is as shown in Table 1, but the mixing ratio of the four amino acids is as follows.
  • the amino acid (tyrosine) was determined based on the mixing ratio of the four amino acids.
  • all amino acids were obtained from Wako Pure Chemical Industries, Ltd.
  • One group was used as a control (water for injection).
  • the four amino acids were orally administered once at 0.5 g / 100 g body weight (5 g / kg).
  • Groups 3 to 5 were treated with a single amino acid group, tyrosine 0.25 g / 10 Og body weight (2.5 g / kg) for group 3, and tyrosine 0.
  • Oral administration of tyrosine once per 25 g / 100 g body weight (1.25 g / kg) did.
  • one group was prepared with a control (water for injection), and the test was performed. .
  • test substance amino acid was suspended in physiological saline, and only saline (Hikari Pharmaceutical Co., Ltd., Japanese Pharmacopoeia physiological saline, Lot. 9911HC) was administered to the control port. . (4) Body temperature measurement
  • the animals were kept in a ballman cage and a probe for measuring the body temperature was inserted into the rectum from the anus and fixed. Measurements were taken every 10 to 15 minutes. When the body temperature stabilized, the test substance was administered, and the body temperature was measured every 10 minutes until 90 minutes later, based on the temperature at the time of ingestion 0 minutes. The average was taken from the results for each group, and the value was shown on the graph. In addition, the maximum value of the elevated body temperature for each individual was averaged for each group, and the difference between each group was shown.
  • Fig. 1 the average of the maximum body temperature increase at each dose of one amino acid (tyrosine) is shown in Fig. 1, and the average of the body temperature elevation temperature and the average of the body temperature at each elapsed time are shown in Figs. 2 and 3, respectively. .
  • test substance-administered group one tyrosine-administered group
  • results of T-test and F-test were significant in two groups (four amino acids) compared to the control group. Significant differences were observed.
  • Tyrosine 1.3 kg, aspartic acid 0.03 kg, glutamic acid 0.58 kg, alanine 0.67 kg, citrate 1 3 ⁇ 4: 3, sucrose 21 ⁇ ⁇ , treja 1 kg of loin, 1 kg of fragrance, and 92.42 kg of water were mixed by heating and dissolved to produce a body temperature-raising amino acid-containing liquid. This was packed in bottles of 200 ml per serving, sterilized, and used as a drink containing aminoamino acid with increased body temperature. The invention's effect
  • the present inventors have found a novel use of an active ingredient composed of a specific amino acid group as having an excellent body temperature increasing effect, and have also clarified, for the first time, that the main body thereof is chin mouth.
  • the body temperature-raising food or drink or medical agent containing tyrosine alone or a group of four amino acids containing tyrosine according to the present work can reduce the body temperature in daily life by administering it. It has the significant effect of increasing energy consumption and increasing basic metabolism. It is also effective in raising basal body temperature, lowering body fat accumulation and improving coldness, etc. It has low toxicity and can be taken for a long time.

Abstract

It is intended to provide an agent for foods, drinks or medical uses which contains amino acid(s) elevating body temperature, characterized by containing tyrosine alone as the amino acid serving as the active ingredients or nothing but 4 amino acids including tyrosine, aspartic acid, glutamic acid and alanine as the amino acids serving as the active ingredients. The above agent is developed by confirming that tyrosine has an effect of elevating body temperature. By administering this agent, body temperature can be elevated and, in its turn, metabolic actions are promoted. As a result, body fat is burnt, thereby achieving effects of reducing accumulated body fat and relieving hypersensitivity to cold temperatures.

Description

明 細 書 体温上昇性ァミノ酸含有飲食品用又は医療用の剤  Description Agents for foods and beverages or medicals containing amino acids that increase body temperature
発明の属する技術分野 Technical field to which the invention belongs
本発明は、 体温を上昇させるのに有効な飲食用又は医療用の剤に関するもの であり、 更に詳細には、 本宪明の剤は、 特定のアミノ酸、 特にチロシンを有効 成分として含有するものであって、 すぐれた生理作用、 特に、 すぐれた体温上 昇作用を有する。 また、 本発明に係る剤は、 体温上昇作用により体内の代謝を 促進することから、 基礎代謝の改善、 さらには体脂肪蓄積の低下、 冷え性の改 善、 寒冷地に冷めた身体を温める手段としても有効である。 従来の技術  The present invention relates to a food or drink or medical agent effective for increasing body temperature. More specifically, the agent of the present invention comprises a specific amino acid, particularly tyrosine, as an active ingredient. It has an excellent physiological effect, especially an excellent body temperature increasing effect. Further, the agent according to the present invention promotes metabolism in the body by the action of increasing body temperature, thereby improving basal metabolism, further reducing body fat accumulation, improving coldness, and as a means for warming a body cooled in a cold region. Is also effective. Conventional technology
従来、 辛味香辛料成分のエネルギー代謝を促進する作用に着目したものとし て、 カブサイシン類を有効成分とする飲料 (例えば、 特許文献 1参照) などが 知られている。 特許文献 1  Conventionally, drinks containing cabsaicin as an active ingredient (for example, see Patent Document 1) have been known as focusing on the action of promoting the energy metabolism of pungent spice components. Patent Document 1
特開 2 0 0 0— 1 8 9 1 2 1号公報 発明が解決しょうとする課題  [Patent Document 1] Japanese Patent Application Laid-Open No. 2000-20089
体温上昇効果があるといわれるカブサイシン類は唐辛子に含まれる辛味成分 である。 多量のカプサイシン類を加えると辛みを強く感じるため、 添加する量 に制限があった。 また、 身体を温めるには温かい飲食物を摂取し体内に熱を取 り込む方法も考えられるが、 これでは効果も一過性である。 そこで、 エネルギ 一代謝改善作用を有する組成物としては、 速やかに効果が得られ、 その後も作 用が継続すること、 経口摂取する場合には、 嗜好性にも優れることなどが求め られる。 課題を解決するための手段 Cabsaicins, which are said to have a body temperature increasing effect, are pungent components contained in pepper. If you add a large amount of capsaicin, you will feel strong spiciness. Had restrictions. In order to warm the body, a method of ingesting warm food and drink and taking in heat into the body can be considered, but this has a temporary effect. Therefore, a composition having an effect of improving energy and metabolism is required to be able to obtain the effect promptly, to continue its action after that, and to have good palatability when taken orally. Means for solving the problem
上記目的を達成するため、 本発明者らは、 各方面から検討の結果、 多数のァ ミノ酸組成物に着目した。 アミノ酸の種類、 その組合せ、 配合量を変えて、 非 常に数多くのアミノ酸組成物を調製し、 これらのアミノ酸組成物について、 そ れらの生理作用をつぶさに検討した。 その結果、 基礎体温を上昇させ、 その作 用が長時間持続する特定組成のアミノ酸組成物をはじめて見出し、 これらのァ ミノ酸群組成物について更に検討の結果、 チロシンを高度に含有する組成物ほ ど体温上昇性が高 V、ことをはじめて見出した。  In order to achieve the above object, the present inventors have focused on a large number of amino acid compositions as a result of studies from various directions. A very large number of amino acid compositions were prepared by changing the types of amino acids, their combinations, and the amounts thereof, and the physiological effects of these amino acid compositions were thoroughly examined. As a result, they found for the first time an amino acid composition of a specific composition that raises basal body temperature and lasts for a long time, and as a result of further study of these amino acid group compositions, a composition with a high content of tyrosine was found. For the first time, I found that the body temperature was high V.
そこで本発明者らは、 このチロシンに着目して研究を行った結果、 これを体 温上昇アミノ酸と同定し、 チロシンについて、 本アミノ酸のみの体温上昇作用 を i n v i v o試験によって確認し、 更に研究の結果、 遂に本発明の完成に 至ったものである。  Therefore, the present inventors conducted a study focusing on this tyrosine, identified it as an amino acid that increased body temperature, confirmed the effect of increasing the body temperature of tyrosine only by this amino acid by an in vivo test, and conducted further studies. Finally, the present invention has been completed.
更にまた、 本発明者らは、 上記方法の課程において、 チロシンにァスパラギ ン酸、 グルタミン酸、 ァラニンを併用したところ、 これら 4種のアミノ酸のみ によるすぐれた体温上昇効果が奏されることもはじめて確認し、 更に研究の結 果、 遂に本発明の完成に至ったものである。  Furthermore, the present inventors have also confirmed for the first time that, in the course of the above method, when tyrosine was used in combination with aspartic acid, glutamic acid, and alanine, only these four amino acids exhibited an excellent body temperature increasing effect. As a result of further research, the present invention has finally been completed.
ある。 図面の簡単な説明 · is there. Brief description of drawings ·
図 1  Figure 1
チロシンを各用量でラットに投与した場合の最高基礎体温上昇度の平均を示 すグラフである。  4 is a graph showing the average of the maximum basal body temperature increase when rats were administered tyrosine at each dose.
図 2  Figure 2
同じく、 各経過時間における基礎体温上昇温度の平均を示すグラフである。 図 3  Similarly, it is a graph which shows the average of the basal body temperature rise temperature in each elapsed time. Fig 3
同じく、 各経過時間における基礎体温の平均を示すグラフである。  Similarly, it is a graph showing the average of the basal body temperature at each elapsed time.
図 4  Fig. 4
本発明に係るアミノ酸組成物 (4種アミノ酸) をラットに投与した場合の最 高基礎体温上昇度の平均を示すグラフである。  1 is a graph showing the average of the highest basal body temperature increase when the amino acid composition (four amino acids) according to the present invention is administered to rats.
図 5  Fig 5
同じく、 各経過時間における基礎体温上昇温度の平均を示すグラフである。 以下、 本発明について詳細に説明する。  Similarly, it is a graph which shows the average of the basal body temperature rise temperature in each elapsed time. Hereinafter, the present invention will be described in detail.
本発明は、 体温上昇ァミノ酸の本体がチロシンであることをはじめてっきと めたものであって、 本発明に係る剤の有効成分はチロシンであることを特徴と するものであり、 チロシンとしては、 それ単独で独立して分離ないし取り出し たものであって、 ひとつの化合物として単離されたものをいい、 市販品も適宜 使用可能である。 また、 チロシン (1種アミノ酸) を含む上記した 4種のアミ ノ酸 (4種アミノ酸) もすぐれた体温上昇作用を有し、 本発明に係る剤の有効 成分として使用可能である。なお、チロシンのほか各種アミノ酸は、天然物(発 酵によるものも含む) 及び合成品のいずれも使用可能であるが、 後者の場合、 D型よりも L型が好ましいがラセミ体も使用可能である。 したがって、 本発明に係るアミノ酸として 「チロシンのみ」 を有効成分とす る剤においては、 有効成分はチロシンのみであって、 有効成分としてチロシン のほかに他のアミノ酸、 ペプチド、 食品その他の体温上昇成分の併用を指すも のではない。 4種アミノ酸の場合も同様である。 The present invention has been made for the first time to determine that the body of the body temperature increasing amino acid is tyrosine, wherein the active ingredient of the agent according to the present invention is tyrosine. Is a compound isolated or taken out independently and isolated as a single compound, and a commercially available product can be used as appropriate. In addition, the above-mentioned four kinds of amino acids (four kinds of amino acids) containing tyrosine (one kind of amino acids) also have an excellent body temperature increasing effect, and can be used as an active ingredient of the agent according to the present invention. In addition to tyrosine, various amino acids can be used, both natural products (including those produced by fermentation) and synthetic products. In the latter case, the L-form is preferable to the D-form, but the racemic form can also be used. is there. Therefore, in the agent according to the present invention containing only tyrosine as the active ingredient as the active ingredient, the active ingredient is only tyrosine, and in addition to tyrosine, other amino acids, peptides, foods and other body temperature increasing ingredients as active ingredients It does not refer to the combination of. The same applies to the case of four amino acids.
本発明に係る剤は、 チロシンのみ、 あるいはチロシン、 ァスパラギン酸、 グ ルタミン酸、 ァラニンのアミノ酸 4種のみを有効成分とするものであるが、 本 発明に係る剤の有効成分としては、 次の態様 1、 2が挙げられる。  The agent according to the present invention contains tyrosine alone or only four amino acids of tyrosine, aspartic acid, glutamic acid, and alanine as active ingredients.The active ingredient of the agent according to the present invention is as follows: 1 and 2.
(1) 1種アミノ酸:チロシン (1) One kind of amino acid: tyrosine
(2) 4種アミノ酸:チロシン + (ァスパラギン酸、 グルタミン酸、 ァラニ ン) .  (2) Four amino acids: tyrosine + (aspartic acid, glutamic acid, aranine).
上記した 4種アミノ酸(態様 2)の場合において、各アミノ酸の配合割合(重 量%) は、 例えば次のようにすることができる。  In the case of the above four amino acids (aspect 2), the mixing ratio (% by weight) of each amino acid can be, for example, as follows.
(好適域)  (Preferred area)
チロシン 40〜65 (45〜60)  Tyrosine 40-65 (45-60)
ァスパラギン酸 0. 1〜; L 0 (0. 5〜5)  Aspartic acid 0.1-; L 0 (0.5-5)
グルタミン酸 10〜35 ( 1 5— 30)  Glutamic acid 10-35 (15-30)
ァラニン 10〜40 (15— 35)  Alanine 10-40 (15-35)
(もちろん、 上記配合は 1例として示したものであって、 上記配合において、 チロシン含量を更に高めることも可能である。)  (Of course, the above composition is shown as an example, and the tyrosine content can be further increased in the above composition.)
本発明に係る剤は、 チロシンを有効成分とするものであるが、 チロシンは単 独でもよいし他のアミノ酸と共存してアミノ酸群 (4種アミノ酸) を構成して いてもよく、 その場合、 各アミノ酸は、 それぞれ特定の組成割合で含有される ことが好適であって、 以下に示される。 すなわち、 各アミノ酸が、 チロシン 0. 5〜1 5モル以上、、 ァスパラギン 酸 0. 02〜0. 4モル、 グノレタミン酸 0. 3〜7モノレ、 ァラニン 0. 7〜1The agent according to the present invention contains tyrosine as an active ingredient. Tyrosine may be used alone or may coexist with other amino acids to form an amino acid group (four amino acids). Each amino acid is preferably contained in a specific composition ratio, and is shown below. That is, each amino acid is tyrosine 0.5 to 15 mol or more, aspartic acid 0.02 to 0.4 mol, gnoretamic acid 0.3 to 7 monole, and aranine 0.7 to 1
4モルの割合で含むことが好ましい。 It is preferable to include it in a ratio of 4 mol.
本発明に係る剤の有効成分を構成するチロシンを含むアミノ酸群 (4種アミ ノ酸 (4AA) の具体例を下記表 1に示す。  Specific examples of tyrosine-containing amino acids (four amino acids (4AA)) constituting the active ingredient of the agent according to the present invention are shown in Table 1 below.
(表 1)  (table 1)
4 AA 4 AA
分子量 m o 1  Molecular weight m o 1
Γ y r 181.2 0.0475 8.6 Γ y r 181.2 0.0475 8.6
As 133.1 0.0015 0.2  As 133.1 0.0015 0.2
G 1 u 147.1 0.0252 3.7  G 1 u 147.1 0.0252 3.7
A 1 a 89.1 0.0483 4.3 total 0.1225 16.8  A 1 a 89.1 0.0483 4.3 total 0.1225 16.8
T y r % 38. 8 51. 2 本究明に係る体温上昇飲食用又は医療用の剤は、 アミノ酸としてチロシンの み又はチロシンを含む 4種アミノ酸群のみを含有成分又は有効成分とするもの であり、 本有効成分のみをそのまま混合してあるいは混合することなく、 粉末 状や水溶液状にして経口摂取してもよいが、 含有又は有効成分は液状であって も、 固状であっても、 味がよくなく、 又飲み込みにくいなどの場合にあっては 含有又は有効成分と飲食用又は医療用に常用される添加料を用いて、 味をよく して飲みやすくしたり、 全体をビスケット状にして食べやすくしたりするのが よい。 例えば、 ドリンク斉 ljは、 含有又は有効成分水性液にクェン酸などの酸味 料や砂糖などの甘味料を添カ卩してのみやすくすることができる。 又、 粉末混合 状態の有効成分に精製澱粉などを加え、 混合し、 焼き上げて、 ビスケット状と すれば、 おいしく食べることができるようになる。 T yr% 38.8 51.2 The food, drink, or medical agent related to the present study that has increased body temperature and contains only tyrosine or only four amino acids containing tyrosine as an amino acid is a component or an active ingredient. The active ingredient alone may be orally ingested in the form of a powder or an aqueous solution without or without mixing, but the contained or active ingredient may be liquid or solid and taste If it is not good, or if it is difficult to swallow, use the contained or active ingredients and additives that are commonly used for eating and drinking or medical use to improve the taste It is better to make it easier to drink or to make the whole biscuit easier to eat. For example, the drinks can be made easier only by adding a souring agent such as citric acid or a sweetener such as sugar to the aqueous liquid containing or containing the active ingredient. Addition of purified starch, etc. to the active ingredient in a powder-mixed state, mixing, baking, and biscuit form makes it possible to eat deliciously.
本発明に係る体温上昇飲食用又は医療用の剤は、 既述したように、 粉末状の ままで摂取しても、 あるいは水に溶解して水溶液等として摂取しても良い。 摂 取方法も、 経口投与、 直腸投与、 静脈注射、 点滴等の一般的な投与経路を経て 投与することもできる。  As described above, the food or drink or medical agent for increasing body temperature according to the present invention may be ingested as a powder or may be dissolved in water and ingested as an aqueous solution or the like. The ingestion method may be oral administration, rectal administration, intravenous injection, intravenous drip, and other general administration routes.
経口投与の場合には、 飲食用に飲みやすくし、 食べやすくして摂取する以外 に、 医薬上許される担体、 賦形剤、 希釈剤と共に混合し、 散剤、 顆粒剤、 錠剤、 力プセル剤、 ト口一チ剤等として用いてもよレ、。 但し固体散剤や錠剤では吸収 に時間を要することがあるため、 有効成分自体の経口投与が望ましい。 この場 合には、 適切な添加剤、 例えば塩化ナトリウムのような塩類、 p H調節剤、 キ レート剤と共に前述した溶液として投与しても良い。 注射剤として使用する場 合には、 適切な緩衝剤や等張剤等を添加し、 滅菌蒸留水に溶解したものを用い れば良い。  In the case of oral administration, in addition to making it easy to drink and eat for eating and drinking, it is mixed with pharmaceutically acceptable carriers, excipients and diluents, and powders, granules, tablets, forcepsels, It may be used as a mouthpiece. However, solid powders and tablets may require time for absorption, so it is preferable to administer the active ingredient orally. In this case, it may be administered as a solution as described above together with a suitable additive, for example, a salt such as sodium chloride, a pH adjusting agent, and a chelating agent. When used as an injection, an appropriate buffer and isotonic agent may be added and dissolved in sterile distilled water.
摂取時期にも格別の制限はなく、 任意の時期に摂取すればよく、 例えばドリ ンク剤 (清涼飲料、 粉末飲料、 乳酸菌飲料、 ドリンクヨーグルト、 乳酸飲料等 の飲食品タイプのほか、 医薬品としての飲料等を含む) として摂取すると好適 である。 ドリンク剤の場合、 有効成分としてチロシンを、 ドリンク剤 2 O O m 1当り、 2 5 m g以上、 好ましくは 2 5 0 m g以上、 更に好ましくは 2 . 5 g 以上含有するように製剤するのが好適である。  There is no particular restriction on the timing of ingestion, and it may be taken at any time. It is preferable to ingest as In the case of drinks, it is preferable to formulate tyrosine as an active ingredient so as to contain at least 25 mg, preferably at least 250 mg, more preferably at least 2.5 g per 2 OO m1 of the drink. is there.
本発明の体温上昇飲食用又は医療用の剤の投与量は広範囲に設定でき、 投与 方法や使用目的に応じて、 経口投与の場合、 有効成分量として通常 1回に 0. 1〜 5 gを投与する。 溶液として投与又は摂取する場合には、 0. 05〜 10 重量 °/0程度の溶液として 1回に 10〜 1000m l、 好ましくは 1〜4重量 °/0 として 1回に 100〜 500m l投与又は摂取する。 The dosage of the food or drink or medical agent of the present invention can be set in a wide range, For oral administration, 0.1 to 5 g of active ingredient is usually administered at a time depending on the method and purpose of use. When administered or ingested as a solution is 10 to once as a solution of about 0.05 to 10 wt ° / 0 1000 m l, preferably 100 to 500 meters l administration or once a 1-4 wt ° / 0 Ingest.
後述する実施例から明らかなように、 本発明に係る体温上昇飲食用又は医療 用の剤は、 すぐれた基礎体温上昇作用を有し、 これと共に、 基礎代謝を高くし、 日常生活での消費エネルギーを上昇させることから、 体脂肪の燃焼が図られ、 その結果、 体脂肪蓄積の低下や冷え性の改善にも有効である。 したがって、 有 効成分を医薬用に製剤することにより、 体温上昇剤、 抗冷え性剤などの各種医 薬品とすることもできる。  As will be apparent from the examples described below, the food or drink or medical agent according to the present invention has an excellent basal body temperature-increasing action, increases basal metabolism, and consumes energy in daily life. As a result, body fat is burned, and as a result, it is also effective in reducing body fat accumulation and improving coldness. Therefore, various pharmaceuticals such as a body temperature increasing agent and an anti-chilling agent can be prepared by formulating the active ingredient as a medicament.
本発明に係る体温上昇飲食用又は医療用の剤は、 極めて有効な体温上昇作用 を有し、 その使用にあたっては、 粉末のまま使用するほカ 前述の通り溶液、 特に水溶液として使用しても良く、 この場合には本発明の組成物をそのまま水 に溶解して溶液を調製しても、 あるいは個々のアミノ酸を別個に水に溶解して 溶液中で前述の組成を実現しても良い。  The food or drink or medical agent according to the present invention has an extremely effective effect of increasing body temperature, and when used, it may be used as a powder. In this case, the composition of the present invention may be dissolved directly in water to prepare a solution, or each amino acid may be separately dissolved in water to realize the above-described composition in the solution.
以下、 本発明の実施例について述べる。  Hereinafter, examples of the present invention will be described.
実施例 1  Example 1
(1) 方法  (1) Method
8〜10週齢の SD系雄性ラットを 6匹 1群として 6群用意し、 一夜絶食し た後、 実験に使用した。 なお、 群分けは、 使用日当日の体重によって行った。  Six SD male rats of 8 to 10 weeks of age were prepared in groups of six, and after fasting overnight, they were used for experiments. The groups were divided according to the weight on the day of use.
(2) 被験物質  (2) Test substance
被験物質としては、 4種アミノ酸 (チロシン、 ァスパラギン酸、 グルタミン 酸、 ァラニン) 及び 1種アミノ酸 (チロシン) を使用した。 配合割合は表 1に 示したとおりであるが、 4種アミノ酸の配合については、 配合割合を次のよう に決定し、 1種アミノ酸 (チロシン) については、 4種アミノ酸の配合割合に 基づいて決定した。 なお、 アミノ酸は、 いずれも和光純薬工業 (株) より入手 した。 As test substances, four kinds of amino acids (tyrosine, aspartic acid, glutamic acid, alanine) and one kind of amino acid (tyrosine) were used. The mixing ratio is as shown in Table 1, but the mixing ratio of the four amino acids is as follows. The amino acid (tyrosine) was determined based on the mixing ratio of the four amino acids. In addition, all amino acids were obtained from Wako Pure Chemical Industries, Ltd.
4種アミノ酸 アミノ酸 成分重量 (%) モル (%) チロシン 50.9 38.5  4 amino acids Amino acid Component weight (%) Mole (%) Tyrosine 50.9 38.5
ァスパラギン酸 1.1 1.1  Aspartic acid 1.1 1.1
グノレタミン酸 22.3 20.8  Gunoretamic acid 22.3 20.8
ァラニン 25.7 39.6  Alanine 25.7 39.6
(3) 投与量 (3) Dosage
1群をコントロール (注射用水) とした。 2群に対しては、 4種アミノ酸を 0. 5 g/体重 100 gあたり (5 g/k g) を 1回経口投与した。 3〜5群 は 1種アミノ酸投与群とし、 3群に対してはチロシンを 0. 25 g/体重 10 O gあたり (2. 5 g/k g)、 同じく 4群に対してはチロシンを 0. 1 25 g/体重 100 gあたり (1. 25 gZk g)、 同じく 5群に対してはチロシ ンを 0. 0625 gZ体重 100 gあたり (0. 625 g/kg) の各用量で 1回経口投与した。 なお、 3〜 5群についてはコントロール (注射用水) をも う 1群用意し、 試験を行った。 .  One group was used as a control (water for injection). For the two groups, the four amino acids were orally administered once at 0.5 g / 100 g body weight (5 g / kg). Groups 3 to 5 were treated with a single amino acid group, tyrosine 0.25 g / 10 Og body weight (2.5 g / kg) for group 3, and tyrosine 0. Oral administration of tyrosine once per 25 g / 100 g body weight (1.25 g / kg), and also for each of the 5 groups at a dose of 0.0625 gZ per 100 g body weight (0.625 g / kg) did. For groups 3 to 5, one group was prepared with a control (water for injection), and the test was performed. .
なお、 被験物質ァミノ酸は生理食塩水に懸濁し、 コント口一ルには生理食塩 液 (光製薬 (株)、 日本薬局方生理食塩液、 L o t. 99 1 1HC) のみを投 与した。 (4) 体温測定 The test substance amino acid was suspended in physiological saline, and only saline (Hikari Pharmaceutical Co., Ltd., Japanese Pharmacopoeia physiological saline, Lot. 9911HC) was administered to the control port. . (4) Body temperature measurement
動物はボールマンケージに入れ保定し、 体温測定用のプローブは肛門から直 腸に挿入し固定した。 10〜15分おきに計測し、 体温が安定したら被験物質 を投与し摂取 0分の際の温度を基準とし、 のち 10分おきに 90分後まで体温 を測定した。 各群ごとに結果より平均を取りその値をグラフに示した。 また、 個体ごとの上昇体温の最高値を群ごとに平均し、 各群間での差を示した。  The animals were kept in a ballman cage and a probe for measuring the body temperature was inserted into the rectum from the anus and fixed. Measurements were taken every 10 to 15 minutes. When the body temperature stabilized, the test substance was administered, and the body temperature was measured every 10 minutes until 90 minutes later, based on the temperature at the time of ingestion 0 minutes. The average was taken from the results for each group, and the value was shown on the graph. In addition, the maximum value of the elevated body temperature for each individual was averaged for each group, and the difference between each group was shown.
すなわち、 1種アミノ酸 (チロシン) の各投与量における最高体温上昇度の 平均を図 1に示し、 各経過時間における体温上昇温度の平均及び体温の平均を、 それぞれ、 図 2及び図 3に示した。  That is, the average of the maximum body temperature increase at each dose of one amino acid (tyrosine) is shown in Fig. 1, and the average of the body temperature elevation temperature and the average of the body temperature at each elapsed time are shown in Figs. 2 and 3, respectively. .
また、 4種アミノ酸については、 最高体温上昇度の平均を図 4に示し、 各経 過時間における体温上昇温度の平均を図 5に示した。  For the four amino acids, the average of the maximum body temperature rise is shown in FIG. 4, and the average of the body temperature rise temperature at each time is shown in FIG.
(5) 結果及び考察  (5) Results and discussion
上記結果から明らかなように、 対照群の温度は時間経過とともにやや上昇し た。 被験物質投与群 (チロシン 1種投与群) では、 〖まぼ用量依存的な体温上昇 を示し、 T一検定、 F—検定の結果、 対照群に比して 2群 (4種アミノ酸) で 有意な差が認められた。  As is clear from the above results, the temperature of the control group slightly increased with time. The test substance-administered group (one tyrosine-administered group) showed a 用量 mabo dose-dependent increase in body temperature, and the results of T-test and F-test were significant in two groups (four amino acids) compared to the control group. Significant differences were observed.
実施例 2  Example 2
チロシン 2. 6 k g、 クェン酸 1 k g、 ショ糖 2 k g、 トレハロース 1 k g、 香料 1 k g、 水 92. 4 k gを加熱溶解混合し、 体温上昇性アミノ酸 含有液を製造した。 これを一回分 2 O Om lづっビン詰め、 殺菌し、 体温上昇 性ァミノ酸含有ドリンク剤とした。  2.6 kg of tyrosine, 1 kg of citrate, 2 kg of sucrose, 1 kg of trehalose, 1 kg of fragrance, and 92.4 kg of water were heated and dissolved and mixed to prepare a liquid containing amino acids with increasing body temperature. This was packed in bottles of 2 O Oml each time and sterilized to give a body temperature-increasing amino acid-containing drink.
実施例 3  Example 3
チロシン 1. 3 k g、 ァスパラギン酸 0. 03 k g、 グルタミン酸 0. 58 k g、 ァラニン 0. 67 k g、 クェン酸 1 ¾: 3、 ショ糖 21^ §、 トレハ ロース 1 k g、 香料 1 k g、 水 92. 42 k gを加熱溶解混合し、 体温上 昇性アミノ酸含有液を製造した。 これを一回分 200mlづっビン詰め、 殺菌 し、 体温上昇个生ァミノ酸含有ドリンク剤とした。 発明の効果 Tyrosine 1.3 kg, aspartic acid 0.03 kg, glutamic acid 0.58 kg, alanine 0.67 kg, citrate 1 ¾: 3, sucrose 21 ^ §, treja 1 kg of loin, 1 kg of fragrance, and 92.42 kg of water were mixed by heating and dissolved to produce a body temperature-raising amino acid-containing liquid. This was packed in bottles of 200 ml per serving, sterilized, and used as a drink containing aminoamino acid with increased body temperature. The invention's effect
本発明者らによって、 特定のアミノ酸群からなる有効成分に、 すぐれた体温 上昇作用を有するという新規用途が見出され、 その本体がチ口シンであること もはじめて明らかにされた。 チロシンのみ、 又は、 チロシンを含む 4種ァミノ 酸群、 を含有してなる本件努明に係る体温上昇飲食用又は医療用の剤は、 これ を投与することで、 日常生活での体温の上昇から消費エネルギーが上昇し、 基 礎代謝が高くなるという著効を奏する。 また基礎体温の上昇、 体脂肪蓄積の低 下や冷え性の改善等にも有効であり、 低毒性であるため、 長期間摂取すること が可能である。  The present inventors have found a novel use of an active ingredient composed of a specific amino acid group as having an excellent body temperature increasing effect, and have also clarified, for the first time, that the main body thereof is chin mouth. The body temperature-raising food or drink or medical agent containing tyrosine alone or a group of four amino acids containing tyrosine according to the present work can reduce the body temperature in daily life by administering it. It has the significant effect of increasing energy consumption and increasing basic metabolism. It is also effective in raising basal body temperature, lowering body fat accumulation and improving coldness, etc. It has low toxicity and can be taken for a long time.

Claims

請 求 の 範 囲 The scope of the claims
1 . アミノ酸としてチロシンのみを含有すること、 を特徴とする体温上 昇性ァミノ酸含有飲食品用又は医療用の剤。 1. An agent for foods or drinks or medicals containing an amino acid that has increased body temperature, comprising only tyrosine as an amino acid.
2 . アミノ酸として、 チロシン、 ァスパラギン酸、 グルタミン酸、 ァラ ニンのみを含有すること、 を特徴とする体温上昇性ァミノ酸含有飲食品用又は 医療用の剤。  2. An agent for foods, drinks, or medicals containing an amino acid with an increased body temperature, characterized by containing only tyrosine, aspartic acid, glutamic acid, and alanine as amino acids.
3 . アミノ酸として、 チロシンを有効成分として含有すること、 を特徴 とする体温上昇性ァミノ酸含有飲食品用又は医療用の剤。  3. An agent for foods and drinks or medicals containing an amino acid with a temperature-increasing temperature, comprising tyrosine as an active ingredient as an amino acid.
4 . アミノ酸として、 チロシン、 ァスパラギン酸、 グルタミン酸、 ァラ ニンを有効成分として含有すること、 を特徴とする体温上昇性ァミノ酸含有飲 食品用又は医療用の剤。  4. An agent for foods, drinks or medicines containing an amino acid with a temperature-increasing amino acid, characterized by containing tyrosine, aspartic acid, glutamic acid, and alanine as amino acids as active ingredients.
5 . チロシンを 2 0 O m 1当り 2 5 m g以上以上含有すること、 を特徴 とする請求項 1〜 4のいずれか 1項に記載の剤。  5. The agent according to any one of claims 1 to 4, comprising at least 25 mg of tyrosine per 20 Om1.
6 . チロシンを該アミノ酸群中 4 0 (重量) %以上含有すること、 を特 徴とする請求項 2又は 4に記載の剤。  6. The agent according to claim 2 or 4, wherein tyrosine is contained in an amount of 40% by weight or more in the amino acid group.
7 . 請求項 1〜 6のいずれか 1項に記載のァミノ酸又はァミノ酸群と飲 食用又は医療用に常用される添加料のみからなること、 を特徴とす る体温上昇性ァミノ酸含有飲食品用又は医療用の剤。  7. A food or beverage containing an amino acid with an increase in body temperature, characterized by comprising only the amino acid or the amino acid group according to any one of claims 1 to 6 and an additive commonly used for eating or drinking or for medical use. Product or medical agent.
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