JP4316224B2 - Medicinal body temperature raising agent - Google Patents
Medicinal body temperature raising agent Download PDFInfo
- Publication number
- JP4316224B2 JP4316224B2 JP2002339733A JP2002339733A JP4316224B2 JP 4316224 B2 JP4316224 B2 JP 4316224B2 JP 2002339733 A JP2002339733 A JP 2002339733A JP 2002339733 A JP2002339733 A JP 2002339733A JP 4316224 B2 JP4316224 B2 JP 4316224B2
- Authority
- JP
- Japan
- Prior art keywords
- body temperature
- tyrosine
- amino acid
- active ingredient
- amino acids
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 230000036760 body temperature Effects 0.000 title claims description 42
- 235000010855 food raising agent Nutrition 0.000 title description 2
- 150000001413 amino acids Chemical class 0.000 claims description 51
- 235000001014 amino acid Nutrition 0.000 claims description 50
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 43
- 235000002374 tyrosine Nutrition 0.000 claims description 43
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 40
- 239000004480 active ingredient Substances 0.000 claims description 25
- 239000003795 chemical substances by application Substances 0.000 claims description 22
- 230000001965 increasing effect Effects 0.000 claims description 11
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 7
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 7
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 7
- 235000004279 alanine Nutrition 0.000 claims description 7
- 235000003704 aspartic acid Nutrition 0.000 claims description 7
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 7
- 235000013922 glutamic acid Nutrition 0.000 claims description 7
- 239000004220 glutamic acid Substances 0.000 claims description 7
- 125000000539 amino acid group Chemical group 0.000 claims description 6
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 5
- 239000000654 additive Substances 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 230000000996 additive effect Effects 0.000 claims description 2
- 239000000203 mixture Substances 0.000 description 15
- 235000013305 food Nutrition 0.000 description 10
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
- 238000002156 mixing Methods 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 239000000843 powder Substances 0.000 description 6
- 230000037396 body weight Effects 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 210000000577 adipose tissue Anatomy 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 230000004060 metabolic process Effects 0.000 description 4
- 241000700159 Rattus Species 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 235000017663 capsaicin Nutrition 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 230000000630 rising effect Effects 0.000 description 3
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 3
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 2
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 2
- 235000015895 biscuits Nutrition 0.000 description 2
- 238000009529 body temperature measurement Methods 0.000 description 2
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 2
- 230000037149 energy metabolism Effects 0.000 description 2
- 230000037406 food intake Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 235000008534 Capsicum annuum var annuum Nutrition 0.000 description 1
- 235000002568 Capsicum frutescens Nutrition 0.000 description 1
- 238000001134 F-test Methods 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241001247145 Sebastes goodei Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 210000000436 anus Anatomy 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 229960002504 capsaicin Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 235000019629 palatability Nutrition 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- -1 sodium chloride Chemical class 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000014214 soft drink Nutrition 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000009967 tasteless effect Effects 0.000 description 1
- 150000003668 tyrosines Chemical class 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 235000013618 yogurt Nutrition 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic 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
- A61K31/198—Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, 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
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/175—Amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Description
【０００１】
【発明の属する技術分野】
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、本発明の剤は、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。
【０００２】
【従来の技術】
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、カプ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。
【０００３】
【特許文献１】
特開２０００−１８９１２１号公報
【０００４】
【発明が解決しようとする課題】
体温上昇効果があるといわれるカプ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、エネルギー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。
【０００５】
【課題を解決するための手段】
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、多数のア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、これらのア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いことをはじめて見出した。
【０００６】
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ｉｎ ｖｉｖｏ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。
更にまた、本発明者らは、上記方法の課程において、チロシンにアスパラギン酸、グルタミン酸、ア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。
以下、本発明について詳細に説明する。
【０００７】
本発明は、体温上昇アミノ酸の本体がチロシンであることをはじめてつ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。
【０００８】
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。
【０００９】
本発明に係る剤は、チロシンのみ、あるいはチロシン、アスパラギン酸、グルタミン酸、アラニンのアミノ酸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。
【００１０】
（態様）
（１）１種アミノ酸：チロシン
（２）４種アミノ酸：チロシン＋（アスパラギン酸、グルタミン酸、アラニン）
【００１１】
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。
【００１２】
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。
【００１３】
すなわち、各アミノ酸が、チロシン０．５〜１５モル以上、、アスパラギン酸０．０２〜０．４モル、グルタミン酸０．３〜７モル、アラニン０．７〜１４モルの割合で含むことが好ましい。
【００１４】
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。
【００１５】
本発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及び／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、ドリンク剤は、含有又は有効成分水性液にクエン酸などの酸味料や砂糖などの甘味料を添加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。
【００１７】
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。
【００１８】
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、カプセル剤、トローチ剤等として用いてもよい。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、ｐＨ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。
【００１９】
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２００ｍｌ当り、２５ｍｇ以上、好ましくは２５０ｍｇ以上、更に好ましくは２．５ｇ以上含有するように製剤するのが好適である。
【００２０】
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０．１〜５ｇ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％程度の溶液として１回に１０〜１０００ｍｌ、好ましくは１〜４重量％として１回に１００〜５００ｍｌ投与又は摂取する。
【００２１】
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。
【００２２】
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か、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。
以下、本発明の実施例について述べる。
【００２３】
【実施例１】
（１）方法
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。
【００２４】
（２）被験物質
被験物質としては、４種アミノ酸（チロシン、アスパラギン酸、グルタミン酸、アラニン）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。
【００２５】
（３）投与量
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０．５ｇ／体重１００ｇあたり（５ｇ／ｋｇ）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０．２５ｇ／体重１００ｇあたり（２．５ｇ／ｋｇ）、同じく４群に対してはチロシンを０．１２５ｇ／体重１００ｇあたり（１．２５ｇ／ｋｇ）、同じく５群に対してはチロシンを０．０６２５ｇ／体重１００ｇあたり（０．６２５ｇ／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。
【００２７】
なお、被験物質アミノ酸は生理食塩水に懸濁し、コントロールには生理食塩液（光製薬（株）、日本薬局方生理食塩液、Ｌｏｔ．９９１１ＨＣ）のみを投与した。
【００２８】
（４）体温測定
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。
【００２９】
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。
【００３０】
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。
【００３１】
（５）結果及び考察
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、ほぼ用量依存的な体温上昇を示し、Ｔ−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。
【００３２】
【実施例２】
チロシン ２．６ｋｇ、クエン酸 １ｋｇ、ショ糖 ２ｋｇ、トレハロース １ｋｇ、香料 １ｋｇ、水 ９２．４ｋｇ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づつビン詰め、殺菌し、体温上昇性アミノ酸含有ドリンク剤とした。
【００３３】
【実施例３】
チロシン １．３ｋｇ、アスパラギン酸 ０．０３ｋｇ、グルタミン酸 ０．５８ｋｇ、アラニン０．６７ｋｇ、クエン酸 １ｋｇ、ショ糖 ２ｋｇ、トレハロース １ｋｇ、香料 １ｋｇ、水 ９２．４２ｋｇ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づつビン詰め、殺菌し、体温上昇性アミノ酸含有ドリンク剤とした。
【００３４】
【発明の効果】
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、その本体がチロシンであることもはじめて明らかにされた。チロシンのみからなる、及び／又は、チロシンを含有してなる本件発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。
【図面の簡単な説明】
【図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。
【図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】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。
【図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。
【図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。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a food or medical agent effective for increasing body temperature. More specifically, the agent of the present invention contains a specific amino acid, particularly tyrosine as an active ingredient. And has an excellent physiological action, particularly an excellent body temperature raising action. In addition, since the agent according to the present invention promotes metabolism in the body by increasing body temperature, it improves basal metabolism, further reduces body fat accumulation, improves coldness, and as a means of warming a body cooled in a cold region. It is valid.
[0002]
[Prior art]
Conventionally, beverages that contain capsaicins as active ingredients (for example, see Patent Document 1) are known as those that focus on the action of promoting energy metabolism of spicy spice ingredients.
[0003]
[Patent Document 1]
JP 2000-189121 A
[Problems to be solved by the invention]
Capsaicins, which are said to have an effect of increasing body temperature, are pungent components contained in chili peppers. When a large amount of capsaicin was added, the amount of addition was limited because it felt strongly hot. Moreover, in order to warm a body, the method of ingesting heat food and taking heat into a body can also be considered, but this is also a temporary effect. Therefore, a composition having an action for improving energy metabolism is required to have an effect quickly, to continue its action thereafter, and to have excellent palatability when taken orally.
[0005]
[Means for Solving the Problems]
In order to achieve the above object, the present inventors have focused on a large number of amino acid compositions as a result of examinations from various directions. Numerous amino acid compositions were prepared by changing the types of amino acids, combinations thereof, and blending amounts, and the physiological effects of these amino acid compositions were thoroughly examined. As a result, we first discovered amino acid compositions with a specific composition that raises basal body temperature and the action lasts for a long time, and as a result of further study on these amino acid group compositions, the higher the composition of tyrosine, the higher the body temperature. I found out for the first time that it is high.
[0006]
Therefore, the present inventors conducted research while paying attention to this tyrosine, and as a result, identified this as an amino acid that increases body temperature, and confirmed the effect of tyrosine alone on the increase in body temperature by in vivo testing. Finally, the present invention has been completed.
Furthermore, the present inventors have confirmed for the first time that in the course of the above method, when aspartic acid, glutamic acid, and alanine are used in combination with tyrosine, an excellent effect of raising body temperature by only these four amino acids is achieved. As a result of further research, the present invention has finally been completed.
Hereinafter, the present invention will be described in detail.
[0007]
The present invention has been found for the first time that the body of the amino acid for raising body temperature is tyrosine, and the active ingredient of the agent according to the present invention is tyrosine, and tyrosine alone In this case, the product is 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 four amino acids (four amino acids) including tyrosine (one amino acid) also have an excellent body temperature raising action and can be used as an active ingredient of the agent according to the present invention. In addition to tyrosine, various amino acids, both natural products (including fermented ones) and synthetic products, can be used. In the latter case, the L form is preferred over the D form, but the racemic form can also be used. .
[0008]
Therefore, in the agent having “tyrosine only” as the active ingredient as the amino acid according to the present invention, the active ingredient is only tyrosine, and in addition to tyrosine, other amino acids, peptides, foods and other body temperature raising components It does not indicate combined use. The same applies to the case of four amino acids.
[0009]
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 includes the following
[0010]
(Aspect)
(1) 1 amino acid: tyrosine (2) 4 amino acids: tyrosine + (aspartic acid, glutamic acid, alanine)
[0011]
In the case of the above-mentioned four kinds of amino acids (Aspect 2), the blending ratio (% by weight) of each amino acid can be set as follows, for example.
[0012]
The agent according to the present invention contains tyrosine as an active ingredient, but tyrosine may be used alone or together with other amino acids to constitute an amino acid group (four kinds of amino acids). Each amino acid is preferably contained in a specific composition ratio, and is shown below.
[0013]
That is, it is preferable that each amino acid contains tyrosine 0.5 to 15 mol or more, aspartic acid 0.02 to 0.4 mol, glutamic acid 0.3 to 7 mol, and alanine 0.7 to 14 mol.
[0014]
Specific examples of the amino acid group (4 kinds of amino acids (4AA)) containing tyrosine constituting the active ingredient of the agent according to the present invention are shown in Table 1 below.
[0015]
The body temperature rising food / drink or medical agent according to the present invention comprises only tyrosine as an amino acid and / or only four kinds of amino acid groups containing tyrosine as an active ingredient or an active ingredient, and only this active ingredient is mixed as it is. Or may be taken orally in the form of a powder or an aqueous solution without mixing, but the contained or active ingredient may be liquid, solid, tasteless and difficult to swallow In some cases, it is better to improve the taste and make it easy to drink, or to make it easy to eat in the form of biscuits, using contained or active ingredients and additives commonly used for food and drink or for medical purposes. . For example, the drink can be made easy only by adding an acidulant such as citric acid or a sweetener such as sugar to the contained or active ingredient aqueous liquid. Moreover, if refined starch etc. are added to the active ingredient of a powder mixed state, and it mixes and baked, and it will be in a biscuit shape, it will become delicious.
[0017]
As described above, the body temperature rising food / drink or medical agent according to the present invention may be ingested as a powder, or dissolved in water as an aqueous solution. The ingestion method can also be administered through a general administration route such as oral administration, rectal administration, intravenous injection, and infusion.
[0018]
In the case of oral administration, in addition to making it easy to drink and eat for eating and drinking, mix with pharmaceutically acceptable carriers, excipients, diluents, powders, granules, tablets, capsules, troches You may use as an agent etc. However, since solid powders and tablets may take time to absorb, oral administration of the active ingredient itself is desirable. In this case, it may be administered as a solution 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 or isotonic agent or the like added and dissolved in sterile distilled water may be used.
[0019]
There is no particular restriction on the intake time, and it can be taken at any time. For example, drinks (soft drinks, powdered drinks, lactic acid bacteria drinks, drink yogurt, lactic acid drinks, etc. It is preferable to take it as In the case of a drink, it is preferable to formulate tyrosine as an active ingredient in an amount of 25 mg or more, preferably 250 mg or more, more preferably 2.5 g or more per 200 ml of drink.
[0020]
The dosage of the food for raising body temperature of the present invention can be set in a wide range, and depending on the administration method and the purpose of use, in the case of oral administration, 0.1 to 5 g is usually administered as an active ingredient at a time. To do. When administered or ingested as a solution, it is administered or ingested as a solution of about 0.05 to 10% by weight, 10 to 1000 ml at a time, preferably 1 to 4% by weight, or 100 to 500 ml at a time.
[0021]
As will be apparent from the examples described below, the body temperature-elevating food or medical agent according to the present invention has an excellent basal body temperature increasing action, and at the same time, increases the basal metabolism and consumes energy in daily life. As a result, body fat can be burned, and as a result, it is effective in reducing body fat accumulation and improving coldness. Accordingly, various pharmaceuticals such as a body temperature raising agent and an anti-chilling agent can be prepared by formulating the active ingredient for pharmaceutical use.
[0022]
The body temperature increasing food and drink or medical agent according to the present invention has a very effective body temperature increasing action, and in its use, in addition to being used as a powder, it may be used as a solution, particularly as an aqueous solution as described above. In this case, the composition of the present invention may be dissolved in water as it is to prepare a solution, or individual amino acids may be dissolved separately in water to realize the above-described composition in the solution.
Examples of the present invention will be described below.
[0023]
[Example 1]
(1) Method 8 to 10 weeks old SD male rats were prepared as 6 groups, and 6 groups were prepared. After fasting overnight, they were used for experiments. The grouping was performed according to the body weight on the day of use.
[0024]
(2) Test substance As test substances, four kinds of amino acids (tyrosine, aspartic acid, glutamic acid, alanine) and one kind of amino acid (tyrosine) were used. The blending ratio is as shown in Table 1, but for the blending of four amino acids, the blending ratio is determined as follows, and for one amino acid (tyrosine), it is determined based on the blending ratio of the four amino acids. did. All amino acids were obtained from Wako Pure Chemical Industries.
[0025]
(3) One group of doses was used as a control (water for injection). For group 2, four amino acids were orally administered once per 0.5 g / 100 g body weight (5 g / kg). Groups 3 to 5 are groups administered with one amino acid, tyrosine is 0.25 g / 100 g body weight (2.5 g / kg) for group 3, and tyrosine is 0.125 g / 100 g body weight for group 4. Per group (1.25 g / kg), and for 5 groups, tyrosine was orally administered once at each dose of 0.0625 g / 100 g body weight (0.625 g / kg). For groups 3 to 5, another group of controls (water for injection) was prepared and tested.
[0027]
The test substance amino acid was suspended in physiological saline, and only physiological saline (Hikari Pharmaceutical Co., Ltd., Japanese Pharmacopoeia physiological saline, Lot. 9911HC) was administered as a control.
[0028]
(4) The body temperature measurement animal was placed in a Ballman cage and held, and a body temperature measurement probe was inserted into the rectum from the anus and fixed. Measurements were taken every 10-15 minutes, and when the body temperature was 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
[0029]
That is, the average of the maximum body temperature rise at each dose of one amino acid (tyrosine) is shown in FIG. 1, and the average of the body temperature rise temperature and the average of the body temperature at each elapsed time are shown in FIG. 2 and FIG. 3, respectively. .
[0030]
Moreover, about 4 types of amino acids, the average of the maximum body temperature rise degree was shown in FIG. 4, and the average of the body temperature rise temperature in each elapsed time was shown in FIG.
[0031]
(5) Results and Discussion As is clear from the above results, the temperature of the control group slightly increased with time. In the test substance-administered group (group of 1 tyrosine group), there was an almost dose-dependent increase in body temperature, and as a result of T-test and F-test, a significant difference was found in 2 groups (4 amino acids) compared to the control group. Was recognized.
[0032]
[Example 2]
2.6 kg of tyrosine, 1 kg of citric acid, 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 produce a body temperature raising amino acid-containing solution. This was bottled in 200 ml portions, sterilized, and used as a drink containing amino acid containing a temperature-enhancing amino acid.
[0033]
[Example 3]
1.3 kg of tyrosine, 0.03 kg of aspartic acid, 0.58 kg of glutamic acid, 0.67 kg of alanine, 1 kg of citric acid, 2 kg of sucrose, 1 kg of trehalose, 1 kg of fragrance and 92.42 kg of water are mixed by heating. A liquid was produced. This was bottled in 200 ml portions, sterilized, and used as a drink containing amino acid containing a temperature-enhancing amino acid.
[0034]
【The invention's effect】
The present inventors have found a novel use that an active ingredient consisting of a specific amino acid group has an excellent effect of raising body temperature, and it has been revealed for the first time that its main body is tyrosine. An agent for increasing body temperature of food and / or medicine according to the present invention comprising only tyrosine and / or containing tyrosine increases the energy consumption from the increase in body temperature in daily life by administering this agent. The basal metabolism is highly effective. It is also effective for raising basal body temperature, reducing body fat accumulation and improving coldness, and has low toxicity and can be taken for a long time.
[Brief description of the drawings]
FIG. 1 is a graph showing the average maximum basal body temperature rise when tyrosine is administered to rats at various doses.
FIG. 2 is also a graph showing the average basal body temperature rise temperature at each elapsed time.
FIG. 3 is also a graph showing the average basal body temperature at each elapsed time.
FIG. 4 is a graph showing the average maximum basal body temperature rise when the amino acid composition (four amino acids) according to the present invention is administered to rats.
FIG. 5 is also a graph showing the average basal body temperature rise temperature at each elapsed time.
Claims (5)
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2002339733A JP4316224B2 (en) | 2002-11-22 | 2002-11-22 | Medicinal body temperature raising agent |
| AU2003302374A AU2003302374A1 (en) | 2002-11-22 | 2003-11-19 | Agent for foods, drinks or medical uses containing body temperature-elevating amino acid |
| PCT/JP2003/014740 WO2004047565A1 (en) | 2002-11-22 | 2003-11-19 | Agent for foods, drinks or medical uses containing body temperature-elevating amino acid |
| TW092132784A TW200418394A (en) | 2002-11-22 | 2003-11-21 | Agents capable of raising body temperature for nutritional and medical uses, which comprise amino acids |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2002339733A JP4316224B2 (en) | 2002-11-22 | 2002-11-22 | Medicinal body temperature raising agent |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009097182A Division JP4829322B2 (en) | 2009-04-13 | 2009-04-13 | Agents for foods that raise body temperature |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2006006101A JP2006006101A (en) | 2006-01-12 |
| JP4316224B2 true JP4316224B2 (en) | 2009-08-19 |
Family
ID=32375785
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2002339733A Expired - Fee Related JP4316224B2 (en) | 2002-11-22 | 2002-11-22 | Medicinal body temperature raising agent |
Country Status (4)
| Country | Link |
|---|---|
| JP (1) | JP4316224B2 (en) |
| AU (1) | AU2003302374A1 (en) |
| TW (1) | TW200418394A (en) |
| WO (1) | WO2004047565A1 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3413898A4 (en) * | 2016-02-08 | 2019-09-25 | Junaxo, Inc. | Use of trehalose for treatment of neurological diseases |
| CA3061710A1 (en) | 2017-04-28 | 2018-11-01 | Stryker Corporation | Control console and accessories for rf nerve ablation and methods of operating the same |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH09220071A (en) * | 1996-02-19 | 1997-08-26 | Q P Corp | Eggshell calcium composition |
| JP2002017296A (en) * | 2000-07-07 | 2002-01-22 | Sanyu:Kk | Food product containing composition of amino acid and sugar |
-
2002
- 2002-11-22 JP JP2002339733A patent/JP4316224B2/en not_active Expired - Fee Related
-
2003
- 2003-11-19 AU AU2003302374A patent/AU2003302374A1/en not_active Abandoned
- 2003-11-19 WO PCT/JP2003/014740 patent/WO2004047565A1/en active Application Filing
- 2003-11-21 TW TW092132784A patent/TW200418394A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| TW200418394A (en) | 2004-10-01 |
| WO2004047565A1 (en) | 2004-06-10 |
| AU2003302374A1 (en) | 2004-06-18 |
| JP2006006101A (en) | 2006-01-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2008203461B2 (en) | Body temperature-raising agent of amino acids for eating or drinking and for medical use | |
| JP6255079B2 (en) | Rapid-acting oral arginine level oral preparation containing citrulline and arginine | |
| CN106061479B (en) | Weak prophylactic | |
| JP5053535B2 (en) | Oral for improving sleep or waking up | |
| JP2001010977A (en) | Composition for oral administration | |
| JP4316224B2 (en) | Medicinal body temperature raising agent | |
| JP4829322B2 (en) | Agents for foods that raise body temperature | |
| JPH11130669A (en) | Amino acid-based nutrient preparation for preventing/ treating bedsore | |
| JP2015214518A (en) | Method for improving quality of sleep and oral composition for improving quality of sleep | |
| JP2011057702A (en) | Agent for body temperature elevating food and drink | |
| JP2007119348A (en) | Ameliorating agent for feeling of cold | |
| CN106573034A (en) | Marine peptides and fish nucleotides, compositions and uses thereof for reducing blood glucose | |
| JPS61289043A (en) | Drug, food and drink having remedying effect on diseases of gynecologic system | |
| JP5827783B2 (en) | Menstrual pain relieving agent | |
| JP2010077102A (en) | Functional foods and pharmaceutical compositions for aged persons | |
| WO2014163151A1 (en) | Yeast culture, and composition for internal application | |
| JP2004099610A (en) | Improving agent for hepatic encephalopathy | |
| JP2005154401A (en) | Deodorizing composition for feces | |
| JP2015214516A (en) | Vitality and/or concentration improver | |
| JP2008195700A (en) | Ameliorant for bone density | |
| JP2015214517A (en) | Vitality and/or concentration improver |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20051003 |
|
| RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7422 Effective date: 20051003 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20081014 |
|
| A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20081215 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090210 |
|
| A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090413 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20090519 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20090520 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 4316224 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120529 Year of fee payment: 3 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120529 Year of fee payment: 3 |
|
| S533 | Written request for registration of change of name |
Free format text: JAPANESE INTERMEDIATE CODE: R313533 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120529 Year of fee payment: 3 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130529 Year of fee payment: 4 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20140529 Year of fee payment: 5 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| LAPS | Cancellation because of no payment of annual fees |