JP2013181019A - Evacuant for poisonous metal and method for evaluating amount of poisonous metal by using the evacuant - Google Patents

Evacuant for poisonous metal and method for evaluating amount of poisonous metal by using the evacuant Download PDF

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JP2013181019A
JP2013181019A JP2012047562A JP2012047562A JP2013181019A JP 2013181019 A JP2013181019 A JP 2013181019A JP 2012047562 A JP2012047562 A JP 2012047562A JP 2012047562 A JP2012047562 A JP 2012047562A JP 2013181019 A JP2013181019 A JP 2013181019A
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harmful metal
harmful
metal excretion
citrulline
lipoic acid
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JP5899008B2 (en
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Yuko Toba
悠子 鳥羽
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Arkray Inc
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Abstract

PROBLEM TO BE SOLVED: To provide a poisonous metal evacuant with which a poisonous metal is efficiently excreted without imposing any burden on oral administration, and a method for evaluating an amount of the poisonous metal by using the evacuant.SOLUTION: A poisonous metal evacuant includes a chelating agent composed of only α-lipoic acid and citrulline. The poisonous metal evacuant desirably includes for instance 1-1,200 mg of α-lipoic acid and 1-3,400 mg of citrulline, and a weight ratio of α-lipoic acid to citrulline is desirably 1:0.5 to 1:20.

Description

本発明は、有害金属***促進剤およびそれを用いた有害金属量評価方法に関する。   The present invention relates to a toxic metal excretion promoter and a toxic metal content evaluation method using the same.

水銀、カドミウム、鉛、砒素等の有害金属は、人体に蓄積され、健康に悪影響を及ぼす有害金属であることが知られている。このため、人体内に蓄積されている有害金属を、体内から尿等に***させることが重要である。また、前記有害金属を尿に***させ、前記***尿中の有害金属量を測定すれば、体内に蓄積する有害金属量を評価することもできるため、健康面の管理や改善等にも有用な情報となる。   It is known that harmful metals such as mercury, cadmium, lead, and arsenic are harmful metals that accumulate in the human body and adversely affect health. For this reason, it is important to excrete toxic metals accumulated in the human body from the body into urine and the like. In addition, if the harmful metals are excreted in urine and the amount of harmful metals in the excreted urine is measured, the amount of harmful metals accumulated in the body can also be evaluated, which is useful for health management and improvement. Information.

体内の有害金属を尿中に***する効果のある物質としては、有害金属と結合する、2,3−ジメルカプト−1−プロパンスルホン酸ナトリウム(以下、「DMPS」ともいう)、ジメルカプトコハク酸(以下、「DMSA」ともいう)、エチレンジアミン四酢酸(以下、「EDTA」ともいう)等のキレート剤が知られている(非特許文献1参照)。また、これらの他に、αリポ酸について、尿中への有害金属の***を促進する効果があることが報告されている(特許文献1、2、3参照)。   Substances that have the effect of excreting toxic metals in the body into urine include sodium 2,3-dimercapto-1-propanesulfonate (hereinafter also referred to as “DMPS”), dimercaptosuccinic acid ( Hereinafter, chelating agents such as “DMSA” and ethylenediaminetetraacetic acid (hereinafter also referred to as “EDTA”) are known (see Non-Patent Document 1). In addition to these, α-lipoic acid has been reported to have an effect of promoting the excretion of harmful metals in urine (see Patent Documents 1, 2, and 3).

特開2008−74835号公報JP 2008-74835 A WO2005/112667号国際公開パンフレットWO2005 / 112667 International Publication Pamphlet US2006/0099239号公報US2006 / 0099239 gazette

Alternative Medicine Review 1998;3:199−207Alternative Medicine Review 1998; 3: 199-207. 健康食品データベース 第一出版 Pharmacist'sLetter/Prescriber's Letterエディターズ 編 (独)国立健康・栄養研究所 監訳Health Food Database First Publication Pharmacist'sLetter / Prescriber's Letter Editors (National Institute of Health and Nutrition) Anaphylactic reaction in a patient sensitized to coriander seed. Manzanedo L, Blanco J, Fuentes M, Caballero ML, Moneo I. Allergy. 2004 Mar; 59(3): 362-3.Anaphylactic reaction in a patient sensitized to coriander seed.Manzanedo L, Blanco J, Fuentes M, Caballero ML, Moneo I. Allergy. 2004 Mar; 59 (3): 362-3. Occupational rhinoconjunctivitis and food allergy because of aniseed sensitization. Garcia-Gonzalez JJ, Bartolome-Zavala B, Fernandez-Melendez S, Barcelo-Munoz JM, Miranda Paez A, Carmona-Bueno MJ, Vega-ChicoteJM, Negro Carrasco MA, Ameal Godoy A, Pamies Espinosa R. Ann Allergy Asthma Immunol. 2002 May; 88(5): 518-22.Garcia-Gonzalez JJ, Bartolome-Zavala B, Fernandez-Melendez S, Barcelo-Munoz JM, Miranda Paez A, Carmona-Bueno MJ, Vega-Chicote JM, Amgro Carrasco MA , Pamies Espinosa R. Ann Allergy Asthma Immunol. 2002 May; 88 (5): 518-22. Occupational protein contact dermatitis from coriander. Kanerva L, Soini M. Contact Dermatitis. 2001 Dec; 45(6): 354-5.Occupational protein contact dermatitis from coriander. Kanerva L, Soini M. Contact Dermatitis. 2001 Dec; 45 (6): 354-5. Occupational asthma due to different spices. Sastre J, Olmo M, Novalvos A, Ibanez D, Lahoz C. Allergy. 1996 Feb; 51(2) :117-20.Occupational asthma due to different spices.Sastre J, Olmo M, Novalvos A, Ibanez D, Lahoz C. Allergy. 1996 Feb; 51 (2): 117-20.

しかしながら、EDTAは、静脈投与で用いる必要があるため、使用が容易ではなく、使用者の負担が大きい。一方、DMSAは、胃腸での吸収が良いことから、経口投与で使用可能であるものの、その匂いや味の性質上、使用者へ投与し難い。また、経口投与後も、使用者が、自身の尿や体臭に特異な臭いを感じる等、不快感等の負担を伴う。他方、αリポ酸は、そのような投与時の困難や、投与後の不快感を与える事は無いため、経口投与し易い。しかしながら、その効果はDMSAと比べて小さい。また、特許文献3には、αリポ酸に加え、一般的に重金属を遊離させる性質を有することが知られる、コリアンダーやシラントロを投与する有害金属***剤が記載されている。しかしながら、コリアンダーやシラントロは、アレルギーを発症した文献(非特許文献2〜6)が報告されている。このため、そのような症状を発症しない有害金属***促進剤が求められている。   However, since it is necessary to use EDTA by intravenous administration, it is not easy to use, and the burden on the user is large. DMSA, on the other hand, has good gastrointestinal absorption, so it can be used by oral administration, but it is difficult to administer to users due to its odor and taste. Moreover, even after oral administration, the user is burdened with discomfort and the like, such as feeling a odor peculiar to his urine and body odor. On the other hand, α-lipoic acid is easy to administer orally because it does not give such difficulties during administration or discomfort after administration. However, the effect is small compared to DMSA. Patent Document 3 describes a harmful metal excretory agent that administers coriander or cilantro, which is generally known to have a property of liberating heavy metals in addition to α-lipoic acid. However, as for coriander and cilantro, literatures (non-patent documents 2 to 6) that have developed allergies have been reported. For this reason, a harmful metal excretion promoter that does not cause such symptoms is desired.

そこで、本発明は、経口投与に負担を与えず、有害金属を効率よく***可能な、有害金属***促進剤およびそれを用いた有害金属量評価方法を提供することを目的とする。   Therefore, an object of the present invention is to provide a harmful metal excretion promoter and a harmful metal amount evaluation method using the same, which can efficiently excrete harmful metals without burdening oral administration.

前記目的を達成するために、本発明の有害金属***促進剤は、αリポ酸のみからなるキレート剤およびシトルリンを含むことを特徴とする。   In order to achieve the above object, the harmful metal excretion promoter of the present invention is characterized by containing a chelating agent consisting only of α-lipoic acid and citrulline.

本発明の有害金属量評価方法は、有害金属***促進剤が投与された被験者の***尿における有害金属量を測定する工程を含み、前記有害金属***促進剤が、前記本発明の有害金属***促進剤であることを特徴とする。   The method for evaluating the amount of toxic metal of the present invention includes a step of measuring the amount of toxic metal in the excreted urine of a subject to which a toxic metal excretion promoter is administered, wherein the toxic metal excretion promoter is the toxic metal excretion promoting agent of the present invention. It is an agent.

本発明によれば、αリポ酸およびシトルリンは、経口投与に負担を与えず、また、投与後も負担を与えない。また、本発明は、αリポ酸とシトルリンとの併用により、十分な有害金属***効果を実現できる。このため、本発明の有害金属***促進剤は、例えば、健康の維持、改善、向上のためのサプリメントや食品添加物、機能性食品としても有用である。また、本発明の有害金属***促進剤によれば、効果的に有害金属を尿中に***できるため、例えば、***尿の有害金属量の評価においても、非常に有用である。   According to the present invention, alpha lipoic acid and citrulline do not impose a burden on oral administration and do not impose a burden after administration. Moreover, this invention can implement | achieve sufficient harmful metal excretion effect by combined use with (alpha) lipoic acid and citrulline. For this reason, the harmful metal excretion promoter of the present invention is useful, for example, as a supplement, food additive, or functional food for maintaining, improving, and improving health. Moreover, according to the harmful metal excretion promoter of the present invention, harmful metals can be effectively excreted in urine. Therefore, for example, it is very useful in evaluating the amount of harmful metals in excreted urine.

図1は、実施例1において、有害金属***促進剤の投与から1時間後までの***尿全量における総水銀量を示すグラフである。FIG. 1 is a graph showing the total amount of mercury in the total amount of excreted urine from the administration of the harmful metal excretion promoter in Example 1 to 1 hour later. 図2は、実施例1において、有害金属***促進剤の投与から2時間後までの***尿全量における総水銀量を示すグラフである。FIG. 2 is a graph showing the total amount of mercury in the total amount of excreted urine from Example 1 until 2 hours after the administration of the harmful metal excretion promoter. 図3は、実施例1において、有害金属***促進剤の投与から3時間後までの***尿全量における総水銀量を示すグラフである。FIG. 3 is a graph showing the total mercury amount in the total amount of excreted urine until 3 hours after administration of the harmful metal excretion promoter in Example 1. 図4は、実施例1において、有害金属***促進剤の投与から4時間後までの***尿全量における総水銀量を示すグラフである。FIG. 4 is a graph showing the total amount of mercury in the total amount of excreted urine from Example 1 until 4 hours after the administration of the harmful metal excretion promoter.

(有害金属***促進剤)
本発明の有害金属***促進剤は、前述のように、αリポ酸のみからなるキレート剤およびシトルリンを含むことを特徴とする。本発明は、キレート剤としてαリポ酸のみを含み、シトルリンと共存させることが特徴であって、その他の構成は何ら制限されない。
(Toxic metal excretion promoter)
As described above, the harmful metal excretion promoter of the present invention is characterized by containing a chelating agent composed only of α-lipoic acid and citrulline. The present invention is characterized by containing only α-lipoic acid as a chelating agent and coexisting with citrulline, and other configurations are not limited at all.

αリポ酸は、チオクト酸ともいい、または、1,2-ジチオラン−3−ペンタン酸という。   Alpha lipoic acid is also referred to as thioctic acid or 1,2-dithiolane-3-pentanoic acid.

本発明の有害金属***促進剤において、αリポ酸とシトルリンとの含有比は、特に制限されない。αリポ酸(L)とシトルリン(C)との含有比(L:C)は、例えば、重量比で表わすことができる。αリポ酸とシトルリンとの重量比(L:C)は、1:0.5〜1:20が好ましく、例えば、1:4である。   In the harmful metal excretion promoter of the present invention, the content ratio of α-lipoic acid and citrulline is not particularly limited. The content ratio (L: C) of α-lipoic acid (L) and citrulline (C) can be expressed by, for example, a weight ratio. The weight ratio (L: C) of α-lipoic acid to citrulline is preferably 1: 0.5 to 1:20, for example 1: 4.

本発明の有害金属***促進剤において、αリポ酸およびシトルリンの含有量は、特に制限されない。αリポ酸の含有量は、上限が、例えば、1200mgであり、下限が、例えば、1mgであり、含有量の範囲が、例えば、1〜1200mgである。シトルリンの含有量は、上限が、例えば、3400mgであり、下限が、例えば、1mgであり、含有量の範囲が、例えば、1〜3400mgである。   In the harmful metal excretion promoter of the present invention, the contents of α lipoic acid and citrulline are not particularly limited. The content of α-lipoic acid has an upper limit of, for example, 1200 mg, a lower limit of, for example, 1 mg, and a content range of, for example, 1 to 1200 mg. The upper limit of the content of citrulline is, for example, 3400 mg, the lower limit is, for example, 1 mg, and the content range is, for example, 1-3400 mg.

前記含有量は、例えば、体重60kgの成人に対する1回あたりの使用量として例示できる。また、前記含有量は、例えば、被験者の年齢、性別、体重等に基づいて、適宜調整可能である。本発明の有害金属***促進剤の投与条件は、特に制限されず、1日あたりの投与回数は、例えば、1〜3回であり、また、1日あたりの投与量は、例えば、αリポ酸が1〜1200mg、シトルリンが1〜3400mgである。   The said content can be illustrated as the usage-amount with respect to the adult with a body weight of 60 kg, for example. Moreover, the said content can be suitably adjusted based on a test subject's age, sex, weight, etc., for example. The administration conditions of the harmful metal excretion promoter of the present invention are not particularly limited, and the number of administrations per day is, for example, 1 to 3 times, and the dose per day is, for example, α lipoic acid. Is 1 to 1200 mg, and citrulline is 1 to 3400 mg.

本発明の有害金属***促進剤の形態は、何ら制限されず、経口投与可能な形態があげられる。前記形態は、例えば、固体状または液体状の経口剤があげられ、具体的には、錠剤、被覆錠剤、丸剤、細粒剤、顆粒剤、散剤、カプセル剤、シロップ剤、乳剤、懸濁剤等があげられる。   The form of the toxic metal excretion promoter of the present invention is not limited at all, and examples include forms that can be administered orally. Examples of the form include solid or liquid oral preparations, and specifically, tablets, coated tablets, pills, fine granules, granules, powders, capsules, syrups, emulsions, suspensions. Agents and the like.

本発明の有害金属***促進剤は、例えば、αリポ酸とシトルリンの他に、例えば、賦形剤、着色剤、保存剤、安定剤、ゲル化剤、酸化防止剤等の添加剤を、適宜含有してもよい。前記添加剤は、特に制限されず、公知のものが使用できる。   The harmful metal excretion promoter of the present invention, for example, in addition to α lipoic acid and citrulline, for example, additives such as excipients, colorants, preservatives, stabilizers, gelling agents, antioxidants, etc. You may contain. The additive is not particularly limited, and known ones can be used.

本発明の有害金属***促進剤は、前述のように、効果的に有害金属を排出できることから、例えば、健康補助食品として使用できる。   Since the harmful metal excretion promoter of the present invention can effectively discharge harmful metals as described above, it can be used, for example, as a health supplement.

本発明の有害金属***促進剤の投与対象は、特に制限されず、例えば、ヒトがあげられ、この他に、サル、ウマ、ブタ、ウシ、ヒツジおよびイヌ等の非ヒト哺乳類、鳥類等の動物があげられる。   The subject of administration of the harmful metal excretion promoter of the present invention is not particularly limited, and examples thereof include humans. In addition, nonhuman mammals such as monkeys, horses, pigs, cows, sheep and dogs, and animals such as birds Can be given.

本発明の有害金属***促進剤の投与方法は、特に制限されず、例えば、経口投与である。本発明の有害金属***促進剤は、例えば、Hg(水銀)、Cd(カドミウム)、Pb(鉛)等の有害重金属、As(砒素)等の有害ミネラル等、各種有害金属の***に利用可能である。   The method for administering the harmful metal excretion promoter of the present invention is not particularly limited, and is, for example, oral administration. The harmful metal excretion promoter of the present invention can be used for excretion of various harmful metals such as harmful heavy metals such as Hg (mercury), Cd (cadmium) and Pb (lead), and harmful minerals such as As (arsenic). is there.

(有害金属***方法)
本発明の有害金属***方法は、被験者に、前記本発明の有害金属***促進剤を投与する工程を含むことを特徴とする。本発明は、前記本発明の有害金属***促進剤を使用することが特徴であって、その他の構成は何ら制限されない。
(Toxic metal excretion method)
The harmful metal excretion method of the present invention includes a step of administering to the subject the harmful metal excretion promoter of the present invention. The present invention is characterized by the use of the harmful metal excretion promoter of the present invention, and other configurations are not limited at all.

本発明において、前記有害金属***促進剤の条件、前記有害金属***促進剤の投与条件等は、本発明の有害金属***促進剤の説明を援用できる。   In the present invention, the description of the harmful metal excretion promoter of the present invention can be used for the conditions of the harmful metal excretion promoter, the administration conditions of the harmful metal excretion promoter, and the like.

(有害金属量の評価方法)
本発明の有害金属量の評価方法は、前述のように、有害金属***促進剤が投与された被験者の***尿における有害金属量を測定する工程を含み、前記有害金属***促進剤が、前記本発明の有害金属***促進剤であることを特徴とする。本発明は、前記本発明の有害金属***促進剤を使用することが特徴であって、その他の構成は何ら制限されない。
(Evaluation method of hazardous metal content)
As described above, the method for evaluating the amount of toxic metal of the present invention includes a step of measuring the amount of toxic metal in the excreted urine of a subject to which the toxic metal excretion promoter is administered, wherein the toxic metal excretion promoter is the book. It is a harmful metal excretion promoter of the invention. The present invention is characterized by the use of the harmful metal excretion promoter of the present invention, and other configurations are not limited at all.

本発明の評価方法において、前記***尿は、被験者に前記本発明の有害金属***促進剤を投与した後の***尿を採取することにより調製できる。前記採取する尿は、例えば、前記有害金属***促進剤の投与後、所定の時間に***された尿でもよいし、投与後から所定時間内に***された蓄積尿であってもよい。後者の場合、例えば、前記有害金属***促進剤の投与後から所定時間内に、尿中に***された有害金属の全量を測定することが可能である。前記所定時間は、特に制限されず、前記有害金属***促進剤の投与後、例えば、2時間以降、4時間以内が好ましく、より好ましくは1時間以降、4時間以内である。中でも、後者の***尿が好ましく、例えば、2時間以降、4時間以内の***尿を蓄積した蓄積尿が好ましく、より好ましくは、1時間以降、4時間以内の***尿を蓄積した蓄積尿である。   In the evaluation method of the present invention, the excretory urine can be prepared by collecting the excreted urine after administering the harmful metal excretion promoter of the present invention to the subject. The collected urine may be, for example, urine excreted at a predetermined time after administration of the harmful metal excretion promoter, or accumulated urine excreted within a predetermined time after administration. In the latter case, for example, it is possible to measure the total amount of harmful metals excreted in urine within a predetermined time after administration of the harmful metal excretion promoter. The predetermined time is not particularly limited, and is preferably, for example, from 2 hours to 4 hours after administration of the harmful metal excretion promoter, and more preferably from 1 hour to 4 hours. Among them, the latter excreted urine is preferable, for example, accumulated urine that accumulates excreted urine within 2 hours after 2 hours is preferable, and more preferably accumulated urine that accumulates excreted urine within 1 hour after 1 hour .

前記***尿における有害金属量の測定方法は、特に制限されず、例えば、前記***尿を、湿式灰化または乾式灰化した後、原子吸光光度計で測定する方法等があげられる。前記湿式灰化は、例えば、水銀分析マニュアル(環境省、平成16年3月)に従って行うことができる。具体例としては、水銀を測定する場合、例えば、前記***尿を湿式灰化処理した後、還元剤を適下することで、水銀の蒸気を発生させ、原子吸光法によって測定する方法、いわゆる、湿式灰化−還元気化原子吸光光度法が採用できる。これによって、前記***尿中の総水銀量が測定できる。測定波長は、例えば、253.7nmであり、測定装置として、例えば、高感度還元気化水銀測定装置(商品名マーキュリーRA−3320A、日本インスツルメンツ(株)製)が使用できる。また、Cd、As、Pb等を測定する場合は、例えば、前記***尿に前処理を施して、原子吸光光度計で測定する方法、ICP−MSで測定する方法等があげられる。   The method for measuring the amount of toxic metal in the excreted urine is not particularly limited, and examples thereof include a method of measuring the excreted urine with an atomic absorption photometer after wet ashing or dry ashing. The wet ashing can be performed, for example, according to a mercury analysis manual (Ministry of the Environment, March 2004). As a specific example, when measuring mercury, for example, after subjecting the excreted urine to a wet ashing treatment, a reducing agent is appropriately applied to generate mercury vapor, which is measured by an atomic absorption method, so-called, Wet ashing-reduction vapor atomic absorption spectrophotometry can be employed. Thereby, the total amount of mercury in the excreted urine can be measured. The measurement wavelength is 253.7 nm, for example, and as the measurement device, for example, a highly sensitive reduced vaporization measurement device (trade name Mercury RA-3320A, manufactured by Japan Instruments Co., Ltd.) can be used. Moreover, when measuring Cd, As, Pb, etc., the method of pre-processing the excretory urine and measuring with an atomic absorption photometer, the method of measuring with ICP-MS, etc. are mention | raise | lifted, for example.

このように、前記有害金属***促進剤を投与した被験者の***尿における有害金属量を測定し、前記***尿の有害金属量を評価することで、例えば、前記被験者の体内における有害金属量を評価できる。   Thus, by measuring the amount of harmful metal in the excreted urine of the subject administered the harmful metal excretion promoter and evaluating the amount of harmful metal in the excreted urine, for example, the amount of harmful metal in the body of the subject is evaluated. it can.

つぎに、本発明の実施例について説明する。なお、本発明は、下記の実施例により制限されない。   Next, examples of the present invention will be described. In addition, this invention is not restrict | limited by the following Example.

[実施例1]
有害金属***促進剤を投与した被験者から***尿を採取し、前記***尿中の水銀量を測定して、水銀***能の比較を行った。
[Example 1]
The excretion urine was collected from the subject administered the harmful metal excretion promoter, and the amount of mercury in the excretion urine was measured to compare the mercury excretion ability.

(1)実施例1
健常な成人男女の被験者8名(A〜H)に、同じ朝食を摂取させ、午前9時に尿を***させた。その後、各被験者に、実施例1の有害金属***促進剤としてαリポ酸200mgおよびシトルリン800mgを同時に経口投与させた。そして、αリポ酸およびシトルリンの投与から、1時間後、2時間後、3時間後および4時間後に、各被験者の***尿を全量採取した。
(1) Example 1
Eight healthy adult male and female subjects (A to H) were allowed to eat the same breakfast and excreted urine at 9 am. Thereafter, each subject was orally administered simultaneously with 200 mg α-lipoic acid and 800 mg citrulline as a harmful metal excretion promoter of Example 1. Then, 1 hour, 2 hours, 3 hours and 4 hours after the administration of α-lipoic acid and citrulline, the total amount of excreted urine from each subject was collected.

前記1時間後、2時間後、3時間後および4時間後の各***尿について、後述する方法により水銀量を測定した。そして、測定結果から、前記投与から1時間後までの***尿全量における総水銀量、前記投与から2時間後までの***尿全量における総水銀量、前記投与から3時間後までの***尿全量における総水銀量、および、前記投与から4時間後までの***尿全量における総水銀量を、それぞれ算出した。   For each excreted urine after 1 hour, 2 hours, 3 hours and 4 hours, the amount of mercury was measured by the method described later. From the measurement results, the total mercury amount in the total amount of excreted urine from 1 hour after the administration, the total mercury amount in the total amount of excreted urine from 2 hours after the administration, and the total amount of excreted urine from 3 hours after the administration The total mercury amount and the total mercury amount in the total amount of excreted urine from 4 hours after the administration were calculated.

前記水銀量の測定は、以下の通りである。まず、前記***尿を水銀分析マニュアル(環境省、平成16年3月)に従って、湿式灰化処理した。処理後のサンプルに、還元剤を適下することで、水銀蒸気を発生させ、原子吸光法によって、前記水銀を測定し、前記***尿中の総水銀量を測定した。測定波長は、253.7nmとし、前記測定には、高感度還元気化水銀測定装置(商品名マーキュリーRA−3320A、日本インスツルメンツ(株)製)を使用した。   The measurement of the amount of mercury is as follows. First, the excreted urine was subjected to wet ashing according to a mercury analysis manual (Ministry of the Environment, March 2004). By applying a reducing agent to the treated sample, mercury vapor was generated, the mercury was measured by atomic absorption method, and the total amount of mercury in the excreted urine was measured. The measurement wavelength was 253.7 nm, and a high-sensitivity reduced vaporization measuring apparatus (trade name Mercury RA-3320A, manufactured by Nippon Instruments Co., Ltd.) was used for the measurement.

(2)コントロール
前記被験者(A〜H)に対して、前記(1)の試験とは別の日に、αリポ酸およびシトルリンを投与しない以外は、前記実施例と同様の試験を行い、***尿中の総水銀量を算出した。
(2) Control The subject (A to H) is excreted by the same test as in the above example, except that α-lipoic acid and citrulline are not administered on a different day from the test of (1). The total amount of mercury in urine was calculated.

(3)比較例1−1
比較例1−1として、前記被験者(A〜H)に対して、前記(1)および(2)の試験とは別の日に、αリポ酸200mgおよびシトルリン800mgに代えて、比較例1−1の有害金属***促進剤としてαリポ酸200mgのみを経口投与させた以外は、前記実施例と同様に試験を行い、***尿中の総水銀量を算出した。
(3) Comparative Example 1-1
As Comparative Example 1-1, instead of the tests of (1) and (2) above on the subjects (A to H), instead of α-lipoic acid 200 mg and citrulline 800 mg, Comparative Example 1- A test was conducted in the same manner as in the above Example, except that only 200 mg of α-lipoic acid was orally administered as 1 harmful metal excretion promoter, and the total mercury content in excreted urine was calculated.

(4)比較例1−2
また、比較例1−2として、前記被験者(A〜H)に対して、前記(1)〜(3)の試験とは別の日に、αリポ酸200mgおよびシトルリン800mgに代えて、比較例1−2の有害金属***促進剤としてシトルリン800mgのみを経口投与させた以外は、前記実施例と同様に試験を行い、***尿中の総水銀量を算出した。
(4) Comparative Example 1-2
Moreover, as Comparative Example 1-2, instead of the tests of (1) to (3) above on the subjects (A to H), instead of α-lipoic acid 200 mg and citrulline 800 mg, Comparative Example A test was conducted in the same manner as in the above Example except that only 800 mg of citrulline was orally administered as a 1-2 harmful metal excretion promoter, and the total amount of mercury in excreted urine was calculated.

これらの結果を、図1〜4に示す。図1〜4は、それぞれ***尿全量における総水銀量(μg)を示すグラフであり、図1は、前記投与から1時間後までの***尿全量における総水銀量、図2は、前記投与から2時間後までの***尿全量における総水銀量、図3は、前記投与から3時間後までの***尿全量における総水銀量、図4は、前記投与から4時間後までの***尿全量における総水銀量を、それぞれ示す。   These results are shown in FIGS. 1 to 4 are graphs each showing the total mercury amount (μg) in the total amount of excreted urine, FIG. 1 is the total mercury amount in the total amount of excreted urine from 1 hour after the administration, and FIG. 3 shows the total mercury amount in the total amount of excreted urine up to 2 hours, FIG. 3 shows the total amount of mercury in the total amount of excreted urine up to 3 hours after the administration, and FIG. 4 shows the total amount in the total amount of excreted urine up to 4 hours after the administration. The amount of mercury is shown respectively.

図1〜4に示すように、αリポ酸とシトルリンとを同時に投与した実施例1は、コントロール、αリポ酸単独投与の比較例1−1およびシトルリン単独投与の比較例1−2と比較した結果、いずれの時間の***尿においても、被験者間で、相対的に高い水銀***量が確認された。特に、投与後から1時間を超えた時点において、実施例1における総水銀量は、コントロール、比較例1−1および1−2と比較して、顕著に増加していることがわかった。この結果から、本発明によれば、効率よく水銀を尿中に***できることが確認できた。   As shown in FIGS. 1 to 4, Example 1 in which α-lipoic acid and citrulline were administered simultaneously was compared with Control, Comparative Example 1-1 in which α-lipoic acid alone was administered, and Comparative Example 1-2 in which citrulline was administered alone. As a result, a relatively high mercury excretion amount was confirmed among the subjects in any time of excretion urine. In particular, it was found that the total mercury amount in Example 1 was remarkably increased as compared to Control and Comparative Examples 1-1 and 1-2 at a time point exceeding 1 hour after administration. From this result, according to the present invention, it was confirmed that mercury can be efficiently excreted in urine.

以上のように、本発明によれば、αリポ酸およびシトルリンは、経口投与することに負担がなく、投与後の負担もないことから、使用者の負担が少ない。また、本発明は、αリポ酸とシトルリンとの併用により、十分な有害金属***効果を実現できる。このため、本発明の有害金属***促進剤は、例えば、健康の維持、改善、向上のためのサプリメントや機能性食品、食品添加物としても有用である。また、本発明の有害金属***促進剤によれば、効果的に有害金属を尿中に***できるため、例えば、***尿の有害金属量の評価においても、非常に有用である。   As described above, according to the present invention, α-lipoic acid and citrulline have no burden on oral administration and no burden after administration, so that the burden on the user is small. Moreover, this invention can implement | achieve sufficient harmful metal excretion effect by combined use with (alpha) lipoic acid and citrulline. For this reason, the harmful metal excretion promoter of the present invention is useful, for example, as a supplement, functional food, or food additive for maintaining, improving, and improving health. Moreover, according to the harmful metal excretion promoter of the present invention, harmful metals can be effectively excreted in urine. Therefore, for example, it is very useful in evaluating the amount of harmful metals in excreted urine.

Claims (10)

αリポ酸のみからなるキレート剤およびシトルリンを含むことを特徴とする有害金属***促進剤。 1. A harmful metal excretion promoter characterized by containing a chelating agent consisting of only α-lipoic acid and citrulline. 前記αリポ酸を1〜1200mg、前記シトルリンを1〜3400mg含む、請求項1記載の有害金属***促進剤。 The harmful metal excretion promoter according to claim 1, comprising 1 to 1200 mg of the α lipoic acid and 1 to 3400 mg of the citrulline. 前記αリポ酸と前記シトルリンとの重量比が、1:0.5〜1:20である、請求項1または2記載の有害金属***促進剤。 The harmful metal excretion promoter according to claim 1 or 2, wherein a weight ratio of the α lipoic acid and the citrulline is 1: 0.5 to 1:20. 前記有害金属が、水銀、カドミウム、鉛および砒素からなる群から選択された少なくとも一つの金属である、請求項1から3のいずれか一項に記載の有害金属***促進剤。 The harmful metal excretion promoter according to any one of claims 1 to 3, wherein the harmful metal is at least one metal selected from the group consisting of mercury, cadmium, lead and arsenic. 経口投与に用いられる、請求項1から4のいずれか一項に記載の有配金属***促進剤。 The distributed metal excretion promoter according to any one of claims 1 to 4, which is used for oral administration. 少なくともαリポ酸を含むキレート剤およびシトルリンを含むことを特徴とする有害金属***促進剤。 A harmful metal excretion promoter comprising a chelating agent containing at least α-lipoic acid and citrulline. 有害金属***促進剤が投与された被験者の***尿における有害金属量を測定する工程を含み、
前記有害金属***促進剤が、請求項1から6のいずれか一項に記載の有害金属***促進剤であることを特徴とする有害金属量の評価方法。
Measuring the amount of harmful metal in the excreted urine of a subject administered the harmful metal excretion promoter,
The harmful metal excretion enhancer according to any one of claims 1 to 6, wherein the harmful metal excretion enhancer is a harmful metal excretion enhancer.
請求項1から6のいずれか一項に記載の有害金属***促進剤を含むことを特徴とするサプリメント。 A supplement comprising the harmful metal excretion promoter according to any one of claims 1 to 6. 請求項1から6のいずれか一項に記載の有害金属***促進剤を含むことを特徴とする機能性食品。 A functional food comprising the harmful metal excretion promoter according to any one of claims 1 to 6. 請求項1から6のいずれか一項に記載の有害金属***促進剤を含むことを特徴とする食品添加物。 A food additive comprising the harmful metal excretion promoter according to any one of claims 1 to 6.
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