JP5823303B2 - Oral amino acid composition - Google Patents
Oral amino acid composition Download PDFInfo
- Publication number
- JP5823303B2 JP5823303B2 JP2012007669A JP2012007669A JP5823303B2 JP 5823303 B2 JP5823303 B2 JP 5823303B2 JP 2012007669 A JP2012007669 A JP 2012007669A JP 2012007669 A JP2012007669 A JP 2012007669A JP 5823303 B2 JP5823303 B2 JP 5823303B2
- Authority
- JP
- Japan
- Prior art keywords
- amino acid
- oral
- acid composition
- dialysis
- bcaa
- 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.)
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Description
本発明は、経口アミノ酸組成物に関する。特に、透析患者用の経口アミノ酸組成物に関する。 The present invention relates to oral amino acid compositions. In particular, it relates to oral amino acid compositions for dialysis patients.
透析患者における栄養障害の原因として、食事摂取量の不足（食欲不振、加齢、食事指導の誤った解釈、食事制限、精神的要素、便秘など）、異化亢進状態（糖尿病、透析に関連した蛋白質およびエネルギーの不足）、合併症（二次性副甲状腺機能亢進症、代謝性アシドーシス）、慢性炎症などに加え、透析による栄養素の漏出が挙げられる。 Causes of malnutrition in dialysis patients include insufficient food intake (appetite loss, aging, misinterpretation of dietary guidance, dietary restrictions, mental factors, constipation, etc.), hypercatabolic status (diabetes, dialysis-related proteins) And lack of energy), complications (secondary hyperparathyroidism, metabolic acidosis), chronic inflammation, etc., and leakage of nutrients by dialysis.
例えば、透析患者の栄養状態を改善するために、アミノ酸注射液ネオアミュー（登録商標）輸液が知られている（非特許文献１）。 For example, in order to improve the nutritional status of dialysis patients, amino acid injection Neo Neo (registered trademark) infusion is known (Non-patent Document 1).
また、透析患者において、血清アルブミン濃度は、生命予後と強く関係する因子である。アルブミンもまた、１回の透析につき、透析器の中空糸膜から数百ｍｇ〜数百ｇが漏出することが分かっている。日本透析医学会の調査により、透析前血清アルブミン濃度が３．５ｇ／ｄＬ以下になると死亡のリスクが高まり、血清アルブミン濃度が低いほど死亡のリスクが高いとの報告がある。また、透析患者の血清アルブミン濃度は、６２％の患者が３．５ｇ／ｄＬ以下であることが報告されている。透析患者の死亡のリスクを減らすために、血清（血中）アルブミン濃度を上げることが課題となっている。 In dialysis patients, serum albumin concentration is a factor strongly related to life prognosis. Albumin has also been found to leak from several hundred mg to several hundred g from the hollow fiber membrane of the dialyzer per dialysis. According to a survey by the Japanese Society for Dialysis Therapy, there is a report that the risk of death increases when the serum albumin concentration before dialysis is 3.5 g / dL or less, and the risk of death increases as the serum albumin concentration decreases. Moreover, it is reported that the serum albumin density | concentration of a dialysis patient is 3.5 g / dL or less in 62% of patients. Increasing serum (blood) albumin concentration is a challenge to reduce the risk of death in dialysis patients.
アルブミンは肝臓で生合成される。肝硬変患者では、肝機能の低下により、アルブミンの合成が低下し、分岐鎖アミノ酸（ＢＣＡＡ；ロイシン、イソロイシン、およびバリンが含まれる）が減少することが知られている。肝硬変患者では、血清アルブミン濃度を上昇させるために、特にＢＣＡＡの補給がなされてきた。 Albumin is biosynthesized in the liver. It is known that in cirrhotic patients, albumin synthesis is reduced and branched chain amino acids (BCAA; including leucine, isoleucine, and valine) are reduced due to a decrease in liver function. In cirrhosis patients, BCAA supplementation has been made specifically to increase serum albumin levels.
肝機能の状態は、ＢＴＲおよびフィッシャー比を指標として知ることができる。ＢＴＲとは、チロシンに対する総ＢＣＡＡのモル比をいい、フィッシャー比とは、芳香族アミノ酸のチロシンおよびフェニルアラニンの合計に対する総ＢＣＡＡのモル比をいう。血液中のＢＣＡＡおよびチロシンは酵素法にて簡便に測定可能であるため、臨床上はＢＴＲがよく用いられる。例えば、ＢＴＲ値が小さいと、ＢＣＡＡが少なく、肝機能が低下していることが分かり、そのような患者の治療にはＢＣＡＡが補給される。 The state of liver function can be known using BTR and Fisher ratio as indices. BTR refers to the molar ratio of total BCAA to tyrosine, and Fischer ratio refers to the molar ratio of total BCAA to the sum of the aromatic amino acids tyrosine and phenylalanine. Since BCAA and tyrosine in blood can be easily measured by an enzymatic method, BTR is often used clinically. For example, if the BTR value is small, it can be seen that BCAA is low and liver function is reduced, and BCAA is supplemented for the treatment of such patients.
しかしながら、透析患者においては、ＢＣＡＡ濃度およびチロシン濃度が共に低く、ＢＴＲは、健常者と同様の値となってしまう。これは、フェニルアラニンは腎臓でチロシンに変換されるが、透析患者は、腎機能が低下しているためフェニルアラニンからチロシンへの変換がうまくできず、健常者と比較して、血液中のフェニルアラニン濃度が大きく、チロシン濃度は小さくなる傾向にあるからである。このため、透析患者では、ＢＣＡＡの減少を適切に判定できないという問題があった。 However, in dialysis patients, both the BCAA concentration and the tyrosine concentration are low, and the BTR becomes the same value as that of a healthy person. This is because phenylalanine is converted to tyrosine in the kidney, but dialysis patients cannot convert phenylalanine to tyrosine well because of decreased kidney function, and the concentration of phenylalanine in the blood is lower than that of healthy subjects. This is because the tyrosine concentration tends to be large and small. For this reason, there has been a problem that dialysis patients cannot appropriately determine a decrease in BCAA.
本発明は、かかる事情に鑑みてなされたものであり、透析患者用の経口アミノ酸組成物を提供することを目的とする。 The present invention has been made in view of such circumstances, and an object thereof is to provide an oral amino acid composition for dialysis patients.
本発明は、透析患者用の経口アミノ酸組成物を提供し、この経口アミノ酸組成物は、分岐鎖アミノ酸および分岐鎖アミノ酸を含むペプチドを含有し、フィッシャー比が６〜９５であり、単体としてフェニルアラニンおよびチロシンを含有しない。 The present invention provides an oral amino acid composition for dialysis patients, wherein the oral amino acid composition contains a branched chain amino acid and a peptide comprising the branched chain amino acid, has a Fisher ratio of 6 to 95, phenylalanine as a simple substance, and Contains no tyrosine.
１つの実施態様では、上記経口アミノ酸組成物は、脂溶性ビタミン（ビタミンＥを除く）を含有しない。 In one embodiment, the oral amino acid composition does not contain fat-soluble vitamins (except vitamin E).
別の実施態様では、上記経口アミノ酸組成物は、コエンザイムＱ１０をさらに含有する。 In another embodiment, the oral amino acid composition further comprises coenzyme Q10.
本発明によれば、透析患者用の経口アミノ酸組成物、特に、血清アルブミン濃度の低下した透析患者用の経口アミノ酸組成物が提供される。本発明の経口アミノ酸組成物は、透析患者に対してＢＣＡＡを適切に投与することができ、血清アルブミン濃度を上昇させることができる。 According to the present invention, there is provided an oral amino acid composition for dialysis patients, particularly an oral amino acid composition for dialysis patients having a reduced serum albumin concentration. The oral amino acid composition of the present invention can appropriately administer BCAA to a dialysis patient, and can increase serum albumin concentration.
本発明において、アミノ酸とは、蛋白質の構成ユニットとなるα−アミノ酸をいう。すなわち、２０種のＬ−アミノ酸をいう。アミノ酸の形態としては、遊離アミノ酸に限定されず、医薬品または飲食品で許容される塩または誘導体の形態であってもよく、例えば無機酸塩、有機酸塩、生体内で加水分解可能なエステル体、Ｎ−アシル誘導体などの形態であってもよい。アミノ酸の由来としては、特に限定されないが、例えば、食用蛋白質を酸または酵素により加水分解して取得するアミノ酸混合物であってもよいし、アミノ酸発酵法により生産されたものであってもよい。 In the present invention, an amino acid refers to an α-amino acid that is a structural unit of a protein. That is, it refers to 20 kinds of L-amino acids. The form of the amino acid is not limited to a free amino acid, and may be in the form of a salt or derivative acceptable in pharmaceuticals or foods and drinks. , N-acyl derivatives and the like. The origin of the amino acid is not particularly limited, and for example, it may be an amino acid mixture obtained by hydrolyzing an edible protein with an acid or an enzyme, or may be produced by an amino acid fermentation method.
本発明において、ペプチドとは、２つ以上の同種あるいは異種のアミノ酸（「構成アミノ酸」ともいう）がペプチド結合により結合した化合物をいう。構成アミノ酸数は、好ましくは２〜９９であり、より好ましくは２〜６０である。 In the present invention, a peptide refers to a compound in which two or more homologous or heterologous amino acids (also referred to as “constituent amino acids”) are bound by peptide bonds. The number of constituent amino acids is preferably 2 to 99, more preferably 2 to 60.
本発明において、分岐鎖アミノ酸（ＢＣＡＡ）とは、ロイシン、イソロイシン、バリンの３種類のアミノ酸をいう。本発明の経口アミノ酸組成物は、ＢＣＡＡを、単体のアミノ酸の形態およびペプチドの形態の両方の形態で含有する。 In the present invention, the branched chain amino acid (BCAA) refers to three types of amino acids: leucine, isoleucine, and valine. The oral amino acid composition of the present invention contains BCAA in both a single amino acid form and a peptide form.
本発明において、ＢＣＡＡを含むペプチドとは、ＢＣＡＡのロイシン、イソロイシンおよびバリンの少なくとも１種、好ましくは２種、より好ましくは３種を含むペプチドをいう。ＢＣＡＡを含むペプチドは、構成アミノ酸として、ＢＣＡＡ以外のアミノ酸を含んでいてもよいが、ＢＣＡＡを、好ましくは５０質量％以上、より好ましくは６０質量％以上含む。 In the present invention, a peptide containing BCAA refers to a peptide containing at least one, preferably two, more preferably three of BCAA leucine, isoleucine and valine. The peptide containing BCAA may contain amino acids other than BCAA as constituent amino acids, but preferably contains BCAA in an amount of 50% by mass or more, more preferably 60% by mass or more.
本発明において、ＢＣＡＡを含むペプチドとしては、ホエイ蛋白質（乳清蛋白質）を分解して得られるホエイペプチド、大豆ペプチド、グルタミンペプチドなどが挙げられる。本発明におけるペプチドは、通常２〜９９個のアミノ酸、好ましくは２〜６０個のアミノ酸が結合したペプチドであり、ＢＣＡＡを主要成分として含む。本発明におけるペプチドは、ＢＣＡＡを、好ましくは３０質量％以上、より好ましくは６０質量％以上含む。 In the present invention, peptides containing BCAA include whey peptides obtained by degrading whey protein (whey protein), soybean peptides, glutamine peptides and the like. The peptide in the present invention is usually a peptide in which 2 to 99 amino acids, preferably 2 to 60 amino acids are bound, and contains BCAA as a main component. The peptide in the present invention contains BCAA, preferably 30% by mass or more, more preferably 60% by mass or more.
本発明の経口アミノ酸組成物は、単体のＢＣＡＡおよびＢＣＡＡを含むペプチドを含有するので、ＢＣＡＡの腸管からの分解・吸収効率が高い。単体のＢＣＡＡとＢＣＡＡを含むペプチドとの含有比は、ＢＣＡＡを含むペプチドの構成アミノ酸の種類または数に依存するが、好ましくは、単体のＢＣＡＡ：ＢＣＡＡを含むペプチド＝１：５〜１０である。 Since the oral amino acid composition of the present invention contains a single BCAA and a peptide containing BCAA, the decomposition and absorption efficiency of BCAA from the intestinal tract is high. The content ratio between a single BCAA and a peptide containing BCAA depends on the type or number of constituent amino acids of the peptide containing BCAA, but is preferably a single BCAA: peptide containing BCAA = 1: 5-10.
ＢＣＡＡのロイシン、イソロイシンおよびバリンの構成比は、バリン：イソロイシン：ロイシンが、好ましくは１：０．５〜２：１〜４、より好ましくは１：１〜１．５：１．２〜２．０である。 The constituent ratio of leucine, isoleucine and valine in BCAA is preferably valine: isoleucine: leucine, preferably 1: 0.5-2: 1-4, more preferably 1: 1-1.5: 1.2-2. 0.
本発明の経口アミノ酸組成物は、単体のフェニルアラニンおよびチロシン（これらをまとめて、芳香族アミノ酸（ＡＡＡ）ともいう）を含まない。すなわち、本発明の経口アミノ酸組成物は、ＢＣＡＡを含むペプチドがＡＡＡを含む場合を除いて、ＡＡＡ（すなわち、フェニルアラニンおよびチロシン）を含まない。 The oral amino acid composition of the present invention does not contain simple phenylalanine and tyrosine (collectively these are also referred to as aromatic amino acids (AAA)). That is, the oral amino acid composition of the present invention does not contain AAA (that is, phenylalanine and tyrosine) unless the peptide containing BCAA contains AAA.
本発明の経口アミノ酸組成物は、フィッシャー比が６〜９５、好ましくは３０〜９５、より好ましくは５０〜９５である。ここで、「フィッシャー比」とは、ＢＣＡＡとＡＡＡ（フェニルアラニンおよびチロシン）とのモル比をいう（ＢＣＡＡ／ＡＡＡ）。フィッシャー比は、単体のアミノ酸およびペプチドに含まれるアミノ酸の合計に基づいて算出される。本発明の経口アミノ酸組成物は、フィッシャー比に着目することで、ＢＣＡＡ濃度を増加させることにより、フェニルアラニンおよびチロシンの濃度を相対的に低下させる。 The oral amino acid composition of the present invention has a Fischer ratio of 6 to 95, preferably 30 to 95, more preferably 50 to 95. Here, “Fischer ratio” refers to the molar ratio of BCAA to AAA (phenylalanine and tyrosine) (BCAA / AAA). The Fisher ratio is calculated based on the sum of the single amino acid and the amino acid contained in the peptide. The oral amino acid composition of the present invention relatively decreases the concentrations of phenylalanine and tyrosine by increasing the BCAA concentration by focusing on the Fisher ratio.
本発明の経口アミノ酸組成物は、透析患者（特に、血清アルブミン濃度の低下した透析患者）に対して、ＢＣＡＡを適切に投与することができ、血清アルブミン濃度を上昇させることができる。また、経口アミノ酸組成物中のＢＣＡＡ濃度の増加は、倦怠感の解消に有効である。倦怠感は、セロトニンやドーパミンといった神経伝達物質が分泌されるため、生じるものと考えられるが、ＢＣＡＡ濃度が増加することにより、神経伝達物質の生合成前駆体のトリプトファンおよびチロシンの濃度を相対的に低下させるため、倦怠感が解消するものと考えられる。経口アミノ酸組成物中のＢＣＡＡ濃度の増加はさらに、食欲増進、筋肉細胞におけるグリコーゲン合成酵素の促進による糖代謝の増加などにも有効である。 The oral amino acid composition of the present invention can appropriately administer BCAA to a dialysis patient (particularly a dialysis patient having a decreased serum albumin concentration), and can increase the serum albumin concentration. Moreover, the increase in the BCAA concentration in the oral amino acid composition is effective in eliminating fatigue. Fatigue is thought to occur because neurotransmitters such as serotonin and dopamine are secreted, but by increasing the BCAA concentration, the concentrations of tryptophan and tyrosine, which are precursors of neurotransmitter biosynthesis, are relatively increased. It is considered that fatigue is resolved because of a decrease. Increasing the BCAA concentration in the oral amino acid composition is also effective for increasing appetite and increasing sugar metabolism by promoting glycogen synthase in muscle cells.
本発明の経口アミノ酸組成物は、単体のＢＣＡＡおよびペプチドに含まれるＢＣＡＡの合計に基づいて、好ましくは３０〜９０質量％、より好ましくは５０〜９０質量％のＢＣＡＡを含有する。 The oral amino acid composition of the present invention preferably contains 30 to 90% by mass, more preferably 50 to 90% by mass of BCAA, based on the total of the single BCAA and BCAA contained in the peptide.
本発明の経口アミノ酸組成物は、脂溶性ビタミンを含有しないことが好ましい。脂溶性ビタミンとしては、ビタミンＡ、ビタミンＤ、ビタミンＥおよびビタミンＫが挙げられる。脂溶性ビタミン、特にビタミンＡは、組織に蓄積され、特に透析患者には好ましくない。ビタミンＤおよびＫは、薬として処方されている場合が多いため補充の必要性はない。ビタミンＥは、蓄積による害はなく、抗酸化剤として使用してもよく、１回摂取当たり、例えば０．０１〜０．１ｍｇの範囲内で含有することができる。 The oral amino acid composition of the present invention preferably contains no fat-soluble vitamin. Examples of fat-soluble vitamins include vitamin A, vitamin D, vitamin E, and vitamin K. Fat-soluble vitamins, especially vitamin A, accumulate in tissues and are particularly undesirable for dialysis patients. Vitamin D and K are often prescribed as drugs, so there is no need for supplementation. Vitamin E is not harmful due to accumulation and may be used as an antioxidant, and may be contained within a range of, for example, 0.01 to 0.1 mg per ingestion.
本発明の経口アミノ酸組成物は、コエンザイムＱ１０をさらに含有することが好ましい。コエンザイムＱ１０は、ユビキノンとも呼ばれ、栄養補助食品として知られている。一般的に、透析患者は基礎代謝が落ちており、コエンザイムＱ１０は、ＴＣＡ回路を活性化させることで代謝を上げる働きがあり、好ましい。コエンザイムＱ１０は、医薬品または飲食品で許容される塩の形態または誘導体の形態であってもよい。高純度のものが好ましい。本発明の経口アミノ酸組成物は、コエンザイムＱ１０を、１回摂取当たり、好ましくは５〜１００ｍｇ、より好ましくは１０〜３０ｍｇ含有するが、含有量は、患者の状態、性別、年齢、体重などに応じて適宜選定することができる。 The oral amino acid composition of the present invention preferably further contains coenzyme Q10. Coenzyme Q10 is also called ubiquinone and is known as a dietary supplement. In general, dialysis patients have decreased basal metabolism, and coenzyme Q10 has a function of increasing metabolism by activating the TCA cycle, which is preferable. Coenzyme Q10 may be in the form of a salt or derivative acceptable in pharmaceuticals or foods and drinks. High purity is preferred. The oral amino acid composition of the present invention contains coenzyme Q10 per ingestion, preferably 5 to 100 mg, more preferably 10 to 30 mg, depending on the patient's condition, sex, age, weight, etc. Can be selected as appropriate.
本発明の経口アミノ酸組成物はさらに、ＢＣＡＡ以外のアミノ酸（但し、フェニルアラニンおよびチロシンは除く）を含有してもよい。ＢＣＡＡ以外のアミノ酸としては、好ましくは、グルタミン、アルギニン、プロリン、リジン、トレオニン、メチオニン、ヒスチジン、トリプトファンなどが挙げられ、より好ましくはグルタミンおよびアルギニンが挙げられる。一般的に、透析患者は血中アンモニア濃度が高く、グルタミンおよびアルギニンは、アンモニアを分解する働きがあり、好ましい。また、透析患者は皮膚が乾燥していることが多く、アルギニンは、真皮のコラーゲンを増加する働きがあり、特にコラーゲンの成分であるプロリンと共に、肌を保湿する効果があり、好ましい。これらのアミノ酸の種類および含有量は、単体のＢＣＡＡの種類および量ならびにＢＣＡＡを含むペプチドに含まれるアミノ酸の種類および量を考慮して、適宜決定される。 The oral amino acid composition of the present invention may further contain amino acids other than BCAA (except phenylalanine and tyrosine). Examples of amino acids other than BCAA preferably include glutamine, arginine, proline, lysine, threonine, methionine, histidine, tryptophan, and more preferably glutamine and arginine. In general, dialysis patients have high blood ammonia concentration, and glutamine and arginine are preferable because they have a function of decomposing ammonia. In addition, dialysis patients often have dry skin, and arginine has a function of increasing collagen in the dermis, and is particularly preferable because it has an effect of moisturizing the skin together with proline which is a component of collagen. The type and content of these amino acids are appropriately determined in consideration of the type and amount of simple BCAA and the type and amount of amino acids contained in the peptide containing BCAA.
本発明の経口アミノ酸組成物はさらに、水溶性ビタミン類を含有してもよい。水溶性ビタミン類としては、好ましくは、ビタミンＢ１（チアミン）、ビタミンＢ２（リボフラビン）、ビタミンＢ３（ナイアシン）、ビタミンＢ５（パントテン酸、パントテン酸カルシウム（Ｃａ））、ビタミンＢ６（ピリドキシン）、ビタミンＢ９（葉酸）、ビタミンＢ１２（シアノコバラミン）、およびビタミンＣ（アスコルビン酸）が挙げられる。透析患者は動脈硬化などを合併症として患っていることが多く、これらの水溶性ビタミンは、動脈硬化性疾患や虚血性心疾患の因子であるホモシステインを、必須アミノ酸であるメチオニンに変換する過程で有用であり、好ましい。水溶性ビタミンの種類および含有量は、適宜決定される。水溶性ビタミンの種類および含有量は、好ましくは、１回摂取当たり、ビタミンＢ１ ０．５〜１．０ｍｇ；ビタミンＢ２ ０．５〜１．２ｍｇ；ビタミンＢ６ ２．０〜６．０ｍｇ；ビタミンＢ１２ ０．００１〜０．１０ｍｇ；ビタミンＢ３（ナイアシン） ３〜１５ｍｇ；ビタミンＢ５（パントテン酸またはパントテン酸Ｃａ） １．５〜４ｍｇ；ビタミンＢ９（葉酸） ０．１〜０．５ｍｇ；およびビタミンＣ １０〜５０ｍｇであるが、含有量は、患者の状態、性別、年齢、体重などに応じて適宜選定することができる。 The oral amino acid composition of the present invention may further contain water-soluble vitamins. The water-soluble vitamins are preferably vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin), vitamin B5 (pantothenic acid, calcium pantothenate (Ca)), vitamin B6 (pyridoxine), vitamin B9. (Folic acid), vitamin B12 (cyanocobalamin), and vitamin C (ascorbic acid). Dialysis patients often suffer from arteriosclerosis as a complication, and these water-soluble vitamins convert homocysteine, a factor in arteriosclerotic diseases and ischemic heart disease, into the essential amino acid methionine. Useful and preferred. The kind and content of the water-soluble vitamin are appropriately determined. The type and content of water-soluble vitamins are preferably 0.5 to 1.0 mg of vitamin B1 per ingestion; 0.5 to 1.2 mg of vitamin B2; vitamin B6 2.0 to 6.0 mg; vitamin B12 0.001 to 0.10 mg; vitamin B3 (niacin) 3 to 15 mg; vitamin B5 (pantothenic acid or pantothenic acid Ca) 1.5 to 4 mg; vitamin B9 (folic acid) 0.1 to 0.5 mg; and vitamin C 10 Although it is -50 mg, content can be suitably selected according to a patient's condition, sex, age, weight, etc.
本発明の経口アミノ酸組成物は、本発明の効果を損なわない範囲で、食品、医薬品に通常用いられる素材、添加剤などを含有してもよい。これらの素材、添加剤としては、例えば、糖類および甘味料（例えば、ブドウ糖、果糖、ショ糖、蜂蜜、還元麦芽糖、還元乳糖、トレハロース、オリゴ糖類、ステビア、スクラロースなど；低熱量性の糖類（還元麦芽糖、還元乳糖、トレハロース、オリゴ糖類など）および甘味料（ステビア、スクラロースなど）が好ましい）、酸味料（クエン酸、リンゴ酸、アスコルビン酸など）、賦形剤（デキストリン、澱粉など）、保存剤（安息香酸ナトリウム、パラオキシ安息香酸など）、ｐＨ調整剤（フィチン酸など）、香料、果汁、着色料、増粘多糖類などが挙げられる。 The oral amino acid composition of the present invention may contain materials, additives and the like that are usually used in foods and pharmaceuticals as long as the effects of the present invention are not impaired. Examples of these materials and additives include sugars and sweeteners (eg, glucose, fructose, sucrose, honey, reduced maltose, reduced lactose, trehalose, oligosaccharides, stevia, sucralose, etc .; low calorific value sugars (reduced Maltose, reduced lactose, trehalose, oligosaccharide etc.) and sweeteners (stevia, sucralose etc. are preferred), acidulants (citric acid, malic acid, ascorbic acid etc.), excipients (dextrin, starch etc.), preservatives (Sodium benzoate, paraoxybenzoic acid, etc.), pH adjusters (phytic acid, etc.), fragrances, fruit juices, coloring agents, thickening polysaccharides and the like.
また、本発明の経口アミノ酸組成物は、上記成分の他、卵殻カルシウム、パテント酸カルシウム、その他のミネラル類、アスタキサンチン、L−カルニチン、ローヤルゼリー、プロポリス、食物繊維、アガリクス、キチン、キトサン、漢方生薬、コンドロイチン、カプサイシン、食用色素、長鎖脂肪酸エステルなどの通常健康食品の成分として使用されている成分を含有してもよい。 The oral amino acid composition of the present invention includes eggshell calcium, calcium patent acid, other minerals, astaxanthin, L-carnitine, royal jelly, propolis, dietary fiber, agaricus, chitin, chitosan, herbal medicine, You may contain the component currently used as a component of normal health foods, such as chondroitin, capsaicin, food coloring, and long-chain fatty acid ester.
本発明の経口アミノ酸組成物の形態は特に限定されず、経口摂取（摂食）できる形態であればいずれの形態でもよい。このような形態としては、適当な賦形剤を使用した散剤、顆粒剤、錠剤、液剤（飲料、ゼリー飲料など）、あるいは医薬品または飲食品で許容される担体、賦形剤、希釈剤などとともに混合して形成した散剤、顆粒剤、錠剤、カプセル剤、トローチ剤、シロップ剤などが挙げられる。 The form of the oral amino acid composition of the present invention is not particularly limited and may be any form as long as it can be taken orally (taken). Examples of such forms include powders, granules, tablets, liquids (beverages, jelly beverages, etc.) using appropriate excipients, and carriers, excipients, diluents, etc. that are acceptable for pharmaceuticals or foods and drinks. Examples thereof include powders, granules, tablets, capsules, troches and syrups formed by mixing.
本発明の経口アミノ酸組成物は、上述の構成を有する限り、形態に応じて当業者が通常用いる製造方法に従って製造される。 The oral amino acid composition of the present invention is produced according to a production method commonly used by those skilled in the art depending on the form as long as it has the above-described configuration.
本発明の経口アミノ酸組成物は、固形剤（散剤、顆粒剤、錠剤、カプセル剤、トローチ剤）の場合そのまま単独または水とともに経口摂取できる。散剤または顆粒剤の場合はオブラートに包んで経口摂取してもよく、あるいは水、牛乳、ジュースなどに溶解または懸濁して経口摂取してもよい。液剤、シロップ剤の場合はそのまま経口摂取してもよく、または水、牛乳、ジュースなどで希釈して経口摂取してもよい。 The oral amino acid composition of the present invention can be taken orally alone or with water in the case of a solid preparation (powder, granule, tablet, capsule, troche). In the case of powders or granules, they may be taken orally by wrapping them in an oblate, or may be taken orally by dissolving or suspending in water, milk, juice or the like. In the case of a liquid or syrup, it may be taken orally as it is, or it may be taken orally after diluting with water, milk, juice or the like.
本発明の経口アミノ酸組成物の摂取方法は、特に限定されないが、毎食後が好ましい。本発明の経口アミノ酸組成物の摂取量は、１日１〜４回、ＢＣＡＡ換算で１回摂取当たり好ましくは１０００〜２０００ｍｇ、より好ましくは１２００〜２０００ｍｇであるが、摂取量は、患者の状態、性別、年齢、体重などに応じて適宜選定することができる。 The method for taking the oral amino acid composition of the present invention is not particularly limited, but is preferably after each meal. The intake amount of the oral amino acid composition of the present invention is preferably 1 to 4 times a day, preferably 1000 to 2000 mg, more preferably 1200 to 2000 mg per intake in terms of BCAA. It can be appropriately selected according to gender, age, weight and the like.
本発明の経口アミノ酸組成物は、主として透析患者用である。特に、透析を受けている慢性の腎炎、腎不全などの患者用である。このような患者としては、例えば、糖尿病性腎症、慢性腎炎（慢性糸球体腎炎）、腎硬化症、ネフローゼ症候群などの罹患患者が挙げられる。合併症（動脈硬化、肝炎など）を併発している透析患者にも用いられる。透析療法には、血液透析および腹膜透析（例えば、持続携帯式腹膜透析（ＣＡＰＤ））の２種があるが、本発明の経口アミノ酸組成物は、血液透析を受けている患者にとって特に好ましいが、腹膜透析を受けている患者にとっても好ましい。週に３回の透析を要するような維持透析患者にとっても好ましい。血清アルブミン濃度が３．５ｇ／ｄＬ以下に低下した透析患者に特に好ましい。 The oral amino acid composition of the present invention is mainly for dialysis patients. In particular, it is for patients with chronic nephritis and renal failure who are undergoing dialysis. Examples of such patients include affected patients such as diabetic nephropathy, chronic nephritis (chronic glomerulonephritis), nephrosclerosis, nephrotic syndrome and the like. It is also used for dialysis patients with complications (arteriosclerosis, hepatitis, etc.). There are two types of dialysis therapy, hemodialysis and peritoneal dialysis (eg continuous ambulatory peritoneal dialysis (CAPD)), although the oral amino acid composition of the present invention is particularly preferred for patients undergoing hemodialysis, It is also preferred for patients undergoing peritoneal dialysis. It is also preferred for maintenance dialysis patients who require dialysis three times a week. It is particularly preferred for dialysis patients whose serum albumin concentration has been reduced to 3.5 g / dL or less.
以下に本発明を実施例により説明するが、本発明はこれらの実施例に限定されるものではない。 EXAMPLES The present invention will be described below with reference to examples, but the present invention is not limited to these examples.
（実施例１：経口アミノ酸組成物）
（１−１：経口アミノ酸組成物の調製）
以下の表１に示す配合で、顆粒剤（全質量３８２６ｍｇ）を常法に従って調製した。
(Example 1: Oral amino acid composition)
(1-1: Preparation of oral amino acid composition)
With the formulation shown in Table 1 below, granules (total mass 3826 mg) were prepared according to a conventional method.
ホエイペプチドは、日本新薬株式会社から入手したものであり、組成としてロイシン、バリン、イソロイシン、グルタミン、アルギニン、プロリン、リジン、トレオニン、メチオニン、ヒスチジン、フェニルアラニン、およびトリプトファンを含む。表１中の処方は、以下のアミノ酸質量（ｍｇ）に相当する：グルタミン（Ｇｌｎ）５００；アルギニン（Ａｒｇ）４３０；ロイシン（Ｌｅｕ）８２０；イソロイシン（Ｉｌｅ）４３０；バリン（Ｖａｌ）５４０；プロリン（Ｐｒｏ）３２；リジン（Ｌｙｓ）６５；トレオニン（Ｔｈｒ）４８；メチオニン（Ｍｅｔ）１５；ヒスチジン（Ｈｉｓ）１３；フェニルアラニン（Ｐｈｅ）２０；トリプトファン（Ｔｒｐ）１３。フィッシャー比は８９．５である。 The whey peptide was obtained from Nippon Shinyaku Co., Ltd., and contains leucine, valine, isoleucine, glutamine, arginine, proline, lysine, threonine, methionine, histidine, phenylalanine, and tryptophan. The formulations in Table 1 correspond to the following amino acid masses (mg): glutamine (Gln) 500; arginine (Arg) 430; leucine (Leu) 820; isoleucine (Ile) 430; valine (Val) 540; Pro) 32; Lysine (Lys) 65; Threonine (Thr) 48; Methionine (Met) 15; Histidine (His) 13; Phenylalanine (Phe) 20; Tryptophan (Trp) 13. The Fisher ratio is 89.5.
（１−２：透析患者への経口アミノ酸組成物の経口摂取後の血清アルブミン濃度）
透析歴７年５ヶ月の糖尿病性腎症を罹患している９３歳の男性患者（以下、「患者１」と称する）に、上記１−１の経口アミノ酸組成物を、１ヶ月間にわたり１日３回毎食後に摂取してもらった（経口摂取）。この患者は、経口摂取前から月に１回の血液透析を行う前およびその終了後に採血を行って血清アルブミン濃度をモニタリングしており、経口摂取開始後も同様にモニタリングを続けた。
(1-2: Serum albumin concentration after oral intake of oral amino acid composition to dialysis patients)
A 93-year-old male patient (hereinafter referred to as “patient 1”) suffering from diabetic nephropathy with 7 years and 5 months of dialysis was treated with the oral amino acid composition of 1-1 above for 1 day for 1 month. They were taken 3 times after each meal (oral intake). This patient monitored blood albumin concentration by collecting blood before or after hemodialysis once a month from before oral intake, and continued monitoring after starting oral intake.
血清アルブミン濃度は、透析前に採血した血液で測定した。結果を図１に示す。 Serum albumin concentration was measured with blood collected before dialysis. The results are shown in FIG.
図１は、患者１における経口アミノ酸組成物の経口摂取開始前および開始後の血清アルブミン濃度の推移を示すグラフである。縦軸は血清アルブミン濃度（ｇ／ｄＬ）を示し、横軸は測定時期を示す。患者１において、血清アルブミン濃度は、経口アミノ酸組成物の経口摂取前では透析により徐々に低下し、経口摂取開始直前の２０１０年１１月には３．０ｇ／ｄＬを下回るまで低下していた。その後、経口摂取を開始してからは、血清アルブミン濃度の上昇が見られ、３．５ｇ／ｄＬ付近まで回復している。 FIG. 1 is a graph showing changes in serum albumin concentration before and after the start of oral intake of an oral amino acid composition in patient 1. The vertical axis represents the serum albumin concentration (g / dL), and the horizontal axis represents the measurement time. In patient 1, the serum albumin concentration gradually decreased by dialysis before oral intake of the oral amino acid composition, and decreased to less than 3.0 g / dL in November 2010 immediately before the start of oral intake. Thereafter, since the start of oral ingestion, the serum albumin concentration increased and recovered to around 3.5 g / dL.
このように、透析を受けている慢性腎不全患者が本実施例の経口アミノ酸組成物を摂取することで、低下していた血清アルブミン濃度を上昇することがわかった。また、本実施例の経口アミノ酸組成物を摂取することで、栄養状態の向上も見られた。 Thus, it was found that a patient with chronic renal failure undergoing dialysis increases the serum albumin concentration that has been reduced by taking the oral amino acid composition of this example. Moreover, the nutritional state was also improved by ingesting the oral amino acid composition of this example.
（比較例１）
週に３回の血液透析を受けている透析歴２年４ヶ月の慢性腎炎（合併症：肺気腫・軽〜中等度の僧帽弁閉鎖不全症）を罹患している８７歳の男性患者（以下、「患者２」と称する）に、推奨される指示どおりにネオアミュー（登録商標）輸液（非特許文献１）を点滴投与し、これを１ヶ月実施した。点滴投与を開始する前に採血し、血清アルブミン濃度を測定しておいた。１ヵ月後にまた採血し、血清アルブミン濃度を測定した。
(Comparative Example 1)
87-year-old male patient suffering from chronic nephritis (complication: emphysema / mild to moderate mitral regurgitation) 2 years and 4 months undergoing hemodialysis 3 times a week (Referred to as “Patient 2”), Neoamu (registered trademark) infusion (Non-patent Document 1) was infused as recommended, and this was carried out for 1 month. Blood was collected before instillation administration and the serum albumin concentration was measured. One month later, blood was collected again and the serum albumin concentration was measured.
その結果、点滴投与開始前の患者２の血清アルブミン濃度は３．２ｇ／ｄＬであるのに対し、点滴投与を１ヵ月行った後の血清アルブミン濃度は２．９ｇ／ｄＬであった。ネオアミュー（登録商標）輸液の点滴投与では、慢性腎不全患者の血清アルブミン濃度を上昇させることはできなかった。 As a result, the serum albumin concentration in Patient 2 before the start of infusion administration was 3.2 g / dL, whereas the serum albumin concentration after one month of infusion administration was 2.9 g / dL. Intravenous administration of Neoamu® infusion failed to increase serum albumin levels in patients with chronic renal failure.
ネオアミュー（登録商標）輸液のフィッシャー比を求めたところ、約４．５であった（バリン（Ｖａｌ）１．５ｇ；ロイシン（Ｌｅｕ）２．０ｇ；イソロイシン（Ｉｌｅ）１．５ｇ；フェニルアラニン（Ｐｈｅ）１．０ｇ；チロシン（Ｔｙｒ）０．１ｇ）。血清アルブミン濃度の上昇には、フィッシャー比により表されるようなＢＣＡＡとＡＡＡとのバランスが影響していると思われる。 The Fischer ratio of Neoamu® infusion was determined to be about 4.5 (Valin 1.5 g; Leucine (Leu) 2.0 g; Isoleucine (Ile) 1.5 g; Phenylalanine (Phe) ) 1.0 g; tyrosine (Tyr) 0.1 g). The increase in serum albumin concentration seems to be affected by the balance between BCAA and AAA as expressed by the Fisher ratio.
（実施例２：透析患者への経口アミノ酸組成物の経口摂取後の血清アルブミン濃度）
透析歴９年のＩｇＡ腎症を罹患している５９歳の男性患者（以下、「患者３」と称する）に、上記１−１の経口アミノ酸組成物を、１ヶ月間にわたり１日３回毎食後に摂取してもらった（経口摂取）。この患者は、経口摂取前から月に１回の血液透析を行う前およびその終了後に採血を行って血清アルブミン濃度をモニタリングしており、経口摂取開始後も同様にモニタリングを続けた。
(Example 2: Serum albumin concentration after oral intake of oral amino acid composition to dialysis patients)
A 59-year-old male patient (hereinafter referred to as “patient 3”) suffering from IgA nephropathy with a history of dialysis of 9 years is given the oral amino acid composition of 1-1 above every day for 3 months. I took it later (oral intake). This patient monitored blood albumin concentration by collecting blood before or after hemodialysis once a month from before oral intake, and continued monitoring after starting oral intake.
血清アルブミン濃度は、透析前に採血した血液で測定した。結果を図２に示す。 Serum albumin concentration was measured with blood collected before dialysis. The results are shown in FIG.
図２は、患者３における経口アミノ酸組成物の経口摂取開始前および開始後の血清アルブミン濃度の推移を示すグラフである。縦軸は血清アルブミン濃度（ｇ／ｄＬ）を示し、横軸は測定時期を示す。患者３においては、血清アルブミン濃度は、経口アミノ酸組成物の経口摂取前では透析により徐々に低下し、経口摂取開始直前の２０１１年２月には３．０ｇ／ｄＬを大きく下回るまで低下していた。その後、経口摂取を開始してからは、血清アルブミン濃度の上昇が見られ、３．５ｇ／ｄＬを超えるまで回復している。 FIG. 2 is a graph showing changes in serum albumin concentration before and after the start of oral intake of the oral amino acid composition in patient 3. The vertical axis represents the serum albumin concentration (g / dL), and the horizontal axis represents the measurement time. In patient 3, the serum albumin concentration gradually decreased by dialysis before oral intake of the oral amino acid composition, and decreased to a level well below 3.0 g / dL in February 2011 immediately before the start of oral intake. . Thereafter, since the start of oral ingestion, the serum albumin concentration increased and recovered until it exceeded 3.5 g / dL.
（実施例３：透析患者への経口アミノ酸組成物の経口摂取後の血清アルブミン濃度）
上記実施例１および２と同様に、透析歴１〜２２年の１０人の腎症患者（男性および女性）に、上記１−１の経口アミノ酸組成物を、１ヶ月間にわたり１日３回毎食後に摂取してもらった（経口摂取）。各患者は、経口摂取前から月に１回の血液透析を行う前およびその終了後に採血を行って血清アルブミン濃度をモニタリングしており、経口摂取開始後も同様にモニタリングを続けた。これらの患者に対する経口アミノ酸組成物の経口摂取およびその採血した血液のモニタリングは、2011年4月から開始し、半年間行った。血清アルブミン濃度は、透析前に採血した血液で測定し、これらの患者における血清アルブミン濃度平均値を算定した。結果を図３に示す。
(Example 3: Serum albumin concentration after oral intake of oral amino acid composition to dialysis patients)
Similar to Examples 1 and 2, 10 nephropathy patients (male and female) with a history of dialysis of 1 to 22 years were given the oral amino acid composition of 1-1 above once a month for 3 months. I took it later (oral intake). Each patient collected blood before and after hemodialysis once a month from the time before oral intake and after that, and monitored the serum albumin concentration, and continued monitoring after the start of oral intake. Oral intake of oral amino acid composition and monitoring of the collected blood for these patients began in April 2011 and were conducted for half a year. Serum albumin concentration was measured with blood collected before dialysis, and the average value of serum albumin concentration in these patients was calculated. The results are shown in FIG.
図３は、透析患者における経口アミノ酸組成物の経口摂取開始後の血清アルブミン濃度の推移を示すグラフである。縦軸は血清アルブミン濃度（ｇ／ｄＬ）を示し、横軸は測定時期を示す。血清アルブミン濃度のデータは、１０人の患者の平均値を示す。血清アルブミン濃度は、経口アミノ酸組成物の経口摂取開始前には３．４７ｇ／ｄＬまで低下しているが、経口摂取６ヶ月後には、３．７ｇ／ｄＬを超えるまで上昇している。この上昇は有意差ありと判定できた。なお、開始３ヵ月後から開始４ヵ月後は７〜８月に該当し、夏場の食欲減退のために血清アルブミン濃度の低下が見られたと考えられた。患者毎に血清アルブミン濃度の値に多少の変動はあるが、どの患者においてもほぼ同様の傾向が見られた。 FIG. 3 is a graph showing the transition of serum albumin concentration after the start of oral intake of the oral amino acid composition in dialysis patients. The vertical axis represents the serum albumin concentration (g / dL), and the horizontal axis represents the measurement time. The serum albumin concentration data represents the average of 10 patients. The serum albumin concentration has decreased to 3.47 g / dL before the start of oral intake of the oral amino acid composition, but has increased to 3.7 g / dL after 6 months of oral intake. This increase was judged to be significant. In addition, 3 months after the start and 4 months after the start corresponded to July to August, and it was considered that a decrease in serum albumin concentration was observed due to decreased appetite in summer. Although there was some variation in the value of serum albumin from patient to patient, almost the same trend was seen in all patients.
上記実施例１〜３に示されるように、上記１−１の経口アミノ酸組成物の摂取により、透析患者の死亡のリスクを低下させたと判断できる。 As shown in Examples 1 to 3 above, it can be judged that the risk of death of a dialysis patient was reduced by ingesting the oral amino acid composition of 1-1.
（実施例４：透析患者への経口アミノ酸組成物の経口摂取後の％クレアチニン産生速度）
上記実施例３と同じ患者について、経口摂取前から月に１回の血液透析を行う前およびその終了後に採血を行って血清クレアチニン濃度をモニタリングしており、経口摂取開始後も同様にモニタリングを続けた。透析前後の血清クレアチニン濃度から患者のクレアチニン産生速度を算定した。算定は、Shinzato Tら, Artif Organs, 21: 864-872, 1997に記載の手順に従って行った。さらに、算定したクレアチニン産生速度を、その評価すべき患者と同性、同年齢の健常人のクレアチニン産生速度の平均値に対する割合（％）として、％クレアチニン産生速度（％Ｃｇｒ）を求めた。これらの患者における％クレアチニン産生速度平均値を算定した。結果を図４に示す。
(Example 4:% creatinine production rate after oral intake of oral amino acid composition to dialysis patient)
For the same patient as in Example 3 above, blood was collected before and after the completion of hemodialysis once a month from before oral intake, and the serum creatinine concentration was monitored. It was. The patient's creatinine production rate was calculated from the serum creatinine concentration before and after dialysis. The calculation was performed according to the procedure described in Shinzato T et al., Artif Organs, 21: 864-872, 1997. Further, the% creatinine production rate (% Cgr) was determined as the ratio (%) of the calculated creatinine production rate to the average value of the creatinine production rate of healthy individuals of the same age and age as the patient to be evaluated. The average% creatinine production rate in these patients was calculated. The results are shown in FIG.
図４は、透析患者における経口アミノ酸組成物の経口摂取開始後の％クレアチニン産生速度の推移を示すグラフである。縦軸は％クレアチニン産生速度（％Ｃｇｒ）を示し、横軸は測定時期を示す。％クレアチニン産生速度のデータは、１０人の患者の平均値を示す。％クレアチニン産生速度は、経口アミノ酸組成物の経口摂取６ヶ月後には、経口アミノ酸組成物の経口摂取開始前と比較して上昇が見られ、この上昇は有意差ありと判定できた。患者毎に％クレアチニン産生速度の値に多少の変動はあるが、どの患者においてもほぼ同様の傾向が見られた。 FIG. 4 is a graph showing the transition of the% creatinine production rate after the start of oral intake of the oral amino acid composition in dialysis patients. The vertical axis indicates% creatinine production rate (% Cgr), and the horizontal axis indicates the measurement time. The% creatinine production rate data represents the average of 10 patients. The% creatinine production rate increased after 6 months of oral intake of the oral amino acid composition as compared to before the start of oral intake of the oral amino acid composition, and this increase was judged to be significantly different. Although there was some variation in the value of% creatinine production rate from patient to patient, almost the same trend was observed in all patients.
％クレアチニン産生速度は、筋肉量を示す指標として用いられ、この値が大きいほど筋肉量が多いことを示す。経口アミノ酸組成物の経口摂取６ヶ月後には、経口アミノ酸組成物の経口摂取開始前と比較して筋肉量が上昇したと判断できる。 The% creatinine production rate is used as an index indicating muscle mass, and the larger this value, the greater the muscle mass. After 6 months of oral intake of the oral amino acid composition, it can be determined that the muscle mass has increased compared to before the start of oral intake of the oral amino acid composition.
％クレアチニン産生速度はまた死亡のリスクに関する指標としても用いられ、この値が大きいほど死亡のリスクは低下する。したがって、本実施例４における％クレアチニン産生速度の結果からも、上記１−１の経口アミノ酸組成物の摂取により透析患者の死亡のリスクを低下させたと判断できる。 The% creatinine production rate is also used as an indicator for the risk of death, the higher this value, the lower the risk of death. Therefore, from the result of% creatinine production rate in Example 4, it can be determined that the risk of death of dialysis patients was reduced by ingestion of the oral amino acid composition of 1-1.
本発明によれば、透析患者において、生命予後と強く関係する因子である血清アルブミン濃度を上昇させることのできる経口アミノ酸組成物が提供される。本発明の経口アミノ酸組成物は、透析を受けている慢性の腎炎、腎不全などの患者の栄養状態を改善し得、死亡のリスクを低下させ得る。 ADVANTAGE OF THE INVENTION According to this invention, the oral amino acid composition which can raise the serum albumin density | concentration which is a factor strongly related to life prognosis in a dialysis patient is provided. The oral amino acid composition of the present invention can improve the nutritional status of patients undergoing dialysis, such as chronic nephritis and renal failure, and can reduce the risk of death.
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| SE542106C2 (en) * | 2016-08-26 | 2020-02-25 | Atif M Dabdoub | Dietary macro/micronutritional supplement for patients undergoing kidney dialysis |
| CN107997182A (en) * | 2017-11-02 | 2018-05-08 | 上海市杨浦区市东医院 | The fixation nutritional agents that a kind of kidney failure dialysis patient uses |
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