JP5370429B2 - Collagen synthesis promoting amino acid composition - Google Patents
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- JP5370429B2 JP5370429B2 JP2011164806A JP2011164806A JP5370429B2 JP 5370429 B2 JP5370429 B2 JP 5370429B2 JP 2011164806 A JP2011164806 A JP 2011164806A JP 2011164806 A JP2011164806 A JP 2011164806A JP 5370429 B2 JP5370429 B2 JP 5370429B2
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Description
本発明は、特定のアミノ酸を５種または４種、すなわち、Ｌ−アルギニンおよび／またはＬ−グルタミン、ならびに、Ｌ−バリン、Ｌ−イソロイシンおよびＬ−ロイシンの５種または４種のアミノ酸を特定の割合で含有することを特徴とするコラーゲン合成促進アミノ酸組成物、およびコラーゲン合成に関連する皮膚老化防止、骨粗しょう症抑制、腱、靱帯再生促進および創傷又は熱傷治癒に有用なアミノ酸組成物に関するものである。 The present invention specifies 5 or 4 specific amino acids, namely L-arginine and / or L-glutamine, and 5 or 4 amino acids of L-valine, L-isoleucine and L-leucine. The present invention relates to a collagen synthesis-promoting amino acid composition characterized in that it is contained in a proportion, and to an amino acid composition useful for preventing skin aging, osteoporosis, tendon, ligament regeneration promotion and wound or burn healing related to collagen synthesis. is there.
体内のタンパク質で最も多いコラーゲンは細胞外マトリックスの成分として結合組織として非常に重要な役割を果たしている。コラーゲンの多い組織として、皮膚、骨組織、腱、靱帯などがある。これらの組織は老化に伴い、シワやたるみ、骨粗しょう症などが引き起こるが、組織コラーゲン量の減少、変性などが大きな要因であると考えられている。 Collagen, the most abundant protein in the body, plays a very important role as a connective tissue as a component of the extracellular matrix. Examples of tissues rich in collagen include skin, bone tissue, tendons, and ligaments. These tissues cause wrinkles, sagging, osteoporosis and the like with aging, but it is thought that a decrease in tissue collagen amount and degeneration are major factors.
コラーゲン合成はビタミンやホルモン、サイトカインなどが作用することで促進されることが知られているが、タンパク質の基質であるアミノ酸もコラーゲン合成を促進することが知られている。繊維芽細胞を用いた検討ではグルタミンがコラーゲン合成を促進することが報告されており（非特許文献１）、ヒトや動物を用いた検討では創傷治癒においてアルギニンそのものやアルギニン、β−ヒドロキシ−β−メチルブチル酸、グルタミン混合物が創傷部位のコラーゲン合成を促進するという報告がある（特許文献１および２、ならびに非特許文献２）。 Collagen synthesis is known to be promoted by the action of vitamins, hormones, cytokines, etc., but amino acids that are protein substrates are also known to promote collagen synthesis. In studies using fibroblasts, it has been reported that glutamine promotes collagen synthesis (Non-Patent Document 1). In studies using humans and animals, arginine itself, arginine, and β-hydroxy-β- are used in wound healing. There are reports that a mixture of methylbutyric acid and glutamine promotes collagen synthesis at the wound site (
また、コラーゲン合成を促すとする製品としてコラーゲンタンパクやコラーゲン組成アミノ酸組成物などが市販されているが、その効果は明確でなく、優れた効果を持つアミノ酸、また、アミノ酸組成物が切望されている。 Collagen proteins and collagen composition amino acid compositions are commercially available as products that promote collagen synthesis, but their effects are not clear, and excellent amino acids and amino acid compositions are highly desired. .
前述の従来技術の背景下に、本発明の目的は、優れたコラーゲン合成促進作用をもつアミノ酸組成物を得ることにある。 Under the background of the aforementioned prior art, an object of the present invention is to obtain an amino acid composition having an excellent collagen synthesis promoting action.
本発明者は、前項記載の課題を解決すべく鋭意研究の結果、Ｌ−アルギニンおよび／またはＬ−グルタミン、ならびに、Ｌ−バリン、Ｌ−イソロイシンおよびＬ−ロイシンの５種または４種のアミノ酸を特定の割合で含むアミノ酸組成物がコラーゲン合成を促進することを見出し、本発明を完成するに至った。 As a result of diligent research to solve the problems described in the preceding paragraph, the present inventor obtained L-arginine and / or L-glutamine, and 5 or 4 amino acids of L-valine, L-isoleucine and L-leucine. The inventors have found that an amino acid composition containing a specific ratio promotes collagen synthesis, and has completed the present invention.
すなわち、本発明は、特定のアミノ酸を特定の割合で含有することを特徴とする、すなわち、Ｌ−アルギニンを１０〜４０質量部および／またはＬ−グルタミンを１０〜４０質量部、ならびに、Ｌ−バリンを５〜２０質量部、Ｌ−イソロイシンを８〜３０質量部、Ｌ−ロイシンを１０〜３５質量部含有することを特徴とするコラーゲン合成促進アミノ酸組成物、ならびに同じ組成の皮膚老化防止アミノ酸組成物、骨粗しょう症抑制アミノ酸組成物、腱、靱帯再生促進アミノ酸組成物、および創傷又は熱傷治癒アミノ酸組成物に関する。 That is, the present invention is characterized by containing a specific amino acid at a specific ratio, that is, 10 to 40 parts by mass of L-arginine and / or 10 to 40 parts by mass of L-glutamine, and L- A collagen synthesis promoting amino acid composition comprising 5 to 20 parts by mass of valine, 8 to 30 parts by mass of L-isoleucine, and 10 to 35 parts by mass of L-leucine, and an amino acid composition for preventing skin aging having the same composition , Osteoporosis-suppressing amino acid composition, tendon, ligament regeneration promoting amino acid composition, and wound or burn healing amino acid composition.
本発明の、特定の５種または４種のアミノ酸組成物によれば、皮膚や骨組織といった体内のコラーゲン合成が促進される。 According to the specific 5 or 4 amino acid composition of the present invention, synthesis of collagen in the body such as skin and bone tissue is promoted.
本発明のアミノ酸組成物は、Ｌ−アルギニンを１０〜４０質量部および／またはＬ−グルタミンを１０〜４０質量部、ならびに、Ｌ−バリンを５〜２０質量部、Ｌ−イソロイシンを８〜３０質量部およびＬ−ロイシンを１０〜３５質量部含有することを特徴とするアミノ酸組成物である。なお、本発明で利用するアミノ酸はそれらのアミノ酸を含むペプチド体であってもよい。 The amino acid composition of the present invention comprises 10 to 40 parts by mass of L-arginine and / or 10 to 40 parts by mass of L-glutamine, 5 to 20 parts by mass of L-valine, and 8 to 30 parts by mass of L-isoleucine. An amino acid composition comprising 10 to 35 parts by mass of L-leucine. The amino acids used in the present invention may be peptide bodies containing those amino acids.
これらのアミノ酸組成物は、これに、適当な添加物、例えば、糖質、脂質、タンパク質、ビタミン、ミネラルなどの他の栄養素いずれか、或いはそれらを組み合わせて配合しても良い。その際には、賦型剤、嬌味剤、色素などと組み合わせることも可能である。このようにして製造された本発明のアミノ酸組成物は、そのまま、すなわち、粉体もしくは液体混合物の形態で流通に置くことができる。また、サプリメント、調味料、加工食品、輸液などの医薬品などの形態で流通に置くこともできる。 These amino acid compositions may be blended with appropriate additives such as carbohydrates, lipids, proteins, vitamins, minerals such as vitamins, or any combination thereof. In that case, it is also possible to combine with an excipient, a flavoring agent, a pigment | dye, etc. The amino acid composition of the present invention thus produced can be put into circulation as it is, that is, in the form of a powder or liquid mixture. It can also be distributed in the form of supplements, seasonings, processed foods, pharmaceuticals such as infusions.
本発明のアミノ酸組成物は、経口投与によることはもちろん、静注により投与することもできる。静注による場合は、静注に適しない添加物を除外した製剤とすることは言うまでもない。 The amino acid composition of the present invention can be administered intravenously as well as by oral administration. In the case of intravenous injection, it goes without saying that the preparation excludes additives that are not suitable for intravenous injection.
また、本発明のアミノ酸組成物の投与量について説明すると、ラットの静脈にアミノ酸組成物を投与し、コラーゲン合成の促進が認められた際の血中アミノ酸濃度の上昇とアミノ酸組成物を経口投与した際の血中濃度の上昇が同程度になる場合を考慮して、経口、静注を問わず、成人１日当り５〜１２ｇ程度とすることができる。 Further, the dose of the amino acid composition of the present invention will be described. The amino acid composition was administered to the rat vein, and the blood amino acid concentration was increased and the amino acid composition was orally administered when promotion of collagen synthesis was observed. In consideration of the case where the increase in blood concentration is about the same, it can be about 5 to 12 g per day for an adult regardless of oral or intravenous injection.
本発明のアミノ酸組成物は、上に説明した投与方法および投与量で、例えば、皮膚老化や骨粗しょう症の症状の現れるおそれのある時期に投与することで、あるいは既に発症している場合に投与することで、発症を予防し、あるいは症状の進行を抑制し、更に症状を改善することができる。 The amino acid composition of the present invention is administered in the above-described administration method and dosage, for example, by administration at a time when there is a possibility that symptoms of skin aging or osteoporosis appear, or when already developed. By doing so, it is possible to prevent the onset or suppress the progression of symptoms and further improve the symptoms.
各群４から６頭からなるＳＤ（ＩＧＳ）雄性ラットに無タンパク食（０％カゼイン）を１週間供与した後に実験に用いた。アミノ酸を投与する実験群としては１）生理食塩水、２）Ｌ−グルタミン、３）Ｌ−アルギニン、４）３種分岐鎖アミノ酸組成物（Ｌ−ロイシン、Ｌ−イソロイシンおよびＬ−バリンを総称してＢＣＡＡともいう）、５）１２種アミノ酸組成物（Ｌ−イソロイシン、Ｌ−ロイシン、Ｌ−バリン、Ｌ−グルタミン、Ｌ−ヒスチジン、Ｌ−リジン、Ｌ−フェニルアラニン、Ｌ−プロリン、Ｌ−スレオニン、Ｌ−メチオニン、Ｌ−トリプトファンおよびＬ−アルギニン）、６）コラーゲン組成アミノ酸組成物（Ｌ−イソロイシン、Ｌ−ロイシン、Ｌ−バリン、Ｌ−ヒスチジン、Ｌ−リジン、Ｌ−フェニルアラニン，Ｌ−プロリン、Ｌ−ヒドロキシプリン，Ｌ−スレオニン、Ｌ−メチオニン、Ｌ−アラニン、Ｌ−アスパラギン酸、Ｌ−グルタミン酸、Ｌ−グリシン、Ｌ−セリンおよびＬ−アルギニン）、７）５種アミノ酸組成物（Ｌ−ロイシン、Ｌ−イソロイシン、Ｌ−バリン、Ｌ−グルタミンおよびＬ−アルギニン）、８）４種アミノ酸組成物１（Ｌ−ロイシン、Ｌ−イソロイシン、Ｌ−バリンおよびＬ−グルタミン）、９）４種アミノ酸組成物２（Ｌ−ロイシン、Ｌ−イソロイシン、Ｌ−バリンおよびＬ−アルギニン）、１０）２種アミノ酸組成物（Ｌ−アルギニンおよびＬ−グルタミン）の計１０群を設けた。アミノ酸組成、投与濃度は下記第１表に示した。 A protein-free diet (0% casein) was given to SD (IGS) male rats consisting of 4 to 6 rats in each group for 1 week before use in the experiment. As experimental groups for administering amino acids, 1) physiological saline, 2) L-glutamine, 3) L-arginine, 4) three kinds of branched chain amino acid compositions (L-leucine, L-isoleucine, and L-valine are generic names). 5) 12 amino acid compositions (L-isoleucine, L-leucine, L-valine, L-glutamine, L-histidine, L-lysine, L-phenylalanine, L-proline, L-threonine, L) -methionine, L-tryptophan and L-arginine), 6) Collagen composition amino acid composition (L-isoleucine, L-leucine, L-valine, L-histidine, L-lysine, L-phenylalanine, L-proline, L) -Hydroxypurine, L-threonine, L-methionine, L-alanine, L-aspartic acid, L-glutamic acid, -Glycine, L-serine and L-arginine), 7) 5 amino acid compositions (L-leucine, L-isoleucine, L-valine, L-glutamine and L-arginine), 8) 4 amino acid compositions 1 ( L) -leucine, L-isoleucine, L-valine and L-glutamine), 9) 4 amino acid composition 2 (L-leucine, L-isoleucine, L-valine and L-arginine), 10) 2 amino acid composition A total of 10 groups (L-arginine and L-glutamine) were provided. The amino acid composition and administration concentration are shown in Table 1 below.
投与液は頸静脈に３時間半前後持続的に投与した。コラーゲン合成速度の測定は、安定同位体Ｌ−フェニルアラニンを用いて、一定時間内にコラーゲンタンパク質に取り込まれる安定同位体Ｌ−フェニルアラニンの標識率を測定することにより合成速度を求めた。組織は皮膚を用い、コラーゲンは中性塩溶液に溶解する新生コラーゲン画分を用いた。その結果を後掲図１に示す。 The administration solution was continuously administered to the jugular vein for about 3 and a half hours. The collagen synthesis rate was determined by measuring the labeling rate of the stable isotope L-phenylalanine incorporated into the collagen protein within a certain time using the stable isotope L-phenylalanine. The tissue used was skin, and the collagen used was a nascent collagen fraction dissolved in a neutral salt solution. The results are shown in FIG.
生理食塩水投与群を対照としｔ−ｔｅｓｔにて検定を実施し、図中＊はｐ＜０．０５を示す。計算方法を下記計算式（１）に示す。 The physiological saline administration group was used as a control, and the test was carried out by t-test. In the figure, * represents p <0.05. The calculation method is shown in the following calculation formula (1).
図１にコラーゲン合成速度の変化を示した。コラーゲン合成速度は５種アミノ酸組成物（図中、ＢＣＡＡ＋Ａｒｇ＋Ｇｌｎ）、４種アミノ酸組成物１（図中、ＢＣＡＡ＋Ｇｌｎ）または４種アミノ酸組成物２（図中、ＢＣＡＡ＋Ａｒｇ）を投与することにより、生理食塩水（図中、ＰＦ）を投与した群に対し有意に促進することが認められた。また、分岐鎖アミノ酸組成物（図中、ＢＣＡＡ）、Ｌ−アルギニン（図中、Ａｒｇ）、Ｌ−グルタミン（図中、Ｇｌｎ）、Ｌ−アルギニン＋Ｌ−グルタミン混合物（図中、Ａｒｇ＋Ｇｌｎ）の投与では回復が認められなかったこと、１２種アミノ酸組成物（図中、ＡＶＰ）やコラーゲン組成アミノ酸組成物に比べコラーゲンの合成速度が促進していることから、この５種または４種のアミノ酸組成物がコラーゲンの合成促進に非常に優れた効果を持つことが示された。 FIG. 1 shows changes in collagen synthesis rate. Collagen synthesis rate is determined by administering 5 amino acid compositions (BCAA + Arg + Gln in the figure), 4 amino acid compositions 1 (BCAA + Gln in the figure) or 4 amino acid compositions 2 (BCAA + Arg in the figure). Significant acceleration was observed for the group to which (PF in the figure) was administered. In addition, in administration of a branched chain amino acid composition (BCAA in the figure), L-arginine (Arg in the figure), L-glutamine (Gln in the figure), L-arginine + L-glutamine mixture (Arg + Gln in the figure) Since the recovery was not recognized and the rate of collagen synthesis was accelerated compared to the 12 amino acid compositions (AVP in the figure) and the collagen composition amino acid composition, these 5 or 4 amino acid compositions were It was shown to have a very good effect on promoting the synthesis of collagen.
Claims (4)
（ａ）１０〜４０重量部
（ｂ）５〜２０重量部
（ｃ）８〜３０重量部
（ｄ）１０〜３５重量部 The amino acid consists of (a) L-glutamine, (b) L-valine, (c) L-isoleucine and (d) L-leucine, and the ratio of the amino acids is described in the following (a) to (d) Skin collagen synthesis promoter characterized by being a part.
(A) 10 to 40 parts by weight (b) 5 to 20 parts by weight (c) 8 to 30 parts by weight (d) 10 to 35 parts by weight
（ａ）１０〜４０重量部
（ｂ）５〜２０重量部
（ｃ）８〜３０重量部
（ｄ）１０〜３５重量部 The amino acid consists of (a) L-glutamine, (b) L-valine, (c) L-isoleucine and (d) L-leucine, and the ratio of the amino acids is described in the following (a) to (d) A skin aging inhibitor characterized by being a part.
(A) 10 to 40 parts by weight (b) 5 to 20 parts by weight (c) 8 to 30 parts by weight (d) 10 to 35 parts by weight
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