JP2010189333A - POWDER COMPOSITION, TABLET, METHOD FOR PREVENTING BROWNING OF gamma-AMINOBUTYRIC ACID AND BROWNING INHIBITOR - Google Patents
POWDER COMPOSITION, TABLET, METHOD FOR PREVENTING BROWNING OF gamma-AMINOBUTYRIC ACID AND BROWNING INHIBITOR Download PDFInfo
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- JP2010189333A JP2010189333A JP2009036446A JP2009036446A JP2010189333A JP 2010189333 A JP2010189333 A JP 2010189333A JP 2009036446 A JP2009036446 A JP 2009036446A JP 2009036446 A JP2009036446 A JP 2009036446A JP 2010189333 A JP2010189333 A JP 2010189333A
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- Prior art keywords
- aminobutyric acid
- acid
- hyaluronic acid
- salt
- browning
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- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 title claims abstract description 67
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- 230000003405 preventing effect Effects 0.000 title claims description 10
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- 239000003112 inhibitor Substances 0.000 title description 3
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- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims abstract description 72
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
本発明は、粉末状組成物およびこれを含有する錠剤、ならびにγ−アミノ酪酸の褐変防止方法および褐変防止剤に関する。より詳細には、γ−アミノ酪酸の褐変を防止し、長期の保存安定性に優れた粉末状組成物およびこれを含有する錠剤に関する。 The present invention relates to a powdery composition, a tablet containing the same, a method for preventing browning of γ-aminobutyric acid, and a browning inhibitor. More specifically, the present invention relates to a powdery composition that prevents browning of γ-aminobutyric acid and is excellent in long-term storage stability, and a tablet containing the same.
γ−アミノ酪酸(GABA)は、非タンパク質構成アミノ酸の一種であり、自然界に広く存在している。生体内においてはグルタミン酸から生合成され、ヒトの脳内で神経伝達物質として働くことが知られている。また、γ−アミノ酪酸の経口摂取により、脳機能改善作用、血圧低下作用、リラックス作用等の生理作用を発揮することから、食品や医薬品に使用されている。 γ-Aminobutyric acid (GABA) is a kind of non-protein constituent amino acid and widely exists in nature. It is known that it is biosynthesized from glutamic acid in vivo and works as a neurotransmitter in the human brain. In addition, γ-aminobutyric acid is used in foods and pharmaceuticals because it exhibits physiological functions such as a brain function improving action, a blood pressure lowering action, and a relaxing action when taken orally.
一方、粉末化したγ−アミノ酪酸は、吸湿性が高い性質を有しており、保存安定性を向上するために、通常、賦形剤を添加している。上記のγ−アミノ酪酸の吸湿性を抑制するために添加される賦形剤としては、乳糖やデキストリン類が広く用いられている。しかしながら、これらを賦形剤として使用した場合、保存条件によっては、γ-アミノ酪酸のアミノ基と糖のカルボニル基がメイラード反応を起こし、粉末が褐変する場合があった。 On the other hand, powdered γ-aminobutyric acid has a high hygroscopic property, and usually an excipient is added to improve storage stability. Lactose and dextrins are widely used as excipients added to suppress the hygroscopicity of the above-mentioned γ-aminobutyric acid. However, when these are used as excipients, depending on the storage conditions, the amino group of γ-aminobutyric acid and the carbonyl group of the sugar may undergo a Maillard reaction and the powder may turn brown.
そこで、γ−アミノ酪酸含有粉末の褐変を防ぐための技術として、賦形剤として環状デキストリンおよび/または重合度3以上の糖を70%以上含有する還元澱粉分解物を賦形剤として使用することが知られている(特許文献1)。特許文献1には、上記賦形剤を使用することにより、保存安定性に優れ、高温下で保存した場合にも褐変が抑えられた、粉末状のγ−アミノ酪酸を高含有する組成物を提供できると記載されている。 Therefore, as a technique for preventing browning of the powder containing γ-aminobutyric acid, a reduced starch degradation product containing 70% or more of cyclic dextrin and / or sugar having a polymerization degree of 3 or more is used as an excipient. Is known (Patent Document 1). Patent Document 1 discloses a composition containing a high amount of powdery γ-aminobutyric acid, which has excellent storage stability by use of the above-mentioned excipients, and has suppressed browning even when stored at a high temperature. It is stated that it can be provided.
特許文献1の賦形剤を使用することにより、確かにγ−アミノ酪酸含有粉末の褐変を防止することができるが、賦形剤ではなく生理活性物質に同様の褐変防止効果があれば、γ−アミノ酪酸含有粉末を経口摂取した際に生理機能を高めたり、相乗効果が得られることが期待される。 By using the excipient of Patent Document 1, it is possible to surely prevent the browning of the powder containing γ-aminobutyric acid. However, if the physiologically active substance, not the excipient, has a similar browning preventing effect, γ -When an aminobutyric acid-containing powder is orally ingested, it is expected that physiological functions are enhanced and a synergistic effect is obtained.
一方、ヒアルロン酸は、生体、特に皮下組織に存在するムコ多糖類であり、その高い保湿機能によりヒアルロン酸またはその塩として、化粧料の原料に広く利用されてきた。また、ヒアルロン酸またはその塩を経口摂取することによって、肌の保湿、弾力性、および柔軟性を改善する効果や(特許文献2)、便秘改善効果(特許文献3)、自己免疫疾患の緩和効果(特許文献4)等の生理効果を有することが知られている。しかしながら、γ−アミノ酪酸の褐変を防止する効果については一切知られていなかった。
本発明の目的は、γ−アミノ酪酸を含有する粉末状組成物の保存安定性が向上し、保存中に褐変し難い粉末状組成物を提供するものである。 An object of the present invention is to provide a powdery composition that improves the storage stability of a powdery composition containing γ-aminobutyric acid and does not easily brown during storage.
本発明者等は、上記目的を達成すべく、γ−アミノ酪酸を含有する粉末状組成物の褐変防止について鋭意研究を重ねた結果、γ−アミノ酪酸とヒアルロン酸および/またはその塩を混合させるならば、意外にも、γ−アミノ酪酸を含有する粉末状組成物の褐変が防止できることを見出し、本発明を完成するに至った。
すなわち、本発明は、
(1)γ−アミノ酪酸を含有する粉末状組成物であって、ヒアルロン酸および/またはその塩を含有し、かつ、平均粒子径が5〜500μmである、粉末状組成物、
(2)ヒアルロン酸および/またはその塩の分子量が1〜200万である、(1)の粉末状組成物、
(3)(1)または(2)の粉末状組成物を含有する錠剤、
(4)(1)または(2)の粉末状組成物を含有するカプセル剤、
(5)γ−アミノ酪酸と、ヒアルロン酸および/またはその塩とを含有せしめ、粉末状組成物を作成することを特徴とする、γ−アミノ酪酸を含有する粉末状組成物の褐変防止方法、
(6)ヒアルロン酸および/またはその塩を含有することを特徴とする、γ−アミノ酪酸の褐変防止剤、
である。
In order to achieve the above object, the present inventors have conducted extensive research on the prevention of browning of a powdery composition containing γ-aminobutyric acid. As a result, γ-aminobutyric acid and hyaluronic acid and / or a salt thereof are mixed. Then, unexpectedly, it discovered that browning of the powdery composition containing (gamma) -aminobutyric acid could be prevented, and came to complete this invention.
That is, the present invention
(1) A powdery composition containing γ-aminobutyric acid, containing hyaluronic acid and / or a salt thereof, and having an average particle size of 5 to 500 μm,
(2) The powdery composition of (1), wherein the molecular weight of hyaluronic acid and / or a salt thereof is 1 to 2 million,
(3) A tablet containing the powdery composition of (1) or (2),
(4) a capsule containing the powdery composition of (1) or (2),
(5) A method for preventing browning of a powdery composition containing γ-aminobutyric acid, which contains γ-aminobutyric acid and hyaluronic acid and / or a salt thereof to prepare a powdery composition,
(6) A browning inhibitor for γ-aminobutyric acid, characterized by containing hyaluronic acid and / or a salt thereof,
It is.
本発明の粉末状組成物は、ヒアルロン酸および/またはその塩を混合することで、γ−アミノ酪酸の褐変が防止できることから、γ−アミノ酪酸の品位を長期間良好に保つことができる。 Since the powdery composition of the present invention can prevent browning of γ-aminobutyric acid by mixing hyaluronic acid and / or a salt thereof, the quality of γ-aminobutyric acid can be kept good for a long period of time.
以下本発明を説明する。なお、本発明において「%」は「質量%」、「部」は「質量部」を意味する。 The present invention will be described below. In the present invention, “%” means “mass%” and “part” means “part by mass”.
本発明の粉末状組成物は、γ−アミノ酪酸を含有することを特徴とする。 The powdery composition of the present invention is characterized by containing γ-aminobutyric acid.
γ−アミノ酪酸は、一般的にGABA(ギャバ)とも呼ばれ、自然界に広く分布している非タンパク質アミノ酸の1種を指す。食品の成分としても、茶、野菜類、穀類などに含まれている。 γ-aminobutyric acid is generally called GABA and refers to one kind of non-protein amino acid widely distributed in nature. It is also contained in tea, vegetables, cereals and the like as ingredients of food.
本実施形態に係る粉末状組成物に用いられるγ−アミノ酪酸は、特に限定されるものではないが、野菜、果物、穀物などから抽出されたγ−アミノ酪酸、発酵法により生産されたγ−アミノ酪酸、有機合成から生産されたγ−アミノ酪酸を使用することができる。中でも、大量且つ安価にγ−アミノ酪酸を得ることができることから、乳酸菌による発酵法が好ましい。前記発酵法による製造方法としては、以下の方法が挙げられる。例えば、グルタミン酸ソ−ダ、ブドウ糖、パン酵母エキス等を含む培養液に、乳酸菌(ラクトバチルス ブレビス(IFO12005)、ラクトバチルス
ヒルガルディーK−3株(FERM P−18422)等の前培養液を添加し、20〜30℃で、1〜3日間培養し、この培養液を、加熱殺菌後、濾過して濾液を得る。上記濾過工程においては、ケイソウ土やセルロース、活性炭などの濾過助剤を用いても良い。なお、乳酸菌としてラクトバチルス ヒルガルディー
K−3株(FERM P−18422)を用いた場合、培養液に5%以上のグルタミン酸ソーダを含有せしめることにより、γ−アミノ酪酸の濃度を特に効果的に高めることができ、上記培養液中のγ−アミノ酪酸含量は約5質量%、固形分当りに換算するとγ−アミノ酪酸は約50%を占める。また、上記培養液のpHを4.5〜5.5とすることにより、乳酸菌の増殖が特に効果的に促進され、培養液中のγ−アミノ酪酸の含量を高めることができる。上記の濾液は、適宜減圧濃縮、真空濃縮等により濃縮し、またはそのまま、あるいは更に噴霧乾燥、凍結乾燥等により乾燥して、本発明の粉末状組成物に用いることができる。さらに、γ−アミノ酪酸の含有量をより高めるために、液体クロマトグラフィー等による精製を行うこともできる。
The γ-aminobutyric acid used in the powdery composition according to the present embodiment is not particularly limited, but γ-aminobutyric acid extracted from vegetables, fruits, cereals and the like, and γ- produced by a fermentation method. Aminobutyric acid, γ-aminobutyric acid produced from organic synthesis can be used. Among them, a fermentation method using lactic acid bacteria is preferable because γ-aminobutyric acid can be obtained in a large amount and at low cost. Examples of the production method by the fermentation method include the following methods. For example, a pre-culture solution such as lactic acid bacteria (Lactobacillus brevis (IFO12005), Lactobacillus hillgardi K-3 strain (FERM P-18422)) is added to a culture solution containing soda glutamate, glucose, baker's yeast extract, etc. Incubate at 20 to 30 ° C. for 1 to 3 days, and heat and sterilize this culture solution to obtain a filtrate by filtration using a filter aid such as diatomaceous earth, cellulose, or activated carbon. In addition, when Lactobacillus hilgardy K-3 strain (FERM P-18422) is used as a lactic acid bacterium, the concentration of γ-aminobutyric acid is particularly effective by adding 5% or more of sodium glutamate to the culture solution. The content of γ-aminobutyric acid in the culture broth is about 5% by mass, and when converted to solid content, γ-aminobutyric acid is about 5%. In addition, by setting the pH of the culture solution to 4.5 to 5.5, the growth of lactic acid bacteria is particularly effectively promoted, and the content of γ-aminobutyric acid in the culture solution can be increased. The above filtrate can be used for the powdery composition of the present invention by appropriately concentrating by reduced pressure concentration, vacuum concentration, etc., or as it is or by further drying by spray drying, freeze drying, etc. Furthermore, γ -In order to increase the content of aminobutyric acid, purification by liquid chromatography or the like can also be performed.
本実施形態に係る粉末状組成物中または錠剤中のγ−アミノ酪酸の検出方法は特に限定されるものではないが、例えば、イオン交換カラムを用いて高速クロマトグラフィー(HPLC)で分離し、オルトフタルアルデヒド(OPA)によるポストカラムでの誘導体化後、蛍光検出器で検出定量する方法や、前記の高速クロマトグラフィーによる分離後、ニンヒドリンによるポストカラムでの誘導体化後、紫外可視検出器で検出定量する方法などが挙げられる。 The method for detecting γ-aminobutyric acid in the powdered composition or tablet according to the present embodiment is not particularly limited. For example, it is separated by high performance chromatography (HPLC) using an ion exchange column, and ortho After derivatization with phthalaldehyde (OPA), after derivatization with a fluorescence detector, after separation by high-speed chromatography, after derivatization with post-column with ninhydrin, detection with a UV-visible detector The method of doing is mentioned.
また、本発明の粉末状組成物は、ヒアルロン酸および/またはその塩を含有することを特徴とする。 The powdery composition of the present invention is characterized by containing hyaluronic acid and / or a salt thereof.
本発明における「ヒアルロン酸」とは、グルクロン酸とN−アセチルグルコサミンとの二糖からなる繰り返し構成単位を1以上有する多糖類をいう。また、「ヒアルロン酸の塩」としては、特に限定されないが、食品または薬学上許容しうる塩であることが好ましく、例えば、ナトリウム塩、カリウム塩、カルシウム塩、亜鉛塩、マグネシウム塩、アンモニウム塩等が挙げられる。 The “hyaluronic acid” in the present invention refers to a polysaccharide having one or more repeating structural units composed of disaccharides of glucuronic acid and N-acetylglucosamine. The “hyaluronic acid salt” is not particularly limited, but is preferably a food or pharmaceutically acceptable salt, for example, sodium salt, potassium salt, calcium salt, zinc salt, magnesium salt, ammonium salt, etc. Is mentioned.
本発明の粉末状組成物で使用するヒアルロン酸および/またはその塩の平均分子量は、好ましくは1〜200万、より好ましくは5〜160万、さらに好ましくは10〜120万である。ヒアルロン酸および/またはその塩の平均分子量が1万未満の場合、本発明の効果が得られ難く、好ましくない。一方、ヒアルロン酸および/またはその塩の平均分子量が200万超の場合は、食品に加工し難い場合がある。 The average molecular weight of hyaluronic acid and / or a salt thereof used in the powdery composition of the present invention is preferably 1 to 2 million, more preferably 5 to 1.6 million, and still more preferably 10 to 1.2 million. When the average molecular weight of hyaluronic acid and / or a salt thereof is less than 10,000, it is difficult to obtain the effects of the present invention, which is not preferable. On the other hand, when the average molecular weight of hyaluronic acid and / or its salt exceeds 2 million, it may be difficult to process into food.
また、本発明で使用する精製ヒアルロン酸の平均分子量は下記の方法に求めた値として定義される。 The average molecular weight of the purified hyaluronic acid used in the present invention is defined as a value determined by the following method.
約0.05gの精製ヒアルロン酸を精密に量り、0.2mol/L濃度の塩化ナトリウム溶液に溶かし、正確に100mLとした溶液およびこの溶液8mL、12mL並びに16mLを正確に量り、それぞれに0.2mol/L濃度の塩化ナトリウム溶液を加えて正確に20mLとした溶液を試料溶液とする。この試料溶液および0.2mol/L濃度の塩化ナトリウム溶液につき、日本薬局方(第十四改正)一般試験法の粘度測定法(第1法 毛細管粘度測定法)により30.0±0.1℃で比粘度を測定し(式(1))、各濃度における還元粘度を算出する(式(2))。還元粘度を縦軸に、本品の換算した乾燥物に対する濃度(g/100mL)を横軸にとってグラフを描き、各点を結ぶ直線と縦軸との交点から極限粘度を求める。ここで求められた極限粘度をLaurentの式(式(3))に代入し、平均分子量を算出する(T.C.
Laurent, M. Ryan, A. Pietruszkiewicz,:B.B.A., 42, 476-485(1960))。
About 0.05 g of purified hyaluronic acid is accurately weighed and dissolved in 0.2 mol / L sodium chloride solution to make exactly 100 mL, and 8 mL, 12 mL and 16 mL of this solution are accurately weighed, and 0.2 mol each. / L concentration of sodium chloride solution is added to make exactly 20 mL as a sample solution. This sample solution and 0.2 mol / L sodium chloride solution were 30.0 ± 0.1 ° C. according to the viscosity measurement method (first method capillary viscometry method) of the Japanese Pharmacopoeia (14th revision) general test method. The specific viscosity is measured by (Equation (1)), and the reduced viscosity at each concentration is calculated (Equation (2)). A graph is drawn with the reduced viscosity on the vertical axis and the concentration (g / 100 mL) of the product converted to dry matter on the horizontal axis, and the intrinsic viscosity is determined from the intersection of the straight line connecting the points and the vertical axis. Substituting the intrinsic viscosity obtained here into Laurent's formula (formula (3)), the average molecular weight is calculated (TC
Laurent, M. Ryan, A. Pietruszkiewicz,: BBA, 42, 476-485 (1960)).
ヒアルロン酸および/またはその塩は、動物等の天然物(例えば鶏冠、さい帯、皮膚、関節液などの生体組織など)から抽出されたものでもよく、または、微生物もしくは動物細胞を培養して得られたもの(例えばストレプトコッカス属の細菌等を用いた発酵法)、化学的もしくは酵素的に合成されたものなどいずれも使用することができる。 Hyaluronic acid and / or a salt thereof may be extracted from natural products such as animals (for example, biological tissues such as chicken crown, umbilical cord, skin, joint fluid, etc.), or obtained by culturing microorganisms or animal cells. And the like (for example, fermentation using a bacterium belonging to the genus Streptococcus, etc.), or those synthesized chemically or enzymatically can be used.
本実施形態に係る粉末状組成物で使用するヒアルロン酸および/またはその塩は、市販品を使用することができるが、例えば、以下の製造法1および2に従って製造することもできる。 Commercially available products can be used as the hyaluronic acid and / or salt thereof used in the powdery composition according to the present embodiment, and for example, it can also be produced according to the following production methods 1 and 2.
1.1.製造法1(鶏冠からの抽出) 鶏冠に加熱処理を施す。加熱処理方法、加熱温度、時間は、鶏冠中の蛋白質が変性したり、酵素が失活したりする範囲内であれば、特に制限がなく、熱水による加熱法を採用する場合は、60〜100℃の熱水中に原料を浸漬するとよい。 1.1. Production method 1 (extraction from chicken crown) The chicken crown is heated. The heat treatment method, the heating temperature, and the time are not particularly limited as long as the protein in the chicken crown is denatured or the enzyme is deactivated. When a heating method using hot water is adopted, 60 to The raw material is preferably immersed in hot water at 100 ° C.
次に、加熱処理した鶏冠をペースト化し、塩酸、硫酸等の酸剤、または水酸化ナトリウム、水酸化カリウム等のアルカリ剤を添加し酸処理またはアルカリ処理してヒアルロン酸を低分子化し、処理後のヒアルロン酸の平均分子量を調整する。調整方法としては、酸剤あるいはアルカリ剤の濃度、添加量および処理時間等を適宜組み合わせて、処理後のヒアルロン酸が所望の分子量となるようにすればよいが、アルカリ処理による方法がヒアルロン酸の分子量をコントロールし易く好ましい。 Next, paste the heat-treated chicken crown, add acid agent such as hydrochloric acid or sulfuric acid, or add alkali agent such as sodium hydroxide or potassium hydroxide to reduce the molecular weight of hyaluronic acid by acid treatment or alkali treatment. The average molecular weight of hyaluronic acid is adjusted. As the adjustment method, the concentration of the acid agent or alkali agent, the amount added, and the treatment time may be appropriately combined so that the hyaluronic acid after treatment has a desired molecular weight. It is preferable because the molecular weight can be easily controlled.
次に、分子量を調整した原料に蛋白分解酵素を添加して、プロテアーゼ処理する。使用する蛋白分解酵素は、市販しているものであれば種類を問わず使用することができ、例えば、ペプシン、トリプシン、パパイン、プロメリン等が挙げられる。 Next, a protease is added to the raw material whose molecular weight has been adjusted, and protease treatment is performed. Any proteolytic enzyme can be used as long as it is commercially available, and examples thereof include pepsin, trypsin, papain, promeline and the like.
最後に、得られたプロテアーゼ処理物からヒアルロン酸を分取して、粗製のヒアルロン酸を得た後、このヒアルロン酸を精製することにより純度90%以上のヒアルロン酸が得られる。 Finally, hyaluronic acid is fractionated from the obtained protease-treated product to obtain crude hyaluronic acid, and then the hyaluronic acid is purified to obtain hyaluronic acid having a purity of 90% or more.
ここで、ヒアルロン酸の分取・精製は、常法に従って行うことができる。例えば、まず、プロテアーゼ処理した原料を濾過して固形物を除去して、粗製のヒアルロン酸を含有した濾液を得る。なお、濾過に先立ち、脱臭・脱色や一部の蛋白分解物を除去する目的で、プロテアーゼ処理物に活性炭を添加し処理してもよい。そして得られた濾液に食塩を溶解させた後、エタノールを添加してヒアルロン酸を沈殿させ、沈殿物を分取する。その後、この沈殿物にエタノール濃度約80〜95容量%の含水エタノールを添加し、ホモゲナイザーで洗浄し、沈殿物を分取する。この含水エタノールによる洗浄を2〜10回程度繰り返し、分取した沈殿物を乾燥することで、製造例1のヒアルロン酸を得ることができる。 Here, the fractionation and purification of hyaluronic acid can be performed according to a conventional method. For example, first, the protease-treated raw material is filtered to remove solids to obtain a filtrate containing crude hyaluronic acid. Prior to filtration, activated carbon may be added to the protease-treated product for the purpose of deodorization / decolorization or removal of some protein degradation products. And after melt | dissolving salt in the obtained filtrate, ethanol is added and hyaluronic acid is precipitated, and a deposit is fractionated. Thereafter, hydrous ethanol having an ethanol concentration of about 80 to 95% by volume is added to the precipitate, washed with a homogenizer, and the precipitate is collected. The hyaluronic acid of Production Example 1 can be obtained by repeating this washing with hydrous ethanol about 2 to 10 times and drying the collected precipitate.
1.2.製造法2(微生物発酵法)
ヒアルロン酸産出ストレプトコッカス属の微生物(Streptococcus Zoopidemicus)の培養液に活性炭を添加して脱臭・脱色処理を行った後、濾過処理する。得られた濾液に食塩を溶解させた後、エタノールを添加してヒアルロン酸を沈殿させ、沈殿物を分取する。その後、この沈殿物にエタノール濃度約80〜95容量%の含水エタノールを添加し、ホモゲナイザーで洗浄し、沈殿物を分取する。この含水エタノールによる洗浄を2〜10回程度繰り返し、分取した沈殿物を乾燥することで、製造例2のヒアルロン酸を得ることができる。
1.2. Production method 2 (microbe fermentation method)
Activated carbon is added to the culture solution of the hyaluronic acid producing Streptococcus genus (Streptococcus Zoopidemicus), followed by deodorization and decolorization treatment, followed by filtration treatment. Sodium chloride is dissolved in the obtained filtrate, ethanol is added to precipitate hyaluronic acid, and the precipitate is collected. Thereafter, hydrous ethanol having an ethanol concentration of about 80 to 95% by volume is added to the precipitate, washed with a homogenizer, and the precipitate is collected. The hyaluronic acid of Production Example 2 can be obtained by repeating this washing with hydrous ethanol about 2 to 10 times and drying the collected precipitate.
なお、本発明において使用するヒアルロン酸の純度は、食品で使用できるレベルであればよく、好ましくは90%以上であればよく、より好ましくは95%以上であればよい。この純度は乾物換算で100%よりヒアルロン酸以外の不純物を除いた値として定義される。ここで、不純物としては、蛋白分解物、脂肪分(粗脂肪)、コンドロイチン硫酸等が挙げられる。具体的に鶏冠を原料とするヒアルロン酸の純度は、以下式(4)で求めることができる。
In addition, the purity of the hyaluronic acid used in the present invention may be a level that can be used in food, preferably 90% or more, more preferably 95% or more. This purity is defined as a value obtained by removing impurities other than hyaluronic acid from 100% in terms of dry matter. Here, examples of the impurities include protein degradation products, fat (crude fat), chondroitin sulfate, and the like. Specifically, the purity of hyaluronic acid using chicken crown as a raw material can be obtained by the following formula (4).
式4中、蛋白分解物(%)はLowry法により求めた値であり、粗脂肪(%)は新・食品分析法(光琳(株)発行)「第1章一般成分および関連成分、1−4脂質、1−4−2エーテル抽出法」により求めた値であり、また、コンドロイチン硫酸(%)は、以下に説明する方法により得た値である。 In Formula 4, the protein degradation product (%) is a value obtained by the Lowry method, and the crude fat (%) is a new food analysis method (published by Korin Co., Ltd.) “Chapter 1 General components and related components, 1- “4 lipids, 1-4-2 ether extraction method”, and chondroitin sulfate (%) is a value obtained by the method described below.
まず、ヒアルロン酸を乾燥し、その50mgを精密に量り、精製水を加えて溶かし、正確に100mLとして試験溶液とし、その試験溶液4mLを試験管にとり、0.5mol/L濃度の硫酸1mLを加えて混和し、水浴中で10分間加熱し、その後冷却して得られた溶液に0.04mol/L濃度の臭化セチルトリメチルアンモニウムを0.2mL加えて混和し、室温で1時間放置し、層長10mm、波長660nmにおける吸光度を測定する。 First, hyaluronic acid is dried, 50 mg of it is accurately weighed, and purified water is added to dissolve it. Make exactly 100 mL to make a test solution, take 4 mL of the test solution in a test tube, and add 1 mL of 0.5 mol / L sulfuric acid. Then, 0.2 mL of 0.04 mol / L cetyltrimethylammonium bromide was added to the solution obtained by heating in a water bath for 10 minutes and then cooling, and the mixture was allowed to stand at room temperature for 1 hour. Absorbance at a length of 10 mm and a wavelength of 660 nm is measured.
次に、得られた吸光度データをコンドロイチン硫酸の検量線に適用して精製ヒアルロン酸中のコンドロイチン硫酸量(%)を求める。ここで、その検量線は、クジラ軟骨由来のコンドロイチン硫酸Aナトリウム塩(SG(Special Grade)、生化学工業株式会社製)を乾燥(減圧、五酸化リン、60℃、5時間)させたものを精密に量り、精製水を加えて溶かし、1mL中に10μg、20μg、30μg、40μgのコンドロイチン硫酸Aナトリウム塩を含む溶液をそれぞれ調製し、それぞれの溶液4mlについて、0.5ml/L濃度の硫酸1mLを加えて混和した後、0.04mol/L濃度の臭化セチルトリメチルアンモニウムを0.2mL加えて混和し、室温で1時間放置した後、同様に吸光度を測定し、その吸光度を縦軸に、対応するコンドロイチン硫酸Aナトリウム塩溶液(μg/mL)を横軸にプロットすることによって作成したものである。 Next, the obtained absorbance data is applied to a calibration curve for chondroitin sulfate to determine the amount (%) of chondroitin sulfate in purified hyaluronic acid. Here, the calibration curve is obtained by drying (depressurization, phosphorus pentoxide, 60 ° C., 5 hours) of chondroitin sulfate A sodium salt (SG (Special Grade), manufactured by Seikagaku Corporation) derived from whale cartilage. Precisely weigh, dissolve in purified water, and prepare solutions containing 10 μg, 20 μg, 30 μg, and 40 μg of chondroitin sulfate A sodium salt in 1 mL, respectively. For each 4 mL of solution, 1 mL of 0.5 mL / L sulfuric acid Then, 0.2 mL of 0.04 mol / L cetyltrimethylammonium bromide was added and mixed. After standing at room temperature for 1 hour, the absorbance was measured in the same manner. It was prepared by plotting the corresponding chondroitin sulfate A sodium salt solution (μg / mL) on the horizontal axis.
本発明の粉末状組成物の平均粒子径は、好ましくは5〜500μmである。粉末状組成物の平均粒子径が上記範囲以下の場合は、粉末状組成物に含まれるγ−アミノ酪酸が保存中に非常に褐変し易く、ヒアルロン酸および/またはその塩を添加することによる褐変防止効果が十分に働かない場合がある。また、粉末状組成物の平均粒子径が上記範囲以上に大きい場合は、粉末状組成物に含まれるγ−アミノ酪酸由来の褐変を起こし難いため、本発明の効果を利用する必要がない場合がある。なお、平均粒子径の測定方法は、一般的に知られたレーザー回折式測定法や、動的光散乱式測定法等を挙げることができる。 The average particle size of the powdery composition of the present invention is preferably 5 to 500 μm. When the average particle size of the powder composition is below the above range, γ-aminobutyric acid contained in the powder composition is very easily browned during storage, and is browned by adding hyaluronic acid and / or a salt thereof. The prevention effect may not work sufficiently. In addition, when the average particle size of the powdery composition is larger than the above range, it is difficult to cause browning derived from γ-aminobutyric acid contained in the powdery composition, and thus it is not necessary to use the effect of the present invention. is there. Examples of the method for measuring the average particle diameter include generally known laser diffraction measurement methods and dynamic light scattering measurement methods.
本発明の粉末状組成物中において、γ−アミノ酪酸1部に対するヒアルロン酸および/またはその塩の含有割合は、0.01部以上であることが好ましく、より好ましくは0.1部以上である。粉末状組成物の中にγ−アミノ酪酸と、ヒアルロン酸またはその塩とを上記比率で含むことにより、γ−アミノ酪酸の褐変を防ぐことができる。なお、γ−アミノ酪酸1部に対するヒアルロン酸および/またはその塩の含有割合が10部超の場合には、それ以上ヒアルロン酸および/またはその塩の含有量を増やしても、γ−アミノ酪酸の褐変防止効果に大きな影響がないため、経済的でない。 In the powdered composition of the present invention, the content ratio of hyaluronic acid and / or a salt thereof to 1 part of γ-aminobutyric acid is preferably 0.01 parts or more, more preferably 0.1 parts or more. . By containing γ-aminobutyric acid and hyaluronic acid or a salt thereof in the powder composition in the above ratio, browning of γ-aminobutyric acid can be prevented. In the case where the content ratio of hyaluronic acid and / or salt thereof to 1 part of γ-aminobutyric acid is more than 10 parts, even if the content of hyaluronic acid and / or salt thereof is further increased, γ-aminobutyric acid There is no significant effect on the browning prevention effect, so it is not economical.
本実施形態に係る錠剤とは、粉末状組成物である、γ−アミノ酪酸と、ヒアルロン酸および/またはその塩とを含有する、タブレット状の食品または医薬品をいう。本発明の粉末状組成物を使用することにより、保存中に褐変の起こり難い錠剤が得られる。 The tablet according to the present embodiment refers to a tablet-like food or medicine containing γ-aminobutyric acid, hyaluronic acid and / or a salt thereof, which is a powdery composition. By using the powdery composition of the present invention, a tablet that hardly undergoes browning during storage can be obtained.
本実施形態に係るカプセル剤とは、粉末状組成物である、γ−アミノ酪酸と、ヒアルロン酸および/またはその塩とを含有する、カプセル状の食品または医薬品をいう。本発明の粉末状組成物を使用することにより、保存中に褐変の起こり難いカプセル剤が得られる。 The capsule according to the present embodiment refers to a capsule-like food or medicine containing γ-aminobutyric acid, hyaluronic acid and / or a salt thereof, which is a powdery composition. By using the powdery composition of the present invention, a capsule that hardly undergoes browning during storage can be obtained.
本発明の粉末状組成物の製造方法は、γ−アミノ酪酸と、ヒアルロン酸および/またはその塩とを含む平均粒子径5〜500μmの粉末状組成物を得ることができる方法であれば、特に限定されるものではない。例えば、γ−アミノ酪酸を含有する溶液と、ヒアルロン酸および/またはその塩を含有する溶液とを混合し、噴霧乾燥、凍結乾燥等により乾燥処理を施した後、必要に応じて粉砕を行う方法や、γ−アミノ酪酸を含有する粉末と、ヒアルロン酸および/またはその塩を含有する粉末とを粉体混合し、平均粒子径を5〜500μmの粉末状組成物を得る方法等が挙げられる。 If the manufacturing method of the powdery composition of this invention can obtain the powdery composition with an average particle diameter of 5-500 micrometers containing (gamma) -aminobutyric acid and hyaluronic acid and / or its salt especially, It is not limited. For example, a method in which a solution containing γ-aminobutyric acid and a solution containing hyaluronic acid and / or a salt thereof are mixed, dried by spray drying, freeze drying, etc., and then pulverized as necessary In addition, there may be mentioned a method in which a powder containing γ-aminobutyric acid and a powder containing hyaluronic acid and / or a salt thereof are mixed to obtain a powdery composition having an average particle size of 5 to 500 μm.
次に、本発明を実施例、比較例および試験例に基づき、さらに詳細に説明する。なお、本発明はこれらに限定されるものではない。 Next, the present invention will be described in more detail based on examples, comparative examples, and test examples. The present invention is not limited to these.
[調製例1]
グルタミン酸ソーダ100g/L、ブドウ糖2g/L、酵母エキス5g/L、グリセリン脂肪酸エステル0.5g/Lの各成分を含有する発酵原料(pH5.0)50Lを、90℃で10分間加熱殺菌した後、キムチ由来の乳酸菌(ラクトバチルス ヒルガルディーK−3株(FERM P−18422))培養液50mLを接種し、30℃で3日間培養した。この発酵液を90℃で10分間加熱殺菌した後、濾過助剤を加えてろ過し、ダイヤイオンSK1B(H型)(三菱化学株式会社製)のカラムに通し、γ−アミノ酪酸を吸着させ、水洗後0.5規定のアンモニア水で溶出して、γ−アミノ酪酸各分を集めた。集めた画分を濃縮し、pH6.2に調整後エタノールを加えて冷却下で保存することにより、純度98%以上のγ−アミノ酪酸結晶を得た。この結晶をパルベライザ(ホソカワミクロン株式会社製)にて粉砕し、平均粒子径を130μmに調整した。なお、以降において、粉末の平均粒子径は、該粉末をエタノールに分散し、SALD−2000A(株式会社島津製作所製)を使用して測定した。
[Preparation Example 1]
After sterilizing 50 L of fermentation raw material (pH 5.0) containing 100 g / L of sodium glutamate, 2 g / L of glucose, 5 g / L of yeast extract, and 0.5 g / L of glycerin fatty acid ester at 90 ° C. for 10 minutes. Inoculated with 50 mL of kimchi-derived lactic acid bacteria (Lactobacillus hilgardy K-3 strain (FERM P-18422)) and cultured at 30 ° C. for 3 days. After sterilizing this fermentation broth at 90 ° C. for 10 minutes, adding a filter aid, filtering, passing through a column of Diaion SK1B (H type) (manufactured by Mitsubishi Chemical Corporation), adsorbing γ-aminobutyric acid, After washing with water and eluting with 0.5N ammonia water, each γ-aminobutyric acid was collected. The collected fractions were concentrated, adjusted to pH 6.2, ethanol was added, and the mixture was stored under cooling to obtain γ-aminobutyric acid crystals having a purity of 98% or more. The crystals were pulverized with a pulverizer (manufactured by Hosokawa Micron Corporation), and the average particle size was adjusted to 130 μm. In the following, the average particle size of the powder was measured by dispersing the powder in ethanol and using SALD-2000A (manufactured by Shimadzu Corporation).
[試験例1]
本試験例では、γ−アミノ酪酸とヒアルロン酸および/またはその塩とを含有する、本発明の粉末状組成物の褐変防止効果について、ヒアルロン酸および/またはその塩の有無による違いを調査した。なお、含有させたヒアルロン酸および/またはその塩、ならびにデキストリンは、平均粒子径が100〜200μmのものを用いた。
[Test Example 1]
In this test example, the difference by the presence or absence of hyaluronic acid and / or its salt was investigated about the browning prevention effect of the powdery composition of this invention containing (gamma) -aminobutyric acid and hyaluronic acid and / or its salt. In addition, the hyaluronic acid and / or salt thereof, and dextrin contained therein had an average particle diameter of 100 to 200 μm.
表1に示す成分(粉末状組成物)を用意し、表1の割合(質量部)で粉体混合を行った。各配合例の粉末状組成物1.0gを取って秤量瓶に入れ、40℃、湿度75%の恒温恒湿器(東京理化器械株式会社製)に保存した。恒温恒湿器に入れる前と入れた後20分後、40分後、60分後の色調の変化を目視で確認した。その結果を表2に示す。 The component (powder composition) shown in Table 1 was prepared, and powder mixing was performed at the ratio (parts by mass) shown in Table 1. 1.0 g of the powdery composition of each formulation was taken and placed in a weighing bottle and stored in a constant temperature and humidity chamber (manufactured by Tokyo Rika Kikai Co., Ltd.) at 40 ° C. and 75% humidity. The change in color tone was visually confirmed before and after 20 minutes, 40 minutes and 60 minutes after putting in the thermo-hygrostat. The results are shown in Table 2.
色調を目視で確認した結果、配合例4のデキストリンにおいては、褐変防止効果はほとんどみられなかった。これに対し、ヒアルロン酸および/またはその塩を含有した、配合例1〜3の粉末状組成物においては、褐変防止効果が確認された。以上より、ヒアルロン酸および/またはその塩には、γ−アミノ酪酸を含有する粉末状組成物の褐変防止効果に優れていることがわかる。 As a result of visually confirming the color tone, in the dextrin of Formulation Example 4, the effect of preventing browning was hardly observed. On the other hand, the browning prevention effect was confirmed in the powdery compositions of Formulation Examples 1 to 3 containing hyaluronic acid and / or a salt thereof. As mentioned above, it turns out that hyaluronic acid and / or its salt are excellent in the browning prevention effect of the powdery composition containing (gamma) -aminobutyric acid.
[配合例5]
調製例1と同様の方法にて発酵を行い、イオン交換樹脂カラムに通液してγ−アミノ酪酸画分液を集めた。これに平均分子量20万のヒアルロン酸(製造法2により調製したもの)を2kg溶解した後、噴霧乾燥を行い、配合例5の粉末状組成物を得た。この粉末状組成物の平均粒子径は35μmであり、γ−アミノ酪酸に対するヒアルロン酸の含有量は0.8であった。
[Formulation Example 5]
Fermentation was carried out in the same manner as in Preparation Example 1 and passed through an ion exchange resin column to collect a γ-aminobutyric acid fraction. 2 kg of hyaluronic acid (prepared by production method 2) having an average molecular weight of 200,000 was dissolved in this, and then spray-dried to obtain a powdery composition of Formulation Example 5. The average particle diameter of this powdery composition was 35 μm, and the content of hyaluronic acid relative to γ-aminobutyric acid was 0.8.
[配合例6]
調製例1と同様の方法にて発酵を行い、イオン交換樹脂カラムに通液してγ−アミノ酪酸画分液を集めた。これに平均分子量8千のヒアルロン酸(製造法2により調製したもの)を2kg溶解した後、噴霧乾燥を行い、配合例6の粉末状組成物を得た。この粉末状組成物の平均粒子径は28μmであり、γ−アミノ酪酸に対するヒアルロン酸の含有量は0.8であった。
[Composition Example 6]
Fermentation was performed in the same manner as in Preparation Example 1 and passed through an ion exchange resin column to collect a γ-aminobutyric acid fraction. 2 kg of hyaluronic acid having an average molecular weight of 8,000 (prepared by the production method 2) was dissolved in this, and then spray-dried to obtain a powdery composition of Formulation Example 6. The average particle diameter of this powdery composition was 28 μm, and the content of hyaluronic acid relative to γ-aminobutyric acid was 0.8.
[試験例2]
本試験例では、本発明のγ−アミノ酪酸とヒアルロン酸および/またはその塩とを含有する粉末状組成物の褐変防止効果について、ヒアルロン酸および/またはその塩の平均分子量による違いを調べるため、色差計による評価を行った。
[Test Example 2]
In this test example, in order to investigate the difference due to the average molecular weight of hyaluronic acid and / or salt thereof, the browning prevention effect of the powdery composition containing γ-aminobutyric acid of the present invention and hyaluronic acid and / or salt thereof, Evaluation by a color difference meter was performed.
[配合例5]、[配合例6]の混合物0.7gを秤量瓶に入れ、40℃、湿度75%の恒温恒湿器(東京理化器械株式会社製)に保存した。恒温恒湿器に入れる前と入れた後60分後の色調の変化を色差計(測色色差計ZE2000、日本電色工業株式会社製)で確認した。色調を色差計で測定した結果を表3に示す。 0.7 g of the mixture of [Composition Example 5] and [Composition Example 6] was put in a weighing bottle and stored in a constant temperature and humidity chamber (manufactured by Tokyo Rika Kikai Co., Ltd.) at 40 ° C. and 75% humidity. A change in color tone before and 60 minutes after putting in a thermo-hygrostat was confirmed with a color difference meter (colorimetric color difference meter ZE2000, manufactured by Nippon Denshoku Industries Co., Ltd.). The results of measuring the color tone with a color difference meter are shown in Table 3.
表3の結果より、色差計による測定の結果、配合例5では保存前後の色調の変化がほとんどみられていないことがわかる。一方、配合例6においては、保存前後の色調の変化が確認された。したがって、ヒアルロン酸および/またはその塩の平均分子量が1万以上のほうが、γ−アミノ酪酸の褐変防止効果により優れていることがわかる。 From the results of Table 3, as a result of measurement with a color difference meter, it can be seen that almost no change in color tone before and after storage was observed in Formulation Example 5. On the other hand, in Formulation Example 6, a change in color tone before and after storage was confirmed. Therefore, it can be seen that the average molecular weight of hyaluronic acid and / or a salt thereof is 10,000 or more is more excellent in the browning prevention effect of γ-aminobutyric acid.
[調製例2]
調製例1と同様の方法にて発酵を行い、純度98%以上のγ−アミノ酪酸結晶を得た。この結晶をパルベライザ(ホソカワミクロン株式会社製)にて粒子径の調整を行いながら粉砕し、平均粒子径3μm、19μm、367μm、649μmの粉末状γ−アミノ酪酸を得た。
[Preparation Example 2]
Fermentation was carried out in the same manner as in Preparation Example 1 to obtain γ-aminobutyric acid crystals having a purity of 98% or more. This crystal was pulverized while adjusting the particle size with a pulverizer (manufactured by Hosokawa Micron Corporation) to obtain powdery γ-aminobutyric acid having an average particle size of 3 μm, 19 μm, 367 μm, and 649 μm.
[試験例3]
本試験例では、本発明のγ−アミノ酪酸とヒアルロン酸および/またはその塩とを含有する粉末状組成物の褐変防止効果について、粉末状組成物の平均粒子径による違いを調査した。なお、含有させたヒアルロン酸(平均分子量20万)は、平均粒子径が4〜707μmのものを用いた。
[Test Example 3]
In this test example, the difference by the average particle diameter of a powdery composition was investigated about the browning prevention effect of the powdery composition containing (gamma) -aminobutyric acid of this invention, hyaluronic acid, and / or its salt. The contained hyaluronic acid (average molecular weight of 200,000) was used having an average particle size of 4 to 707 μm.
表4に示す成分(粉末状組成物)を用意し、表4の割合で粉体混合を行った。各配合例の粉末状組成物1.0gを取って秤量瓶に入れ、40℃、湿度75%の恒温恒湿器(東京理化器械株式会社製)に保存した。恒温恒湿器に入れる前と入れた後20分後、40分後、60分後の色調の変化を目視で確認した。その結果を表6に示す。また、表5に示すように、参考例2〜5として、γ−アミノ酪酸粉末単独での保存を行い、同様に色調の変化を目視で確認した。その結果を表7に示す。 The components (powder composition) shown in Table 4 were prepared, and powder mixing was performed at the ratio shown in Table 4. 1.0 g of the powdery composition of each formulation was taken and placed in a weighing bottle and stored in a constant temperature and humidity chamber (manufactured by Tokyo Rika Kikai Co., Ltd.) at 40 ° C. and 75% humidity. The change in color tone was visually confirmed before and after 20 minutes, 40 minutes and 60 minutes after putting in the thermo-hygrostat. The results are shown in Table 6. Moreover, as shown in Table 5, as Reference Examples 2 to 5, the γ-aminobutyric acid powder was stored alone, and the change in color tone was confirmed visually. The results are shown in Table 7.
表6および表7の結果から、粉末状組成物の平均粒子径が5μm未満である配合例7および参考例2の場合、γ−アミノ酪酸の褐変度合いが非常に大きいため、ヒアルロン酸および/またはその塩の添加によっても、褐変の防止効果が不十分であることが分かる。一方、粉末状組成物の平均粒子径が5〜500μmである配合例8、9および参考例3、4においては、ヒアルロン酸および/またはその塩の添加によって効果的に保存中の褐変が防止されている。また、粉末状組成物の平均粒子径が500μm超である配合例10および参考例5の場合、保存中のγ−アミノ酪酸の褐変が起こりにくいことがわかる。 From the results of Table 6 and Table 7, in the case of Formulation Example 7 and Reference Example 2 in which the average particle size of the powdery composition is less than 5 μm, the degree of browning of γ-aminobutyric acid is very large, and thus hyaluronic acid and / or It can be seen that the effect of preventing browning is insufficient even by the addition of the salt. On the other hand, in Formulation Examples 8 and 9 and Reference Examples 3 and 4 where the average particle size of the powdery composition is 5 to 500 μm, browning during storage is effectively prevented by the addition of hyaluronic acid and / or a salt thereof. ing. Moreover, in the case of the blending example 10 and the reference example 5 whose average particle diameter of a powdery composition is over 500 micrometers, it turns out that the browning of (gamma) -aminobutyric acid during a preservation | save does not occur easily.
[試験例4]
本試験例では、γ−アミノ酪酸とヒアルロン酸および/またはその塩とを含有する、本発明の粉末状組成物の褐変防止効果について、ヒアルロン酸および/またはその塩の含有量による違いを調査した。
[Test Example 4]
In this test example, the difference due to the content of hyaluronic acid and / or a salt thereof was investigated for the browning prevention effect of the powdery composition of the present invention containing γ-aminobutyric acid and hyaluronic acid and / or a salt thereof. .
表8に示す成分(粉末状組成物)を用意し、表8の割合(質量部)で粉体混合を行った。各配合例の粉末状組成物1.0gを取って秤量瓶に入れ、40℃、湿度75%の恒温恒湿器(東京理化器械株式会社製)に保存した。恒温恒湿器に入れる前と入れた後20分後、40分後、60分後の色調の変化を目視で確認した。その結果を表9に示す。なお、含有させたヒアルロン酸ナトリウム(平均分子量3万)は、平均粒子径が182μmのものを用いた。 The components (powder composition) shown in Table 8 were prepared, and powder mixing was performed at the ratio (parts by mass) shown in Table 8. 1.0 g of the powdery composition of each formulation was taken and placed in a weighing bottle and stored in a constant temperature and humidity chamber (manufactured by Tokyo Rika Kikai Co., Ltd.) at 40 ° C. and 75% humidity. The change in color tone was visually confirmed before and after 20 minutes, 40 minutes and 60 minutes after putting in the thermo-hygrostat. The results are shown in Table 9. The sodium hyaluronate contained (average molecular weight 30,000) was used having an average particle size of 182 μm.
表9の結果から、粉末状組成物中のγ−アミノ酪酸1部に対するヒアルロン酸および/またはその塩の含有量は、0.01部以上であることが好ましく、より好ましくは0.1部以上であることがわかる。一方、γ−アミノ酪酸1部に対するヒアルロン酸の含有量が10部以上(配合例13、14)の場合、十分に褐変防止効果に優れており、含有量を増やしてもその効果に大きな変化がないことがわかる。 From the results of Table 9, the content of hyaluronic acid and / or salt thereof with respect to 1 part of γ-aminobutyric acid in the powdery composition is preferably 0.01 parts or more, more preferably 0.1 parts or more. It can be seen that it is. On the other hand, when the content of hyaluronic acid with respect to 1 part of γ-aminobutyric acid is 10 parts or more (Formulation Examples 13 and 14), the effect is sufficiently excellent in preventing browning, and even if the content is increased, the effect is greatly changed. I understand that there is no.
[配合例15]
配合例5の粉末状組成物を使用して、以下の配合にて、一錠が250mgとなるように錠剤を製した。この錠剤を蓋付きガラス瓶に充填し、25℃(湿度60%)で保存したところ、1年間の保存中にも褐変はみられず、良好な品位を保っていた。
[Formulation Example 15]
Using the powdery composition of Formulation Example 5, tablets were prepared with the following formulation so that one tablet would be 250 mg. When this tablet was filled in a glass bottle with a lid and stored at 25 ° C. (humidity 60%), no browning was observed even during storage for one year, and good quality was maintained.
<配合割合>
配合例5の粉末状組成物 15%
乳糖 50%
結晶セルロース 20%
コーンスターチ 10%
グリセリン脂肪酸エステル 5%
――――――――――――――――――――――――――
計 100%
<Combination ratio>
15% of powdered composition of Formulation Example 5
Lactose 50%
20% crystalline cellulose
Corn starch 10%
Glycerin fatty acid ester 5%
――――――――――――――――――――――――――
Total 100%
[配合例16]
配合例2の粉末状組成物を使用して、以下の配合にて、一錠が300mgとなるように、ゼラチンを被包剤として、ソフトカプセル充填機によりソフトカプセルを製した。このカプセル剤を蓋付きガラス瓶に充填し、25℃(湿度60%)で保存したところ、1年間の保存中にも褐変はみられず、良好な品位を保っていた。
[Composition Example 16]
Using the powdery composition of Formulation Example 2, soft capsules were produced with a soft capsule filling machine using gelatin as an encapsulant so that one tablet would be 300 mg in the following formulation. When this capsule was filled in a glass bottle with a lid and stored at 25 ° C. (humidity 60%), browning was not observed even during storage for one year, and good quality was maintained.
<配合割合>
配合例2の粉末状組成物 10%
ビタミンE 15%
大豆レシチン 7%
サフラワー油 55%
ビタミンC 8%
グリセリン脂肪酸エステル 2%
ミツロウ 3%
――――――――――――――――――――――――――
計 100%
<Combination ratio>
10% of powdery composition of Formulation Example 2
Vitamin E 15%
Soy lecithin 7%
Safflower oil 55%
Vitamin C 8%
Glycerin fatty acid ester 2%
Beeswax 3%
――――――――――――――――――――――――――
Total 100%
本発明の粉末状組成物は、γ−アミノ酪酸の保存中の褐変が防止されることから、流通中や保存後にも品位の良好なγ−アミノ酪酸含有粉末状組成物を提供できる。また、本発明の粉末状組成物を、食品や医薬品に配合して使用することが可能である。
Since the powdery composition of the present invention prevents the browning of γ-aminobutyric acid during storage, it can provide a γ-aminobutyric acid-containing powdered composition with good quality during distribution and after storage. Moreover, it is possible to mix | blend and use the powdery composition of this invention for a foodstuff or a pharmaceutical.
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JP2016220660A (en) * | 2015-06-04 | 2016-12-28 | ユニテックフーズ株式会社 | Jelly premix suitable for person with difficulty in digestion or swallowing |
JP2017225388A (en) * | 2016-06-22 | 2017-12-28 | ユーハ味覚糖株式会社 | Functional hard candy and manufacturing method therefor |
JP2020534302A (en) * | 2017-09-19 | 2020-11-26 | ダイアミド・メディカル・アクチボラゲットDiamyd Medical Ab | New formulation of gamma-aminobutyric acid |
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Publication number | Priority date | Publication date | Assignee | Title |
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JP2016220660A (en) * | 2015-06-04 | 2016-12-28 | ユニテックフーズ株式会社 | Jelly premix suitable for person with difficulty in digestion or swallowing |
JP2017225388A (en) * | 2016-06-22 | 2017-12-28 | ユーハ味覚糖株式会社 | Functional hard candy and manufacturing method therefor |
JP2020534302A (en) * | 2017-09-19 | 2020-11-26 | ダイアミド・メディカル・アクチボラゲットDiamyd Medical Ab | New formulation of gamma-aminobutyric acid |
JP7225221B2 (en) | 2017-09-19 | 2023-02-20 | ダイアミド・メディカル・アクチボラゲット | A novel formulation of gamma-aminobutyric acid |
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JP7513336B1 (en) | 2024-01-22 | 2024-07-09 | 株式会社ファーマフーズ | Method for producing powder containing gamma-aminobutyric acid (GABA) and products using the same |
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