JP2007001922A - Renal disease ameliorating agent in dialysis patient or functional food - Google Patents
Renal disease ameliorating agent in dialysis patient or functional food Download PDFInfo
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- JP2007001922A JP2007001922A JP2005183546A JP2005183546A JP2007001922A JP 2007001922 A JP2007001922 A JP 2007001922A JP 2005183546 A JP2005183546 A JP 2005183546A JP 2005183546 A JP2005183546 A JP 2005183546A JP 2007001922 A JP2007001922 A JP 2007001922A
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- coenzyme
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Abstract
Description
本発明は、コエンザイムQ10を有効成分として含有することを特徴とする透析患者における酸化ストレスに起因する症状又は疾患の予防及び/又は改善剤に関する。特に、腎疾患改善剤、又は機能性食品に関する。また、透析患者における腎疾患の改善用組成物を製造するためのコエンザイムQ10の使用、透析患者における腎疾患の改善のためのコエンザイムQ10の使用に関する。或いは、ビタミンE固定化中空糸膜型ダイアライザーと組み合わせて用いられる、コエンザイムQ10を有効成分として含有することを特徴とする動脈硬化の予防及び/又は改善剤に関する。 The present invention relates to a preventive and / or ameliorating agent for symptoms or diseases caused by oxidative stress in dialysis patients, characterized by containing coenzyme Q10 as an active ingredient. In particular, it relates to a renal disease ameliorating agent or a functional food. The present invention also relates to the use of coenzyme Q10 for producing a composition for improving renal disease in dialysis patients and the use of coenzyme Q10 for improving renal disease in dialysis patients. Alternatively, the present invention relates to an agent for preventing and / or improving arteriosclerosis characterized by containing coenzyme Q10 as an active ingredient, which is used in combination with a vitamin E-immobilized hollow fiber membrane dialyzer.
コエンザイムQ10はベンゾキノン誘導体であり、広く生物界に分布していることからユビキノン(酸化型コエンザイムQ10)と命名された。これを2電子還元したヒドロキノン体がユビキノール(還元型コエンザイムQ10)である。イソプレノイド側鎖の長さ(n)の違いにより多数の同族体が存在するが(n=1〜12)、生合成されるため、主たる同族体は種によって決まっている。哺乳類ではn=9,10が主であり、例えばマウス、ラットではn=9が多く、ウサギでn=10が多い。ヒトはn=10である。 Coenzyme Q10 is a benzoquinone derivative and is widely distributed in the living world, so it was named ubiquinone (oxidized coenzyme Q10). A hydroquinone form obtained by reducing this by two electrons is ubiquinol (reduced coenzyme Q10). Although many homologues exist depending on the length (n) of the isoprenoid side chain (n = 1 to 12), the main homologue is determined by the species because it is biosynthesized. In mammals, n = 9 and 10 are mainly used. For example, n = 9 is often used in mice and rats, and n = 10 is often used in rabbits. For humans, n = 10.
コエンザイムQ10は、生体内の細胞中におけるミトコンドリアの電子伝達系構成成分として存在する生理学的成分であり、生体内において酸化と還元を繰り返すことで電子伝達系における伝達成分としての機能を担っている。コエンザイムQ10は生体内において、エネルギー生産及び抗酸化活性を示すことから、その有用性は広く知られている。コエンザイムQ10はヒトの体内で生合成される分子であるが、加齢と共に生合成量が低下すること、あるいはさまざまな疾患における生体中のコエンザイムQ10量の減少が報告されている。このような疾患では外部からのコエンザイムQ10の供給が良好な結果をもたらしている。更に、罹患時だけでなく老人あるいは肉体的に疲労したときなど、平常時でもコエンザイムQ10の補給が必要であると考えられている。 Coenzyme Q10 is a physiological component that exists as a constituent component of the mitochondrial electron transfer system in cells in the living body, and plays a role as a transfer component in the electron transfer system by repeating oxidation and reduction in the living body. Since coenzyme Q10 exhibits energy production and antioxidant activity in vivo, its usefulness is widely known. Coenzyme Q10 is a molecule that is biosynthesized in the human body, but it has been reported that the amount of biosynthesis decreases with age, or that the amount of coenzyme Q10 in the body in various diseases is decreased. In such diseases, external supply of coenzyme Q10 has yielded good results. Furthermore, it is considered that coenzyme Q10 needs to be replenished not only at the time of illness but also at normal times such as when the elderly or physically fatigued.
酸化型コエンザイムQ10は、鬱血性心不全薬として医薬用途に用いられている。医薬用途以外では、ビタミン類同様、栄養剤、栄養補助剤、更に、痴呆症などの老人性の疾患、アレルギー疾患に対する有用性、あるいは運動能力の増加等も報告されており、また、その安全性が高いことから有用な栄養補給の手段と言われている。 Oxidized coenzyme Q10 is used for pharmaceutical use as a congestive heart failure drug. In addition to vitamins, as with vitamins, nutritional supplements, nutritional supplements, senile diseases such as dementia, usefulness for allergic diseases, and increased exercise capacity have also been reported, and their safety It is said to be a useful means of nutrition because it is expensive.
現在、日本国内で約24万人が透析療法を受けており、更に、毎年約3万人が新しく透析療法を開始している。透析療法を受ける患者数は高齢者の増加や、糖尿病患者の増加に伴って今後ますます増えることが予想されている。 Currently, about 240,000 people are receiving dialysis therapy in Japan, and about 30,000 new dialysis therapy is started every year. The number of patients receiving dialysis therapy is expected to increase in the future as the number of elderly people increases and the number of diabetic patients increases.
長期透析患者においては合併症として、透析アミロイドーシス、動脈硬化性疾患等の発生率が増加している事が知られている。その原因としては透析療法に使用する透析膜を生体異物と認識して白血球や血小板が膜に吸着し、このとき多くのフリーラジカルが生産され血液が高酸化ストレス状態になるためと考えられる。つまり長期的に透析療法を受けている患者の中には、血中抗酸化作用の低下や過酸化脂質の高値などが確認されている(非特許文献1)。そのため、透析患者が受ける酸化ストレスを抑制することにより、患者のQOL(Quality of life)や予後を改善する可能性が高いことが指摘されている。 In long-term dialysis patients, it is known that the incidence of dialysis amyloidosis, arteriosclerotic disease, etc. is increasing as a complication. This is probably because the dialysis membrane used in dialysis therapy is recognized as a xenobiotic and leukocytes and platelets are adsorbed to the membrane, and at this time, many free radicals are produced and the blood is in a high oxidative stress state. That is, in patients receiving dialysis therapy for a long time, a decrease in blood antioxidant action, a high level of lipid peroxide, and the like have been confirmed (Non-patent Document 1). Therefore, it has been pointed out that suppressing oxidative stress experienced by dialysis patients has a high possibility of improving the patient's QOL (Quality of Life) and prognosis.
このような問題を解決するため、生体内抗酸化作用、生体膜安定化作用、血小板凝集抑制作用など種々の生理作用を有するビタミンEの被膜を透析膜の表面に被覆した固定化中空糸膜型ダイアライザーが開発された。ビタミンEは過酸化脂質の前駆体である脂質ペルオキシドを生体内で最も効率的に補足することが知られている。しかし、ビタミンEは脂質ペルオキシドを還元する反応において自らが酸化されてビタミンEラジカルとなる。このビタミンEラジカルは抗酸化能を有していないために、継続的に脂質ペルオキシドを消去するためにはビタミンEラジカルを還元して脂質ペルオキシドを補足可能なビタミンEにもどしてやる必要がある。つまり、ビタミンE固定化中空糸膜型ダイアライザーを用いて透析を行うだけではまだ不十分でさらなる血液を酸化ストレスから保護させる方法が望まれていた。
こうした背景から、透析患者に対する腎疾患改善剤、又は機能性食品の開発が強く望まれていた。
Against this background, development of a renal disease ameliorating agent or functional food for dialysis patients has been strongly desired.
本発明の目的は、透析患者に対する酸化ストレスに起因する症状又は疾患の予防及び/又は改善剤を提供することにある。特に、透析患者に対する腎疾患改善剤、透析患者に対する動脈硬化の予防及び/又は改善剤、或いは機能性食品を提供し、さらにはそれらを用いた応用方法を提供することにある。 An object of the present invention is to provide a preventive and / or ameliorating agent for symptoms or diseases caused by oxidative stress on dialysis patients. In particular, it is to provide a renal disease ameliorating agent for dialysis patients, an arteriosclerosis prevention and / or ameliorating agent for dialysis patients, or a functional food, and further provide an application method using them.
本発明者らは上記課題を解決するために鋭意検討した結果、コエンザイムQ10に透析患者における腎疾患改善効果があることを見出した。具体的には、ビタミンE固定化中空糸膜型ダイアライザーと組み合わせてなる、コエンザイムQ10を有効成分として含有する組成物を摂取または塗布することにより、透析患者における腎疾患を何ら副作用無く、治療、又は改善することを見出して本発明を完成するに至った。
すなわち、本発明は、以下の構成を有する。
(1)コエンザイムQ10を有効成分として含有する透析患者における腎疾患改善剤。
(2)ビタミンE固定化中空糸膜型ダイアライザーと組み合わせて用いられる、コエンザイムQ10を有効成分として含有する酸化ストレスに起因する症状又は疾患の予防又は改善剤。
(3)酸化ストレスに起因する症状又は疾患が、疲労、老化、皮膚の変性、心疾患、肝疾患、脳疾患、腎疾患、動脈硬化、糖尿病及びこれらの合併症からなる群より選ばれる1以上の症状又は疾患である上記(2)に記載の予防及び/又は改善剤。
(4)コエンザイムQ10を有効成分として含有する透析患者における腎疾患の改善効果を有する機能性食品。
(5)透析患者における腎疾患の改善用組成物を製造するためのコエンザイムQ10の使用。
(6)透析患者における腎疾患の改善のためのコエンザイムQ10の使用。
(7)コエンザイムQ10を有効成分として含有する組成物を摂取することを特徴とする、透析患者における腎疾患の改善方法。
(8)コエンザイムQ10を有効成分として含有する組成物と、ビタミンE固定化中空糸膜型ダイアライザーを組み合わせて用いることを特徴とする、酸化ストレスに起因する症状又は疾患の予防又は治療方法。
(9)酸化ストレスに起因する症状又は疾患が、疲労、老化、皮膚の変性、心疾患、肝疾患、脳疾患、腎疾患、動脈硬化、糖尿病及びこれらの合併症からなる群より選ばれる1以上の症状又は疾患である前記(8)に記載の予防又は治療方法。
(10)コエンザイムQ10を有効成分として含有する組成物と組み合わせて用いられる、ビタミンE固定化中空糸膜型ダイアライザー。
As a result of intensive studies to solve the above problems, the present inventors have found that coenzyme Q10 has an effect of improving renal disease in dialysis patients. Specifically, by ingesting or applying a composition containing Coenzyme Q10 as an active ingredient in combination with a vitamin E-immobilized hollow fiber membrane dialyzer, treatment of renal disease in dialysis patients without any side effects, or The present invention has been completed by finding an improvement.
That is, the present invention has the following configuration.
(1) A renal disease ameliorating agent in a dialysis patient containing coenzyme Q10 as an active ingredient.
(2) A preventive or ameliorating agent for symptoms or diseases caused by oxidative stress containing coenzyme Q10 as an active ingredient, used in combination with a vitamin E-immobilized hollow fiber membrane dialyzer.
(3) One or more symptoms or diseases caused by oxidative stress are selected from the group consisting of fatigue, aging, skin degeneration, heart disease, liver disease, brain disease, renal disease, arteriosclerosis, diabetes and these complications The preventive and / or ameliorating agent according to (2) above, wherein
(4) A functional food having an effect of improving renal disease in dialysis patients containing coenzyme Q10 as an active ingredient.
(5) Use of coenzyme Q10 for producing a composition for improving renal disease in dialysis patients.
(6) Use of coenzyme Q10 to improve renal disease in dialysis patients.
(7) A method for improving renal disease in a dialysis patient, comprising ingesting a composition containing coenzyme Q10 as an active ingredient.
(8) A method for preventing or treating a symptom or disease caused by oxidative stress, comprising using a composition containing coenzyme Q10 as an active ingredient in combination with a vitamin E-immobilized hollow fiber membrane dialyzer.
(9) One or more symptoms or diseases caused by oxidative stress are selected from the group consisting of fatigue, aging, skin degeneration, heart disease, liver disease, brain disease, renal disease, arteriosclerosis, diabetes and these complications The prevention or treatment method according to (8) above, wherein
(10) A vitamin E-immobilized hollow fiber membrane dialyzer used in combination with a composition containing coenzyme Q10 as an active ingredient.
本発明により、コエンザイムQ10を有効成分として含有することを特徴とする酸化ストレスに起因する症状又は疾患の予防及び/又は改善剤、酸化ストレスに起因する症状又は疾患の予防及び/又は改善効果を有する機能性食品、化粧料、さらには酸化ストレスに起因する症状又は疾患の予防及び/又は改善用組成物を調整するためのコエンザイムQ10の使用、そして、該化合物を有効成分として含有する組成物を摂取することを特徴とする酸化ストレスに起因する症状又は疾患の予防及び/又は改善剤方法を提供することができる。 According to the present invention, it has a preventive and / or ameliorating agent for symptoms or diseases caused by oxidative stress characterized by containing coenzyme Q10 as an active ingredient, and has a preventive and / or ameliorating effect on symptoms or diseases caused by oxidative stress Use of functional foods, cosmetics, and further coenzyme Q10 for preparing a composition for preventing and / or improving symptoms or diseases caused by oxidative stress, and ingesting a composition containing the compound as an active ingredient It is possible to provide a method for preventing and / or improving symptoms or diseases caused by oxidative stress.
本発明について、以下具体的に説明する。本発明に用いられるコエンザイムQ10は医薬又は食品として服用又は食用可能なコエンザイムQ10であればその由来および製法は何ら限定されるものでは無いが、好ましくは市販のものが良い。また、生体内でコエンザイムQ10に変換する化合物であってもよい。 The present invention will be specifically described below. Coenzyme Q10 used in the present invention is not limited in its origin and production method as long as it is coenzyme Q10 that can be taken or edible as a medicine or food, but a commercially available product is preferred. Further, it may be a compound that converts to coenzyme Q10 in vivo.
コエンザイムQ10の医薬及び食品中の含有量は、酸化ストレスに起因する症状又は疾患の予防及び/又は改善効果が得られる量であれば何ら限定されるものではないが、1日のコエンザイムQ10の摂取量が1〜2000mgとなるような量、好ましくは10〜500mg、さらに好ましくは30〜300mgとなるような量が良い。 The content of coenzyme Q10 in medicines and foods is not limited as long as it is an amount that can prevent and / or improve symptoms or diseases caused by oxidative stress, but daily intake of coenzyme Q10 The amount is such that the amount is 1 to 2000 mg, preferably 10 to 500 mg, more preferably 30 to 300 mg.
コエンザイムQ10は融点の低い親油性の固体であり、水に難溶性のために経口投与における吸収性が低いことが知られている。このため、医薬製剤及び食品中のコエンザイムQ10の分散安定性、結晶析出防止性などの性状の安定性及び生体吸収性を向上させることが好ましい。本発明において、コエンザイムQ10の性状を安定化したものを用いても良い。例えば、コエンザイムQ10を鶏卵タンパク質、乳タンパク質、肉タンパク質等の動物性タンパク質、大豆タンパク質もしくは大豆ペプチド等の植物性タンパク質又はこれらの加水分解物と配合する、又は、更にでんぷん等の糖質等と配合することによりコエンザイムQ10を安定化し、更に生体吸収性を向上させた後に使用しても良い。 Coenzyme Q10 is a lipophilic solid having a low melting point, and is known to have low absorbability in oral administration due to poor solubility in water. For this reason, it is preferable to improve stability of properties such as dispersion stability of coenzyme Q10 in pharmaceutical preparations and foods, and prevention of crystal precipitation, and bioabsorbability. In the present invention, a stabilized product of coenzyme Q10 may be used. For example, coenzyme Q10 is blended with animal protein such as chicken egg protein, milk protein, meat protein, vegetable protein such as soy protein or soy peptide, or a hydrolyzate thereof, or further blended with sugar such as starch. By doing so, it may be used after coenzyme Q10 is stabilized and bioabsorbability is further improved.
コエンザイムQ10を乳化組成物として用いる場合には、例えばコエンザイムQ10を油相成分としてショ糖酢酸イソ酪酸エステル等のショ糖脂肪酸エステル、ポリ(モノ)グリセロール脂肪酸エステル等に溶解し、多価アルコール及び乳化剤を用いて乳化処理するか、又は有機酸等の添加剤の存在下又は不存在下に、アラビアガム、寒天、水溶性コーンファイバー、デンプン、ゼラチン、キサンタンガム、カゼイン、デキストリン、カルメロールナトリウム、ポリビニルピロリドン等の水溶性物質中にコエンザイムQ10を分散、乳化するか、又はシクロデキストリン等の包摂化合物中に包摂させることにより性状の安定性、生体吸収性を向上させた後に使用すれば良い。 When coenzyme Q10 is used as an emulsified composition, for example, coenzyme Q10 is dissolved in a sucrose fatty acid ester such as sucrose acetate isobutyric acid ester, poly (mono) glycerol fatty acid ester, etc. as an oil phase component, and a polyhydric alcohol and an emulsifier Or gum arabic, agar, water-soluble corn fiber, starch, gelatin, xanthan gum, casein, dextrin, carmelol sodium, polyvinylpyrrolidone in the presence or absence of additives such as organic acids Coenzyme Q10 may be dispersed and emulsified in a water-soluble substance such as, or incorporated into an inclusion compound such as cyclodextrin and then used after improving the stability of properties and bioabsorbability.
本発明に係わる酸化ストレスに起因する症状又は疾患の予防及び/又は改善剤、組成物又は食品を摂取する対象は、ヒト又は動物である。本発明において動物とは産業用動物、伴侶動物及び実験動物を指す。産業動物とはウシ、ウマ、ブタ、ヤギ、ヒツジ等の家畜、ニワトリ、アヒル、ウズラ、七面鳥、ダチョウ等の家禽、ブリ、ハマチ、マダイ、マアジ、コイ、ニジマス、ウナギ等の魚類など産業上飼養することが必要とされている動物である。又、伴侶動物とはイヌ、ネコ、マーモセット、ビーグル犬、ミニブタ、アカゲザル、カニクイザルなど医学、生物学、農学、薬学等の分野で研究に共用される動物を示す。 The subject who receives the preventive and / or ameliorating agent, composition or food for symptoms or diseases caused by oxidative stress according to the present invention is a human or an animal. In the present invention, animals refer to industrial animals, companion animals, and experimental animals. Industrial animals include domestic animals such as cattle, horses, pigs, goats, and sheep, poultry such as chickens, ducks, quails, turkeys, and ostriches, and fish such as yellowtail, yellowtail, red sea bream, red sea bream, carp, rainbow trout, and eels. It is an animal that is needed to do. The companion animal refers to animals commonly used for research in the fields of medicine, biology, agriculture, pharmacology, such as dogs, cats, marmosets, beagle dogs, minipigs, rhesus monkeys, and cynomolgus monkeys.
本発明の対象となる酸化ストレスに起因する症状又は疾患は酸化ストレスに起因する症状又は疾患であれば何ら限定されるものではない。酸化ストレスに起因する症状又は疾患としては疲労、老化、皮膚の変性、心疾患、肝疾患、脳疾患、腎疾患、動脈硬化、糖尿病、アレルギー、リュウマチ性疾患、ガン、エイズ、パーキンソン病、アルツハイマー型痴呆症、糖尿病性網膜症、白内障、心筋梗塞、脳梗塞、高血圧、胃潰瘍、虚血性腸炎、慢性膵炎、腎不全及び尿毒症等が挙げられる。 The symptom or disease caused by oxidative stress as a target of the present invention is not limited as long as it is a symptom or disease caused by oxidative stress. Symptoms or diseases caused by oxidative stress include fatigue, aging, skin degeneration, heart disease, liver disease, brain disease, kidney disease, arteriosclerosis, diabetes, allergy, rheumatic disease, cancer, AIDS, Parkinson's disease, Alzheimer type Examples include dementia, diabetic retinopathy, cataract, myocardial infarction, cerebral infarction, hypertension, gastric ulcer, ischemic enteritis, chronic pancreatitis, renal failure and uremia.
又、本発明の組成物は肉体疲労改善剤又はエネルギー産生賦活剤であっても良い。肉体疲労改善剤とは肉体疲労予防剤、妊娠・授乳期や病中病後における体力低下の改善剤を含む。エネルギー産生賦活剤は、運動や加齢によって酸化ストレス障害を受けた細胞活性を改善する作用を有する。 The composition of the present invention may be a physical fatigue improving agent or an energy production activator. The physical fatigue improving agent includes a physical fatigue preventing agent, and an agent for reducing physical fitness during pregnancy / lactation and after sickness. An energy production activator has the effect | action which improves the cell activity which received the oxidative stress disorder | damage | failure by exercise and aging.
又、本発明の対象となる腎疾患としては腎疾患であれば何ら限定されるものではない。腎疾患は、腎臓そのものに異常が生じておこる疾患と、腎臓以外の臓器の異常や変化によって腎臓が機能障害を起こす疾患の二つに分けられる。 In addition, the kidney disease that is the subject of the present invention is not limited as long as it is a kidney disease. Renal diseases are divided into two types: diseases caused by abnormalities in the kidneys themselves and diseases in which the kidneys malfunction due to abnormalities or changes in organs other than the kidneys.
腎臓そのものに異常が生じて起こる疾患においては、腎臓を構成している腎糸球体、尿細管、間質(結合組織)、及び血管のいずれか、或いは全てに異常が現れる。腎臓そのものに異常が生じておこる疾患は、遺伝性と後天性に分けられ、遺伝性としては、多発性のう胞腎や遺伝性腎炎が挙げられ、後天性としては、糸球体腎炎、尿細管・間質性腎炎、腎盂腎炎、膀胱炎、腎結核、腎結石、尿管結石などの結石に起因する疾患及び腎癌、膀胱癌などの癌に起因する疾患が挙げられる。 In diseases caused by abnormalities in the kidney itself, abnormalities appear in any or all of the glomeruli, tubules, stroma (connective tissue), and blood vessels that make up the kidney. Diseases caused by abnormalities in the kidney itself are divided into hereditary and acquired. Examples of hereditary diseases include multiple cystic kidneys and hereditary nephritis. Acquired diseases include glomerulonephritis, tubules / intervals. Examples include diseases caused by stones such as interstitial nephritis, pyelonephritis, cystitis, kidney tuberculosis, kidney stones, and ureteral stones, and diseases caused by cancers such as kidney cancer and bladder cancer.
腎臓以外の臓器の異常や変化によって腎臓が機能障害を起こす疾患としては、代謝性の疾患に起因する腎疾患、血液疾患に関する腎疾患など、様々な腎疾患がある。代謝性疾患に起因する腎疾患としては、糖尿病性腎症、痛風腎、アミロイド腎などが挙げられ、血液疾患に起因する腎疾患としては、多発性骨髄腫による多発性骨髄腫腎、溶血性尿毒症性症候群、高血圧による腎硬化症などが挙げられ、その他としても、例えば、膠原病によるループス腎炎、慢性の肝臓病による肝性糸体硬化症などが挙げられる。これらの腎疾患の代表的な症状は、尿の異常、むくみ(浮腫)、高血圧の三つである。 Examples of diseases in which the kidneys are impaired due to abnormalities or changes in organs other than the kidney include various renal diseases such as renal diseases caused by metabolic diseases and renal diseases related to blood diseases. Examples of renal diseases caused by metabolic diseases include diabetic nephropathy, gout kidney, and amyloid kidney. Examples of renal diseases caused by hematological diseases include multiple myeloma kidney caused by multiple myeloma, hemolytic uremic toxin. Syndrome, nephrosclerosis due to hypertension, etc., and other examples include lupus nephritis due to collagen disease, hepatic glomerulosclerosis due to chronic liver disease, and the like. There are three typical symptoms of these kidney diseases: abnormal urine, swelling (edema), and hypertension.
腎疾患において、腎機能異常により腎臓の働きが正常の30%以下になり、体内の老廃物や余分な水分が排泄できない状態は腎不全と呼ばれ、さらに腎不全が進行し、自覚症状を伴うようになったものは尿毒症と呼ばれ、該尿毒症を発症した患者は透析療法を受けている。 In kidney disease, the kidney function is less than 30% of normal due to abnormal renal function, and the state in which waste and excess water in the body cannot be excreted is called renal failure, and further renal failure progresses with subjective symptoms What has become known is called uremia, and the patient who developed the uremic disease is receiving dialysis therapy.
本発明のコエンザイムQ10を有効成分として含有する組成物は、摂取によって酸化ストレスに起因する症状又は疾患の予防及び/又は改善に有効な組成物であればよい。該組成物を摂取することを特徴とする酸化ストレスに起因する症状又は疾患の予防及び/又は改善方法も本発明の範囲内である。摂取には経口、非経口いずれも含まれ、非経口には、塗布、注射、点滴、経鼻などによるものがある。 The composition containing coenzyme Q10 of the present invention as an active ingredient may be any composition that is effective for preventing and / or improving symptoms or diseases caused by oxidative stress by ingestion. A method for preventing and / or improving a symptom or disease caused by oxidative stress characterized by ingesting the composition is also within the scope of the present invention. Ingestion includes both oral and parenteral, and parenteral includes application, injection, infusion, and nasal administration.
また、本発明のコエンザイムQ10の使用は、酸化ストレスに起因する症状又は疾患の予防及び/又は改善用組成物を調製するための使用であれば特に限定されない。酸化ストレスに起因する症状又は疾患の予防及び/又は改善に有効な組成物としては、酸化ストレスに起因する症状又は疾患の予防及び/又は改善剤としての医薬、及び酸化ストレスに起因する症状又は疾患の予防及び/又は改善効果を有する機能性食品、化粧料などが挙げられる。 The use of coenzyme Q10 of the present invention is not particularly limited as long as it is used for preparing a composition for preventing and / or improving symptoms or diseases caused by oxidative stress. The composition effective for preventing and / or ameliorating symptoms or diseases caused by oxidative stress includes a drug as an agent for preventing and / or improving symptoms or diseases caused by oxidative stress, and symptoms or diseases caused by oxidative stress. Functional foods having a preventive and / or improving effect, cosmetics and the like.
本発明のコエンザイムQ10を含有する医薬としては、酸化ストレスに起因する症状又は疾患の予防及び/又は改善効果が得られるものであれば何ら限定されない。該医薬の剤型としては、散在、顆粒剤、丸剤、ソフトカプセル、ハードカプセル、錠剤、チュアブル錠、速崩錠、シロップ、液剤、懸濁剤、座剤、軟膏、クリーム剤、ゲル剤、粘付剤、吸入剤、注射剤等が挙げられる。これらの製剤は常法に従って調製されるが、コエンザイムQ10は水に難溶性であるため、植物性油、動物性油等の非親水性有機溶媒に溶解するか又は、乳化剤、分散剤もしくは界面活性剤等とともに、ホモジナイザー(高圧ホモジナイザー)を用いて水溶液中に分散、乳化させて用いる。更に、コエンザイムQ10の吸収性を高めるために、平均粒子系を1ミクロン程度まで微粉砕して用いることも可能である。 The pharmaceutical containing coenzyme Q10 of the present invention is not limited in any way as long as it can prevent and / or improve the symptoms or diseases caused by oxidative stress. The pharmaceutical dosage form includes scattered, granule, pill, soft capsule, hard capsule, tablet, chewable tablet, quick-disintegrating tablet, syrup, liquid, suspension, suppository, ointment, cream, gel, sticky Agents, inhalants, injections and the like. These preparations are prepared according to conventional methods. However, since Coenzyme Q10 is hardly soluble in water, it can be dissolved in non-hydrophilic organic solvents such as vegetable oils and animal oils, or emulsifiers, dispersants or surfactants. Along with the agent, etc., it is used after being dispersed and emulsified in an aqueous solution using a homogenizer (high pressure homogenizer). Furthermore, in order to increase the absorbability of coenzyme Q10, the average particle system can be finely pulverized to about 1 micron.
製剤化のために用いることができる添加剤には、例えば大豆油、サフラー油、オリーブ油、胚芽油、ひまわり油、牛脂、いわし油等の動物性油、ポリエチレングリコール、プロピレングリコール、グリセリン、ソルビトール等の多価アルコール、ソルビタン脂肪酸エステル、ショ糖脂肪酸エステル、グリセリン脂肪酸エステル、ポリグリセリン脂肪酸エステル等の界面活性剤、精製水、乳糖、デンプン、結晶セルロース、D−マンニトール、レシチン、アラビアガム、ソルビトール液、糖液等の賦形剤、甘味料、着色料、pH調整剤、香料などをあげることができる。尚、液体製剤は、服用時に水又は他の適当な媒体に溶解又は懸濁する形であってもよい。また、錠剤、顆粒剤は周知の方法でコーティングしても良い。 Additives that can be used for formulation include animal oils such as soybean oil, safflower oil, olive oil, germ oil, sunflower oil, beef tallow, sardine oil, polyethylene glycol, propylene glycol, glycerin, sorbitol, etc. Surfactant such as polyhydric alcohol, sorbitan fatty acid ester, sucrose fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, purified water, lactose, starch, crystalline cellulose, D-mannitol, lecithin, gum arabic, sorbitol solution, sugar Examples thereof include excipients such as liquid, sweeteners, colorants, pH adjusters, and fragrances. The liquid preparation may be dissolved or suspended in water or other appropriate medium when taken. Tablets and granules may be coated by a known method.
注射剤の形で投与する場合には、静脈内、腹腔内、筋肉内、皮下、経皮、関節内、滑液嚢内、胞膜内、骨膜内、舌下、口腔内等に投与することが好ましく、特に静脈内投与又は腹腔内投与が好ましい。静脈内投与は、点滴投与、ポーラス投与のいずれであってもよい。 When administered in the form of an injection, it can be administered intravenously, intraperitoneally, intramuscularly, subcutaneously, transdermally, intraarticularly, within the bursa, intravesicular, intraperiosteally, sublingually, orally. In particular, intravenous administration or intraperitoneal administration is preferred. Intravenous administration may be either drip administration or porous administration.
本発明のコエンザイムQ10を含有する機能性食品としては、酸化ストレスに起因する症状又は疾患の改善効果が得られるものであれば何ら限定されるものでは無く、例えばコエンザイムQ10含有サプリメント(散在、顆粒剤、ソフトカプセル、ハードカプセル、錠剤、チュアブル錠、速崩錠、シロップ、液剤等)、コエンザイムQ10含有飲料(お茶、炭酸飲料、乳酸飲料、スポーツ飲料等)、コエンザイムQ10含有菓子(グミ、ゼリー、ガム、チョコレート、クッキー、キャンデー等)、コエンザイムQ10含有油、コエンザイムQ10含有油脂食品(マヨネーズ、ドレッシング、バター、クリーム、マーガリン等)コエンザイムQ10含有ケチャップ、コエンザイムQ10含有ソース、コエンザイムQ10含有流動食、コエンザイムQ10含有乳製品(牛乳、ヨーグルト、チーズ等)、コエンザイムQ10含有パン類、コエンザイムQ10含有麺類(うどん、そば、ラーメン、パスタ、やきそば、きしめん、そーめん、ひやむぎ、ビーフン等)等が挙げられる。 The functional food containing coenzyme Q10 of the present invention is not limited in any way as long as the effect of ameliorating symptoms or diseases caused by oxidative stress is obtained. For example, a coenzyme Q10-containing supplement (scattered, granule) , Soft capsules, hard capsules, tablets, chewable tablets, quick-disintegrating tablets, syrups, liquids, etc., beverages containing coenzyme Q10 (tea, carbonated beverages, lactic acid beverages, sports drinks, etc.), confectionery containing coenzyme Q10 (gummy, jelly, gum, chocolate) , Cookies, candy, etc.), oil containing coenzyme Q10, fat and oil food containing coenzyme Q10 (mayonnaise, dressing, butter, cream, margarine, etc.) coenzyme Q10 containing ketchup, coenzyme Q10 containing sauce, coenzyme Q10 containing liquid food, coenzyme Q10-containing dairy products (milk, yogurt, cheese, etc.), Coenzyme Q10-containing bread, coenzyme Q10-containing noodles (udon, soba, ramen, pasta, fried noodle, noodles, somen, hiyamugi, vermicelli, etc.) and the like.
本発明に用いられるコエンザイムQ10を含有する機能性食品には、必要に応じて各種栄養素、各種ビタミン類(ビタミンA、ビタミンB1、ビタミンB2、ビタミンB6、ビタミンB12、ビタミンC、ビタミンD、ビタミンE、ビタミンK等)、各種ミネラル類(マグネシウム、亜鉛、鉄、ナトリウム、カリウム、セレン、酸化チタニウム等)、食物繊維、糖類(セルロース、デキストリン、キチン等)、多価不飽和脂肪酸(アラキドン酸、ドコサヘキサエン酸、エイコサペンタエン酸、ドコサペンタエン酸等)、共役脂肪酸類(共役リノール酸等)、リン脂質(レシチン、ホスファチジン酸、ホスファチジルセリン、ホスファチジルエタノールアミン、ホスファチジルグリセロール、ホスファチジルコリン、ホスファチジルイノシトール、ホスファチジルDHA等)、糖脂質類(セレブロシド等)、カロチノイド類(β-カロチン、リコピン、アスタキサンチン、β−クリプトキサンチン等)、フラボノイド類(ケルセチン、ルテオリン、イソフラボン等)、キサントフィル類(カプサンチン、ルテイン、ゼアキサンチン等)、アミノ酸類(グリシン、セリン、アラニン、グルタミン、バリン、ロイシン、イソロイシン、リジン、アルギニン、アスパラギン酸、グルタミン酸、トリプトファン、フェニルアラニン、ヒスチジン、プロリン、メチオニン、システイン等)、その他の栄養素(カルニチン、セサミン、α−リポ酸、イノシトール、D−カイロイノシトール、ピニトール、タウリン、グルコサミン、コンドロイチン硫酸、S−アドノシルメチオニン、クルクミン、γ−オリザノール、グルタチオン、γ−アミノ酪酸、シネフリン、ピロロキノリンキノン、カテキン、カプサイシン等)、分散剤、乳化剤等の安定剤、甘味料(ソルビトール、ショ糖等)、呈味成分(クエン酸、リンゴ酸等)、フレーバー、ローヤルゼリー、蜂蜜、蜜ロウ、プロポリス、アガリクス等を配合することができる。また、ペパーミント、ベルガモット、カモンミール、ラベンダーなどのハーブ類を配合してもよい。また、テアニン、デヒドロエピアンドステロン、メラトニンなどの素材を配合してもよい。また、食品や化粧品として加工する過程において物理的条件または共存する他の成分によって酸化型コエンザイムQ10から生じる還元型コエンザイムQ10を含有しても何ら問題はない。 The functional food containing coenzyme Q10 used in the present invention includes various nutrients, various vitamins (vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E as necessary. , Vitamin K, etc.), various minerals (magnesium, zinc, iron, sodium, potassium, selenium, titanium oxide, etc.), dietary fiber, sugars (cellulose, dextrin, chitin, etc.), polyunsaturated fatty acids (arachidonic acid, docosahexaene) Acid, eicosapentaenoic acid, docosapentaenoic acid, etc.), conjugated fatty acids (conjugated linoleic acid, etc.), phospholipids (lecithin, phosphatidic acid, phosphatidylserine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, phosphatidylinositol) , Phosphatidyl DHA, etc.), glycolipids (such as cerebroside), carotenoids (such as β-carotene, lycopene, astaxanthin, β-cryptoxanthin), flavonoids (such as quercetin, luteolin, isoflavone), xanthophylls (capsanthin, lutein, etc.) Zeaxanthin), amino acids (glycine, serine, alanine, glutamine, valine, leucine, isoleucine, lysine, arginine, aspartic acid, glutamic acid, tryptophan, phenylalanine, histidine, proline, methionine, cysteine, etc.), other nutrients (carnitine, Sesamin, α-lipoic acid, inositol, D-kaileunositol, pinitol, taurine, glucosamine, chondroitin sulfate, S-adnosylmethionine, curcumin, γ-o Zanol, glutathione, γ-aminobutyric acid, synephrine, pyrroloquinoline quinone, catechin, capsaicin, etc., stabilizers such as dispersants, emulsifiers, sweeteners (sorbitol, sucrose, etc.), taste ingredients (citric acid, malic acid, etc. ), Flavor, royal jelly, honey, beeswax, propolis, agarics and the like. Moreover, you may mix | blend herbs, such as peppermint, bergamot, camomile meal, and lavender. Moreover, you may mix | blend raw materials, such as theanine, a dehydroepiandosterone, and melatonin. Moreover, there is no problem even if reduced coenzyme Q10 produced from oxidized coenzyme Q10 is contained in the process of processing as food or cosmetics due to physical conditions or other coexisting components.
本発明の化粧料としては、クリーム、乳液、ローション、マイクロエマルジョンエッセンス、入浴剤などが挙げられ、香料等を混合してもよい。 Examples of the cosmetic of the present invention include creams, emulsions, lotions, microemulsion essences, bathing agents, and the like, and fragrances and the like may be mixed.
酸化ストレスに起因する症状又は疾患の予防及び/又は改善度を評価する方法としては酸化ストレスに起因する症状又は疾患の予防及び/又は改善度を評価する方法であれば良く、例えば酸化ストレスマーカーを測定する方法が挙げられる。酸化ストレスマーカーとしては酸化ストレスマーカーであれば何ら限定されるものではないが、例えば酸化LDL、CRP、8−ヒドロキシデオキシグアノシン、FRAS、過酸化脂質、マロンジアルデヒド、カルボキシメチルリジン、ペントシジン、ヘキサノイルリジン、4−ヒドロキシノネナール、アクロレイン、コエンザイムQ10の酸化率、グルタチオンペルオキシダーゼ、スーパーオキシドジスムターゼ及びカタラーゼ等の酸素活性値が挙げられる。 The method for evaluating the degree of prevention and / or improvement of symptoms or diseases caused by oxidative stress may be any method for evaluating the degree of prevention and / or improvement of symptoms or diseases caused by oxidative stress. The method of measuring is mentioned. The oxidative stress marker is not limited as long as it is an oxidative stress marker. For example, oxidized LDL, CRP, 8-hydroxydeoxyguanosine, FRAS, lipid peroxide, malondialdehyde, carboxymethyllysine, pentosidine, hexanoyl Examples include oxidation rates of lysine, 4-hydroxynonenal, acrolein, coenzyme Q10, and oxygen activity values such as glutathione peroxidase, superoxide dismutase, and catalase.
本発明に用いるビタミンE固定化中空糸膜型ダイアライザーはビタミンEが固定化されているダイアライザーであれば何ら限定されるものではない。
本発明のダイアライザーとしては、透析膜、血液濾過膜等の体液処理膜を介した透析や濾過の作用により血液中から老廃物を血液外へ移動させ除去する機能を有しており、数nmから数μmの微細多孔を有するものが挙げられ、具体的には、血液透析器、血液濾過器、同時血液透析濾過器、血漿分離器、血漿分画フィルターなどが挙げられる。使用される中空糸膜の材料としては、ポリエチレン、ポリメチルメタクリレート、ポリスチレン、ポリプロピレン、ポリスルホン、ポリヒドロキシエチルメタクリレート、ナイロン66、ポリアクリロニトリル、ポリビニルアルコール、エチレン−ビニルアルコール共重合体、ポリカーボネート等が挙げられる。また、セルロース系の材料として、再生セルロース、ケン化セルロース、セルロースジアセテート、セルローストリアセテートあるはジエチルアミノエチルセルロース等が挙げられる。さらに、前記中空糸膜材料を単独でまたは2種以上を組み合わせてもよい。また、本発明の抗酸化作用物質が被覆される表面が、前記中空糸膜の材料に反応性モノマーや高分子化合物等で改質されていてもよい。
The vitamin E-immobilized hollow fiber membrane type dialyzer used in the present invention is not limited as long as it is a dialyzer in which vitamin E is immobilized.
The dialyzer of the present invention has a function of removing waste products from the blood by removing them from the blood by the action of dialysis and filtration through body fluid treatment membranes such as dialysis membranes and blood filtration membranes. Specific examples include those having micropores of several μm, and specifically, hemodialyzers, hemofilters, simultaneous hemodialyzers, plasma separators, plasma fraction filters, and the like. Examples of the material of the hollow fiber membrane used include polyethylene, polymethyl methacrylate, polystyrene, polypropylene, polysulfone, polyhydroxyethyl methacrylate, nylon 66, polyacrylonitrile, polyvinyl alcohol, ethylene-vinyl alcohol copolymer, polycarbonate, and the like. . Examples of the cellulose material include regenerated cellulose, saponified cellulose, cellulose diacetate, cellulose triacetate, and diethylaminoethyl cellulose. Furthermore, the hollow fiber membrane materials may be used alone or in combination of two or more. Moreover, the surface on which the antioxidant substance of the present invention is coated may be modified with a reactive monomer, a polymer compound or the like on the material of the hollow fiber membrane.
前記中空糸膜の形態としては、内径10μmから1000μm、好ましくは100μmから300μm、膜厚5μmから100μm、好ましくは20μmから60μmであり、膜の断面において一部に緻密層を有する不均一膜でも、緻密層を有さない均一膜でもよい。 As the form of the hollow fiber membrane, the inner diameter is 10 μm to 1000 μm, preferably 100 μm to 300 μm, the film thickness is 5 μm to 100 μm, preferably 20 μm to 60 μm, and even a non-uniform membrane partially having a dense layer in the cross section of the membrane, A uniform film having no dense layer may be used.
本発明に使用されるビタミンEとしては、α−トコフェロール、β−トコフェロール、γ−トコフェロール、δ−トコフェロール、α−トコトリエノール、β−トコトリエノール、γ−トコトリエノール、γ−トコトリエノール、α−酢酸トコフェロール、β−酢酸トコフェロール、γ−酢酸トコフェロール、δ−酢酸トコフェロール、α−ニコチン酸トコフェロール、β−ニコチン酸トコフェロール、γ−ニコチン酸トコフェロール、δ−ニコチン酸トコフェロールがある。ビタミンEは、コエンザイムQとは電子相与性があり、組み合わせる事により、抗酸化性が向上する為、より好適である。中でもα−トコフェロールは生体内抗酸化作用、生体膜安定化作用、血小板凝集抑制作用などの種々の生理作用を有するため、特に好ましい。
ビタミンEの中空糸への被覆量としては、1mg/m2から1000mg/m2が好ましい。より好ましくは、50mg/m2から300mg/m2である。
血液透析器の中空糸膜の内表面をビタミンEで被覆する場合を例に挙げて説明する。ビタミンE及びビタミンEの溶媒からなるビタミンE溶液を作製し、これを中空糸膜の内腔部に流入することにより、ビタミンEを中空糸膜内表面に付着させる。流入方法は、例えば、循環ポンプを利用して、被覆用のビタミンE溶液を血液透析器のヘッダーノズルから中空糸内腔部に導入する方法が簡便である。
Vitamin E used in the present invention includes α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, α-tocotrienol, β-tocotrienol, γ-tocotrienol, γ-tocotrienol, α-tocopherol acetate, β- There are tocopherol acetate, γ-tocopherol acetate, δ-tocopherol acetate, α-tocopherol α-nicotinate, tocopherol β-nicotinate, tocopherol γ-nicotinate, and tocopherol δ-nicotinate. Vitamin E is more suitable because it has an electron-contributing property to coenzyme Q and, when combined, improves antioxidant properties. Among them, α-tocopherol is particularly preferable because it has various physiological actions such as in vivo antioxidant action, biological membrane stabilizing action, and platelet aggregation inhibitory action.
The coating amount of vitamin E on the hollow fiber is preferably 1 mg / m 2 to 1000 mg / m 2 . More preferably, it is 50 mg / m 2 to 300 mg / m 2 .
The case where the inner surface of the hollow fiber membrane of the hemodialyzer is coated with vitamin E will be described as an example. A vitamin E solution composed of vitamin E and a vitamin E solvent is prepared, and this is introduced into the lumen of the hollow fiber membrane, thereby attaching vitamin E to the inner surface of the hollow fiber membrane. As an inflow method, for example, a method of introducing a vitamin E solution for coating from the header nozzle of the hemodialyzer into the hollow fiber lumen using a circulation pump is simple.
〔参考例〕
ビタミンE固定化ダイアライザーの作成方法
内径約200μm、外径約280μm、孔径(内表面500nm)、長さ約24cmのポリスルホン中空糸膜5を10,300本用い、図1に示すように、筒状本体4内に挿入し、両端をポリウレタン系ポッティング剤6、7で固定し、さらに両端にヘッダー10、11を取り付け、キャップ12、13により固着してダイアライザー(人工腎臓)1を作成した。なお、このダイアライザー1の膜面積は1.5m2であった。ビタミンEの中空糸の被覆量は70mg/m2であった(特開平11−178919号公報)。
[Reference example]
Method for preparing vitamin E-immobilized dialyzer Using 10,300 polysulfone hollow fiber membranes having an inner diameter of about 200 μm, an outer diameter of about 280 μm, a pore diameter (inner surface of 500 nm), and a length of about 24 cm, as shown in FIG. Inserted into the main body 4, both ends were fixed with polyurethane potting agents 6, 7, headers 10, 11 were attached to both ends, and fixed with caps 12, 13 to create a dialyzer (artificial kidney) 1. The dialyzer 1 had a membrane area of 1.5 m 2 . The coating amount of the hollow fiber of vitamin E was 70 mg / m 2 (Japanese Patent Laid-Open No. 11-178919).
本発明を製剤例、食品製造例、化粧料製造例、及び実施例に基づいて説明するが、本発明は以下の実施例のみに限定されるものではない。 The present invention will be described based on formulation examples, food production examples, cosmetic production examples, and examples, but the present invention is not limited to the following examples.
[製剤例1]
<錠剤>
コエンザイムQ10 120g
結晶セルロース 330g
カルメロース−カルシウム 15g
ヒドロキシプロピルセルロース 10g
精製水 60ml
上記組成物を通常の方法にて配合、乾燥した後、10gのステアリン酸マグネシウムを添加し、打錠を行い、1錠あたりコエンザイムQ10を20mg含有する100mgの錠剤を得た。
[Formulation Example 1]
<Tablets>
Coenzyme Q10 120g
Crystalline cellulose 330g
Carmellose-calcium 15g
Hydroxypropylcellulose 10g
60 ml of purified water
The above composition was blended and dried in the usual manner, 10 g of magnesium stearate was added, and tableting was performed to obtain 100 mg tablets containing 20 mg of coenzyme Q10 per tablet.
[製剤例2]
<ソフトカプセル>
200gのコエンザイムQ10をオリーブオイル400gに添加して、約60℃で溶解、均一に撹拌した後に冷却し、コエンザイムQ10含有素材を得た。ゼラチン70%、グリセリン30%を混和、膨潤させ、溶解ゼラチンシートを作成した。このゼラチンシートに内溶液としてコエンザイムQ10含有素材を1カプセルあたり300mgの内容量になるように充填し、乾燥させ、1カプセルあたりコエンザイムQ10を100mg含有するソフトカプセルを得た。
[Formulation Example 2]
<Soft capsule>
200 g of coenzyme Q10 was added to 400 g of olive oil, dissolved at about 60 ° C., stirred uniformly, and then cooled to obtain a coenzyme Q10-containing material. Gelatin 70% and glycerin 30% were mixed and swollen to prepare a dissolved gelatin sheet. This gelatin sheet was filled with a coenzyme Q10-containing material as an internal solution so as to have an internal volume of 300 mg per capsule and dried to obtain soft capsules containing 100 mg of coenzyme Q10 per capsule.
[食品製造例1]
<飲料>
30gのコエンザイムQ10を60℃に加温し、油相を得た。グリセリン90gに乳化剤としてグリセロール脂肪酸エステル10gを添加し、70℃に加温して溶解させた。この溶液に先の油相を撹拌しながら徐々に添加する。混合液を、乳化機を用いて高圧乳化処理して乳化組成物を得た。この乳化組成物20gに水180mlを添加、撹拌してコエンザイムQ10含有飲料を得た。
[Food Production Example 1]
<Beverage>
30 g of coenzyme Q10 was heated to 60 ° C. to obtain an oil phase. 10 g of glycerol fatty acid ester as an emulsifier was added to 90 g of glycerin and heated to 70 ° C. to dissolve. The previous oil phase is gradually added to this solution with stirring. The mixed solution was subjected to high-pressure emulsification using an emulsifier to obtain an emulsified composition. To 20 g of this emulsified composition, 180 ml of water was added and stirred to obtain a coenzyme Q10-containing beverage.
[食品製造例2]
<パン>
1gのコエンザイムQ10、砂糖15g、食塩2g、脂肪粉乳5gを湯70gに溶かし、鶏卵2個を添加してよく混ぜた。これを小麦粉130gとドライイースト2gを混合した混合物に加え、手でこねた後、バター約30gを加えて更にこね、30個のロールパン生地を作った。ついで、発酵させた後、表面に溶き卵を塗り、オーブンにて180℃で15分間焼き、ロールパンを得た。
[Food Production Example 2]
<Bread>
1 g of coenzyme Q10, 15 g of sugar, 2 g of salt and 5 g of fat powdered milk were dissolved in 70 g of hot water, and 2 eggs were added and mixed well. This was added to a mixture of 130 g of wheat flour and 2 g of dry yeast, kneaded by hand, then kneaded with about 30 g of butter to make 30 roll bread dough. Next, after fermenting, a beaten egg was applied to the surface and baked in an oven at 180 ° C. for 15 minutes to obtain a roll.
[食品製造例3]
<うどん>
小麦粉400gに対して、水200gにコエンザイムQ10を2g、食塩20gを添加して、よくこねて寝かした。この後、生地を延伸し、幅約6mmで切断してうどんを製造した。
[Food Production Example 3]
<Udon>
To 400 g of wheat flour, 2 g of coenzyme Q10 and 20 g of sodium chloride were added to 200 g of water and kneaded well. Thereafter, the dough was stretched and cut into widths of about 6 mm to produce udon.
[化粧料製造例1]
<クリーム>
コエンザイムQ10、ステアリルアルコール、プロピレングリコール、ソルビトール、パラベン、ビタミンE、香料、精製水を適当量、定法に従って配合し、クリームを得た。
[Cosmetics Production Example 1]
<Cream>
Coenzyme Q10, stearyl alcohol, propylene glycol, sorbitol, paraben, vitamin E, fragrance, and purified water were blended in appropriate amounts according to a conventional method to obtain a cream.
[実施例1]
<ビタミンEを固定化しないダイアライザーを用いて透析治療を受けている患者へのコエンザイムQ10の投与>
ビタミンEを固定化しないダイアライザーとしては、PS膜、PMMA膜(東レ)、酢酸セルロース(ニプロ)、PEPA(日機装)、EVAL膜(クラレ)等を用いて以下の試験を行った。
本試験ではコエンザイムQ10(100mg)含有組成物としてコエンザイムQ10を100mg含有するソフトカプセル(製剤例2)を用いた。
腎疾患患者で透析を実施している患者6人にコエンザイムQ10含有(100mg)ソフトカプセルを2ヶ月間、毎夕食後服用させ、服用前と服用開始1、2ヶ月後に酸化マーカーとして酸化LDLを測定した。その結果を表1に示した。コエンザイムQ10を服用した患者の酸化LDL値について、服用後は服用前に比べて明らかに改善されていた(表1)。
[Example 1]
<Administration of coenzyme Q10 to patients undergoing dialysis treatment using a dialyzer that does not immobilize vitamin E>
The following tests were performed using PS membrane, PMMA membrane (Toray), cellulose acetate (Nipro), PEPA (Nikkiso), EVAL membrane (Kuraray), etc. as a dialyzer not immobilizing vitamin E.
In this test, a soft capsule (formulation example 2) containing 100 mg of coenzyme Q10 was used as a composition containing coenzyme Q10 (100 mg).
Six patients undergoing dialysis with renal disease were given a coenzyme Q10-containing (100 mg) soft capsule every 2 months after dinner, and the oxidized LDL was measured as an oxidative marker before and 1 and 2 months after the start of administration. . The results are shown in Table 1. The oxidized LDL value of patients taking coenzyme Q10 was clearly improved after taking compared to before taking (Table 1).
[実施例2]
<ビタミンE固定化中空糸膜型ダイライザーを用いて透析治療を受けている患者へのコエンザイムQ10の投与>
本試験ではコエンザイムQ10(100mg)含有組成物としてコエンザイムQ10を100mg含有するソフトカプセル(製剤例2)を用いた。
参考例に従って作成された透析器を用いて透析を実施している患者6人にコエンザイムQ10含有(100mg)ソフトカプセルを2ヶ月間、毎夕食後服用させ、服用前と服用開始1、2ヶ月後に酸化マーカーとして酸化LDLを測定した。その結果を表1に示した。コエンザイムQ10を服用した患者の酸化LDL値はコエンザイムQ10を服用していない患者に比べて明らかに改善されていた(表2)。コエンザイムQ10を服用した患者の酸化LDL値について、服用後は服用前に比べて明らかに改善されていた(表2)。実施例1と実施例2を比較すると、実施例2の方が酸化LDL値が改善されていることから、ビタミンEを固定化した透析器との組み合わせにおいてコエンザイムQ10を服用することで一層酸化ストレスが軽減されることがわかる。
[Example 2]
<Administration of coenzyme Q10 to a patient undergoing dialysis treatment using a vitamin E-immobilized hollow fiber membrane type riser>
In this test, a soft capsule (formulation example 2) containing 100 mg of coenzyme Q10 was used as a composition containing coenzyme Q10 (100 mg).
Six patients undergoing dialysis using a dialyzer prepared according to the reference example were to take a coenzyme Q10-containing (100 mg) soft capsule every 2 months after dinner, and oxidize before taking and after taking 1 or 2 months after taking Oxidized LDL was measured as a marker. The results are shown in Table 1. The oxidized LDL value of patients taking coenzyme Q10 was clearly improved compared to patients not taking coenzyme Q10 (Table 2). The oxidized LDL value of patients taking coenzyme Q10 was clearly improved after taking compared to before taking (Table 2). A comparison of Example 1 and Example 2 shows that the oxidized LDL value is improved in Example 2, so that more oxidative stress can be obtained by taking Coenzyme Q10 in combination with a dialyzer immobilized with vitamin E. Can be seen to be reduced.
本発明のコエンザイムQ10を有効成分として含有することを特徴とする透析患者における腎疾患改善効果を有する機能性食品は、医薬及び/又は食品の分野で好適に利用できる。 A functional food having an effect of improving renal disease in dialysis patients characterized by containing coenzyme Q10 of the present invention as an active ingredient can be suitably used in the field of medicine and / or food.
1 ダイアライザー
2 透析液入口管
3 透析液出口管
4 筒状本体
5 中空糸膜
6 ポッティング剤
7 ポッティング剤
8 体液流入口
9 体液排出口
10 ヘッダー
11 ヘッダー
12 キャップ
13 キャップ
14 チューブ
15 チューブ
16 中空糸膜
17 被膜
DESCRIPTION OF SYMBOLS 1 Dialyzer 2 Dialysate inlet pipe 3 Dialysate outlet pipe 4 Tubular
Claims (10)
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| JP2005183546A JP2007001922A (en) | 2005-06-23 | 2005-06-23 | Renal disease ameliorating agent in dialysis patient or functional food |
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| JP2005183546A JP2007001922A (en) | 2005-06-23 | 2005-06-23 | Renal disease ameliorating agent in dialysis patient or functional food |
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| JP2007001922A true JP2007001922A (en) | 2007-01-11 |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2009179576A (en) * | 2008-01-30 | 2009-08-13 | Kaneka Corp | QOL improver |
| JP2012526554A (en) * | 2009-05-11 | 2012-11-01 | バーグ バイオシステムズ,エルエルシー | Methods for the diagnosis of metabolic disorders using epimetabolic shifters, multidimensional intracellular molecules, or environmentally affecting factors |
| JP2016102125A (en) * | 2008-07-18 | 2016-06-02 | エー1エム ファーマ エービーA1M Pharma AB | Medical use of radical scavenger and antioxidant alpha-1-microglobulin |
| US9901542B2 (en) | 2013-09-04 | 2018-02-27 | Berg Llc | Methods of treatment of cancer by continuous infusion of coenzyme Q10 |
| US10376477B2 (en) | 2011-04-04 | 2019-08-13 | Berg Llc | Method of treating or preventing tumors of the central nervous system |
| US10933032B2 (en) | 2013-04-08 | 2021-03-02 | Berg Llc | Methods for the treatment of cancer using coenzyme Q10 combination therapies |
| US11077085B2 (en) * | 2016-08-26 | 2021-08-03 | Atif Dabdoub | Dietary macro/micronutritional supplement for patients undergoing kidney dialysis |
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| WO2003032968A1 (en) * | 2001-10-12 | 2003-04-24 | Kaneka Corporation | Compositions for lessening oxidative stress |
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| JPS6241738B2 (en) * | 1982-09-09 | 1987-09-04 | Terumo Corp | |
| WO2003032968A1 (en) * | 2001-10-12 | 2003-04-24 | Kaneka Corporation | Compositions for lessening oxidative stress |
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| JP2009179576A (en) * | 2008-01-30 | 2009-08-13 | Kaneka Corp | QOL improver |
| JP2016102125A (en) * | 2008-07-18 | 2016-06-02 | エー1エム ファーマ エービーA1M Pharma AB | Medical use of radical scavenger and antioxidant alpha-1-microglobulin |
| US10350268B2 (en) | 2008-07-18 | 2019-07-16 | A1M Pharma Ab | Medical use of the radical scavenger and antioxidant alpha-1-microglobulin |
| JP2012526554A (en) * | 2009-05-11 | 2012-11-01 | バーグ バイオシステムズ,エルエルシー | Methods for the diagnosis of metabolic disorders using epimetabolic shifters, multidimensional intracellular molecules, or environmentally affecting factors |
| JP2017018134A (en) * | 2009-05-11 | 2017-01-26 | バーグ エルエルシー | Methods for the diagnosis of metabolic disorders using epimetabolic shifters, multidimensional intracellular molecules, or environmentally affecting factors |
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| US11028446B2 (en) | 2009-05-11 | 2021-06-08 | Berg Llc | Methods for treatment of oncological disorders using an epimetabolic shifter (coenzyme Q10) |
| US12209285B2 (en) | 2009-05-11 | 2025-01-28 | Bpgbio, Inc. | Methods for treatment of oncological disorders using an epimetabolic shifter (coenzyme Q10) |
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