JP2023156553A - Ovarian function activators, anti-aging agents, pharmaceuticals, cosmetics, and foods or beverages - Google Patents
Ovarian function activators, anti-aging agents, pharmaceuticals, cosmetics, and foods or beverages Download PDFInfo
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Abstract
Description
本発明は、卵巣機能活性化剤、抗老化剤、医薬品、化粧品および食品または飲料に関するものである。 The present invention relates to ovarian function activators, anti-aging agents, pharmaceuticals, cosmetics, and foods or beverages.
女性は生まれたときには卵巣内にすべての卵子の元がすでに存在するが、加齢とともに卵子数は少なくなり、その質も低下する。女性の結婚年齢が年々高くなっている現代、明らかな不妊の原因がなくても、加齢による卵巣機能の低下、すなわち卵巣内の卵子の数の低下及び質の低下によって妊娠しにくい女性が増えているとも言われている。さらに卵巣機能が低下することは、肌ツヤなど女性としての外見的な魅力にも影響するとも言われる。 When a woman is born, all of her eggs are already present in her ovaries, but as she ages, the number of eggs decreases and their quality declines. Nowadays, the age at which women get married is increasing year by year, and even if there is no obvious cause of infertility, an increasing number of women have difficulty conceiving due to age-related declines in ovarian function, i.e., a decline in the number and quality of eggs in the ovaries. It is also said that there are Furthermore, a decline in ovarian function is said to affect the appearance of women, such as the luster of their skin.
卵母細胞、卵原幹細胞(OSC)を新たに作り出すことは困難であるが、体外から導入する幹細胞に分化誘導の刺激を与えて卵巣へのホーミング効果を高めることによって卵巣機能の維持または向上を達成できれば、女性が抱える様々な問題の解決につながる。
すなわち、抗老化(アンチエイジング)を図るため、女性の美と健康を保持するため、または回復させるために卵巣機能の維持、向上は欠かせない因子である。
Although it is difficult to newly generate oocytes and oogonia stem cells (OSC), it is possible to maintain or improve ovarian function by stimulating the differentiation of stem cells introduced from outside the body and increasing the homing effect to the ovary. If this can be achieved, it will lead to the resolution of various problems faced by women.
In other words, maintaining and improving ovarian function is an essential factor for anti-aging, maintaining or restoring women's beauty and health.
なお、生殖細胞におけるホーミング効果としては、例えば、特許文献1において精巣機能改善剤が提案されている。特許文献1には、精巣機能改善剤は、精巣内を循環し、痛んだ組織(幹細胞も含む)を見つけると、ホーミング効果により、組織(幹細胞)自身が活性化し修復再生することが記載されている。 As for the homing effect on germ cells, for example, a testicular function improving agent is proposed in Patent Document 1. Patent Document 1 describes that a testicular function improving agent circulates within the testis, and when it finds damaged tissue (including stem cells), the homing effect activates the tissue (stem cells) themselves and repairs and regenerates them. There is.
本発明の目的は、卵巣へのホーミング効果を高めることによって卵巣機能の維持または向上を達成することができる卵巣機能活性化剤、抗老化剤、医薬品、化粧品および食品または飲料を提供することである。 An object of the present invention is to provide an ovarian function activator, an anti-aging agent, a pharmaceutical, a cosmetic, and a food or beverage that can maintain or improve ovarian function by enhancing the homing effect to the ovary. .
本発明者らは、鋭意検討の結果、所定の成分を配合させることにより、上記目的を達成できることを見出し、本発明を完成するに至った。 As a result of extensive studies, the present inventors have discovered that the above object can be achieved by blending predetermined components, and have completed the present invention.
すなわち、本発明によれば、
(1) イソフラボン、エクオール、グルタチオン、L-カルニチン、bFGF、ビタミンC、ビタミンB1、ビタミンB2およびビタミンB6の群からなる少なくとも1種と、幹細胞とを含んでなる卵巣機能活性化剤、
(2) (1)に記載の卵巣機能活性化剤を含有する抗老化剤、
(3) (1)に記載の卵巣機能活性化剤を含有する医薬品、
(4) (1)に記載の卵巣機能活性化剤を含有する化粧品
(5) (1)に記載の卵巣機能活性化剤を含有する食品または飲料
が提供される。
That is, according to the present invention,
(1) An ovarian function activator comprising at least one member of the group consisting of isoflavones, equol, glutathione, L-carnitine, bFGF, vitamin C, vitamin B 1 , vitamin B 2 and vitamin B 6 , and stem cells;
(2) an anti-aging agent containing the ovarian function activator according to (1);
(3) Pharmaceutical products containing the ovarian function activator described in (1),
(4) Cosmetics containing the ovarian function activator according to (1) (5) A food or drink containing the ovarian function activator according to (1) is provided.
本発明によれば、卵巣へのホーミング効果を高めることによって卵巣機能の維持または向上を達成することができる卵巣機能活性化剤、抗老化剤、医薬品、化粧品および食品または飲料が提供される。 According to the present invention, there are provided ovarian function activators, anti-aging agents, pharmaceuticals, cosmetics, and foods or beverages that can maintain or improve ovarian function by enhancing the homing effect to the ovaries.
以下、本発明の卵巣機能活性化剤について説明する。本発明の卵巣機能活性化剤は、イソフラボン、エクオール、グルタチオン、L-カルニチン、bFGF、ビタミンC、ビタミンB1、ビタミンB2およびビタミンB6からなる群(以下、「配合成分」ということがある。)の少なくとも1種と、幹細胞とを含んでなる。 Hereinafter, the ovarian function activating agent of the present invention will be explained. The ovarian function activator of the present invention contains a group consisting of isoflavones, equol, glutathione, L-carnitine, bFGF, vitamin C, vitamin B1, vitamin B2, and vitamin B6 (hereinafter sometimes referred to as "compounded ingredients"). and stem cells.
(配合成分)
本発明の卵巣機能活性化剤は、イソフラボン、エクオール、グルタチオン、L-カルニチン、bFGF、ビタミンC、ビタミンB1、ビタミンB2およびビタミンB6からなる群(以下、「配合成分」ということがある。)の少なくとも1種を含む。
(Ingredients)
The ovarian function activator of the present invention comprises a group consisting of isoflavones, equol, glutathione, L-carnitine, bFGF, vitamin C, vitamin B 1 , vitamin B 2 and vitamin B 6 (hereinafter sometimes referred to as "compounded ingredients"). .).
イソフラボンとしては、3-フェニルクロモンを好ましく用いることができるが、3-フェニルクロモンを基本骨格とするフラボノイドであるイソフラボン類を一部または全部に用いてもよい。 As the isoflavone, 3-phenylchromone can be preferably used, but isoflavones, which are flavonoids having 3-phenylchromone as a basic skeleton, may be used in part or in whole.
エクオールは、具体的には、7-ヒドロキシ-3-(4′-ヒドロキシフェニル)-クロマンを指すものである。ここで、エクオールは、イソフラボン類に属するダイゼインが腸内細菌や消化酵素等により代謝されて生成する物質であり、本発明に用いるエクオールとしては、ダイゼイン類を化学的に還元することにより得られる合成エクオールを用いてもよいし、ダイゼイン類を含む原料を腸内細菌の一種であるエクオール産生菌により代謝させた代謝物を用いてもよい。なお、ダイセイン類としては、ダイゼイン、ジヒドロダイゼイン、ダイゼイン配糖体等が挙げられる。
グルタチオンは、グルタミン酸、システイン、グリシンが、この順番でペプチド結合したトリペプチドである。
L-カルニチンは、リジンとメチオニンから合成される物質である。
Equol specifically refers to 7-hydroxy-3-(4'-hydroxyphenyl)-chroman. Here, equol is a substance produced by metabolizing daidzein, which belongs to isoflavones, by intestinal bacteria, digestive enzymes, etc. Equol used in the present invention is a synthetic substance obtained by chemically reducing daidzein. Equol may be used, or a metabolite obtained by metabolizing a raw material containing daidzeins by equol-producing bacteria, which is a type of intestinal bacteria, may be used. Note that daidzeins include daidzein, dihydrodaidzein, daidzein glycosides, and the like.
Glutathione is a tripeptide consisting of glutamic acid, cysteine, and glycine bonded in this order.
L-carnitine is a substance synthesized from lysine and methionine.
bFGF(塩基性線維芽細胞増殖因子)は、多面的な作用を示す増殖(成長)因子である。なお、塩基性繊維芽細胞増殖因子として、ケラチノサイト成長因子KGF、KGF-2としても知られている塩基性線維芽細胞増殖因子7(FGF-7)、塩基性線維芽細胞増殖因子10(FGF-10)が挙げられる場合もあるが、本発明においては、bFGF(または、FGF2とも呼ばれる。)を用いることが好ましい。 bFGF (basic fibroblast growth factor) is a proliferation (growth) factor that exhibits pleiotropic actions. In addition, basic fibroblast growth factors include basic fibroblast growth factor 7 (FGF-7), also known as keratinocyte growth factor KGF, KGF-2, and basic fibroblast growth factor 10 (FGF-2). 10) may be mentioned, but in the present invention, it is preferable to use bFGF (or also referred to as FGF2).
ビタミンC、ビタミンB1、ビタミンB2およびビタミンB6は、ビタミン類であり、合成されたものを用いてもよいし、天然物から抽出されたものを用いてもよい。 Vitamin C, vitamin B 1 , vitamin B 2 and vitamin B 6 are vitamins, and may be synthesized or extracted from natural products.
以下において、イソフラボン、エクオール、グルタチオン、L-カルニチン、bFGF(塩基性線維芽細胞増殖因子)、ビタミンC、ビタミンB1、ビタミンB2およびビタミンB6を全て含有するものを「Stem-X」という場合があるが、Stem-Xを構成する各成分の配合比は特に限定されない。 In the following, the product containing all isoflavones, equol, glutathione, L-carnitine, bFGF (basic fibroblast growth factor), vitamin C, vitamin B 1 , vitamin B 2 and vitamin B 6 will be referred to as "Stem-X". However, the blending ratio of each component constituting Stem-X is not particularly limited.
(幹細胞)
本発明の卵巣機能活性化剤に用いる幹細胞は、特に限定されないが、間葉系幹細胞、造血幹細胞、神経幹細胞、表皮幹細胞、胚性幹(ES)細胞、胚性生殖(EG)細胞、卵巣由来幹細胞、その他全ての組織幹細胞等を用いることができる。これらのなかでも卵巣由来幹細胞を好ましく用いることができる。また、幹細胞を用いる際に、Exosomeを含む状態で用いることが好ましい。
(stem cells)
Stem cells used in the ovarian function activating agent of the present invention are not particularly limited, but include mesenchymal stem cells, hematopoietic stem cells, neural stem cells, epidermal stem cells, embryonic stem (ES) cells, embryonic reproductive (EG) cells, and ovarian-derived stem cells. Stem cells, all other tissue stem cells, etc. can be used. Among these, ovary-derived stem cells can be preferably used. Furthermore, when using stem cells, it is preferable to use them in a state containing exosomes.
また、幹細胞は、ヒト由来(自家細胞)であってもよいし、異種由来(他家細胞)であってもよい。異種由来の幹細胞の種として、牛、馬、豚、犬、猫、マウス、ラット、羊等が挙げられる。また、自家細胞を用いる場合、自己の細胞を用いてもよいし、他人の細胞を用いてもよい。 Further, the stem cells may be of human origin (autologous cells) or of xenogeneic origin (allogeneic cells). Species of stem cells derived from different species include cows, horses, pigs, dogs, cats, mice, rats, sheep, and the like. In addition, when using autologous cells, the cells may be one's own or cells from another person may be used.
(卵巣機能活性化剤)
本発明の卵巣機能活性化剤は、上記の配合成分と、幹細胞とを含んでなる。また、配合成分と、幹細胞の配合比率は特に限定されないが、好ましくは重量基準で5:95~95:5である。
(ovarian function activator)
The ovarian function activating agent of the present invention contains the above-mentioned ingredients and stem cells. Further, the blending ratio of the ingredients to the stem cells is not particularly limited, but is preferably 5:95 to 95:5 on a weight basis.
本発明の卵巣機能活性化剤は、上記の配合成分と、幹細胞とを一定の比率で配合したものをそのまま用いてもよいし、幹細胞に対して上記の配合成分を添加し、所定の条件にて培養した後に用いてもよい。 The ovarian function activator of the present invention may be used as is by combining the above-mentioned ingredients and stem cells at a certain ratio, or by adding the above-mentioned ingredients to the stem cells and adjusting the mixture under predetermined conditions. It may also be used after culturing.
本発明の卵巣機能活性化剤は、一定量の数種配合試薬(イソフラボン、エクオール、グルタチオン、L-カルニチン、bFGF、ビタミンC、ビタミンB1、ビタミンB2およびビタミンB6からなる群の少なくとも一種)を間葉系幹細胞培養液に添加することで、投与された幹細胞、またはもともと体内に存在する幹細胞が卵母細胞、卵原幹細胞(OSC)様細胞へと誘導され、他の幹細胞を引き連れて卵巣に集まり再生が促され、結果的に卵巣機能を向上させる。 The ovarian function activator of the present invention comprises a certain amount of several combination reagents (at least one of the group consisting of isoflavones, equol, glutathione, L-carnitine, bFGF, vitamin C, vitamin B 1 , vitamin B 2 and vitamin B 6 ). ) to the mesenchymal stem cell culture medium, the administered stem cells or stem cells originally existing in the body are induced to become oocytes and oogonia stem cells (OSC)-like cells, bringing other stem cells with them. It gathers in the ovaries and promotes regeneration, resulting in improved ovarian function.
具体的には卵巣の卵子数の増加、分泌ホルモン(エストロゲン等)量が上昇することで、卵巣機能が上昇した指標となり、さらにその波及効果として皮膚老化、特にたるみを抑制するための皮膚老化抑制効果が期待できる。 Specifically, an increase in the number of eggs in the ovary and an increase in the amount of secreted hormones (estrogen, etc.) are indicators of increased ovarian function, and as a ripple effect, skin aging is inhibited, especially to suppress sagging. You can expect good results.
また、卵巣機能を示す別の指標として、卵巣に残っている卵子の数が何歳相当であるかを表すものがあり、「卵巣年齢」と呼んでいる。卵巣年齢は、卵子の周りの細胞から出るホルモンであるAMH(アンチミューラリアンホルモン)の測定結果に基づいて算出される。また皮膚年齢は水分量、皮膚の粘弾性、皮膚明度、およびゼラチナーゼの上昇によるコラーゲン、エラスチンの破壊に由来するシワによって影響を受ける。 Another indicator of ovarian function is the age equivalent of the number of eggs remaining in the ovary, which is called ``ovarian age.'' Ovarian age is calculated based on the measurement results of AMH (Anti-Mullerian Hormone), a hormone released by cells surrounding the egg. In addition, skin age is influenced by moisture content, skin viscoelasticity, skin brightness, and wrinkles resulting from destruction of collagen and elastin due to increased gelatinase.
卵母細胞、卵原幹細胞(OSC)を新たに作り出すことは困難であるが、本発明によれば、体外から導入する幹細胞に分化誘導の刺激を与えて卵巣へのホーミング効果を高めることによって卵巣機能の維持または向上を図ることができる。 Although it is difficult to newly generate oocytes and oogonia stem cells (OSCs), according to the present invention, stem cells introduced from outside the body are stimulated to induce differentiation, thereby increasing the homing effect to the ovary. Functions can be maintained or improved.
(用途)
本発明の卵巣機能活性化剤は、美容と健康を維持向上させることを目的とするものであり、美容・健康の維持向上のための用途や、抗老化(アンチエイジング)のための用途に用いることができる。即ち、特に女性特有の疾患に対する治療などの用途よりも、前記の用途に用いることができるため、全ての女性だけでなく、肌の若見せ効果の用途を鑑みると、男性も用いることが可能である。
(Application)
The ovarian function activator of the present invention is intended to maintain and improve beauty and health, and is used for purposes of maintaining and improving beauty and health, and for anti-aging purposes. be able to. In other words, it can be used for the above-mentioned purposes rather than for the treatment of diseases peculiar to women, so it can be used not only by all women, but also by men, considering its use for younger-looking skin. be.
また、本発明の卵巣機能活性化剤は、抗老化(アンチエイジング)の作用効果を有するため、これらを目的とした医薬品に配合させることもできる。医薬品としては、予防薬、治療薬のいずれにも用いることができる。 Furthermore, since the ovarian function activator of the present invention has anti-aging effects, it can also be incorporated into pharmaceuticals intended for these purposes. As a pharmaceutical, it can be used as either a preventive drug or a therapeutic drug.
医薬品に配合させる場合には、成分配合品を単独で用いてもよいし、又は一般に製剤上許容される添加剤と共に混和し、製剤化してもよい。また、投与形態としては、錠剤、顆粒剤、カプセル剤、丸剤、散剤、液剤、懸濁剤、乳剤、シロップ剤、エリキシル剤、エキス剤等の経口剤を用いた投与形態または、注射剤、液剤、坐剤、軟膏剤、貼付剤、パップ剤、ローション剤等の非経口剤を用いた投与形態等が挙げられるが、特に制限はなく、治療や予防の目的等に応じて適宜選択することができる。 When incorporated into pharmaceuticals, the component combination product may be used alone, or may be mixed with additives that are generally acceptable in pharmaceutical formulations to form a formulation. In addition, the dosage forms include oral dosage forms such as tablets, granules, capsules, pills, powders, solutions, suspensions, emulsions, syrups, elixirs, and extracts, or injections, Examples include dosage forms using parenteral agents such as liquids, suppositories, ointments, patches, poultices, and lotions; however, there are no particular limitations, and the dosage form should be selected as appropriate depending on the purpose of treatment or prevention. Can be done.
また、錠剤、顆粒剤、丸剤、カプセル剤、散剤の場合には、賦形剤、結合剤、崩壊剤、滑沢剤等の添加剤を含有させることができる。賦形剤としては、デンプン、カルボキシメチルセルロース、白糖、デキストリン、コーンスターチ等を挙げることができる。 Furthermore, in the case of tablets, granules, pills, capsules, and powders, additives such as excipients, binders, disintegrants, and lubricants can be included. Examples of excipients include starch, carboxymethylcellulose, sucrose, dextrin, cornstarch, and the like.
結合剤としては、結晶セルロース、結晶セルロース・カルメロースナトリウム、メチルセルロース、ヒドロキシプロピルセルロース、低置換度ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、ヒドロキシプロピルメチルセルロースフタレート、ヒドロキシプロピルメチルセルロースアセテートサクシネート、カルメロースナトリウム、エチルセルロース、カルボキシメチルエチルセルロース、ヒドロキシエチルセルロース、コムギデンプン、コメデンプン、トウモロコシデンプン、バレイショデンプン、デキストリン、アルファー化デンプン、部分アルファー化デンプン、ヒドロキシプロピルスターチ、プルラン、ポリビニルピロリドン、アミノアルキルメタクリレートコポリマーE、アミノアルキルメタクリレートコポリマーRS、メタクリル酸コポリマーL、メタクリル酸コポリマー、ポリビニルアセタールジエチルアミノアセテート、ポリビニルアルコール、アラビアゴム、アラビアゴム末、寒天、ゼラチン、白色セラック、トラガント、精製白糖、マクロゴールが挙げられる。 As a binder, crystalline cellulose, crystalline cellulose/carmellose sodium, methylcellulose, hydroxypropylcellulose, low-substituted hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, carmellose sodium, ethylcellulose, Carboxymethylethyl cellulose, hydroxyethyl cellulose, wheat starch, rice starch, corn starch, potato starch, dextrin, pregelatinized starch, partially pregelatinized starch, hydroxypropyl starch, pullulan, polyvinylpyrrolidone, aminoalkyl methacrylate copolymer E, aminoalkyl methacrylate copolymer RS , methacrylic acid copolymer L, methacrylic acid copolymer, polyvinyl acetal diethylaminoacetate, polyvinyl alcohol, gum arabic, gum arabic powder, agar, gelatin, white shellac, tragacanth, refined white sugar, and macrogol.
崩壊剤としては、結晶セルロース、メチルセルロース、低置換度ヒドロキシプロピルセルロース、カルメロース、カルメロースカルシウム、カルメロースナトリウム、クロスカルメロースナトリウム、コムギデンプン、コメデンプン、トウモロコシデンプン、バレイショデンプン、部分アルファー化デンプン、ヒドロキシプロピルスターチ、カルボキシメチルスターチナトリウム、トラガントが挙げられる。 Disintegrants include crystalline cellulose, methylcellulose, low-substituted hydroxypropylcellulose, carmellose, carmellose calcium, carmellose sodium, croscarmellose sodium, wheat starch, rice starch, corn starch, potato starch, partially pregelatinized starch, hydroxy Examples include propyl starch, sodium carboxymethyl starch, and tragacanth.
滑沢剤としては、コムギデンプン、コメデンプン、トウモロコシデンプン、ステアリン酸、ステアリン酸カルシウム、ステアリン酸マグネシウム、含水二酸化ケイ素、軽質無水ケイ酸、合成ケイ酸アルミニウム、乾燥水酸化アルミニウムゲル、タルク、メタケイ酸アルミン酸マグネシウム、リン酸水素カルシウム、無水リン酸水素カルシウム、ショ糖脂肪酸エステル、ロウ類、水素添加植物油、ポリエチレングリコールが挙げられる。 As lubricants, wheat starch, rice starch, corn starch, stearic acid, calcium stearate, magnesium stearate, hydrated silicon dioxide, light anhydrous silicic acid, synthetic aluminum silicate, dry aluminum hydroxide gel, talc, aluminum metasilicate Examples include magnesium acid, calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate, sucrose fatty acid ester, waxes, hydrogenated vegetable oil, and polyethylene glycol.
また、液剤、シロップ剤、懸濁剤、乳剤、エリキシル剤の場合には、水や植物油等の一般的に用いられる不活性な希釈剤の他、着色剤、矯味剤、着香剤等を添加剤として含有させてもよい。 In addition, in the case of solutions, syrups, suspensions, emulsions, and elixirs, in addition to commonly used inert diluents such as water and vegetable oil, coloring agents, flavoring agents, flavoring agents, etc. are added. It may also be included as an agent.
また、注射剤の場合には、懸濁液、乳濁液、用時溶解剤等の添加剤を含有させることができる。また、軟膏剤、坐剤の場合には、脂肪、脂肪油、ラノリン、ワセリン、パラフィン、ろう、樹脂、プラスチック、基剤、グリコール類、高級アルコール、水、乳化剤、懸濁化剤等を添加剤として含有させることができる。また、パップ剤の場合にはグリセリン、水、水溶性高分子、吸水性高分子等を添加物として含有させることができる。また、ローション剤の場合には、溶剤、乳化剤、懸濁化剤等を添加剤として含有させることができる。 Furthermore, in the case of injections, additives such as suspensions, emulsions, and solubilizers for use can be included. In the case of ointments and suppositories, additives such as fat, fatty oil, lanolin, petrolatum, paraffin, wax, resin, plastic, base, glycols, higher alcohol, water, emulsifiers, suspending agents, etc. It can be contained as. In the case of poultices, glycerin, water, water-soluble polymers, water-absorbing polymers, etc. can be contained as additives. Further, in the case of a lotion, a solvent, an emulsifier, a suspending agent, etc. can be included as additives.
また、本発明の卵巣機能活性化剤を化粧品に配合することもできる。化粧品としては、化粧水、乳液、洗顔料、クレンジング、美容液、クリーム、ファンデーション、アイブロー、マスカラ、アイシャドウ、アイライン、口紅、グロス、チーク、白粉、マニキュア等が挙げられる。また、化粧品の形態としては、液体、クリーム、固体、スティック、粉末等の形態を採用することができる。 Moreover, the ovarian function activator of the present invention can also be blended into cosmetics. Cosmetics include lotions, milky lotions, face washes, cleansers, serums, creams, foundations, eyebrows, mascara, eye shadows, eyeliners, lipsticks, glosses, cheeks, white powder, nail polish, and the like. Furthermore, the cosmetics may be in the form of liquid, cream, solid, stick, powder, or the like.
また、本発明の卵巣機能活性化剤を、食品や飲料等に配合させてもよい。食品としては、パン類、麺類、菓子類、食肉加工品、魚介加工品、冷凍食品、ゼリー類、アイスクリーム類、乳製品、各種調味料等が挙げられる。また、一般食品の他、特定保健用食品、医薬部外品、健康食品、サプリメントにも配合させることができる。飲料としては、清涼飲料水、乳飲料、酒類、茶、紅茶飲料、コーヒー、果汁飲料、炭酸飲料、ミネラルウォーター類、果実・野菜飲料等が挙げられる。
また、本発明の卵巣機能活性化剤を配合させた食品や飲料を、錠剤、カプセル剤、シロップ等の経口投与製剤と同様の形態としてもよい。
Furthermore, the ovarian function activator of the present invention may be incorporated into foods, drinks, and the like. Examples of foods include breads, noodles, confectionery, processed meat products, processed seafood products, frozen foods, jellies, ice creams, dairy products, and various seasonings. In addition to general foods, it can also be incorporated into foods for specified health uses, quasi-drugs, health foods, and supplements. Beverages include soft drinks, milk drinks, alcoholic beverages, tea, black tea drinks, coffee, fruit juice drinks, carbonated drinks, mineral waters, fruit and vegetable drinks, and the like.
Furthermore, foods and drinks containing the ovarian function activating agent of the present invention may be in the same form as oral preparations such as tablets, capsules, and syrups.
また、本発明の卵巣機能活性化剤を配合させた食品や飲料を製造する際に、本発明の効果を妨げない範囲で必要に応じて、甘味料、着色料、保存料、増粘剤、安定化剤、ゲル化剤、酸化防止剤、発色剤、漂白剤、乳化剤、膨張剤、酸味料、光沢剤、香料等の添加剤;溶剤;油を添加してもよい。これらの添加剤は各種類を単独で用いてもよいし、二種類以上を組み合わせて用いてもよい。 In addition, when producing foods and beverages containing the ovarian function activator of the present invention, sweeteners, colorants, preservatives, thickeners, Additives such as stabilizers, gelling agents, antioxidants, coloring agents, bleaching agents, emulsifiers, swelling agents, acidulants, brighteners, fragrances, solvents, and oils may be added. Each type of these additives may be used alone, or two or more types may be used in combination.
上記食品や飲料中に配合される本発明の卵巣機能活性化剤の割合は、使用目的に応じて適宜調整することができるが、上記食品や飲料中に配合される成分配合品の割合は、好ましくは0.01~20重量%、より好ましくは0.01~15重量%、さらに好ましくは0.1~10重量%である。 The proportion of the ovarian function activator of the present invention blended into the above foods and drinks can be adjusted as appropriate depending on the purpose of use, but the proportion of the ingredient combination product blended into the above foods and drinks: The amount is preferably 0.01 to 20% by weight, more preferably 0.01 to 15% by weight, and even more preferably 0.1 to 10% by weight.
以下に、実施例を挙げて本発明を説明するが、本発明はこれに限定されるものではない。
イソフラボン、エクオール、グルタチオン、L-カルニチン、bFGF、ビタミンC、ビタミンB1、ビタミンB2およびビタミンB6を超純水または生理食塩水に溶解させ「Stem-X」溶液の準備をした。
The present invention will be explained below with reference to Examples, but the present invention is not limited thereto.
A "Stem-X" solution was prepared by dissolving isoflavones, equol, glutathione, L-carnitine, bFGF, vitamin C, vitamin B 1 , vitamin B 2 and vitamin B 6 in ultrapure water or physiological saline.
老齢マウス(ICR;25週令、雌性)に「Stem-X」溶液及びマウス卵巣由来幹細胞懸濁液を尾静脈から0.5mlで投与した。同じく幹細胞のみ、溶液のみの投与群も作成した。無投与群マウスも含めて4群のマウスを同様の飼育条件下で3週間、及び6週間経過観察した。6週間群は3週間経過した段階で、1回目と同様の投与を追加実施した(2回目投与)。観察期間中、同一の固形飼料と飲料水は自由に摂取させた。3週間、及び6週間経過した各群のマウスから採尿し、尿中エストロゲン量(エストロン、17β-エストラジオール、エストリオール)をそれぞれELISA法 ( Estrone; K031-H1, 17β-Estradiol; K030-H1, Estriol; K064-H1, 全てArbor Assays社)にて測定した。また眼静脈叢、及びネンブタール麻酔下で頸静脈採血後、血中のAMH(アンチミューラリアンホルモン)量をAnti-Mullerian Hormone (AMH) ELISA Kit (Cloud-Clone Corp. Wuhan; CEA228BO)にて測定した。 The "Stem-X" solution and mouse ovary-derived stem cell suspension were administered in 0.5 ml via the tail vein to old mice (ICR; 25 weeks old, female). Similarly, groups to which only stem cells and only solution were administered were also created. Four groups of mice, including mice in the non-administration group, were observed for 3 weeks and 6 weeks under the same breeding conditions. In the 6-week group, after 3 weeks had elapsed, an additional administration similar to the first administration was conducted (second administration). During the observation period, the same chow and drinking water were available ad libitum. Urine was collected from mice in each group after 3 weeks and 6 weeks, and the amount of urinary estrogen (oestrone, 17β-estradiol, estriol) was measured by ELISA method (Estrone; K031-H1, 17β-estradiol; K030-H1, Estriol). ; K064-H1, all measured using Arbor Assays). In addition, after collecting blood from the ophthalmic plexus and jugular vein under Nembutal anesthesia, the amount of AMH (anti-Mullerian hormone) in the blood was measured using the Anti-Mullerian Hormone (AMH) ELISA Kit (Cloud-Clone Corp. Wuhan; CEA228BO). .
マウスの性周期は4~5日とされることから、尿中エストロゲン量は、3週目(6wks)、6週目(6wks)、それぞれ21日~25日まで、及び42日~46日までの5日間連続で測定し、同一週令の非投与マウスの値を100%とした際の%で表示した。AMHの測定は21日目と42日目は眼静脈叢採血により、25日目と46日目は頸静脈採血により行った。(3週間実験群と6週間実験群はそれぞれ別のマウスで実施した) Since the estrous cycle of mice is said to last 4 to 5 days, the amount of urinary estrogen was measured at the 3rd week (6wks), the 6th week (6wks), from the 21st to the 25th, and from the 42nd to the 46th, respectively. Measurements were made for 5 consecutive days, and expressed as a percentage, with the value of non-administered mice of the same week taken as 100%. AMH measurements were performed by ophthalmic venous plexus blood sampling on the 21st and 42nd days, and by jugular vein blood sampling on the 25th and 46th days. (The 3-week experimental group and the 6-week experimental group were conducted using different mice.)
また、実験開始から25日目(Day 25)と45日目(day 45)実験終了時のマウスから後背部皮膚を採取し、水分含有量を常圧加熱乾燥法(MX-50; 株式会社エーアンドデイ製)にて、皮膚ヒアルロン酸量をELISA法(Hyaluronan Quantikine ELISA Kit; R&D systems製)にて測定した。ヒアルロン酸測定用皮膚は個体ごとに,凍結粉砕し、液体窒素下で皮膚を粉状になるまで粉砕した。得られた凍結粉砕皮膚をエタノール(99.5%)中、4°Cの条件にて一晩脱脂を行った。次にプロテアーゼ阻害剤入りPBS(-)(5 mM ベンズアミジン塩酸塩/10 mM EDTA-2Na/0.1 M アミノヘキサン酸をPBS(-)に溶解,pH7.4)を加え、4°Cで3~4時間ローテーターにより回転させ、遠心分離し、上清を除去した後、沈殿物をプロテアーゼ阻害剤入りPBS(-)に溶解し、ELISA用検体とした。 In addition, the skin from the back of the mouse was collected on Day 25 from the start of the experiment and at the end of the experiment on Day 45, and the water content was determined using normal pressure heat drying method (MX-50; A&D Co., Ltd.). The amount of hyaluronic acid in the skin was measured using the ELISA method (Hyaluronan Quantikine ELISA Kit; manufactured by R&D systems). The skin for measuring hyaluronic acid was freeze-ground for each individual, and the skin was ground under liquid nitrogen until it became powder. The obtained frozen and crushed skin was defatted in ethanol (99.5%) at 4°C overnight. Next, add PBS(-) containing protease inhibitor (5 mM benzamidine hydrochloride/10 mM EDTA-2Na/0.1 M aminohexanoic acid dissolved in PBS(-), pH 7.4) and incubate at 4°C for 3 to 4 hours. After rotating with a rotator for a time, centrifuging, and removing the supernatant, the precipitate was dissolved in PBS(-) containing a protease inhibitor and used as a sample for ELISA.
尿中エストロゲン量の測定結果を図1に、血中のAMH量の測定結果を図2に、皮膚水分量およびヒアルロン酸量の測定結果を図3に、それぞれ示した。なお、図1~3における実験群は以下のとおりである。
1群;生理食塩水投与群
2群;マウス卵巣由来幹細胞懸濁液
3群;Stem-X溶液投与群
4群;マウス卵巣由来幹細胞懸濁液及びStem-X溶液投与群
The measurement results of the amount of estrogen in the urine are shown in FIG. 1, the results of the measurement of the amount of AMH in the blood are shown in FIG. 2, and the results of the measurement of the amount of skin moisture and hyaluronic acid are shown in FIG. 3, respectively. The experimental groups in FIGS. 1 to 3 are as follows.
Group 1; Physiological saline administration group 2; Mouse ovary-derived stem cell suspension group 3; Stem-X solution administration group 4; Mouse ovary-derived stem cell suspension and Stem-X solution administration group
図1に示すように尿中エストロゲン(エストロン,17β-エストラジオール,エストリオール)の測定結果は、3週目(3wks)、6週目(6wks)においてほぼ同様であり、1群よりも、2群(マウス卵巣由来幹細胞懸濁液を単独投与した群)および3群(Stem-X溶液を単独投与した群)の方がエストロゲン値が上昇していた。さらに、2群および3群よりも、4群(マウス卵巣由来幹細胞懸濁液及びStem-X溶液の両方を投与した群)の方がエストロゲン値が上昇していた。 As shown in Figure 1, the measurement results of urinary estrogen (estrone, 17β-estradiol, estriol) were almost the same at 3 weeks (3wks) and 6 weeks (6wks), and group 2 was more effective than group 1. (Group to which mouse ovary-derived stem cell suspension was administered alone) and Group 3 (Group to which Stem-X solution was administered alone) had higher estrogen levels. Furthermore, the estrogen level was higher in Group 4 (the group to which both the mouse ovary-derived stem cell suspension and Stem-X solution were administered) than in Groups 2 and 3.
図2に示すように、血清中AMH量の測定結果は、尿中エストロゲンと同様の傾向で、1群よりも、2群(マウス卵巣由来幹細胞懸濁液を単独投与した群)および3群(Stem-X溶液を単独投与した群)の方がAMH量が上昇していた。さらに、2群および3群よりも、4群(マウス卵巣由来幹細胞懸濁液及びStem-X溶液の両方を投与した群)の方がAMH量が上昇していた。また、6週目(6wks;2回投与群)のほうが、3週目(3wks;1回投与)よりも高い結果が示された。このことから、定期的に投与する優位性が考えられた。 As shown in Figure 2, the measurement results for the amount of AMH in serum had the same tendency as that for urinary estrogen, and were higher in group 2 (the group in which the mouse ovary-derived stem cell suspension was administered alone) and group 3 (in which the mouse ovary-derived stem cell suspension was administered alone) than in group 1. The amount of AMH was higher in the group to which Stem-X solution was administered alone. Furthermore, the amount of AMH was higher in Group 4 (the group to which both the mouse ovary-derived stem cell suspension and Stem-X solution were administered) than in Groups 2 and 3. Furthermore, higher results were shown in the 6th week (6wks; 2-time administration group) than in the 3rd week (3wks; 1-time administration). This suggests the advantage of regular administration.
図3に示すように、皮膚水分量およびヒアルロン酸量共に3群、4群で高い値が示され、それは3週目(3wks)、6週目(6wks)共に同様の傾向であった。2回投与したことで、4群のヒアルロン酸量がもっとも高値であった。 As shown in FIG. 3, both the skin moisture content and the hyaluronic acid content were high in Groups 3 and 4, and this trend was the same at 3 weeks (3wks) and 6 weeks (6wks). By administering the drug twice, the amount of hyaluronic acid in Group 4 was the highest.
実験期間を通して外見上マウスの体毛は1群よりも2、3、4群で明らかに滑らかであった。その他、マウス体重や卵巣重量には各群間で差異は認められなった。さらに長期間、繰り返し投与することによって変化が認められる可能性はあるが、今回の2回投与においてすでに体内の指標(尿、血液)では良好な方向に改善されたことが確認された。 The body hair of the mice was apparently smoother in groups 2, 3, and 4 than in group 1 throughout the experimental period. In addition, no differences were observed in mouse body weight or ovary weight between groups. Although it is possible that changes may be observed with repeated administration over a longer period of time, it has been confirmed that internal indicators (urine, blood) have already improved in the positive direction after the two administrations.
これらの結果から、本試薬、「Stem-X」は体外で幹細胞培養液に添加した場合、または幹細胞と共に体内に導入された場合に、幹細胞を卵巣に向かわせること(ホーミング効果)や、体内に元々存在していた幹細胞を呼び寄せる、あるいは卵巣に直接的に働きかけるなどして卵巣機能を高めることが想定された。さらに「Stem-X」は体内循環による副作用として皮膚老化を抑制することも示唆された。 Based on these results, this reagent, "Stem-X", when added to a stem cell culture medium outside the body or introduced into the body together with stem cells, has the ability to direct stem cells to the ovaries (homing effect) and cause them to enter the body. It was assumed that ovarian function would be enhanced by attracting pre-existing stem cells or acting directly on the ovaries. Furthermore, it has been suggested that "Stem-X" suppresses skin aging as a side effect of circulation in the body.
Claims (5)
幹細胞と
を含んでなる卵巣機能活性化剤。 at least one member of the group consisting of isoflavones, equol, glutathione, L-carnitine, bFGF, vitamin C, vitamin B 1 , vitamin B 2 and vitamin B 6 ;
An ovarian function activator containing stem cells.
A food or drink containing the ovarian function activator according to claim 1.
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