JP5176127B2 - Preventive or ameliorating agent for visual impairment - Google Patents
Preventive or ameliorating agent for visual impairment Download PDFInfo
- Publication number
- JP5176127B2 JP5176127B2 JP2007001909A JP2007001909A JP5176127B2 JP 5176127 B2 JP5176127 B2 JP 5176127B2 JP 2007001909 A JP2007001909 A JP 2007001909A JP 2007001909 A JP2007001909 A JP 2007001909A JP 5176127 B2 JP5176127 B2 JP 5176127B2
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- Prior art keywords
- retinal
- extract
- vitamin
- keihi
- preventive
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- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Description
本発明は、長期間服用しても安全で有効な視覚機能障害の予防または改善に有効な医薬品、医薬部外品または食品に関する。 The present invention relates to a pharmaceutical, a quasi-drug, or a food effective for preventing or improving visual dysfunction that is safe and effective even after long-term use.
高齢化社会、コンピュータ社会の到来とともに、視覚機能の低下が問題となっている。網膜の黄斑は、視力の中心を担っており、健全な視覚機能を維持する上で必要不可欠な組織である。その一方で、網膜は常に光に曝されているため、酸化ストレスを受けやすく障害を受けやすい部位である。網膜の障害は、眼精疲労、視力低下、老視、かすみ目、視野低下、暗順応低下、加齢黄斑変性症または網膜色素変性症といった症状で現れ、著しい視覚機能の低下を引き起こす。その結果、筋肉、神経等に過剰な負荷が生じ、眼精疲労を引き起こす（非特許文献１参照）。 With the arrival of an aging society and a computer society, deterioration of visual functions has become a problem. The macula of the retina plays a central role in visual acuity and is an indispensable tissue for maintaining a healthy visual function. On the other hand, since the retina is always exposed to light, it is a site susceptible to oxidative stress and easily damaged. Retinal disorders appear as symptoms such as eye strain, decreased visual acuity, presbyopia, blurred vision, visual field loss, dark adaptation, age-related macular degeneration, or retinitis pigmentosa, and cause significant visual impairment. As a result, an excessive load is generated on muscles, nerves, and the like, causing eye strain (see Non-Patent Document 1).
眼に入った光は、角膜、水晶体、硝子体を通って網膜へと到達する。中でも、この光を捉える部位である網膜が視覚機能の中心を担っている。網膜は、眼球の内側から内境界膜、視神経線維層、神経節細胞層、内網状層、内顆粒層、外網状層、外顆粒層、外境界膜、視細胞層、網膜色素上皮層の１０層からなる。 The light that enters the eye reaches the retina through the cornea, lens, and vitreous. Above all, the retina, the part that captures this light, plays a central role in visual function. The retina is composed of the inner boundary membrane, the optic nerve fiber layer, the ganglion cell layer, the inner reticular layer, the inner granule layer, the outer reticular layer, the outer granule layer, the outer boundary membrane, the photoreceptor layer, and the retinal pigment epithelium layer from the inside of the eyeball. Consists of layers.
これら網膜の各部位の機能を評価する方法としては、電気生理学的な手法である網膜電図が広く用いられている。網膜電図はａ波、ｂ波、ｃ波および律動様小波の４つの波形に大きく分類される。ａ波は視細胞を、ｂ波はミュラー細胞や双曲細胞を、ｃ波は網膜色素上皮細胞を、律動様小波はアマクリン細胞を起源とする波形を示している。つまり、網膜電図を測定することにより、網膜の障害部位を特定することができ、視覚機能を評価することが可能である。また、これらの波形は光暴露によっても減弱することが知られている（非特許文献２参照）。 As a method for evaluating the function of each part of the retina, an electroretinogram which is an electrophysiological technique is widely used. Electroretinograms are roughly classified into four waveforms: a-wave, b-wave, c-wave and rhythm-like wavelet. The a wave indicates a waveform originating from a photoreceptor cell, the b wave indicates a Muller cell or hyperbolic cell, the c wave indicates a retinal pigment epithelial cell, and a rhythmic wavelet indicates a waveform originating from an amacrine cell. In other words, by measuring the electroretinogram, it is possible to identify the damaged part of the retina and evaluate the visual function. Further, it is known that these waveforms are attenuated by light exposure (see Non-Patent Document 2).
網膜障害モデル動物としても、光障害モデルが広く用いられており、光照射を行うことにより、網膜電図の各波形が減弱するとともに、網膜にアポトーシスが生じることが知られている（非特許文献３及び４参照）。近年、網膜疾患の原因の一つとして、単なる光による酸化ストレスではなく、青色光による網膜細胞のアポトーシスが注目されている。網膜に青色光が照射されると網膜素上皮細胞に蓄積するリポフスチンと特異的に反応し、網膜色素上皮細胞のアポトーシスを誘導することが知られている（非特許文献５及び６参照）。 As a retinal damage model animal, a light damage model is widely used, and it is known that, when light irradiation is performed, each waveform of an electroretinogram is attenuated and apoptosis occurs in the retina (Non-Patent Document). 3 and 4). In recent years, as a cause of retinal diseases, apoptosis of retinal cells by blue light has attracted attention, not just oxidative stress by light. It is known that when the retina is irradiated with blue light, it specifically reacts with lipofuscin accumulated in the retinoid epithelial cells to induce apoptosis of the retinal pigment epithelial cells (see Non-Patent Documents 5 and 6).
すなわち網膜電図の測定、青色光による網膜細胞のアポトーシスの測定により、眼精疲労、視力低下、老視、かすみ目、視野低下、暗順応低下、加齢黄斑変性症または網膜色素変性症の評価をすることができる。 That is, by measuring electroretinogram and measuring apoptosis of retinal cells by blue light, evaluation of eyestrain, visual acuity, presbyopia, blurred vision, visual field loss, dark adaptation, age-related macular degeneration or retinitis pigmentosa Can do.
網膜は、一度障害を受けると自然に再生することができない組織であり、現在のような高齢化社会、コンピュータ社会において、長期間の光刺激から網膜を保護することは質の高いＱＯＬを維持する上で必要不可欠である。 The retina is an organization that cannot be naturally regenerated once it is damaged. In today's aging society and computer society, protecting the retina from long-term light stimulation maintains a high quality of life. Indispensable above.
天然物由来の網膜障害予防剤としては、茶の抽出物を有効成分とした網膜障害予防剤（特許文献１及び２参照）が知られている。また、一部の抗酸化物質が網膜疾患に有効との報告もあるが、逆に負の相関があるとの報告もあり、未だ、十分効果のある予防及び治療薬は存在していない（非特許文献７）。 As a retinal disorder preventive agent derived from a natural product, a retinal disorder preventive agent containing tea extract as an active ingredient is known (see Patent Documents 1 and 2). There are reports that some antioxidants are effective for retinal diseases, but there is also a report that there is a negative correlation, and there are still no prophylactic and therapeutic drugs that are sufficiently effective (non- Patent Document 7).
ケイヒ（桂皮）はクスノキ科（Lauraceae）のケイヒ（Cinnamomum Cassia）およびその他同属植物の主に樹皮を乾燥したものであり、健胃、駆風、矯味、発汗、解熱、鎮痛薬として、中枢神経系の興奮を鎮静し、水分代謝を調節し、体表の毒を去り、これを和解する作用があることから、頭痛、発熱、のぼせ、感冒、身体疼痛などに対する効果が知られている（非特許文献８）。また、ケイヒの網膜のアポトーシス抑制作用や網膜障害に由来する視覚機能障害に対する効果は知られていない。 Caihi (Cinnamon) is mainly dried bark of Cinnamomum Cassia of Lauraceae and other related genera. It is a central nervous system as a healthy stomach, gust, taste, sweating, antipyretic, analgesic. It is known to have effects on headaches, fever, hot flashes, colds, body pain, etc. Reference 8). Moreover, Keihi's effect on the retinal apoptosis inhibition and visual dysfunction derived from retinal damage is not known.
レイシカクは，ムクロジ科（Sapindaceae）のレイシ（Litchi Chinensis）の果実の種子を乾燥したものであり、収斂、鎮痛、消炎薬として、瘰癧、胃痛、腸疝痛、睾丸炎腫痛、咳などに対する効果が知られている（非特許文献９）。また、レイシカクのアポトーシスに関する知見としては、ライチ抽出物を有効成分とするアポトーシス誘導剤（特許文献４）が知られているが、網膜に対するアポトーシス抑制作用や網膜障害に由来する視覚機能障害に対する効果は知られていない。 Ganoderma is a dried seed of the fruit of Sapindaceae Litchi Chinensis, and is effective as an astringent, analgesic, anti-inflammatory agent for epilepsy, stomach pain, bowel colic, testicular inflammation, cough, etc. It is known (Non-Patent Document 9). Moreover, as a knowledge about the apoptosis of lychee, an apoptosis inducer (Patent Document 4) containing a lychee extract as an active ingredient is known. unknown.
本発明は、長期間服用しても安全で有効な視覚機能障害の予防または改善剤を提供することを目的とする。 An object of the present invention is to provide a preventive or ameliorating agent for visual dysfunction that is safe and effective even when taken for a long period of time.
本発明者らは、上記課題を解決するために鋭意検討を行った結果、ケイヒおよびレイシカクエキスが光照射により生じる網膜障害モデルラットに対する視覚機能障害の予防効果及び網膜アポトーシス抑制効果を有することを見出し、本発明を完成した。すなわち、本発明は、
（１）ケイヒおよびレイシカクから選ばれる１種または２種を配合したことを特徴とする視覚機能障害の予防または改善剤、
（２）視覚機能障害が網膜障害である（１）に記載の予防または改善剤、
（３）ケイヒおよびレイシカクから選ばれる１種または２種を配合したことを特徴とする網膜アポトーシス抑制剤、
である。
As a result of intensive studies to solve the above problems, the present inventors have found that Keihi and Reishikaku extract have a visual dysfunction prevention effect and a retinal apoptosis inhibition effect on retinal disorder model rats caused by light irradiation. The headline and the present invention were completed. That is, the present invention
(1) A preventive or ameliorating agent for visual dysfunction characterized by comprising one or two selected from Keihi and Reishikaku,
(2) The preventive or ameliorating agent according to (1), wherein the visual dysfunction is a retinal disorder,
(3) A retinal apoptosis inhibitor comprising one or two selected from Keihi and Reishikaku,
It is.
本発明により、光などにより生じる視覚機能障害の予防または改善に有効で安全性の高い医薬品、医薬部外品または食品の提供が可能になった。 According to the present invention, it is possible to provide a highly safe pharmaceutical, quasi-drug, or food that is effective in preventing or improving visual dysfunction caused by light or the like.
本発明に用いるケイヒおよびレイシカクは、そのまま生薬末として、または水、有機溶媒、それらの混合溶媒などで抽出したエキスとして使用できる。またエキスは、乾燥エキス、流エキスなどを用いることもできる。 Keihi and Reishikaku used in the present invention can be used as a crude drug powder as they are or as an extract extracted with water, an organic solvent, a mixed solvent thereof or the like. As the extract, a dry extract, a flow extract, or the like can be used.
本発明に用いるケイヒはクスノキ科（Lauraceae）のCinnamomum Cassiaおよびその他同属植物の樹皮又は周皮の一部を除いたもの、枝、果実、葉などを使用することができる。好ましくは、Cinnamomum Cassia Blume又はその他同属植物の樹皮又は周皮の一部を除いたものである。 As the cinnamon used in the present invention, Cinnamomum Cassia of Lauraceae and other bark or peripheries of other plants belonging to the same genus, branches, fruits, leaves and the like can be used. Preferably, Cinnamomum Cassia Blume or other bark of the same genus plant is excluded.
本発明に用いるレイシカクは、ムクロジ科（Sapindaceae）のレイシ（Litchi Chinensis）の果実及びその種子を使用することができる。好ましくは、成熟果実の種子である。 As the lychee used in the present invention, the fruit of Litchi Chinensis of Sapindaceae and its seed can be used. Preferably, it is a seed of a mature fruit.
ケイヒおよびレイシカクの抽出に用いる溶媒は特に限定されず、例えば、抽出溶媒として水、エタノール、メタノール、プロピレングリコール、１，３−ブチレングリコール、酢酸エチル、ベンゼン、ヘキサン、エチルエーテル、アセトン、塩化メチレンなどがあげられる。またこれら溶媒は、一種または二種以上を組み合わせて使用することができる。そのうちで、好ましい抽出溶媒としては、水、エタノールまたはそれらの混合溶媒が好ましく、有効成分を効率良く抽出するためには、エタノール濃度１５〜８５質量％の含水エタノールがさらに好ましい。 Solvents used for extraction of Keihi and Reishikaku are not particularly limited. For example, water, ethanol, methanol, propylene glycol, 1,3-butylene glycol, ethyl acetate, benzene, hexane, ethyl ether, acetone, methylene chloride, etc. are used as extraction solvents. Can be given. These solvents can be used alone or in combination of two or more. Among these, water, ethanol, or a mixed solvent thereof is preferable as a preferable extraction solvent, and hydrous ethanol having an ethanol concentration of 15 to 85% by mass is more preferable in order to efficiently extract an active ingredient.
本発明で用いるケイヒおよびレイシカクの投与量は、年齢、性別、体重などを考慮して適宜増減できるが、通常、成人で1日、原生薬換算量として、経口剤の場合１ｍｇ〜５０ｇ、好ましくは１００ｍｇ〜１５ｇであり、非経口剤の場合０．０１ｍｇ〜５ｇ、好ましくは０．０５ｍｇ〜２ｇである。 The dose of Keihi and Reishikaku used in the present invention can be appropriately increased or decreased in consideration of age, sex, body weight, etc., but is usually 1 mg to 50 g in the case of an oral drug as an active ingredient equivalent to a daily drug substance, preferably 100 mg to 15 g, and 0.01 mg to 5 g, preferably 0.05 mg to 2 g in the case of a parenteral preparation.
本発明においては、より優れた効果の点から、さらにビタミン類を添加すると好ましい。ビタミン類としてはビタミンＡ、ビタミンＢ群、ビタミンＣ、ビタミンＤ、ビタミンＥ、ビタミンＨ、ビタミンＫおよびその誘導体等があげられ、これらの一種または二種以上を配合することができ、より好ましいものとしては、ビタミンＢ群があげられる。 In the present invention, it is preferable to further add vitamins from the viewpoint of more excellent effects. Examples of vitamins include vitamin A, vitamin B group, vitamin C, vitamin D, vitamin E, vitamin H, vitamin K, and derivatives thereof, and more preferably one or more of these can be added. Examples include vitamin B group.
本発明に使用されるビタミンＢ群としては、ビタミンＢ１、ビタミンＢ２、ビタミンＢ６、ビタミンＢ１２、ナイアシン、パントテン酸、葉酸、ニコチン酸等があげられ、ビタミンＢ１、ビタミンＢ６、ビタミンＢ１２、葉酸がより好ましく、ビタミンＢ６が特に好ましい。 Examples of the vitamin B group used in the present invention include vitamin B1, vitamin B2, vitamin B6, vitamin B12, niacin, pantothenic acid, folic acid, nicotinic acid and the like, and vitamin B1, vitamin B6, vitamin B12, and folic acid are more preferable. Vitamin B6 is particularly preferred.
本発明に使用されるビタミンＢ１としては、塩酸チアミン、硝酸チアミン、硝酸ビスチアミン、チアミンジスルフィド、チアミンジセチル硫酸エステル塩、塩酸ジセチアミン、塩酸フルスルチアミン、オクトチアミン、シコチアミン、ビスイブチアミン、ビスベンチアミン、フルスルチアミン、プロスルチアミン、ベンフォチアミン等があげられる。 Vitamin B1 used in the present invention includes thiamine hydrochloride, thiamine nitrate, bisthiamine nitrate, thiamine disulfide, thiamine dicetyl sulfate ester, dicetiamine hydrochloride, fursultiamine hydrochloride, octothiamine, chicotiamine, bisbutiamine, bisbenchamine , Fursultiamine, prosultiamine, benfotiamine and the like.
本発明に使用されるビタミンＢ６としては、塩酸ピリドキシン、リン酸ピリドキサール等があげられる。 Examples of vitamin B6 used in the present invention include pyridoxine hydrochloride and pyridoxal phosphate.
本発明に使用されるビタミンＢ１２としては、メコバラミン、塩酸ヒドロキソコバラミン、酢酸ヒドロキソコバラミン、シアノコバラミン、ヒドロキソコバラミン等があげられる。 Examples of vitamin B12 used in the present invention include mecobalamin, hydroxocobalamin hydrochloride, hydroxocobalamin acetate, cyanocobalamin, hydroxocobalamin and the like.
本発明は、発明の効果を損なわない質的および量的範囲で、アミノ酸、賦形剤、pH調整剤、清涼化剤、懸濁化剤、消泡剤、粘稠剤、溶解補助剤、崩壊剤、結合剤、滑沢剤、抗酸化剤、コーティング剤、着色剤、矯味矯臭剤、界面活性剤、可塑剤、香料などを配合することができ、常法により、錠剤、液剤、カプセル剤、散剤、顆粒剤、チュアブル錠、ドライシロップ剤、点眼剤、点鼻剤、クリーム剤、ローション剤、ゲル剤、軟膏剤、貼付剤、乳剤などの経口または非経口製剤とすることができる。 The present invention includes amino acids, excipients, pH adjusting agents, cooling agents, suspending agents, antifoaming agents, thickeners, solubilizers, disintegrations within the qualitative and quantitative ranges that do not impair the effects of the invention. Agents, binders, lubricants, antioxidants, coating agents, coloring agents, flavoring agents, surfactants, plasticizers, fragrances, etc. can be blended, and tablets, liquids, capsules, Oral or parenteral preparations such as powders, granules, chewable tablets, dry syrups, eye drops, nasal drops, creams, lotions, gels, ointments, patches and emulsions can be used.
以下に実施例および試験例をあげ、本発明をさらに具体的に説明する。 The following examples and test examples further illustrate the present invention.
原生薬量５００ｇのケイヒを細切後、１０倍量の５０％エタノールを加え、沸騰状態で３０分間加熱抽出し、濾過後減圧下でエタノールを留去し、さらに、濃縮を行うことによりエキスを得た。 After chopping cinnamon with 500 g of the drug substance, add 10 times the amount of 50% ethanol, heat extract for 30 minutes in a boiling state, distill off ethanol under reduced pressure after filtration, and further concentrate to extract the extract. Obtained.
原生薬量５００ｇのケイヒを細切後、１０倍量の水を加え、１００℃で３０分間加熱抽出し、濾過後減圧下で濃縮を行うことによりエキスを得た。 After chopping cinnamon of 500 g of the drug substance, 10 times the amount of water was added, extracted by heating at 100 ° C. for 30 minutes, filtered and concentrated under reduced pressure to obtain an extract.
原生薬量５００ｇのレイシカクを細切後、１０倍量の５０％エタノールを加え、沸騰状態で３０分間加熱抽出し、濾過後減圧下でエタノールを留去し、さらに、濃縮を行うことによりエキスを得た。 After shredding 500 g of the raw drug amount of garlic, add 10 times the amount of 50% ethanol, heat extract for 30 minutes in a boil, filter and evaporate the ethanol under reduced pressure, and further concentrate to extract the extract. Obtained.
実施例３で得られたレイシカクエキスに等量のデキストリンを添加し、乾燥粉末を得た。 An equivalent amount of dextrin was added to the lychee extract obtained in Example 3 to obtain a dry powder.
原生薬量５００ｇのレイシカクを細切後、１０倍量の水を加え、１００℃で３０分間加熱抽出し、濾過後減圧下で濃縮を行うことによりエキスを得た。 After mincing the 500 g of the crude drug amount, 10 times the amount of water was added, extracted by heating at 100 ° C. for 30 minutes, filtered and concentrated under reduced pressure to obtain an extract.
実施例１で得られたケイヒエキスを１．６ｇ秤量し、精製水を加え、全量１００mLとし、エキス濃度が原生薬換算１．０ｇ／１０mLとなる液剤を調整した。 1.6 g of the cinnamon extract obtained in Example 1 was weighed, purified water was added to make a total volume of 100 mL, and a liquid preparation having an extract concentration of 1.0 g / 10 mL in terms of drug substance was prepared.
実施例３で得られたレイシカクエキスを１．３ｇ秤量し、精製水を加え、全量１００mLとし、エキス濃度が原生薬換算１．０ｇ／１０mLとなる液剤を調整した。 1.3 g of the lychee extract obtained in Example 3 was weighed, purified water was added to make a total volume of 100 mL, and a liquid preparation having an extract concentration of 1.0 g / 10 mL in terms of drug substance was prepared.
実施例１で得られたケイヒエキスを０．８ｇ、実施例３で得られたレイシカクエキスを０．６５ｇ秤量し、精製水を加え、全量１００mLとし、エキス濃度が原生薬換算１．０ｇ／１０mLとなる液剤を調整した。 0.8 g of the cinnamon extract obtained in Example 1 and 0.65 g of the lychee extract obtained in Example 3 were weighed and purified water was added to make a total volume of 100 mL. The liquid agent which becomes 10 mL was adjusted.
実施例１で得られたケイヒエキスを０．１６ｇ、実施例３で得られたレイシカクエキスを０．１３ｇ、硝酸チアミンを０．１ｇ、塩酸ピリドキシンを０．１ｇ、シアノコバラミンを０．００１５ｇ秤量し、精製水を加え、全量１００mLとなる液剤を調整した。 0.16 g of the cinnamon extract obtained in Example 1, 0.13 g of the lychee extract obtained in Example 3, 0.1 g of thiamine nitrate, 0.1 g of pyridoxine hydrochloride, and 0.0015 g of cyanocobalamin were weighed. Then, purified water was added to prepare a liquid agent having a total amount of 100 mL.
ケイヒ末を１ｇを秤量し、精製水を加え、全量１００mLとなる懸濁液剤を調整した。 1 g of cinnamon powder was weighed and purified water was added to prepare a suspension with a total volume of 100 mL.
実施例３で得られたレイシカクエキスを０．１３ｇ秤量し、精製水を加え、全量１００mLとなる液剤を調整した。 0.13 g of the lychee extract obtained in Example 3 was weighed and purified water was added to prepare a liquid agent having a total amount of 100 mL.
ケイヒ末を１ｇ、実施例３で得られたレイシカクエキスを０．１３ｇ、塩酸ピリドキシンを１ｇ秤量し、精製水を加え、全量１００mLとなる液剤を調整した。 1 g of cinnamon powder, 0.13 g of the lychee extract obtained in Example 3 and 1 g of pyridoxine hydrochloride were weighed, and purified water was added thereto to prepare a liquid solution having a total amount of 100 mL.
試験例１
試験にはＳＤ系雄性ラット９週齢オス（日本チャールスリバー）を用いた。ラットに実施例６及び実施例７にて得られた液剤を１０mL／Kgの用量で１日１回、２週間経口投与した。１２日目に中心波長約４７０ｎｍの青色光を２４時間照射した。照射終了４８時間後に約１５時間の暗順応の後、ケタミン−キシラジン麻酔下にて網膜電図を測定し、ａ波およびｂ波の振幅（μＶ）を測定した。また、比較対照群として、無処置群および光照射のみを行った光照射群を設定した。なお、すべての群の例数は１０とした。
Test example 1
For the test, SD male male 9-week-old male (Nippon Charles River) was used. The solution obtained in Example 6 and Example 7 was orally administered to rats once a day for 2 weeks at a dose of 10 mL / Kg. On the 12th day, blue light with a central wavelength of about 470 nm was irradiated for 24 hours. After dark adaptation for about 15 hours 48 hours after the end of irradiation, electroretinograms were measured under ketamine-xylazine anesthesia, and amplitudes (μV) of a and b waves were measured. Moreover, the non-treatment group and the light irradiation group which performed only light irradiation were set as a comparison control group. The number of examples in all groups was 10.
結果を表１に示した。なお、表中数字は平均値±標準誤差を示している。 The results are shown in Table 1. In addition, the number in a table | surface has shown the average value +/- standard error.
表１で示したように、無処置群と比較して、光照射群では、ａ波、ｂ波共に有意に振幅が低下した。一方、ケイヒエキス投与群およびレイシカクエキス投与群は光照射群と比較して、ａ波、ｂ波共に有意に振幅の低下が抑制された。 As shown in Table 1, in the light irradiation group, both the a wave and the b wave significantly decreased in amplitude compared with the untreated group. On the other hand, compared with the light irradiation group, the decrease in amplitude was significantly suppressed in the Keihi extract-administered group and the Reishikaku extract-administered group.
以上の結果、ケイヒエキスおよびレイシカクエキスは光照射により生じる網膜障害を防ぎ、視覚機能の低下を予防あるいは改善することが明らかになった。 As a result, it became clear that Keihi extract and Reishikaku extract prevent retinal damage caused by light irradiation and prevent or improve deterioration of visual function.
試験例２
試験にはＳＤ系雄性ラット６週齢オス（日本チャールスリバー）を用いた。ラットに実施例１２にて得られた液剤を１０mL／Kgの用量で１日１回、１０日間経口投与した。無処置群及び光照射群には精製水を投与した。１２日目に中心波長約４７０ｎｍの青色光を２４時間照射した。照射終了４８時間後に約１５時間の暗順応の後、ケタミン−キシラジン麻酔下にて網膜電図を測定し、ａ波の振幅（μＶ）を測定した。また、比較対照群として、無処置群および光照射のみを行った光照射群を設定した。なお、すべての群の例数は１０とした。
Test example 2
SD male 6-week-old male (Nippon Charles River) was used for the test. The solution obtained in Example 12 was orally administered to rats at a dose of 10 mL / Kg once a day for 10 days. Purified water was administered to the untreated group and the light irradiation group. On the 12th day, blue light with a central wavelength of about 470 nm was irradiated for 24 hours. 48 hours after the end of irradiation, after dark adaptation for about 15 hours, electroretinogram was measured under ketamine-xylazine anesthesia, and a-wave amplitude (μV) was measured. Moreover, the non-treatment group and the light irradiation group which performed only light irradiation were set as a comparison control group. The number of examples in all groups was 10.
結果を表２に示した。なお、表中数字は平均値を示している。 The results are shown in Table 2. In addition, the number in a table | surface has shown the average value.
表２で示したように、無処置群と比較して、光照射群では、ａ波の振幅が有意に低下した。実施例１２投与群では光照射群と比較して、ａ波の振幅の低下が有意に抑制された。 As shown in Table 2, the amplitude of the a wave significantly decreased in the light irradiation group as compared with the untreated group. In the administration group of Example 12, a decrease in the amplitude of the a wave was significantly suppressed as compared with the light irradiation group.
以上の結果、ケイヒ、レイシカク、ビタミンを併用することにより、光照射により生じる網膜障害の抑制作用が増強されることが明らかになった。 As a result, it has been clarified that the combined use of Keihi, Reishikaku, and vitamins enhances the inhibitory effect on retinal damage caused by light irradiation.
試験例３
網膜色素上皮細胞を９６穴プレートにＤ−ＭＥＭ／Ｆ１２培地を用いて１ウェル当たり１×１０４個になるように藩種し、ＣＯ２インキュベータ内で培養した。正常サンプル以外にはリポフスチンを約２５μＭになるよう添加し、さらにケイヒエキスサンプル及びレイシカクエキスサンプルには実施例１または実施例３で得られたそれぞれのエキスを１００μｇ／mLになるよう添加した。約２４時間の培養の後、中心波長約４７０ｎｍの青色光をＣＯ２インキュベータ内で１時間照射し、翌日、正常サンプルの細胞の生存率を１００％としたときの各群の生存率をＣｅｌｌ Ｃｏｕｎｔｉｎｇ Ｋｉｔ−８（和光純薬工業）を用いて算出した。また、細胞死の形態がアポトーシスであることはアポトーシススクリーニングキットワコー（和光純薬工業）を用いて確認した。結果を表３に示した。
Test example 3
Retinal pigment epithelial cells were seeded in a 96-well plate at 1 × 10 4 cells per well using D-MEM / F12 medium and cultured in a CO 2 incubator. In addition to the normal sample, lipofuscin was added to a concentration of about 25 μM, and each extract obtained in Example 1 or Example 3 was added to the cinnamon extract sample and the lychee extract sample to a concentration of 100 μg / mL. After culturing for about 24 hours, blue light with a central wavelength of about 470 nm was irradiated in a CO 2 incubator for 1 hour. It calculated using Kit-8 (Wako Pure Chemical Industries). Moreover, it was confirmed using apoptosis screening kit Wako (Wako Pure Chemical Industries) that the form of cell death was apoptosis. The results are shown in Table 3.
表３で示したように対照群と比較してケイヒエキスサンプル及びレイシカクエキスサンプルでは、対照サンプルと比較して高い生存率を示した。すなわち、ケイヒ及びレイシカクは網膜細胞のアポトーシスを強く抑制し、網膜保護作用を示すことが明らかになった。 As shown in Table 3, compared to the control group, the cinnamon extract sample and the lychee extract sample showed a higher survival rate than the control sample. That is, it has been clarified that Keihi and Reishikaku strongly suppress apoptosis of retinal cells and show a retinal protective action.
ケイヒおよびレイシカクは、網膜アポトーシスにより生じる網膜機能低下の抑制に有効であることから、本発明は視覚機能障害を予防あるいは改善するための医薬品、医薬部外品または食品に使用可能である。 Since Keihi and Reishikaku are effective in suppressing the decrease in retinal function caused by retinal apoptosis, the present invention can be used for pharmaceuticals, quasi drugs or foods for preventing or improving visual dysfunction.
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