JP2007091728A - Oral preparation for preventing or alleviating asthenopia - Google Patents

Oral preparation for preventing or alleviating asthenopia Download PDF

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JP2007091728A
JP2007091728A JP2006232940A JP2006232940A JP2007091728A JP 2007091728 A JP2007091728 A JP 2007091728A JP 2006232940 A JP2006232940 A JP 2006232940A JP 2006232940 A JP2006232940 A JP 2006232940A JP 2007091728 A JP2007091728 A JP 2007091728A
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oral preparation
retinal
peppermint
vitamin
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JP5731091B2 (en
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Akihisa Morito
暁久 森戸
Kazumi Umakado
和美 馬門
Michio Kurachi
道雄 倉地
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Taisho Pharmaceutical Co Ltd
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Abstract

<P>PROBLEM TO BE SOLVED: To provide an oral preparation effective for the prevention and alleviation of retinopathy caused by light or aging and asthenopia caused by the retinopathy and having high safety, even on using for a long period. <P>SOLUTION: This oral preparation for preventing or alleviating the retinopathy is characterized by blending peppermint. The oral preparation for preventing and alleviating the asthenopia is characterized by blending the peppermint. Thereby, the oral preparation is useful as a drug, quasi drug and food for the prevention and alleviation of the retinopathy and asthenopia caused by the retinopathy. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

本発明は、長期間服用しても安全で有効な網膜障害及び網膜障害に起因する眼精疲労の予防又は緩和に有効な医薬品、医薬部外品又は食品に関する。   The present invention relates to a retinal disorder that is safe and effective even when taken for a long period of time, and a pharmaceutical, a quasi-drug, or a food effective for preventing or alleviating eye strain caused by retinal disorder.

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、加齢によっても障害を受けやすい部位である。網膜の障害は、視力や視野の低下、かすみ目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)。   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 susceptible to oxidative stress and is susceptible to damage due to aging. Retinal disorders appear with symptoms such as vision loss, visual field loss, and blurred vision, and cause significant visual function deterioration. As a result, an excessive load is generated on muscles, nerves, and the like, causing eye strain (Non-Patent Document 1).

眼から入った光は、角膜、水晶体、硝子体を通って網膜へと到達する。この光を捉える網膜の中央部が黄斑であり、ここには視細胞が集中している。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。   Light entering the eye passes through the cornea, lens, and vitreous to reach the retina. The central part of the retina that captures this light is the macula, where photoreceptor cells are concentrated. 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波及び律動様小波の4つの波形に大きく分類される。a波は視細胞を、b波は双極細胞及びミュラー細胞を、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可能である。また、これらの波形は光暴露や加齢変化によっても減弱することが知られている(非特許文献2)
特に網膜の障害には光による酸化ストレスが大きく影響しており、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いる(非特許文献3)。網膜障害の原因物質の一つであり、網膜疾患の原因物質の一つとして考えられている過酸化脂質の一種であるリポフスチンも光照射によって生じることが知られている(非特許文献4)。
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 small wave. The a wave shows the waveform originating from the photoreceptor cell, the b wave from the bipolar cell and the Müller cell, the c wave from the retinal pigment epithelial cell, and the rhythm-like wave from the amacrine cell. That is, by measuring the electroretinogram, it is possible to identify the retinal lesion site. Further, it is known that these waveforms are attenuated by light exposure and aging change (Non-patent Document 2).
In particular, oxidative stress due to light greatly affects retinal damage, and a light damage model is widely used as a retinal damage model animal (Non-patent Document 3). It is known that lipofuscin, which is one of the causative substances of retinal disorders and is a kind of lipid peroxide considered as one of causative substances of retinal diseases, is also produced by light irradiation (Non-patent Document 4).

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)が知られている。
ペパーミント(Mentha Piperita)はシソ科の植物で、地上部全草又は葉を乾燥したものであり、西洋ハッカとも称されている。ペパーミントは、メントール、メントン等の精油、フラボノイド、カロチノイド、アズレン等の数多くの成分を含み、食欲増進や健胃効果を目的に用いられている。さらに、発汗作用、殺薗作用、利尿作用、リュウマチ、神経痛に対する効果が知られているが、内服による網膜保護作用や網膜障害に由来する眼精疲労に対する効果は知られていない。
As a retinal disorder preventive agent derived from a natural product, a retinal disorder preventive agent containing a tea extract as an active ingredient (Patent Documents 1 and 2) is known.
Peppermint (Mentha Piperita) is a plant belonging to the family Lamiaceae, which is obtained by drying the above-ground whole grass or leaves, and is also called Western mint. Peppermint contains many components such as essential oils such as menthol and mentone, flavonoids, carotenoids, and azulene, and is used for the purpose of promoting appetite and improving the stomach. Furthermore, the effects on perspiration, slaughter, diuresis, rheumatism, and neuralgia are known, but the effects on internal eye retinal protection and retinal damage resulting from retinal damage are not known.

あたらしい眼科, 14(9),1289-1293,1997New Ophthalmology, 14 (9), 1289-1293,1997 加齢と眼, 48-50,1999Aging and the eyes, 48-50, 1999 Jpn. J. Ophthalmol.,44(6),615-619,2000Jpn. J. Ophthalmol., 44 (6), 615-619,2000 Biol. Chem.,383,537-545Biol. Chem., 383,537-545 特開2001−270832号公報JP 2001-270832 A 特開2002−220340号公報JP 2002-220340 A

本発明は、長期間服用しても安全で有効な網膜障害及び網膜障害に起因する眼精疲労の予防又は緩和剤を提供することを目的とする。   An object of the present invention is to provide a retinal disorder that is safe and effective even after long-term use and an agent for preventing or alleviating eye strain caused by retinal disorder.

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、ペパーミント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予防効果を有することを見いだし、本発明を完成した。すなわち、本発明は、
1)ペパーミントを配合したことを特徴とする網膜障害の予防又は緩和のための経口剤
2)ペパーミントを配合したことを特徴とする眼精疲労の予防又は緩和のための経口剤
である。
As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that peppermint extract has a preventive effect on a model rat having a retinal disorder caused by light irradiation, and completed the present invention. That is, the present invention
1) An oral preparation for preventing or alleviating retinal disorders characterized by blending peppermint 2) An oral composition for preventing or alleviating eye strain characterized by blending peppermint.

本発明により、光又は加齢により生じる網膜障害を予防又は緩和することができ、さらには、網膜障害に起因する眼精疲労の予防又は緩和に有効で安全性の高い薬剤あるいは食品の提供が可能になった。   According to the present invention, it is possible to prevent or alleviate retinal damage caused by light or aging, and furthermore, it is possible to provide a highly safe drug or food effective in preventing or reducing eye strain caused by retinal damage. Became.

本発明において網膜障害とは、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、網膜色素変性等を挙げることができる。   Examples of the retinal disorder in the present invention include decreased visual acuity, presbyopia, blurred vision, decreased visual field, decreased dark adaptation, age-related macular degeneration, and retinal pigment degeneration.

本発明に用いるペパーミントは、そのまま生薬末として、又は水、極性溶媒、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が、水とアルコールを等量混合して抽出したエキスが望ましい。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。   The peppermint used in the present invention can be used as a crude drug powder as it is or as an extract extracted with water, a polar solvent, a mixed solvent thereof or the like, but an extract obtained by mixing an equal amount of water and alcohol is desirable. As the extract, a dry extract, a flow extract, or the like can be used.

本発明に用いるペパーミントの投与量は、年齢、性別等を考慮して適宜増減できるが、通常成人に対し、原生薬換算量で100mg〜50gの範囲で用いることができ、好ましくは500mg〜30gである。   The amount of peppermint used in the present invention can be appropriately increased or decreased in consideration of age, sex, etc., but it can be used in the range of 100 mg to 50 g, preferably 500 mg to 30 g, in terms of drug substance for normal adults. is there.

本発明においては、さらにビタミン類を添加することによって、より優位な効果を得ることができる。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及びその誘導体等が挙げられ、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群が挙げられる。   In the present invention, a more advantageous effect can be obtained by further adding vitamins. 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、ニコチン酸等が挙げられ、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. preferable.

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挙げられる。   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挙げられる。
本発明に使用されるビタミンB12としては、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、メコバラミン等が挙げられる。
Examples of vitamin B6 used in the present invention include pyridoxine hydrochloride and pyridoxal phosphate.
Examples of vitamin B12 used in the present invention include hydroxocobalamin hydrochloride, hydroxocobalamin acetate, cyanocobalamin, hydroxocobalamin, mecobalamin and the like.

本発明においては、発明の効果を損なわない質的及び量的範囲で、キサンチン誘導体、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、香料などを配合して、常法により、液剤、錠剤、顆粒剤、散剤、カプセル剤、ドライシロップ剤、チュアブル錠、経粘膜剤などの経口製剤とすることができる。   In the present invention, a xanthine derivative, an amino acid, an excipient, a pH adjuster, a cooling agent, a suspending agent, an antifoaming agent, a thickening agent, a dissolution, within a qualitative and quantitative range that does not impair the effects of the invention. Additives, disintegrants, binders, lubricants, antioxidants, coating agents, coloring agents, flavoring agents, surfactants, plasticizers, fragrances, etc. Preparations, powders, capsules, dry syrups, chewable tablets, transmucosal agents and the like.

以下に実施例及び試験例を挙げ、本発明をさらに具体的に説明する。
(実施例1)
原生薬量500gのペパーミントを細切後、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。
Hereinafter, the present invention will be described more specifically with reference to examples and test examples.
Example 1
After chopping peppermint with an active ingredient amount of 500 g, add 10 times the amount of 50% ethanol, heat extract for 30 minutes in a boil, filter and evaporate the ethanol under reduced pressure. Got.

(実施例2)
原生薬量500gのペパーミントを細切後、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。
(Example 2)
After chopping peppermint with a drug substance amount of 500 g, 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3)
実施例1で得られたエキスを4g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15g/100mLとなる液剤を調整した。
(Example 3)
4 g of the 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 15 g / 100 mL in terms of drug substance was prepared.

(実施例4)
実施例2で得られたエキスを4g、ポリオキシエチレン硬化ヒマシ油60を1g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15g/100mLとなる液剤を調整した。
Example 4
4 g of the extract obtained in Example 2 and 1 g of polyoxyethylene hydrogenated castor oil 60 were weighed, and purified water was added to make a total volume of 100 mL.

(実施例5)
実施例1で得られたエキスを400mg、硝酸チアミンを100mg、塩酸ピリドキシンを100mg、シアノコバラミンを1.5mg秤量し、精製水を加え、全量100mLとなる液剤を調整した。
(Example 5)
400 mg of the extract obtained in Example 1, 100 mg of thiamine nitrate, 100 mg of pyridoxine hydrochloride and 1.5 mg of cyanocobalamin were weighed, and purified water was added to prepare a liquid preparation having a total volume of 100 mL.

(試験例1)
非特許文献3に記載の方法を参考に以下の試験を行った。
試験にはSD系雄性ラット8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1にて得られたペパーミントエキスを1.5g/kg(原生薬換算)の用量で1日1回、2週間経口投与した。15日目に中心波長470nm、約3000luxの青色光を12時間(7:00〜19:00)照射した。照射終了後15時間の暗順応の後、塩酸ケタミン−塩酸キシラジン麻酔下にて網膜電図を測定し、a波及びb波の振幅(μV)を測定した。また、比較対照群として、無処置群及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。
結果を表1に示した。
(Test Example 1)
The following tests were conducted with reference to the method described in Non-Patent Document 3.
SD male 8 week old males (Nippon Charles River) were used for the test. The peppermint extract obtained in Example 1 was orally administered to rats once a day for 2 weeks at a dose of 1.5 g / kg (in terms of drug substance). On the 15th day, blue light having a central wavelength of 470 nm and about 3000 lux was irradiated for 12 hours (7:00 to 19:00). After dark adaptation for 15 hours after the end of irradiation, electroretinogram was measured under anesthesia with ketamine hydrochloride-xylazine hydrochloride, and the amplitudes (μV) of a-wave and b-wave 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.
The results are shown in Table 1.

Figure 2007091728
Figure 2007091728

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減少した。一方、ペパーミント投与群は光照射群と比較して、a波、b波共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, in the peppermint administration group, a decrease in amplitude was suppressed for both the a wave and the b wave as compared to the light irradiation group.

以上の結果、ペパーミントエキスは光照射により生じる網膜機能の低下を予防又は緩和することが明らかになった。   As a result, it was revealed that peppermint extract prevents or alleviates the decrease in retinal function caused by light irradiation.

ペパーミントの内服投与は、光又は加齢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、本発明の経口用組成物は網膜障害及び網膜障害に起因する眼精疲労の予防又は緩和するための医薬品、医薬部外品又は食品に有用である。
Since oral administration of peppermint is effective in suppressing retinal function decline caused by light or aging, the oral composition of the present invention is for preventing or alleviating eye strain caused by retinal disorders and retinal disorders. Useful for pharmaceuticals, quasi drugs or foods.

Claims (2)

ペパーミントを配合したことを特徴とする網膜障害の予防又は緩和のための経口剤   An oral preparation for preventing or alleviating retinal disorders characterized by containing peppermint ペパーミントを配合したことを特徴とする眼精疲労の予防又は緩和のための経口剤
An oral preparation for preventing or alleviating eye strain characterized by containing peppermint
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CN103751358A (en) * 2014-01-20 2014-04-30 臧家良 Traditional Chinese medicinal composition for treating eye diseases due to refractive errors

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