JP3407384B2 - Intraocular perfusion / cleansing agent and eyeball preservative - Google Patents
Intraocular perfusion / cleansing agent and eyeball preservativeInfo
- Publication number
- JP3407384B2 JP3407384B2 JP02117394A JP2117394A JP3407384B2 JP 3407384 B2 JP3407384 B2 JP 3407384B2 JP 02117394 A JP02117394 A JP 02117394A JP 2117394 A JP2117394 A JP 2117394A JP 3407384 B2 JP3407384 B2 JP 3407384B2
- Authority
- JP
- Japan
- Prior art keywords
- preservative
- present
- eye
- eyeball
- intraocular
- Prior art date
- 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.)
- Expired - Fee Related
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- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Description
【０００１】[0001]
【産業上の利用分野】本発明は、有用な眼内灌流・洗浄
剤および眼球保存剤に関する。さらに詳しくは、本発明
はアスコルビン酸とトコフェロールとのリン酸ジエステ
ル化合物またはその薬理学的に許容できる塩を含有して
なる有用な眼内灌流・洗浄剤および眼球保存剤に関す
る。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a useful intraocular perfusion / washing agent and eye preservative. More specifically, the present invention relates to a useful intraocular perfusion / detergent and eye preservative containing a phosphodiester compound of ascorbic acid and tocopherol or a pharmacologically acceptable salt thereof.
【０００２】[0002]
【従来の技術】近年、白内障手術や角膜、虹彩および硝
子体移植などの眼科手術の進歩と普及に伴い、これらの
眼科手術時に眼内組織を保護するための優れた眼内灌流
・洗浄剤が求められている。眼科手術時の眼内組織保護
が不充分で、眼内組織が生理的損傷を受けた場合、術後
の経過を悪くし、角膜混濁、緑内障や網膜炎などを併発
するおそれがある。上記の眼内灌流・洗浄剤としては自
然の房水に近い組成のものが好ましいが、従来、眼内灌
流・洗浄剤として生理食塩液、乳酸リンゲル液、ＢＳＳ
（Ｂａｌａｎｃｅｄ ｓａｌｔ ｓｏｌｕｔｉｏｎ）
（商品名）およびＢＳＳ ＰＬＵＳ（商品名）などが主
に用いられている。しかしながら、これら眼内灌流・洗
浄剤は眼内組織、特に、眼科手術の際生理的損傷を最も
受けやすい角膜（内皮）細胞の保護という点で未だ充分
満足すべきものとは言い難い。したがって、眼科分野に
おいて、眼内組織、特に角膜（内皮）細胞の、より優れ
た保護作用を有する眼内灌流・洗浄剤が求められている
のが現状である。2. Description of the Related Art In recent years, with the progress and spread of ophthalmic surgery such as cataract surgery and corneal, iris and vitreous transplantation, excellent intraocular perfusion / cleansing agents for protecting intraocular tissues during these ophthalmic surgery have been developed. It has been demanded. When the intraocular tissue is not sufficiently protected during ophthalmic surgery and the intraocular tissue is physiologically damaged, the postoperative course may be deteriorated and corneal opacity, glaucoma, retinitis, etc. may occur. The above-mentioned intraocular perfusion / cleansing agent preferably has a composition close to that of natural aqueous humor, but conventionally, physiological saline, lactated Ringer's solution, BSS was used as the intraocular perfusion / cleansing agent.
(Balanced salt solution)
(Trade name) and BSS PLUS (trade name) are mainly used. However, it is difficult to say that these intraocular perfusion / cleansing agents are still sufficiently satisfactory in terms of protection of intraocular tissues, particularly corneal (endothelial) cells most susceptible to physiological damage during ophthalmic surgery. Therefore, in the field of ophthalmology, there is a current demand for an intraocular perfusion / cleansing agent having a superior protective effect on intraocular tissues, particularly corneal (endothelial) cells.
【０００３】一方、角膜、網膜および水晶体などの眼球
組織移植手術の際にはドナーから摘出した眼球組織をレ
シピエントに移植するまでの間、摘出した眼球組織の生
理機能を維持させなければならない。摘出した眼球組織
の生理機能を維持させるため、種々の眼球保存剤が試み
られているが、これら保存剤の有効期限は最大わずか２
週間程度に過ぎない。たとえば、現在日本国内において
眼球保存剤として３．５％デキストラン含有のグルコー
スフォスフェートリンゲル液が一般的に使用されている
が、そこに含まれているデキストラン（ＤＸ）は保存初
期に（数日で）角膜（上皮、実質、内皮）に浸透し、こ
れが各組織に水分を引き込み角膜の著明な膨潤を引き起
こすと言われている。また、デキストランは角膜内皮と
デスメ膜との接着を弱め、内皮細胞の機能を低下させる
と言われている。そこで、デキストランの代わりにコン
ドロイチン硫酸（ＣＳ）を用いた眼球保存剤などが検討
されているが、これら欠点が充分改善されたとは言い難
い。従って、現在のところ充分満足すべき眼球保存剤は
見あたらないのが現状である。On the other hand, in the operation of transplanting ocular tissues such as the cornea, retina and lens, the physiological function of the excised ocular tissues must be maintained until the ocular tissues excised from the donor are transplanted to the recipient. Various eye preservatives have been tried in order to maintain the physiological function of the extracted eye tissue, but the expiration date of these preservatives is only 2 at maximum.
Only about a week. For example, currently in Japan, glucose phosphate Ringer's solution containing 3.5% dextran is commonly used as an eye preservative, but dextran (DX) contained therein is used at the initial stage of storage (in a few days). It is said that it penetrates into the cornea (epithelium, parenchyma, endothelium), which draws water into each tissue and causes remarkable swelling of the cornea. In addition, dextran is said to weaken the adhesion between the corneal endothelium and the Descemet's membrane and reduce the function of endothelial cells. Therefore, an eye preservative using chondroitin sulfate (CS) instead of dextran has been studied, but it cannot be said that these drawbacks have been sufficiently improved. Therefore, at present, no satisfactory eye preservative is found.
【０００４】[0004]
【発明が解決しようとする課題】このような状況下にお
いて、本発明者らは、アスコルビン酸とトコフェロール
とのリン酸ジエステル化合物およびその薬理学的に許容
できる塩の薬効を鋭意検討するうちに、これら化合物が
優れた眼内組織保護作用を示すことを見出し、この新知
見に基づいてさらに検討を重ね本発明の眼内灌流・洗浄
剤および眼球保存剤を完成するに至った。Under the circumstances, the present inventors have conducted extensive studies on the pharmacological effects of a phosphodiester compound of ascorbic acid and tocopherol and a pharmacologically acceptable salt thereof. It was found that these compounds exhibit an excellent intraocular tissue protective action, and further investigations have been conducted based on this new finding to complete the intraocular perfusion / detergent and the eye preservative of the present invention.
【０００５】[0005]
【課題を解決するための手段】すなわち、本発明は、次
の式That is, the present invention provides the following formula:
【０００６】[0006]
【化２】 [Chemical 2]
【０００７】［式中、Ｒ1 およびＲ2 は、同一または異
なって水素原子またはメチル基を示す。］で表されるリ
ン酸ジエステル化合物またはその薬理学的に許容できる
塩（以下「本化合物」という。）を含有してなる眼内灌
流・洗浄剤および眼球保存剤に関する。[In the formula, R 1 and R 2 are the same or different and each represents a hydrogen atom or a methyl group. ] It relates to an intraocular perfusion / detergent and an eye preservative containing a phosphodiester compound represented by the following formula or a pharmacologically acceptable salt thereof (hereinafter referred to as "the present compound").
【０００８】本発明の眼内灌流・洗浄剤および眼球保存
剤に用いられる本化合物は、例えば特公平２−４４４７
８号公報や特公平５−２３２７４号公報記載の方法また
はこれらに準じて適宜合成することができる。The compound used in the intraocular perfusion / cleansing agent and the eye preservative of the present invention is, for example, Japanese Patent Publication No. 2-4447.
It can be appropriately synthesized according to the methods described in JP-B No. 8 and JP-B-5-23274, or in accordance with these.
【０００９】本発明の眼内灌流・洗浄剤および眼球保存
剤に用いられる本化合物は、抗白内障剤、更年期障害予
防・治療剤、美肌作用を有する化粧品（特公平２−４４
４７８号）、抗炎症剤（特公平１−２７００４号）、抗
潰瘍剤（特開昭６３−２７０６２号）さらに虚血性臓器
障害予防・治療剤（特開平２−１１１７２２号）など種
々の用途が既に知られている。The present compound used in the intraocular perfusion / cleansing agent and the eye preservative of the present invention is an anti-cataract agent, a prophylactic / therapeutic agent for menopausal disorders, and a cosmetic having a skin beautifying effect (Japanese Patent Publication No. 2-44).
No. 478), an anti-inflammatory agent (Japanese Patent Publication No. 1-20704), an anti-ulcer agent (JP-A-63-27062), and a preventive / therapeutic agent for ischemic organ injury (JP-A-2-111722). Already known.
【００１０】しかしながら、これら化合物が、眼内灌流
・洗浄剤および眼球保存剤の成分として有用であること
は未だ知られていない。However, it has not yet been known that these compounds are useful as components of intraocular perfusion / cleansing agents and eye preservatives.
【００１１】上記の式で表される本化合物は、遊離のも
のであっても、その薬理学的に許容できる塩であって
も、本発明の目的のため適宜に用いることができる。そ
の塩としては、たとえばナトリウム塩やカリウム塩など
のアルカリ金属塩あるいはカルシウム塩やマグネシウム
塩などのアルカリ土類金属塩が挙げられるが、これら以
外の塩であっても薬理学的に許容できる塩であればいず
れのものであっても適宜使用することができる。The present compound represented by the above formula, whether it is a free compound or a pharmaceutically acceptable salt thereof, can be appropriately used for the purpose of the present invention. Examples of the salt include alkali metal salts such as sodium salt and potassium salt, and alkaline earth metal salts such as calcium salt and magnesium salt, and other salts are pharmacologically acceptable salts. Any of them can be used as appropriate.
【００１２】本発明の眼内灌流・洗浄剤および眼球保存
剤には、目的と必要に応じて、本化合物のうち１種また
は２種以上を適宜組み併せて含有させることもできる。The intraocular perfusion / detergent and the eye preservative of the present invention may contain one or more of the present compounds in an appropriate combination depending on the purpose and need.
【００１３】本発明の眼内灌流・洗浄剤および眼球保存
剤は、予め液剤の形にしておいてもよく、あるいは固形
剤として使用時に溶解して用いてもよい。固形剤は、た
とえば精製水や生理食塩液などに溶解、懸濁または乳化
させるのがよい。固形剤としては錠剤、顆粒剤や散剤な
どが挙げられ、これらは公知の方法により適宜製造する
ことができる。これらの製剤は、無菌濾過や加熱滅菌な
どの公知の方法により無菌とするのがよい。The intraocular perfusion / detergent and the eye preservative of the present invention may be prepared in the form of a liquid in advance, or may be dissolved and used as a solid before use. The solid agent is preferably dissolved, suspended or emulsified in, for example, purified water or physiological saline. Examples of solid agents include tablets, granules and powders, which can be appropriately manufactured by known methods. These preparations may be sterilized by a known method such as sterile filtration or heat sterilization.
【００１４】本発明の眼内灌流・洗浄剤および眼球保存
剤に用いられる本化合物は、毒性がきわめて低く安全性
に優れているので、各種眼科手術の際および眼球保存の
際有利に用いられる［たとえば、Ｌ−アスコルビン酸、
ＤＬ−α−トコフェロールリン酸ジエステルナトリウム
（以下ＥＰＣ−Ｎａと略称する）のＬＤ50：経口投与１
０ｇ／ｋｇ（ラット）以上、皮下注射７９３ｍｇ／ｋｇ
（ラット）以上］。Since the present compound used for the intraocular perfusion / cleansing agent and the eye preservative of the present invention has extremely low toxicity and excellent safety, it is advantageously used in various ophthalmic surgery and eyeball preservation [ For example, L-ascorbic acid,
LD 50 of DL-α-tocopherol phosphate diester sodium (hereinafter abbreviated as EPC-Na): Oral administration 1
0 g / kg (rat) or more, subcutaneous injection 793 mg / kg
(Rat) and above].
【００１５】本発明の製剤を眼内灌流・洗浄剤として用
いる場合の本化合物の濃度は、使用する本化合物の種類
などによっても異なるが、最終濃度として、通常約０．
０１μｇ／ｍｌ〜２００μｇ／ｍｌ程度、好ましくは約
０．５μｇ／ｍｌ〜１０μｇ／ｍｌ程度がよい。The concentration of the present compound when the preparation of the present invention is used as an intraocular perfusion / detergent varies depending on the kind of the present compound used and the like, but the final concentration is usually about 0.
It is about 01 μg / ml to 200 μg / ml, preferably about 0.5 μg / ml to 10 μg / ml.
【００１６】本発明の製剤を眼球保存剤として用いる場
合の本化合物の濃度は、使用する本化合物の種類、眼球
の状態、眼球保存温度、目的とする保存時間などによっ
て異なるが、使用時の最終濃度としては、通常約５×１
０-9ｇ／ｍｌ〜５×１０-3ｇ／ｍｌ程度、好ましくは約
５×１０-8ｇ／ｍｌ〜５×１０-5ｇ／ｍｌ程度がよい。When the preparation of the present invention is used as an eye preservative, the concentration of the present compound varies depending on the type of the present compound used, the condition of the eyeball, the eyeball storage temperature, the intended storage time, and the like. Concentration is usually about 5 x 1
It is preferably about 0 -9 g / ml to 5 × 10 -3 g / ml, preferably about 5 × 10 -8 g / ml to 5 × 10 -5 g / ml.
【００１７】本発明の眼内灌流・洗浄剤および眼球保存
剤を液剤とした時のｐＨは、公知の方法によって、約
６．５〜７．５程度に調整するのがよい。When the intraocular perfusion / detergent and the eye preservative of the present invention are used as a liquid, the pH is preferably adjusted to about 6.5 to 7.5 by a known method.
【００１８】本発明の眼内灌流・洗浄剤および眼球保存
剤を液剤としたときの浸透圧は、公知の方法によって、
約０．５〜５圧比、好ましくは約０．８〜２圧比に調整
するのがよい。また、その液剤のｐＨは、公知の方法に
よって、約３〜１０、好ましくは約４〜９程度に調整す
るのがよい。The osmotic pressure when the intraocular perfusion / detergent and the eye preservative of the present invention are used as a liquid is determined by a known method.
It is preferable to adjust the pressure ratio to about 0.5 to 5, preferably about 0.8 to 2. The pH of the liquid agent may be adjusted to about 3 to 10, preferably about 4 to 9 by a known method.
【００１９】本発明の製剤を眼内灌流・洗浄剤として用
いる場合、本発明の目的に反しない限り、通常眼内灌流
・洗浄剤に用いられるその他の成分、たとえば塩化カル
シウム、塩化マグネシウム、硫酸マグネシウム、酢酸ナ
トリウム、リン酸ナトリウム、リン酸カリウム、クエン
酸ナトリウムおよび炭酸水素ナトリウムなどの各種の電
解質、ブドウ糖などの単糖類、グルタチオンおよびグル
タチオンジスルフィドなどのペプタイド類、ペニシリン
Ｇなどの抗生物質などを通常用いられる量適宜配合する
ことができる。When the preparation of the present invention is used as an intraocular perfusion / cleansing agent, other components usually used for intraocular perfusion / cleansing agents, such as calcium chloride, magnesium chloride, magnesium sulfate, unless the object of the present invention is impaired. , Sodium acetate, sodium phosphate, potassium phosphate, various electrolytes such as sodium citrate and sodium hydrogen carbonate, monosaccharides such as glucose, peptides such as glutathione and glutathione disulfide, antibiotics such as penicillin G The amount can be appropriately mixed.
【００２０】本発明の製剤を眼球保存剤として用いる場
合、本発明の目的に反しない限り、通常眼球保存剤に用
いられる成分、たとえば栄養剤、等張化剤、ｐＨ調整
剤、防腐剤、溶解剤、粘性剤などを通常用いられる量適
宜含有させてもよい。それらの成分としては、たとえば
糖類、塩類、アミノ酸や有機酸などが例示される。糖類
としては、ショ糖、ブドウ糖、乳糖、デキストロース、
マンニトールが例示される。塩類としては、塩化ナトリ
ウム、クエン酸ナトリウム、リン酸ナトリウムなどが挙
げられる。アミノ酸としては、グリシン、グルタミン
酸、リジンが例示される。さらに、有機酸としてはクエ
ン酸、酢酸、乳酸が例示される。本発明の眼球保存剤に
は、本発明の目的に反しない限り、その他の薬効成分、
たとえば免疫抑制剤、抗生物質や虚血性疾患治療剤など
を適宜配合させてもよい。When the preparation of the present invention is used as an eye preservative, components that are usually used in eye preservatives, such as nutrients, tonicity adjusting agents, pH adjusters, preservatives, and dissolution agents, are used unless they are against the object of the present invention. Agents, viscous agents, etc. may be contained in an amount usually used. Examples of these components include sugars, salts, amino acids and organic acids. As sugars, sucrose, glucose, lactose, dextrose,
An example is mannitol. Examples of the salts include sodium chloride, sodium citrate, sodium phosphate and the like. Examples of amino acids include glycine, glutamic acid, and lysine. Furthermore, examples of the organic acid include citric acid, acetic acid, and lactic acid. In the eye preservative of the present invention, other medicinal components, unless it goes against the purpose of the present invention,
For example, immunosuppressive agents, antibiotics, ischemic disease therapeutic agents and the like may be appropriately mixed.
【００２１】本発明の製剤を眼球保存剤として用いる場
合の眼球保存温度は、使用する本化合物の種類や用量、
眼球の状態、目的とする保存時間などによっても異なる
が、通常約−５℃〜２０℃、好ましくは０℃〜１５℃程
度がよい。When the preparation of the present invention is used as an eye preservative, the eye preservation temperature depends on the kind and dose of the compound used,
The temperature is usually about -5 ° C to 20 ° C, preferably about 0 ° C to 15 ° C, though it varies depending on the condition of the eyeball, the intended storage time, and the like.
【００２２】本発明の製剤を眼球保存剤として用いる場
合、目的に応じて、眼球自体をそのまま保存してもよい
し、眼球の各組織、たとえば強角膜、網膜および水晶体
保存であってもいずれでもよい。When the preparation of the present invention is used as an eyeball preservative, the eyeball itself may be preserved as it is, or each tissue of the eyeball, for example, sclera, retina and lens may be preserved. Good.
【００２３】本発明の製剤を眼球保存剤として用いて眼
球を保存する際は、公知の眼球保存用容器や装置を適宜
使用することができる。When the eyeball is preserved by using the preparation of the present invention as an eyeball preservative, a known eyeball preservation container or apparatus can be appropriately used.
【００２４】[0024]
【実施例】以下、実験例および実施例を挙げて、本発明
をさらに詳細に説明する。EXAMPLES The present invention will be described in more detail below with reference to experimental examples and examples.
【００２５】［実験例１］角膜保護に対する本化合物の
効果
Ｌ−アスコルビン酸、ＤＬ−α−トコフェロールリン酸
ジエステルモノカリウム（以下、ＥＰＣ−Ｋと略称す
る。）の角膜組織保護作用を評価するため、ＥＰＣ−Ｋ
を配合した製剤およびＥＰＣ−Ｋを除いた製剤を調製
し、ウサギ強角膜片を用いて内皮細胞の保護作用につい
て、比較検討した。[Experimental Example 1] of the present compound for corneal protection
Effect EPC-K for evaluating the corneal tissue protecting effect of L-ascorbic acid and DL-α-tocopherol phosphate diester monopotassium (hereinafter abbreviated as EPC-K).
Was prepared, and a preparation excluding EPC-K was prepared, and a rabbit scleral piece was used to compare and evaluate the protective effect on endothelial cells.
【００２６】［被験物質］後記の実施例１に示したＥＰ
Ｃ−Ｋを配合した製剤およびその処方からＥＰＣ−Ｋを
除いた製剤を用いて試験した。[Test substance] EP shown in Example 1 below.
The test was conducted using a formulation containing CK and a formulation excluding EPC-K from the formulation.
【００２７】［試験方法］眼に異常のない日本白色種雄
性ウサギ６匹を用い、屠殺後眼球を摘出して強角膜片と
した。ＥＰＣ−Ｋ配合の製剤に６眼、ＥＰＣ−Ｋを除い
た製剤に６眼を割り当てた。各々の強角膜片を６穴のプ
レートにとり、各製剤を入れ４℃で保存し、各製剤は毎
日交換した。７日後に角膜を固定して内皮の走査型電子
顕微鏡標本を作製して鏡検を行った後、角膜内皮の写真
撮影を行い、六角形細胞数の割合を計測した。[Test Method] Six Japanese white male rabbits having no abnormalities in the eyes were used, and the eyeballs were excised after slaughter to obtain scleral corneal pieces. 6 eyes were assigned to the formulation containing EPC-K, and 6 eyes were assigned to the formulation without EPC-K. Each scleral corneal piece was placed in a 6-well plate, and each preparation was placed and stored at 4 ° C., and each preparation was exchanged daily. After 7 days, the cornea was fixed, a scanning electron microscope sample of the endothelium was prepared, and microscopic examination was performed. Then, the corneal endothelium was photographed and the ratio of the number of hexagonal cells was measured.
【００２８】［試験結果］鏡検観察を行った結果、ＥＰ
Ｃ−Ｋを配合した処方においては以下の表１に示すとお
り、六角形細胞の割合が高く、より優れた角膜の保護作
用があると認められた（図１および図２参照）。図１よ
り明らかなように、本発明の製剤を用いた場合、六角形
細胞の変性が少なく、大きさバラツキも対照群に比べ軽
度であった。また、図２より明らかなように、本化合物
を除いた処方の製剤を用いた場合、図の中央部の矢印で
示した細胞のように、正常な形態である六角形から変性
し、多角・巨大化した細胞が顕著に認められた。[Test Results] As a result of microscopic observation, EP
As shown in Table 1 below, in the formulation containing CK, the ratio of hexagonal cells was high, and it was recognized that the formulation had a superior corneal protective effect (see FIGS. 1 and 2). As is clear from FIG. 1, when the preparation of the present invention was used, the hexagonal cells were less denatured and the variation in size was milder than in the control group. In addition, as is clear from FIG. 2, when the formulation excluding the present compound was used, cells such as cells indicated by arrows in the center of the figure were denatured from the normal hexagon, Giant cells were noticeable.
【００２９】[0029]
【表１】 六角形細胞の割合 ＥＰＣ−Ｋ配合の製剤 ７０．８ ± ３．８＊ ＥＰＣ−Ｋを除いた製剤 ６５．５ ± ４．５ ＊：対照群に対し有意差あり（ｐ＜０．０５）[Table 1] Proportion of hexagonal cells Preparation with EPC-K formulation 70.8 ± 3.8 * Preparation without EPC-K 65.5 ± 4.5 *: Significantly different from control group (p <0 .05)
【００３０】［実施例１］下記の成分を用いて、公知の
方法により無菌製剤を調製して眼内灌流・洗浄剤および
眼球保存剤とする。
ＥＰＣ−Ｋ ７０．６μｇ
塩化ナトリウム ０．７７５ｇ
塩化カリウム ０．０４１ｇ
塩化カルシウム二水和物 ０．０１７２ｇ
硫酸マグネシウム七水和物 ０．０２１８ｇ
リン酸二水素ナトリウム ０．０１６ｇ
リン酸水素二ナトリウム ０．１０３１ｇ
クエン酸ナトリウム ０．０９ｇ
グルコース ０．７８２ｇ
コンドロイチン硫酸ナトリウム ２．５ｇ
ペニシリン Ｇ ２０，０００Ｕ
精製水 適量
全量 全量１００ｍｌ
ｐＨ ７．４３[Example 1] Using the following components, a sterile preparation is prepared by a known method to prepare an intraocular perfusion / detergent and an eye preservative. EPC-K 70.6 μg Sodium chloride 0.775 g Potassium chloride 0.041 g Calcium chloride dihydrate 0.0172 g Magnesium sulfate heptahydrate 0.0218 g Sodium dihydrogen phosphate 0.016 g Disodium hydrogen phosphate 0.1031 g Sodium citrate 0.09 g Glucose 0.782 g Chondroitin sulfate sodium 2.5 g Penicillin G 20,000 U Purified water Suitable amount Total amount 100 ml pH 7.43
【００３１】［実施例２］下記の成分を用いて、公知の
方法により無菌製剤を調製して眼内灌流・洗浄剤および
眼球保存剤とする。
ＥＰＣ−Ｋ ０．１ｍｇ
塩化ナトリウム ０．６６ｇ
塩化カリウム ０．０３６ｇ
塩化カルシウム二水和物 ０．０１８ｇ
硫酸マグネシウム七水和物 ０．０３ｇ
炭酸水素ナトリウム ０．２５ｇ
クエン酸 ０．０８ｇ
酢酸ナトリウム三水和物 ０．０６ｇ
グルコース ０．１５ｇ
水酸化ナトリウム 適量
塩酸 適量
精製水 適量
全量 １００ｍｌ
ｐＨ ６．６[Example 2] Using the following components, a sterile preparation is prepared by a known method to prepare an intraocular perfusion / detergent and an eye preservative. EPC-K 0.1 mg Sodium chloride 0.66 g Potassium chloride 0.036 g Calcium chloride dihydrate 0.018 g Magnesium sulfate heptahydrate 0.03 g Sodium hydrogen carbonate 0.25 g Citric acid 0.08 g Sodium acetate trihydrate 0.06g Glucose 0.15g Sodium hydroxide Proper amount hydrochloric acid Proper amount Purified water Proper amount Total 100ml pH 6.6
【００３２】［実施例３］下記の成分を用いて、公知の
方法により無菌固形剤および無菌液剤を調製し、使用時
に固形剤を液剤に溶解する。
（１）液剤
塩化ナトリウム ０．７ｇ
塩化カリウム ０．０４ｇ
塩化カルシウム二水和物 ０．０２ｇ
硫酸マグネシウム七水和物 ０．０３ｇ
炭酸水素ナトリウム ０．３ｇ
クエン酸 ０．１ｇ
酢酸ナトリウム三水和物 ０．１ｇ
水酸化ナトリウム 適量
塩酸 適量
精製水 適量
全量 １００ｍｌ
ｐＨ ７．３
（２）固形剤
ＥＰＣ−Ｋ １ｍｇ
グルコース ０．１５ｇ[Example 3] Using the following components, a sterile solid preparation and a sterile liquid preparation are prepared by a known method, and the solid preparation is dissolved in the liquid preparation at the time of use. (1) Liquid sodium chloride 0.7 g Potassium chloride 0.04 g Calcium chloride dihydrate 0.02 g Magnesium sulfate heptahydrate 0.03 g Sodium hydrogen carbonate 0.3 g Citric acid 0.1 g Sodium acetate trihydrate 0 .1 g Sodium hydroxide, proper amount, hydrochloric acid, proper amount, purified water, proper amount, total amount 100 ml, pH 7.3 (2) Solid agent EPC-K 1 mg, glucose 0.15 g
【００３３】[0033]
【発明の効果】本発明の製剤は、眼内組織、特に、眼科
手術の際生理的損傷を最も受けやすい角膜（内皮）細胞
の保護という点で優れているので、各種眼科手術を安全
に行うことができる。また、本発明の製剤は、眼球の各
組織を損傷することなくその生理機能を長期間維持する
ので、角膜、網膜や水晶体などの眼球組織の保存のため
有利に用いることができる。INDUSTRIAL APPLICABILITY The preparation of the present invention is excellent in that it protects intraocular tissues, in particular, corneal (endothelial) cells that are most susceptible to physiological damage during ophthalmic surgery. be able to. Further, since the preparation of the present invention maintains its physiological function for a long period of time without damaging each tissue of the eyeball, it can be advantageously used for preservation of eye tissue such as cornea, retina and lens.
【図１】図１は、実験例１において、本発明の製剤を用
いた場合の走査型電子顕微鏡による角膜内皮細胞写真の
トレースを示す。FIG. 1 shows a trace of a corneal endothelial cell photograph taken by a scanning electron microscope when the preparation of the present invention was used in Experimental Example 1.
【図２】図２は、実験例１において、本化合物を除いた
処方の製剤を用いた場合の走査型電子顕微鏡による角膜
内皮細胞写真のトレースを示す。FIG. 2 shows a trace of a corneal endothelial cell photograph by a scanning electron microscope in the case of using a formulation having a formulation excluding the present compound in Experimental Example 1.
───────────────────────────────────────────────────── フロントページの続き (56)参考文献 特開 昭62−205091（ＪＰ，Ａ) 特開 昭59−219295（ＪＰ，Ａ) 特開 昭63−139972（ＪＰ，Ａ) 特開 昭64−71888（ＪＰ，Ａ) 特開 昭61−233622（ＪＰ，Ａ) 特開 平５−25001（ＪＰ，Ａ) 特開 昭59−29616（ＪＰ，Ａ) 特開 昭62−145019（ＪＰ，Ａ) 特開 平３−255027（ＪＰ，Ａ) (58)調査した分野(Int.Cl.7，ＤＢ名) A61N 1/02 A61K 31/665 A61P 27/04 ＣＡＰＬＵＳ（ＳＴＮ) ＲＥＧＩＳＴＲＹ（ＳＴＮ)─────────────────────────────────────────────────── ─── Continuation of the front page (56) Reference JP 62-205091 (JP, A) JP 59-219295 (JP, A) JP 63-139972 (JP, A) JP 64-64 71888 (JP, A) JP 61-233622 (JP, A) JP 5-25001 (JP, A) JP 59-29616 (JP, A) JP 62-145019 (JP, A) JP-A-3-255027 (JP, A) (58) Fields investigated (Int.Cl. 7 , DB name) A61N 1/02 A61K 31/665 A61P 27/04 CAPLUS (STN) REGISTRY (STN)
Claims (2)
子またはメチル基を示す。］で表されるリン酸ジエステ
ル化合物またはその薬理学的に許容できる塩を含有して
なる眼科手術時の眼内灌流・洗浄剤。1. The following formula: [In the formula, R 1 and R 2 are the same or different and each represents a hydrogen atom or a methyl group. ] An intraocular perfusion / detergent at the time of ophthalmic surgery, which comprises a phosphodiester compound represented by or a pharmacologically acceptable salt thereof.
子またはメチル基を示す。］で表されるリン酸ジエステ
ル化合物またはその薬理学的に許容できる塩を含有して
なる眼球保存剤。2. The following formula: [In the formula, R 1 and R 2 are the same or different and each represents a hydrogen atom or a methyl group. ] An eye preservative comprising a phosphodiester compound represented by the formula or a pharmaceutically acceptable salt thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP02117394A JP3407384B2 (en) | 1993-02-22 | 1994-02-18 | Intraocular perfusion / cleansing agent and eyeball preservative |
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3165093 | 1993-02-22 | ||
| JP5-31650 | 1993-02-22 | ||
| JP9941693 | 1993-04-26 | ||
| JP5-99416 | 1993-04-26 | ||
| JP02117394A JP3407384B2 (en) | 1993-02-22 | 1994-02-18 | Intraocular perfusion / cleansing agent and eyeball preservative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0710701A JPH0710701A (en) | 1995-01-13 |
| JP3407384B2 true JP3407384B2 (en) | 2003-05-19 |
Family
ID=27283317
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP02117394A Expired - Fee Related JP3407384B2 (en) | 1993-02-22 | 1994-02-18 | Intraocular perfusion / cleansing agent and eyeball preservative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3407384B2 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4944126B2 (en) | 2006-11-24 | 2012-05-30 | 富士高分子工業株式会社 | Light guide sheet and electronic device using the same |
| US10420736B2 (en) | 2015-09-30 | 2019-09-24 | Tohoku University | Antioxidizing intraocular perfusion solution |
-
1994
- 1994-02-18 JP JP02117394A patent/JP3407384B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0710701A (en) | 1995-01-13 |
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