JPH01279836A - Remedy for cornea - Google Patents
Remedy for corneaInfo
- Publication number
- JPH01279836A JPH01279836A JP63105495A JP10549588A JPH01279836A JP H01279836 A JPH01279836 A JP H01279836A JP 63105495 A JP63105495 A JP 63105495A JP 10549588 A JP10549588 A JP 10549588A JP H01279836 A JPH01279836 A JP H01279836A
- Authority
- JP
- Japan
- Prior art keywords
- fibronectin
- cornea
- remedy
- hyaluronic acid
- treatment
- 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.)
- Pending
Links
- 210000004087 cornea Anatomy 0.000 title abstract description 13
- 102000016359 Fibronectins Human genes 0.000 claims abstract description 28
- 108010067306 Fibronectins Proteins 0.000 claims abstract description 28
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims abstract description 17
- 229920002674 hyaluronan Polymers 0.000 claims abstract description 17
- 229960003160 hyaluronic acid Drugs 0.000 claims abstract description 17
- 238000011282 treatment Methods 0.000 claims abstract description 14
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 239000011343 solid material Substances 0.000 claims description 3
- 239000007787 solid Substances 0.000 abstract description 8
- 102000008186 Collagen Human genes 0.000 abstract description 6
- 108010035532 Collagen Proteins 0.000 abstract description 6
- 229920001436 collagen Polymers 0.000 abstract description 6
- 239000003814 drug Substances 0.000 abstract description 5
- 230000007547 defect Effects 0.000 abstract description 4
- 229940079593 drug Drugs 0.000 abstract description 4
- 239000006172 buffering agent Substances 0.000 abstract description 2
- 102000034240 fibrous proteins Human genes 0.000 abstract description 2
- 108091005899 fibrous proteins Proteins 0.000 abstract description 2
- 230000002035 prolonged effect Effects 0.000 abstract description 2
- 210000000981 epithelium Anatomy 0.000 abstract 2
- 230000004304 visual acuity Effects 0.000 abstract 2
- 238000004090 dissolution Methods 0.000 abstract 1
- 239000011814 protection agent Substances 0.000 abstract 1
- 206010052428 Wound Diseases 0.000 description 4
- 208000027418 Wounds and injury Diseases 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 230000029663 wound healing Effects 0.000 description 4
- 230000027455 binding Effects 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 210000002919 epithelial cell Anatomy 0.000 description 3
- 239000003889 eye drop Substances 0.000 description 3
- 229940012356 eye drops Drugs 0.000 description 3
- 229920002385 Sodium hyaluronate Polymers 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 210000003560 epithelium corneal Anatomy 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- 230000002085 persistent effect Effects 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000008929 regeneration Effects 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- 229940010747 sodium hyaluronate Drugs 0.000 description 2
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 2
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 1
- 229920001287 Chondroitin sulfate Polymers 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 108010017707 Fibronectin Receptors Proteins 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 102000006395 Globulins Human genes 0.000 description 1
- 108010044091 Globulins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 1
- 102000016611 Proteoglycans Human genes 0.000 description 1
- 108010067787 Proteoglycans Proteins 0.000 description 1
- 206010038848 Retinal detachment Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229920001222 biopolymer Polymers 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229940059329 chondroitin sulfate Drugs 0.000 description 1
- 229960005188 collagen Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 230000019305 fibroblast migration Effects 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 229950006780 n-acetylglucosamine Drugs 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 230000004264 retinal detachment Effects 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 210000001179 synovial fluid Anatomy 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000011345 viscous material Substances 0.000 description 1
- 210000004127 vitreous body Anatomy 0.000 description 1
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
［産業上の利用分野］
本発明のフィブロネクチンを接着した高分子ヒアルロン
酸含有固形体はヒト角膜の治療のための医療に関する。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The polymeric hyaluronic acid-containing solid material to which fibronectin is adhered according to the present invention relates to medical treatment for the treatment of human corneas.
［従来技術の説明］
従来、遷延性角膜上皮創傷の治療には、コンドロイチン
硫酸のような粘性物質の点眼、眼軟膏盗人による強制閉
瞼、眼瞼縫合術、あるいは治療用ソフトコンタクトレン
ズの連続装用などの、外界から角膜への刺激を減らし、
上皮欠損が自然に修復するのを待つと言う方法と、フィ
ブロネクチンの点眼により角膜上皮細胞の再生を促進さ
せようとする方法がある。[Description of the Prior Art] Conventionally, persistent corneal epithelial wounds have been treated by instillation of viscous substances such as chondroitin sulfate, forced lid closure by eye ointment thieves, lid suturing, or continuous wearing of therapeutic soft contact lenses. , reducing irritation to the cornea from the outside world,
There are two methods: waiting for the epithelial defect to repair naturally, and another method using fibronectin eye drops to promote regeneration of corneal epithelial cells.
［解決しようとする問題点］
しかし、種々の治療に抵抗する難治性角膜上皮障害の治
療にはこれら従来の治療方法では長期間の治療となる場
合が多い。[Problems to be Solved] However, these conventional treatment methods often require long-term treatment for intractable corneal epithelial disorders that resist various treatments.
その上、治療期間中は視力矯正に困難を伴う場合が多く
、角膜上皮の早期治癒が望まれている。Moreover, it is often difficult to correct vision during the treatment period, and early healing of the corneal epithelium is desired.
［問題点を解決する手段］
そこで、角膜上皮創傷の治療を行うためにフィブロネク
チンを接着した高分子ヒアルロン酸を含有した固形体を
角膜上に装用する。そして、この固形体を緩衡剤として
コンタクトレンズを装用して視力矯正を行う。[Means for Solving the Problems] Therefore, in order to treat corneal epithelial wounds, a solid body containing a polymeric hyaluronic acid to which fibronectin is adhered is worn on the cornea. Then, vision correction is performed by wearing contact lenses using this solid body as a buffering agent.
［実施例］
ヒアルロン酸は人の血液中にも多量にあるＮ−アセチル
グルコサミンとグルクロン酸が交互に結合し、構成され
ている高分子多糖類で生体適合性があるため、医薬品と
して用いても人体の拒否反応はほとんど無い、 ヒアル
ロン酸はを椎動物の結合組織の中でも鎖帯、関節液およ
び硝子体に高濃度で存在する。 この医薬品としてその
粘弾性、保水性、透明性を持つ生体高分子化合物として
のヒアルロン酸ナトリウム溶液は、関節治療剤および、
眼科医の前眼部手術補助剤となっている。 そして、よ
り高濃度で製膜化、ゲル化、或いは固形化したヒアルロ
ン酸ナトリウムは緑内障や網膜剥離の治療剤、そして角
膜保護剤としての利用が試みられている。[Example] Hyaluronic acid is a high-molecular polysaccharide composed of alternating bonds of N-acetylglucosamine and glucuronic acid, which are present in large amounts in human blood, and is biocompatible, so it can be used as a drug. There is almost no rejection reaction by the human body.Hyaluronic acid exists in high concentrations in the connective tissues of vertebrates, such as the chain strands, synovial fluid, and vitreous body. This pharmaceutical sodium hyaluronate solution, which is a biopolymer compound with viscoelasticity, water retention, and transparency, is a joint treatment agent and
It is used as an aid for anterior segment surgery by ophthalmologists. Sodium hyaluronate, which has been formed into a film, gelled, or solidified at a higher concentration, is being used as a therapeutic agent for glaucoma and retinal detachment, and as a corneal protectant.
本発明では、高分子ヒアルロン酸を含有した固形体で角
膜保護剤としたものにフィブロネクチンを接着させ、角
膜上皮細胞の再生を促進させようとしたものである。
。The present invention aims to promote the regeneration of corneal epithelial cells by adhering fibronectin to a solid material containing polymeric hyaluronic acid and serving as a corneal protective agent.
.
フィブロネクチンは血液中のグロブリン分画に存在し、
低温にすると沈殿する糖蛋白質として１９７０年に始め
て分離精製された。 フィブロネクチンは細胞の接着、
伸展や移動を制御する接着性蛋白質であるのみならず、
その他にも多くの機能を持つ多機能蛋白質であることが
明確になってきている。 フィブロネクチンの分子は、
２２〜２５万の分子量を持つほぼ同じサブユニット２個
がジスルフィド結合（Ｓ−３結合）によって連結してダ
イマー（２量体）を形成している。 フィブロネクチン
は唾液中に存在するフィブリン、フィブリノーゲンある
いはコラーゲンなとの！ｌ維性蛋白質と結合する機能が
あり、コラーゲン、プロテオグリカン、ヒアルロン酸、
など細胞間質に存在する分子や、細胞膜に存在するフィ
ブロネクチン受容体などに対して特異的な幾つかの結合
部位を持っている。Fibronectin is present in the globulin fraction in the blood.
It was first isolated and purified in 1970 as a glycoprotein that precipitates when exposed to low temperatures. Fibronectin promotes cell adhesion,
It is not only an adhesive protein that controls extension and movement, but also
It is becoming clear that it is a multifunctional protein with many other functions. The fibronectin molecule is
Two almost identical subunits with a molecular weight of 220,000 to 250,000 are linked by a disulfide bond (S-3 bond) to form a dimer. Fibronectin is fibrin, fibrinogen, or collagen that exists in saliva! It has the function of binding to fibrous proteins such as collagen, proteoglycans, hyaluronic acid,
It has several specific binding sites for molecules present in the interstitium of cells, such as fibronectin receptors present in cell membranes.
このフィブロネクチンは細胞が移動するための基質とし
て機能すると同時に、細胞を誘引する化学定性因子とし
ても機能している。 この機能として創傷治癒が上げら
れる。 創傷部に存在するフィブロネクチンにより、創
傷部への線維芽細胞の移動が促進される。 フィブロネ
クチンの濃度のより高いほうに向かって、線維芽細胞が
移動する。This fibronectin functions as a substrate for cell migration, and at the same time, it also functions as a chemoqualitative factor that attracts cells. This function includes wound healing. Fibronectin present at the wound site promotes fibroblast migration to the wound site. Fibroblasts migrate toward higher concentrations of fibronectin.
角膜の主成分がコラーゲンであると言う事と、フィブロ
ネクチンに創傷治癒機能があると言うことより、遷延性
角膜上皮欠損の治療に臨床応用されている。 フィブロ
ネクチン点眼療法は上皮細胞の接着性に作用し、上皮欠
損部の再被覆を促進するが、抗ウィルス作用や、抗生物
質のような殺菌作用はないと言われている。Because collagen is the main component of the cornea and fibronectin has a wound healing function, it has been clinically applied to treat persistent corneal epithelial defects. Fibronectin eye drops affect the adhesion of epithelial cells and promote the recoating of epithelial defects, but it is said to have no antiviral effect or bactericidal effect like antibiotics.
つまり、原因疾患が治療された後にも持続するような遷
延化した角膜上皮障害が最も適当なフィブロネクチンの
適応であり、フィブロネクチンは角膜上皮のリハビリテ
ーションに極めて有効であると言える。 また、高濃度
の点眼剤を用いたほうがより高い有効率を示し、治療に
要した日数もより短縮すると報告されている。In other words, the most appropriate indication for fibronectin is a prolonged corneal epithelial disorder that persists even after the causative disease has been treated, and it can be said that fibronectin is extremely effective in rehabilitating the corneal epithelium. It has also been reported that the use of high-concentration eye drops shows a higher efficacy rate and reduces the number of days required for treatment.
本発明では、このフィブロネクチンの創傷治癒効果と、
フィブロネクチンと結合部位を持つヒアルロン酸とを接
着し、角膜治療剤としたものである。In the present invention, the wound healing effect of fibronectin,
Fibronectin and hyaluronic acid, which has a binding site, are bonded together to form a corneal treatment agent.
精製あるいは製造したヒアルロン酸及びフィブロネクチ
ンは、高純度とする。 純度が低いと、フィブロネクチ
ンはヒアルロン酸以外のコラーゲンや細胞などとの結合
部位でその不純物と接着し、生理活性の度合いが低下す
る。Purified or manufactured hyaluronic acid and fibronectin should be of high purity. When purity is low, fibronectin adheres to impurities at binding sites with collagen other than hyaluronic acid, cells, etc., and the degree of physiological activity decreases.
［発明の効果］
以上説明したように高分子ヒアルロン酸を含有した固形
体にフィブロネクチンを接着させた角膜治療剤を角膜上
皮創傷治癒に使うことにより、他の、フィブロネクチン
を使用しない治療方法より治癒日数を短縮する事が出来
る。[Effects of the Invention] As explained above, by using a corneal treatment agent in which fibronectin is adhered to a solid body containing polymeric hyaluronic acid for corneal epithelial wound healing, the healing time is longer than that of other treatment methods that do not use fibronectin. can be shortened.
そして、この治療期間中の患者の視力矯正にコンタクト
レンズが使用できるので、視力の改善が行える。 なお
、角膜上での装用時に、高分子ヒアルロン酸含有固形体
のヒアルロン酸が機械的な分解作用により徐々に低分子
化され、溶解すると共にフィブロネクチンがこの高分子
ヒアルロン酸含有固形体より分離し、その周囲に滞留し
、その後、流失するので、薬効時間を長く保つことがで
きる。Since contact lenses can be used to correct the patient's vision during this treatment period, the patient's vision can be improved. In addition, when worn on the cornea, the hyaluronic acid in the solid body containing high molecular weight hyaluronic acid is gradually reduced to a lower molecular weight by mechanical decomposition, and as it dissolves, fibronectin is separated from this solid body containing high molecular weight hyaluronic acid. Since it stays around the area and then washes away, the drug's effectiveness can be maintained for a long time.
Claims (1)
ンを接着した事を特徴とする角膜治療剤。A corneal treatment agent characterized by adhering fibronectin to a solid material containing high molecular weight hyaluronic acid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63105495A JPH01279836A (en) | 1988-04-30 | 1988-04-30 | Remedy for cornea |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63105495A JPH01279836A (en) | 1988-04-30 | 1988-04-30 | Remedy for cornea |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH01279836A true JPH01279836A (en) | 1989-11-10 |
Family
ID=14409181
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63105495A Pending JPH01279836A (en) | 1988-04-30 | 1988-04-30 | Remedy for cornea |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH01279836A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5654267A (en) * | 1988-12-20 | 1997-08-05 | La Jolla Cancer Research Center | Cooperative combinations of ligands contained within a matrix |
| US5789462A (en) * | 1995-09-13 | 1998-08-04 | Seikagaku Kogyo Kabushiki Kaisha (Seikagaku Corporation) | Photocured crosslinked-hyaluronic acid contact lens |
| US5955578A (en) * | 1988-12-20 | 1999-09-21 | La Jolla Cancer Research Foundation | Polypeptide-polymer conjugates active in wound healing |
| WO2003007969A1 (en) * | 2001-07-17 | 2003-01-30 | Baylor College Of Medicine | Bio-compatible molecules for improving vision |
| JP2007063218A (en) * | 2005-09-01 | 2007-03-15 | Teika Seiyaku Kk | Agent for treatment of corneal disease |
-
1988
- 1988-04-30 JP JP63105495A patent/JPH01279836A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5654267A (en) * | 1988-12-20 | 1997-08-05 | La Jolla Cancer Research Center | Cooperative combinations of ligands contained within a matrix |
| US5830504A (en) * | 1988-12-20 | 1998-11-03 | La Jolla Cancer Research Foundation | Cooperative combinations of ligands contained within a matrix |
| US5955578A (en) * | 1988-12-20 | 1999-09-21 | La Jolla Cancer Research Foundation | Polypeptide-polymer conjugates active in wound healing |
| US5789462A (en) * | 1995-09-13 | 1998-08-04 | Seikagaku Kogyo Kabushiki Kaisha (Seikagaku Corporation) | Photocured crosslinked-hyaluronic acid contact lens |
| WO2003007969A1 (en) * | 2001-07-17 | 2003-01-30 | Baylor College Of Medicine | Bio-compatible molecules for improving vision |
| JP2007063218A (en) * | 2005-09-01 | 2007-03-15 | Teika Seiyaku Kk | Agent for treatment of corneal disease |
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