JPH0723317B2 - Corneal epithelial disorder treatment - Google Patents
Corneal epithelial disorder treatmentInfo
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- JPH0723317B2 JPH0723317B2 JP63062028A JP6202888A JPH0723317B2 JP H0723317 B2 JPH0723317 B2 JP H0723317B2 JP 63062028 A JP63062028 A JP 63062028A JP 6202888 A JP6202888 A JP 6202888A JP H0723317 B2 JPH0723317 B2 JP H0723317B2
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- epithelial layer
- corneal epithelial
- corneal
- hyaluronic acid
- molecular weight
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Description
【発明の詳細な説明】 ［産業上の利用分野］ 本発明は、ヒアルロン酸又はその塩からなる角膜上皮層
障害症治療剤に関するものである。TECHNICAL FIELD The present invention relates to a therapeutic agent for corneal epithelial layer disorder comprising hyaluronic acid or a salt thereof.
［従来の技術及び発明が解決しようとする課題］ 角膜は、上皮細胞層、ボーマン膜、実質層、デスメ膜、
内皮細胞層の５層からなる。[Problems to be Solved by Conventional Techniques and Inventions] The cornea includes an epithelial cell layer, Bowman's membrane, parenchymal layer, Descemet's membrane,
It consists of 5 layers of endothelial cells.
角膜ヘルペス、外傷、アルカリ、酸等によって、前記上
皮細胞層が障害を受け欠損することがあるが、これまで
に角膜の感染や乾燥を防止して、自然治癒を維持するほ
かに積極的な治療法はなく、かかる障害の治癒を促進す
るような薬剤は知られていなかった。The epithelial cell layer may be damaged and lost due to corneal herpes, trauma, alkali, acid, etc., but to prevent corneal infection and desiccation to maintain natural healing as well as active treatment so far. There is no law and no drug has been known to promote healing of such disorders.
最近、患者自身の血漿から調製したフィブロネクチンが
上皮の再被覆に著効を示すことが報告され（Nishida,
T.,et al:Ophthalmol.,92,213（1985）;Watanabe,K.,et
al:Invest.Ophthalmol.Vis.Sci.,28,205（1987））、
一部の病院で使用されているが、安定性や抗原性に難点
があり汎用性に乏しい。Recently, fibronectin prepared from patient's own plasma was reported to be highly effective in recoating epithelium (Nishida,
T., et al: Ophthalmol., 92 , 213 (1985); Watanabe, K., et
al: Invest.Ophthalmol.Vis.Sci., 28 , 205 (1987)),
It is used in some hospitals, but it lacks stability and antigenicity and is not versatile.
一方、ヒアルロン酸は、水分の保持、潤滑作用、高い粘
弾性等の物理的性質を有するとともに種々の生理活性を
有することが知られている。眼科領域では、前記物理的
性質に基く角膜保護作用及び角膜表面の乾燥防止作用を
利用して角膜乾燥症の治療に適用されている（特開昭60
−84225号公報）。On the other hand, hyaluronic acid is known to have physical properties such as water retention, lubrication, high viscoelasticity, and various physiological activities. In the field of ophthalmology, it is applied to the treatment of xerokeratosis by utilizing the corneal protective action and the dryness preventing action of the cornea surface based on the above physical properties (JP-A-60
-84225).
しかしながら、ヒアルロン酸について角膜上皮層の障害
に対する積極的治療効果に関しては何ら報告はなされて
いない。However, no report has been made on the positive therapeutic effect of hyaluronic acid on disorders of the corneal epithelial layer.
そこで、本発明らは、ヒアルロン酸の角膜上皮層に対す
る効果について鋭意研究を重ねた結果、ヒアルロン酸が
角膜上皮層の伸展促進作用を有することを見出し、本発
明を完成するに至った。Then, as a result of intensive studies on the effect of hyaluronic acid on the corneal epithelial layer, the present inventors have found that hyaluronic acid has an action of promoting the extension of the corneal epithelial layer, and completed the present invention.
［課題を解決するための手段］ 本発明は、ヒアルロン酸又はその塩を有効成分として含
有することを特徴とする角膜上皮層障害症治療剤に関す
るものである。[Means for Solving the Problems] The present invention relates to a therapeutic agent for corneal epithelial layer disorder, which comprises hyaluronic acid or a salt thereof as an active ingredient.
本発明の治療剤は、ヒトを含む哺乳動物の涙液分泌不全
を伴わない角膜上皮層障害症、すなわち点状表層角膜炎
（SPK）、角膜上皮びらん、角膜上皮欠損、角膜潰瘍な
どの障害の治療を促進する治療剤として、疾患部位に局
所的に投与される薬剤である。The therapeutic agent of the present invention is a corneal epithelial layer disorder without lacrimal insufficiency of mammals including human, that is, punctate surface keratitis (SPK), corneal epithelial erosion, corneal epithelial defect, corneal ulcer and other disorders. As a therapeutic agent for promoting treatment, it is a drug that is locally administered to a disease site.
ヒアルロン酸の塩としては、通常、ナトリウム塩を用い
るが、カリウム塩等を用いてもよい。As the salt of hyaluronic acid, a sodium salt is usually used, but a potassium salt or the like may be used.
本発明に用いるヒアルロン酸又はその塩としては、その
分子量が50万〜300万であるものが好ましく、60万〜120
万であるものが更に好ましい。分子量が50万未満又は30
0万を超えると角膜上皮層の伸展促進作用が低下する。The hyaluronic acid or salt thereof used in the present invention preferably has a molecular weight of 500,000 to 3,000,000, and 600,000 to 120.
It is more preferable that the amount is 10,000. Molecular weight less than 500,000 or 30
If it exceeds 0,000, the action of promoting the extension of the corneal epithelial layer is reduced.
分子量が60万〜120万であるヒアルロン酸は、鵜冠をプ
ロテアーゼ消化、塩化メチルピリジニウム沈殿、エタノ
ール分画（日本国特許第1284023号、特公昭61−21241
号）することにより得ることができる。Hyaluronic acid having a molecular weight of 600,000 to 1.2 million is produced by digesting cormorant with a protease, precipitating methylpyridinium chloride, and ethanol fractionation (Japanese Patent No. 1284023, Japanese Patent Publication No. 61-21241).
No.).
本発明の角膜上皮層障害症治療剤は、本発明の目的に適
合する限り、眼科用の医薬品製剤として公知の任意の製
剤形態として用いることができるが、好ましくはヒアル
ロン酸又はその塩の水溶液、すなわち点眼用液体製剤と
して用いる。そのときのヒアルロン酸の濃度は、好まし
くは200〜5,000μg/mlである。該濃度が200μg/ml未満
又は5,000μg/mlを超えると角膜上皮層の伸展促進作用
が低下する。点眼用液体製剤の場合、5,000μg/mlを超
えると取扱い及び投与（適用）が困難となる。The therapeutic agent for corneal epithelial layer disease of the present invention can be used in any formulation form known as an ophthalmic pharmaceutical formulation, as long as it is compatible with the object of the present invention, but preferably an aqueous solution of hyaluronic acid or a salt thereof, That is, it is used as a liquid preparation for eye drops. The concentration of hyaluronic acid at that time is preferably 200 to 5,000 μg / ml. If the concentration is less than 200 μg / ml or more than 5,000 μg / ml, the extension promoting action of the corneal epithelial layer is reduced. In the case of liquid formulations for eye drops, handling and administration (application) become difficult if the amount exceeds 5,000 μg / ml.
本発明の角膜上皮層障害症治療剤には、ヒアルロン酸以
外に他の添加物、例えば、塩化ナトリウム、リン酸水素
二ナトリウム、リン酸水素一カリウムなどの塩類、パラ
オキシ安息香酸エステル類、塩化ベンザルコニウムなど
の保存剤、コンドロイチン硫酸やグリチルリチンなどの
抗炎症剤等を適宜添加してもよい。In the therapeutic agent for corneal epithelial layer disorder of the present invention, other additives besides hyaluronic acid, for example, sodium chloride, disodium hydrogen phosphate, salts such as monopotassium hydrogen phosphate, paraoxybenzoic acid esters, benzal chloride. Preservatives such as ruconium and anti-inflammatory agents such as chondroitin sulfate and glycyrrhizin may be added as appropriate.
本発明の角膜上皮層障害症治療剤を点眼用液体製剤とし
て臨床に適用するに際しては、リン酸塩緩衝化生理食塩
液に分子量50万〜300万、好ましくは60万〜120万のヒア
ルロン酸ナトリウムを200〜5,000μg/mlの濃度で溶解し
たものを一日１〜10回、１回１〜３滴点眼する。なお、
ヒアルロン酸の安全性（毒性・非炎症性）については、
既に数多くの実験がなされており、その安全性が確認さ
れている。例えば、眼毒性については、ウサギを用いた
実験により刺激性、抗原性がないことが確認されている
（上野則夫他：日本眼科紀要35,584（1984）及び同35,8
03（1984））。When clinically applying the therapeutic agent for corneal epithelial disorder of the present invention as a liquid formulation for eye drops, sodium hyaluronate having a molecular weight of 500,000 to 3,000,000, preferably 600,000 to 1,200,000 in a phosphate buffered saline solution. What was melt | dissolved in the density | concentration of 200-5,000 microg / ml is 1-10 times a day, and 1 to 3 drops is instilled once. In addition,
Regarding the safety of hyaluronic acid (toxic and non-inflammatory),
A number of experiments have already been carried out, and its safety has been confirmed. For example, for ocular toxicity, irritation by experiments in rabbits, it is no antigenicity have been identified (Norio Ueno Other: Japan Ophthalmology Bulletin 35, 584 (1984) and ibid 35, 8
03 (1984)).
［実施例］ 以下、実施例により本発明を更に詳細に説明するが、こ
れらの実施例は本発明の範囲を何ら制限するものではな
い。[Examples] Hereinafter, the present invention will be described in more detail with reference to Examples, but these Examples do not limit the scope of the present invention in any way.
実施例１ 1.動物 体重2.8〜3.0kgの日本白色在来種ウサギ（雄）60匹を使
用した。Example 1 1. Animals 60 Japanese white native rabbits (male) weighing 2.8 to 3.0 kg were used.
2.ヒアルロン酸ナトリウム、コンドロイチン硫酸ナトリ
ウム、ヘパラン硫酸ナトリウム 試験に供する試料として以下のグリコサミノグリカン
（GAG）を使用した。ヒアルロン酸ナトリウム（Na−H
A）は分子量４千、２万、10万、50万、68万、102万のも
のを使用した。コンドロイチン硫酸ナトリウム（Na−Ch
s）とヘパラン硫酸ナトリウム（Na−HS）は分子量３万
のものを使用した。Na−HAは鵜冠から、Na−Chsはサメ
軟骨から、Na−HSはウシ腎臓から精製されたもので、い
ずれも生化学工業株式会社製造のものである。2. Sodium hyaluronate, sodium chondroitin sulfate, sodium heparan sulfate The following glycosaminoglycan (GAG) was used as a sample for the test. Sodium hyaluronate (Na-H
As A), those having a molecular weight of 40,000, 100,000, 500,000, 680,000, and 1.02 million were used. Sodium chondroitin sulfate (Na-Ch
s) and sodium heparan sulfate (Na-HS) having a molecular weight of 30,000 were used. Na-HA was purified from cormorant, Na-Chs was purified from shark cartilage, and Na-HS was purified from bovine kidney, both manufactured by Seikagaku Corporation.
3.角膜片の培養 Watanabeらの方法（Watanabe,T.,et al:Invest.Ophthal
mol.Vis.Sci.,28,205（1987））に準じて培養した。3. Culture of corneal pieces Watanabe et al. (Watanabe, T., et al: Invest.Ophthal
Mol.Vis.Sci., 28 , 205 (1987)).
ウサギ摘出眼球から強角膜片を分離し、中央部で垂直に
２分割した。２分割した一方をデキストランT40を５％
含む199培地で培養し、対照群とした。他方は更に各種
のグリコサミノグリカン（GAG）を添加した培地で培養
した。GAGの濃度は400μg/mlとした。また、分子量68万
のNa−HAについては、濃度50、100、200、400、800、2,
500μg/mlについても検討した。A piece of corneal cornea was separated from the rabbit eyeball and vertically divided into two at the center. Dextran T40 is 5% in one of the two divided
The cells were cultured in 199 medium containing them and used as a control group. The other was further cultured in a medium supplemented with various glycosaminoglycans (GAG). The concentration of GAG was 400 μg / ml. Further, for Na-HA having a molecular weight of 680,000, the concentrations are 50, 100, 200, 400, 800, 2,
500 μg / ml was also examined.
各濃度、分子量のGAG群について９眼を使用し、それぞ
れに対照群を設け、独立して実験を行った。培養時間は
20時間、温度は37℃、CO2濃度は５％とした。Nine eyes were used for the GAG group of each concentration and molecular weight, a control group was set for each, and the experiment was performed independently. Culture time
The temperature was 37 ° C. and the CO 2 concentration was 5% for 20 hours.
4.病理標本の作製 培養終了後、角膜片をリン酸緩衝化生理食塩液（PBS）
で洗浄し、３％のグルタルアルデヒド、2.5％のホルム
アルデヒドを含む100mMのリン酸ナトリウム緩衝液（pH
7.2）で15時間固定した。固定後、更に２分割し、強膜
を除いて更に24時間以上固定した。次に、常法どおりパ
ラフィン包理、薄切、へマトキシリン−エオシン染色
（Ｈ−Ｅ染色）、封入した。4. Preparation of pathological specimen After completion of the culture, the corneal piece is treated with phosphate buffered saline (PBS)
Wash with 3% glutaraldehyde, 2.5% formaldehyde in 100 mM sodium phosphate buffer (pH
Fixed at 7.2) for 15 hours. After fixation, it was further divided into two, and the sclera was removed, and the fixation was continued for 24 hours or more. Next, paraffin embedding, thin sectioning, hematoxylin-eosin staining (HE staining), and encapsulation were carried out as usual.
5.上皮層伸展距離の測定 角膜実質層切断面を100倍で写真撮影し、85×120mmに引
き伸ばしたプリンド上から上皮層の伸展距離を測定し
た。測定後、平均値と標準偏差を算出し、有意差の検定
を行った。検定には対応のある２標本間のｔ−検定を用
いた。5. Measurement of epithelial layer extension distance The cut surface of the corneal stroma layer was photographed at 100 times and the extension distance of the epithelial layer was measured on the plind stretched to 85 × 120 mm. After the measurement, the average value and the standard deviation were calculated and the significant difference was tested. A paired t-test between two samples was used for the test.
［結果］ 角膜上皮層の伸展に対する種々の濃度のNa−HA（分子量
68万）の作用を図１に示す。結果は対照群に対する百分
率で表示してある。濃度200、400、800μg/mlで有意な
上皮層伸展促進効果が認められ、400μg/mlの濃度で最
も伸展距離が長かった（ｐ＜0.005）。そこで、以下の
実験では、濃度を400μg/mlに固定して検討した。[Results] Different concentrations of Na-HA (molecular weight
The effect of 680,000) is shown in FIG. The results are expressed as a percentage of the control group. At the concentrations of 200, 400, and 800 μg / ml, a significant effect of promoting epithelial layer extension was observed, and at the concentration of 400 μg / ml, the extension distance was the longest (p <0.005). Therefore, in the following experiments, the concentration was fixed at 400 μg / ml for study.
角膜上皮層の伸展に対する種々な分子量のNa−HA（濃度
400μg/ml）の作用を図２に示す。いずれの分子量のNa
−HAも伸展を促進する作用を示し、分子量50万、68万、
102万では有意であった。Na-HA of various molecular weights (concentration
The effect of 400 μg / ml) is shown in FIG. Na of any molecular weight
-HA also has the effect of promoting extension, and has a molecular weight of 500,000, 680,000,
It was significant at 1.02 million.
角膜上皮層の進展に対する他のGAGの作用を図３に示
す。分子量３万、濃度400μg/mlのNa−Chs,及びNa−HS
は僅かに伸展を促進したが、有意差は認められたかっ
た。The effect of other GAGs on the development of the corneal epithelial layer is shown in FIG. Na-Chs and Na-HS with a molecular weight of 30,000 and a concentration of 400 μg / ml
Slightly promoted extension, but wanted no significant difference.
実施例２ 1.動物 体重2.6〜3.5kgの日本白色在来種ウサギ（雄）６匹を使
用した。Example 2 1. Animals Six Japanese white native rabbits (male) weighing 2.6 to 3.5 kg were used.
2.ヒアルロン酸ナトリウム 分子量72万のNa−HAを生理食塩液に0.5％の濃度で溶解
したものを使用した。2. Sodium hyaluronate Na-HA having a molecular weight of 720,000 was dissolved in physiological saline at a concentration of 0.5% and used.
3.角膜上皮層の剥離 一定面積の上皮層を剥離するために、内径10mm、長さ約
50mmのリム付き試験管にヨードを20g入れ、先端にガラ
スウールを詰めたものを使用した。（Parkison,G.,et a
l:Invest.Ophthalmol.Vis.Sci.,18,103（1979））。3. Detachment of corneal epithelial layer In order to detach a certain area of epithelial layer, inner diameter 10mm, length approx.
A test tube with a rim of 50 mm was charged with 20 g of iodine, and the tip of which was filled with glass wool was used. (Parkison, G., et a
l: Invest.Ophthalmol.Vis.Sci., 18 , 103 (1979)).
ウサギをペントバルビタールで全身麻酔し、塩酸オキシ
ブプロカインを点眼して局所麻酔した後、前述のヨード
を充填した試験管の開口部をウサギ角膜中央部に3.5分
間軽く圧着して、上皮層をヨードガスで障害した。障害
後２〜３時間で上皮層は剥離した。ヨードガスによる障
害は午前9:00に行い、午後1:00及び5:00,翌日の午前9:0
0,午後1:00,5:00に点眼した。右眼には0.5％のNa−HA、
左眼には生理食塩液を点眼した。After general anesthesia of the rabbit with pentobarbital and local anesthesia by instilling oxybuprocaine hydrochloride, the opening of the test tube filled with iodine described above was lightly crimped to the center of the rabbit cornea for 3.5 minutes, and the epithelial layer was iodine gas. I was disturbed. The epithelial layer was detached 2-3 hours after the injury. Obstacles due to iodine gas will occur at 9:00 am, 1:00 and 5:00 pm, 9: 0 am the next day
The eye drops were applied at 0, 1:00 and 5:00. 0.5% Na-HA for the right eye,
The left eye was instilled with physiological saline.
4.剥離部位の染色と写真撮影 ヨードガスによる障害後48時間に、フルオレッセインの
２％生理食塩液溶液を点眼して上皮層の剥離部位を染色
し、356nmの紫外線下で写真撮影した。剥離部位の直径
は写真プリント上から測定し、平均値と標準偏差を算出
した。有意差の検定には対応のある２標本間のｔ−検定
を用いた。4. Staining and Photographing of Exfoliated Site 48 hours after the injury due to iodine gas, a 2% physiological saline solution of fluorescein was instilled to stain the exfoliated site of the epithelial layer and photographed under UV light at 356 nm. The diameter of the peeled portion was measured on the photographic print, and the average value and standard deviation were calculated. A t-test between two corresponding samples was used for testing the significant difference.
［結果］ ヨードガスによる障害後48時間に、フルオレッセインで
染色した角膜を肉眼的に観察した結果、生理食塩液を点
眼した角膜に比べて、0.5％Na−HAを点眼した角膜の上
皮層剥離部が小さくなっているのが観察された。[Results] 48 hours after the injury due to iodine gas, the cornea stained with fluorescein was observed macroscopically, and as a result, 0.5% Na-HA was applied to the cornea, and the epithelial layer of the cornea was peeled compared to the cornea instilled with physiological saline. It was observed that the part became smaller.
図４に上皮層剥離部の直径の測定値を示す。Na−HA点眼
群では生理食塩液群に比べて、有意（Ｐ＜0.05）に直径
が小さくなっていた。FIG. 4 shows the measured values of the diameter of the epithelial layer peeling portion. The diameter of the Na-HA eye drop group was significantly (P <0.05) smaller than that of the physiological saline solution group.
以上のように、0.5％のNa−HAを点眼したin vivoの系に
おいても、上皮層の再被覆を促進する作用が認められた
ことは、Na−HAが遷延化した角膜上皮層障害症に対して
有効な治療薬になり得ることを示唆するものである。As described above, even in the in vivo system in which 0.5% Na-HA was instilled, the action of promoting recoating of the epithelial layer was observed, which indicates that Na-HA has a prolonged corneal epithelial layer disorder. On the other hand, it suggests that it can be an effective therapeutic drug.
［発明の効果］ 本発明によれば、角膜上皮層障害の治療薬及び角膜移植
後の上皮層治癒促進薬を提供することができる。EFFECTS OF THE INVENTION According to the present invention, a therapeutic agent for corneal epithelial layer disorder and an epithelial layer healing promoting agent after corneal transplantation can be provided.
図１は、角膜上皮層伸展に対する種々の濃度のNa−HAの
作用を示す図である。図２は、角膜上皮層伸展に対する
種々の分子量のNa−HAの作用を示す図である。図３は、
角膜上皮層伸展に対する種々のGAGの作用を示す図であ
る。図４は、ヨードガスで障害後48時間の角膜上皮層剥
離部位直径を示す図である。FIG. 1 is a diagram showing the effects of various concentrations of Na-HA on corneal epithelial layer extension. FIG. 2 is a figure which shows the effect | action of Na-HA of various molecular weights with respect to corneal epithelial layer extension. Figure 3
It is a figure which shows the effect of various GAGs with respect to corneal epithelial layer extension. FIG. 4 is a diagram showing the diameter of the corneal epithelial layer detachment site 48 hours after the injury with iodine gas.
Claims (3)
含有することを特徴とする角膜上皮層障害症治療剤。1. A therapeutic agent for corneal epithelial layer disease, which comprises hyaluronic acid or a salt thereof as an active ingredient.
300万である請求項１記載の角膜上皮層障害症治療剤。2. The molecular weight of hyaluronic acid or a salt thereof is from 500,000 to
The therapeutic agent for corneal epithelial layer disease according to claim 1, which is 3 million.
ml含有する水溶液である請求項１記載の角膜上皮層障害
症治療剤。3. Hyaluronic acid or a salt thereof is added in an amount of 200 to 5.000 μg /
The therapeutic agent for corneal epithelial layer disorder according to claim 1, which is an aqueous solution containing ml.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63062028A JPH0723317B2 (en) | 1988-03-17 | 1988-03-17 | Corneal epithelial disorder treatment |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63062028A JPH0723317B2 (en) | 1988-03-17 | 1988-03-17 | Corneal epithelial disorder treatment |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP10012203A Division JP3014357B2 (en) | 1998-01-26 | 1998-01-26 | Corneal epithelial layer extension promoter |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH01238530A JPH01238530A (en) | 1989-09-22 |
| JPH0723317B2 true JPH0723317B2 (en) | 1995-03-15 |
Family
ID=13188305
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63062028A Expired - Lifetime JPH0723317B2 (en) | 1988-03-17 | 1988-03-17 | Corneal epithelial disorder treatment |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0723317B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101411067B1 (en) * | 2005-10-12 | 2014-06-27 | 세이가가쿠 고교 가부시키가이샤 | Agent for applying to mucosa and method for production thereof |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1247175B (en) * | 1991-04-19 | 1994-12-12 | Fidia Spa | PROCEDURE FOR PURIFICATION OF HYALURONIC ACID AND FRACTION OF PURE HYALURONIC ACID FOR OPHTHALMIC USE. |
| EP0763754B1 (en) * | 1995-09-13 | 2003-01-08 | Seikagaku Kogyo Kabushiki Kaisha (Seikagaku Corporation) | Photocured crosslinked-hyaluronic acid contact lens |
| US20030018382A1 (en) * | 2001-07-17 | 2003-01-23 | Pflugfelder Stephen C. | Process for improving vision |
| ES2304913T3 (en) * | 2002-04-30 | 2012-03-01 | Sifi S.P.A. | REEPITELIALIZING PHARMACEUTICAL COMPOSITIONS CONTAINING XANTAN GUM. |
| AU2012201314B2 (en) * | 2005-10-12 | 2014-04-10 | Seikagaku Corporation | Agent for applying to mucosa and method for production thereof |
| ITMI20052036A1 (en) * | 2005-10-26 | 2007-04-27 | Professional Dietetics Srl | PHARMACEUTICAL COMPOSITIONS OPHTHALMIC BASED ON AMINO ACIDS AND SODIUM HYALURONATE |
| CN101484177B (en) | 2006-06-28 | 2011-12-28 | 日本乐敦制药株式会社 | Ophthalmic composition containing alginic acid or salt thereof |
| JP2008255061A (en) * | 2007-04-06 | 2008-10-23 | Shiseido Co Ltd | Soluble cross-linked hyaluronic acid-containing ophthalmic composition |
| TW201322982A (en) * | 2011-11-01 | 2013-06-16 | Otsuka Pharma Co Ltd | A medicament for treating anterior eye disease comprising rebamipide and a tear-retaining agent |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4141973A (en) * | 1975-10-17 | 1979-02-27 | Biotrics, Inc. | Ultrapure hyaluronic acid and the use thereof |
| IT1212892B (en) * | 1983-10-11 | 1989-11-30 | Della Valle Francesco | HYALURONIC ACID OBTAINED BY MEANS OF MOLECULAR FILTRATION WITHOUT INFLAMMATORY ACTIVITY AND ITS THERAPEUTIC USE |
| JPS6084225A (en) * | 1983-10-17 | 1985-05-13 | Hiroko Shimizu | Eye drop |
| JPH068323A (en) * | 1992-06-26 | 1994-01-18 | Asahi Tec Corp | Repairing method of underground piping |
-
1988
- 1988-03-17 JP JP63062028A patent/JPH0723317B2/en not_active Expired - Lifetime
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101411067B1 (en) * | 2005-10-12 | 2014-06-27 | 세이가가쿠 고교 가부시키가이샤 | Agent for applying to mucosa and method for production thereof |
| KR101428153B1 (en) * | 2005-10-12 | 2014-08-07 | 세이가가쿠 고교 가부시키가이샤 | Agent for applying to mucosa and method for production thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH01238530A (en) | 1989-09-22 |
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