JPH05503527A - artificial tears - Google Patents
artificial tearsInfo
- Publication number
- JPH05503527A JPH05503527A JP3504155A JP50415591A JPH05503527A JP H05503527 A JPH05503527 A JP H05503527A JP 3504155 A JP3504155 A JP 3504155A JP 50415591 A JP50415591 A JP 50415591A JP H05503527 A JPH05503527 A JP H05503527A
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- Prior art keywords
- eye
- carrier
- artificial tear
- dry
- tear composition
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
- A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
Abstract
(57)【要約】本公報は電子出願前の出願データであるため要約のデータは記録されません。 (57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.
Description
【発明の詳細な説明】 人工涙液 技術分野 本発明は人工涙液組成物に関し、特にリン脂質と、所望に応じてのヒアルロン酸 またはその塩類を含有する人工涙液に関する。[Detailed description of the invention] artificial tears Technical field The present invention relates to artificial tear compositions, in particular phospholipids and optionally hyaluronic acid. or artificial tears containing salts thereof.
従来技術 人工涙液は現在点眼液として入手可能であり、乾燥眼球症候群の限定的な救済ｆ ｒｅｌｉｅｆｌを約束する。この種の従来技術組成物は時としてヒアルロン酸を 含有するが、それはこれが天然涙液の主成分だからである。Conventional technology Artificial tears are currently available as eye drops and offer limited relief for dry eye syndrome. I promise relief. Prior art compositions of this type sometimes contain hyaluronic acid. This is because it is the main component of natural tear fluid.
乾燥眼球症候群に対抗する為に眼球に僅かな救済を約束するのみである上述の欠 点を克服する、またはこれを改善すると共にただれ眼およびその他の乾燥眼球状 態の処１として使用される改良された人工涙溶液を提供することが、本発明の目 的である。The above-mentioned deficiencies that promise only marginal relief to the eyeballs to combat dry eye syndrome. Overcoming or improving eye sores and other dry eye conditions It is an object of the present invention to provide an improved artificial tear solution for use in the first aspect of the present invention. It is true.
従って、理想的には次の特性の一つまたはそれ以上のものを有する人工涙液組成 物の必要性が存在する、即ち、眼球表面またはコンタクトレンズの表面と眼瞼と の無意識な摺動を可能とする優れた潤滑性、悪く固定されているコンタクトレン ズに伴う高い負荷に耐えている状態での及び眼球の回転時のハイスポット（ｈｉ ｇｈ ５ｐｏｔｌ圧力の下での優秀な潤滑性を提供する可能性、涙液膜を維持す る為の液体の蒸発の減少、涙液膜を損ない眼球表面に乾燥スポットを生じる可能 性のある分離圧力の減少、コンタクトレンズまたは眼瞼への眼球表面の付着を防 止する非付看性表面の生成、または細菌又はウィルスのような空気中の病原体の 眼球中への侵入に対する生物学的障壁の発生、がそれである。Therefore, an artificial tear composition ideally has one or more of the following properties: There is a need for objects, i.e. the ocular surface or contact lens surface and the eyelids. Excellent lubricity that enables unconscious sliding of contact lenses that are poorly fixed. The high spot (hi gh 5potl potential to provide excellent lubricity under pressure, maintain tear film Reduced evaporation of fluid due to dryness, which can damage the tear film and cause dry spots on the ocular surface Reduces potential separation pressure and prevents ocular surface adhesion to contact lenses or eyelids. the creation of unobtrusive surfaces that prevent airborne pathogens such as bacteria or viruses; This is the creation of a biological barrier to entry into the eye.
生理的食塩水中の少なくとも１種の表面活性リン脂質と、ヒアルロン酸またはそ の水溶性塩類から成る潤滑組成物は表面、特に動物および人類の関節表面の。At least one surface active phospholipid in physiological saline and hyaluronic acid or the like. Lubricating compositions consisting of water-soluble salts of the surfaces, especially joint surfaces of animals and humans.
および相互に接触する組織表面間の潤滑を改善するすることにより、関節炎、変 形性関節炎、およびリューマチ性疾患の処！に効果的であることがＰＣＴ／ＡＵ ８８１００３２２から公知である。ＰＣＴ／ＡＵ８８１００３２２に開示されて いるように、ある種のリン脂質、特に不飽和フォスファチジルコリン（レシチン ）、が０．０１以下の０．００２程度に低い運動摩擦係数を与え得る。また、こ れらの低摩擦係数は１３ｋｇ／ｃｍ２程度の高い負荷に対して得られることも知 見されている。Arthritis, osteoarthritis, and osteoarthritis by improving lubrication between tissue surfaces in contact with each other. A place for plastic arthritis and rheumatic diseases! PCT/AU is effective in No. 88100322. Disclosed in PCT/AU88100322 Certain phospholipids, particularly unsaturated phosphatidylcholine (lecithin), ), can provide a coefficient of kinetic friction as low as 0.002, which is 0.01 or less. Also, this It is also known that these low friction coefficients can be obtained under high loads of about 13 kg/cm2. Being watched.
ヒアルロン酸は、自然に発生する、Ｂ１−３グルコロニデイツクとＢ１−４ゲル コサミニディック結合を交互に有する高粘度のムコ多糖体である。ヒアルロン酸 は原料、製造方法および分析方法に応じての５０，０００ないし８，０００，０ ００の範囲の中の分子量を有する。ヒアルロン酸及びその塩類は、動物組織及び ある種の細菌、例えば請帯、硝子体液（ｖｉｔｒｉｏｕｓ ｈｕｍｏｕｒ） 、 滑液、ロースタ−コム（ｒｏｏｓｔｅｒｃｏｍｂ）、病的関節、グループＡとＣ のヒモリティック・ストレプトコッカス（ｈｙｌＴｌｏｌｉｔｉｃ ５ｔｒｅｐ ｔｏｃｏｃｃｉｌおよび皮膚内に並びに合成原料中から得られる。Hyaluronic acid is naturally occurring, B1-3 glucolonidic acid and B1-4 gel. It is a highly viscous mucopolysaccharide with alternating cosaminidic bonds. hyaluronic acid 50,000 to 8,000,000 depending on raw materials, manufacturing method and analytical method It has a molecular weight within the range of 0.00. Hyaluronic acid and its salts are used in animal tissues and Certain types of bacteria, such as pharyngeal fluid, vitreous humor, synovial fluid, roostercomb, pathological joints, groups A and C hylTlolitic Streptococcus (hylTlolitic 5trep It is obtained in tococcil and skin as well as in synthetic sources.
通常レシチンと称されるフォスファチジルコリンは、全ての生命のある有機体（ 植物および動物）に見られるリン脂質である。これは生物体膜の構成物質であり 、透過性、酸化性りん酸化、食菌、および化学的および電気的な刺激、に必要と される。レシチンは多数の動物組織および器管例えば脳、神経系、肝臓、心臓、 肺臓、腎臓、血液、乳汁、性液、中に、微生物中に、また全植物類中に確認され ている。Phosphatidylcholine, commonly referred to as lecithin, is found in all living organisms ( A phospholipid found in plants and animals. This is a constituent of biological membranes. , permeability, oxidative phosphorylation, phagocytosis, and chemical and electrical stimulation, required for be done. Lecithin is found in numerous animal tissues and organs such as the brain, nervous system, liver, heart, Found in the lungs, kidneys, blood, milk, sexual fluids, microorganisms, and all plants. ing.
レシチンはりん酸のコリンエステルに結合されたステアリン酸、バエルミティッ クｆｐａｅｒｍｉｔｉｃｌ酸、およびオレイン酸のジグリセライドの混合物であ り、一般式■で表示し得る、 ここで、Ｒ’ とＲ２とは脂肪酸基である。通常一つの酸基は飽和で他方の酸基 は不飽和である。Lecithin is stearic acid, baermitic acid, bound to the choline ester of phosphoric acid. It is a mixture of triglyceride, fpaermitic acid, and diglyceride of oleic acid. can be expressed by the general formula■, Here, R' and R2 are fatty acid groups. Usually one acid group is saturated and the other acid group is saturated. is unsaturated.
所望に応じてまたヒアルロン酸（ＨＡ）またはその塩類を有する表面活性リン脂 質の、眼に対して生理学的に（ｏｐｔｈａ１ｍｉｃａｌｌｙｌ適合した希釈液キ ャリア中への溶液が乾燥眼球その他の状態の処置、潤滑が可能であると共に、た だれ眼の処置を行い得ることが驚異的に知見された。その他の眼に対して生理学 的に適合した応用には眼内のレンズの潤滑、および白内障外科手術後の、並びに 新しい眼の化粧用としての用途がある。a surface-active phospholipid optionally also containing hyaluronic acid (HA) or its salts; A diluent kit of high quality and physiologically compatible with the eye. The solution in the carrier can be used to treat dry eyeballs and other conditions, as well as to lubricate and It has surprisingly been discovered that droopy eyes can be treated. Physiology for other eyes Suitable applications include intraocular lens lubrication, and after cataract surgery, and There is a new use for eye cosmetics.
その他の使用には結膜炎および類似の状態の処置がある。結膜炎の処置のための 医薬処方にリン脂質を添加する事は強い痛み、特に眼球に対して眼瞼を動かした 時の痛みを、潤滑を与えて、動作を容易にすることによって緩和する事に役立つ 。Other uses include the treatment of conjunctivitis and similar conditions. for the treatment of conjunctivitis Adding phospholipids to pharmaceutical formulations can cause severe pain, especially when moving the eyelids against the eyeballs. Helps relieve pain by providing lubrication and facilitating movement .
茜服Ω朋示 本発明の一つの側面は、眼に対して生理学的に適合するキャリアまたは希釈剤中 へのリン脂質の懸濁液または溶液から成る人工涙液に関する。Akane Clothing Omega Show One aspect of the invention is to provide the Artificial lachrymal fluid consisting of a suspension or solution of phospholipids in water.
また、開示されているのは、乾燥した眼球の処置／潤滑方法に関し、これは眼球 に眼に対して生理学的に適合するキャリアまたは希釈剤中のリン脂質の懸濁液ま たは溶液から成る人工涙液を施すことによって構成される。Also disclosed is a dry eye treatment/lubrication method, which A suspension or diluent of phospholipids in a carrier or diluent that is physiologically compatible with the eye. It is constructed by applying an artificial tear fluid consisting of a tear or a solution.
好ましくは処理用の組成物はまたヒアルロン酸または生理学的に適当なその塩類 を含有している。Preferably the treatment composition also contains hyaluronic acid or a physiologically suitable salt thereof. Contains.
本発明の別の側面はこの溶液を眼瞼と眼球表面またはコンタクトレンズとの間に 潤滑剤として使用される場合である。Another aspect of the invention is to apply this solution between the eyelid and the ocular surface or contact lens. This is the case when it is used as a lubricant.
ある種のリン脂質懸濁液は、特にヒアルロン酸またはその塩類を含有しているも のの場合、粘性が大きいが、本発明の人工涙液組成物の場合、出来た組成物の粘 度は必要なればリン脂質溶液の濃度によって、ヒアルロン酸が存在する場合。Certain phospholipid suspensions, especially those containing hyaluronic acid or its salts, However, in the case of the artificial tear composition of the present invention, the viscosity of the resulting composition is high. Depending on the concentration of the phospholipid solution, if hyaluronic acid is present.
ヒアルロン酸の適当な分子量の選定によって調節可能である。この人工涙液は眼 球に施すために眼に対して生理学的に適合するキャリア乃至希釈液によって適当 な粘度に希釈可能である。It can be adjusted by selecting an appropriate molecular weight of hyaluronic acid. This artificial tear fluid is suitable for application to the eye using a carrier or diluent that is physiologically compatible with the eye. It can be diluted to a certain viscosity.
本発明において有用な若干のリン脂質を次の表に記載する。Some phospholipids useful in the present invention are listed in the following table.
本溶液に使用する好ましい保存剤はヒドロゲルとコンパチブルな、任意の効果的 な、非刺激性の保存剤である。若干の適当な保存剤の中にはソルビン酸とＥＤＴ Ａが含まれる。The preferred preservative for use in this solution is any effective preservative that is compatible with the hydrogel. It is a non-irritating preservative. Some suitable preservatives include sorbic acid and EDT. Contains A.
任意の生物静力学的な量の、溶液の汚染を防止する保存剤が使用できる。Any biostatic amount of preservative that prevents contamination of the solution can be used.
本発明で有用な表面活性剤は眼球に非刺激性のものであり、好ましくは非イオン 的なものである。本発明の滴液中の有用な医薬的に活性な化合物は眼球障害に予 防的なまたは治療効果を有するものである。医薬的に有用な化合物の若干の例に は、例えば、緑内障、結膜炎、の処置用の化合物、赤色眼の処置用の化合物、お よび炎症性の肉眼の状態に対する化合物、が含まれる。Surfactants useful in the present invention are non-irritating to the eye and are preferably non-ionic. It is something like that. Useful pharmaceutically active compounds in the drops of the present invention may be useful in preventing ocular disorders. It has a protective or therapeutic effect. Some examples of pharmaceutically useful compounds For example, compounds for the treatment of glaucoma, conjunctivitis, compounds for the treatment of red eye, and and inflammatory macroscopic conditions.
本発明の人工涙溶液は低負荷での優秀な潤滑を示すが、これは従来の学説によれ ばヒアルロン酸の溶液によるものとされている。液がこのような低い速力で摺動 する両表面の間から絞り出されるような高負荷においてはリン脂質のオリゴラメ ラ−（ｏｌｉｇｏＬａｍｅｌｌａｒｌな層によって作られた優秀な境界潤滑があ る。この固体潤滑はコロイド上のグラファイトがギアオイルに混合されたときに 機能するのと同様に生じるものと考えられるが、これは摺動面とその対向面に直 接に結合した層を形成するものである。ある時期にリン脂質の層が直接に眼球表 面に結合されることが知られていたが、現在までのところこれに明瞭に起因する ものとされてはいない。The artificial tear solution of the present invention exhibits excellent lubrication at low loads, which is contrary to conventional theory. It is believed that this is caused by a solution of hyaluronic acid. The liquid slides at such a low speed. Under high loads such as those squeezed out from between both surfaces, phospholipid oligolamellar There is excellent boundary lubrication created by the oligolamellar layer. Ru. This solid lubrication occurs when colloidal graphite is mixed with gear oil. It is thought that this occurs in the same way as the sliding surface and its opposite surface. It forms a tangentially bonded layer. At some point, the phospholipid layer directly forms on the ocular surface. was known to be bonded to a surface, but so far it has been clearly attributed to this It is not considered a thing.
その潤滑特性を要約するとこの製品は摩擦係数を０．０２乃至０．００６の値に 、時としては０．０００７の程度に減少させることができる。この製品の主要な 長所は、非常に低い摩擦が高負荷（１ｇｋｇ／ｃｍ” ）の下での低速度で得ら れると言う事である。To summarize its lubricating properties, this product has a friction coefficient of 0.02 to 0.006. , sometimes as low as 0.0007. The main features of this product The advantage is that very low friction is obtained at low speeds under high loads (1 gkg/cm”). This means that it can be done.
この人工涙溶液はまたレリーズ［ｒｅｌｅａｓｅｌ特性を有する。レシチンはレ リーズ剤として広く使用されているが、これは接着性またはアンチスチック特性 に対するものである。これはまたコンタクトレンズまたは眼瞼のスチックを防止 するために眼球表面に与λられねばならない。試験によると蛋白質による接着力 は、ある状態において９９％まで減少する可能性があることが判明している。This artificial tear solution also has release properties. Lecithin is Widely used as a leasing agent, it has adhesive or anti-stick properties. It is for. This also prevents contact lenses or eyelid sticks In order to do so, λ must be applied to the ocular surface. Tests show that protein-based adhesion It has been found that in some conditions it can be reduced by up to 99%.
本発明の人工涙溶液は少なくとも２種の要領で涙フィルムによって液の保持性を 強化する。第１に、ヒアルロン酸は水分をその長い親水性分子との緩い結合によ って保持する傾向があることはよく知られている。第２に、リン脂質はモルイヤ を形成して空気−水インターフェースでの蒸発を減少する可能性があること、工 業用表面活性剤がダム上で水の蒸発を防止するのと同様である。The artificial tear solution of the present invention improves fluid retention by the tear film in at least two ways. Strengthen. First, hyaluronic acid absorbs water through loose bonds with its long hydrophilic molecules. It is well known that there is a tendency to maintain Second, phospholipids are evaporation at the air-water interface. Similar to the way commercial surfactants prevent water evaporation on dams.
本発明の人工涙溶液はまたフィルムの破損を防止する。疎水性表面の上にある水 の層は高い分離圧力を有して乾燥して表面に露出して層の破損をもたらす傾向が ある。この現象はテフロンをライニングしたフライパンの水の弾きから同意され る。水の深さが約１乃至１．５ミリメータに減少すると、層は突如破壊して乾燥 面が露出するのはやはり疎水性のものであり、従って人が２０秒程度ごとに瞬き をしないと涙フィルムが破損する傾向がある。発明者らの試験によると、テフロ ンに対する１０８°、濡れる可能性のある表面に対する０°に比較して牛の眼球 上で約７０°の接触角を得た。接触角とは固体表面と、全ての３相が出会う３重 、尭での空気−液体インターフェースの切線との間の角度である。The artificial tear solution of the present invention also prevents film breakage. water on top of a hydrophobic surface The layers have a high separation pressure and tend to dry out and lead to layer failure when exposed to the surface. be. This phenomenon is confirmed by the water repellency of Teflon-lined frying pans. Ru. When the water depth decreases to about 1 to 1.5 mm, the layer suddenly breaks down and dries out. The surface that is exposed is still hydrophobic, so when a person blinks every 20 seconds or so, Otherwise, the tear film tends to be damaged. According to the inventors' tests, Teflo 108° to the surface, compared to 0° to potentially wet surfaces. A contact angle of approximately 70° was obtained above. The contact angle is the triple contact angle between the solid surface and all three phases. , the angle between the tangential line of the air-liquid interface at the angle.
分離圧力、従って、フィルムの破損する傾向は組織−液体および空気−液体の両 者の表面エネルギーが減少するならば減少させ得るにの後者は濡れ性の酸として 作用するヒアルロン酸によって減少され、一方前者は表面張力を減少する涙フィ ルムの表面の表面活性モルイヤーの存在によって減少する。これは表面蒸発を減 少させるモルイヤーと同一のもので達成し得る。The separation pressure, and therefore the tendency of the film to fail, is influenced by both tissue-liquid and air-liquid The latter can be reduced if the surface energy of the The former is reduced by hyaluronic acid, which acts on tear filaments that reduce surface tension. reduced by the presence of surface active mole layers on the surface of the lume. This reduces surface evaporation. This can be achieved with the same mole year that reduces the amount of water.
兄里五叉施しエニ上 本発明を以下実例によって説明する。Anisato five-pronged alms-giving The invention will now be illustrated by way of example.
例上 リン脂質組成物の眼球上での潤滑効果に関して定量を行った。リン脂質組成物は ３ｍｇ／ｍｌのＤＰＬ （フォスファチジルコリン）を１０ｍｇ／ｍｌのヒアル ロン酸に超音波分散によって懸濁させて用意した。example The lubricating effect of the phospholipid composition on the eyeball was determined. The phospholipid composition is 3mg/ml DPL (phosphatidylcholine) and 10mg/ml Hyal It was prepared by suspending it in ronic acid by ultrasonic dispersion.
５匹の屠殺したばかりの新鮮な羊の眼球１０個が摩擦機械で試験されて０．Ｏｌ ないし０口４の間に広がる運動摩擦係数（μ）が得られた。同一の眼球は溶液（ ２：１クロロフォルム：メタノール）で１０分間すすいで、存在する天然リン脂 質を除去して再試験した。摩擦は非常に増加して、事実、トランスジューサの目 盛りが振り切れたが、これはμ〉０．１に相当する。リン脂質組成物を次に眼球 に与えて運動摩擦係数を再定量すると、μは０．０１ないし０，０４の範囲内と なった。Ten eyeballs from five freshly slaughtered sheep were tested in a friction machine with a score of 0. Ol A coefficient of kinetic friction (μ) ranging between 0 and 4 was obtained. Identical eyeballs are in solution ( Rinse with 2:1 chloroform:methanol for 10 minutes to remove any natural phospholipids present. The quality was removed and retested. The friction increases so much that in fact the transducer eye Although the peak has been shaken out, this corresponds to μ>0.1. Phospholipid composition then eyeball If we requantify the coefficient of kinetic friction by giving became.
型皿 別の試験は潤滑能力モード、即ち例Ｉで使用した同一のリン脂質組成物の磨耗性 、である。３個のボールベアリングをこれらが運動できないように相互にクラン プし、次にその他のものと３点で接触するように第４番目を加えて４−ボール試 験を行った。第４ボールベアリングに溶接したシャフトを４０ｋｇの荷重の下で １５００ｒｐｍで１時間回転し、３固定ボールベアリングに出来た溝の深さを顕 微鏡で測定して平均した。例■のリン脂質組成物の使用の下で溝は平均０．７０ ｍｍであった。別のリン脂質組成物で、この場合リン脂質濃度を４ｍｇ／ｍｌで 、ヒアルロン酸を１０ｍｇ／ｍｌに止めて試験を繰り返したが、出来た溝の平均 の深さの値は０．６９ｍｍであった。mold plate Another test was performed in the lubricity mode, i.e. the abrasive properties of the same phospholipid composition used in Example I. , is. Clamp the three ball bearings together so that they cannot move. and then add a fourth to make 3-point contact with the others for a 4-ball attempt. Test was carried out. The shaft welded to the fourth ball bearing is placed under a load of 40 kg. Rotate at 1500 rpm for 1 hour to reveal the depth of the groove formed in the 3 fixed ball bearings. Measured with a microscope and averaged. Under the use of the phospholipid composition of Example ■, the grooves averaged 0.70 It was mm. Another phospholipid composition, in this case with a phospholipid concentration of 4 mg/ml. , the test was repeated with hyaluronic acid kept at 10 mg/ml, but the average of the grooves formed was The depth value was 0.69 mm.
これらの結果は、潤滑剤としてのリン脂質の有効性を示す。リン脂質を使用する 試験結果は牛乳に対する１、４ｍｍ、非常に良好な潤滑油の０．３５ｍｍ、典型 的な市販水溶性潤滑剤の０．７乃至０．９ ｍｍと良好に比較される。These results demonstrate the effectiveness of phospholipids as lubricants. use phospholipids Test results are 1,4mm for milk, 0.35mm for very good lubricating oil, typical This compares well with the 0.7 to 0.9 mm of commercially available water-soluble lubricants.
凱里 プロピレングリコールに溶解したレシチン組成物を用意したが、例■のそれと類 似の長所が発見された。プロピレングリコールに溶解したレシチンとヒアルロン 酸の組成物も成功的な結果を生じた。Kaili A lecithin composition dissolved in propylene glycol was prepared, but it was similar to that in Example ■. Similar advantages were discovered. Lecithin and hyaluron dissolved in propylene glycol Acid compositions have also produced successful results.
要約署 リン脂質と所望に応じてヒアルロン酸またはその塩類を適当なキャリア中に有す る乾燥眼球症候群またはただれ目の処置または予防に使用する人工涙組成物。Summary station phospholipids and optionally hyaluronic acid or its salts in a suitable carrier. An artificial tear composition used for the treatment or prevention of dry eye syndrome or sore eyes.
キャリアは好ましくは等張付の塩出の溶液、例えば生理的食塩水またはその他で はプロピレングリコールである。記載のような組成物を使用してのただれ目また は乾燥根症候群の処置方法。この方法はコンタクトレンズを付けた眼球の処置に も使用し得る。The carrier is preferably an isotonic salt solution, such as saline or the like. is propylene glycol. Sore eyes can also be treated using compositions such as those described. is a treatment method for dry root syndrome. This method is used to treat eyes with contact lenses. may also be used.
国際調査報告 ＡＮ）ＥＫ ’ＩＯ升侶り打Ｅ田幼ｘＶ】ＱＬ ＩＥＥＡＲＯ！ ＲＥＰ！ゴｆ ｆＧｊ摺形称肩ｄ症扁Ｑ貫１世：にｐｑ丁四弛ＱＩＥ ４［１３９１７５ＥＰ ３１６３４５ ＩＣ８８００Ｂ２４ ＴＥ ４８０４５３９ｗ０９０１１７８１ ＡＩＪ５４２９７／９０ ０ｋ ２０１３７７０ ＺＡ ９００２５９３ＡＩ Ｊ ２７５５３／８４ ｆｆ ３３１６０１２ り １００９６４ ｍ、 ７１ ７１２ＪＰ５９０４４３２６ ＺＡ ８４０３２５４ １１！３２２ｅ６２９謄 りＣＦＡＮＩξＸinternational search report AN) EK 'IO Masuari Uta Edenyo xV] QL IEEARO! REP! Go f fGj Suriform name shoulder d syndrome Bian Q Kan 1st: ni pq Ding Shiro QIE 4 [139175EP] 316345 IC8800B24 TE 4804539w09011781 AIJ54297/90 0k 2013770 ZA 9002593AI J 27553/84 ff 3316012 ri 100964 m, 71 712JP59044326 ZA 8403254 11!322e629 riCFANIξX
Claims (9)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AUPJ876390 | 1990-02-22 | ||
| AU8763 | 1990-02-22 | ||
| PCT/AU1991/000063 WO1991012808A1 (en) | 1990-02-22 | 1991-02-22 | Artificial tears |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH05503527A true JPH05503527A (en) | 1993-06-10 |
Family
ID=3774513
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3504155A Pending JPH05503527A (en) | 1990-02-22 | 1991-02-22 | artificial tears |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0516685A4 (en) |
| JP (1) | JPH05503527A (en) |
| AU (1) | AU655919B2 (en) |
| WO (1) | WO1991012808A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008517043A (en) * | 2004-10-20 | 2008-05-22 | インターファーム ディベロップメント エスエー | Bioadhesive composition by release programming |
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| WO1995014488A1 (en) * | 1993-11-24 | 1995-06-01 | Ocutech, Inc. | Compositions and methods for the treatment of dry eyes and other ocular disorders |
| AU699375B2 (en) * | 1995-12-19 | 1998-12-03 | Macnaught Medical Pty Limited | Phospholipid and propylene glycol based lubricant |
| AUPN723395A0 (en) * | 1995-12-19 | 1996-01-18 | Macnaught Medical Pty Limited | Lubrication methods |
| ES2127110B1 (en) * | 1996-05-24 | 1999-12-01 | Univ Valladolid | PROCEDURE TO VARY THE ELECTRICAL PROPERTIES OF THE HUMAN EYE MOCO AND SUBSTITUTES FOR OPHTHALMIC USE. |
| IL120005A (en) * | 1997-01-14 | 2000-08-31 | Ramot University Authority Of | Pharmaceutical compositions for the treatment of the eye |
| GB9716376D0 (en) * | 1997-08-01 | 1997-10-08 | Isis Innovation | Artificial tear formulation |
| EP0982025A1 (en) * | 1998-08-28 | 2000-03-01 | Wilhelm Prof. Dr. Stoffel | Synthetic tear fluid |
| US6458854B2 (en) | 1999-11-09 | 2002-10-01 | Alcon Universal Ltd. | Phospholipids of hydroxyeicosatetraenoic acid-like derivatives and methods of use |
| DE60020591T2 (en) | 1999-11-09 | 2005-11-10 | Alcon Inc. | BENZENOID DERIVATIVES OF 15-HYDROXYEICOSATETRAIC ACID AND METHOD FOR USE FOR THE TREATMENT OF DRY EYE |
| CN1387504A (en) | 1999-11-09 | 2002-12-25 | 爱尔康公司 | Omega-chain modified 15-hydroxyeicosatetraenoic acid derivatives and methods of their use for treatment of dry eye |
| US6552084B2 (en) | 1999-11-09 | 2003-04-22 | Alcon Universal Ltd. | Hydroxyeicosatetraenoic acid analogs and methods of their use in treating dry eye disorders |
| PL355998A1 (en) | 1999-11-09 | 2004-05-31 | Alcon Inc. | Compositions containing hydroxyeicosatetraenoic acid derivatives and methods of use in treating dry eye disorders |
| US6353032B1 (en) | 1999-11-09 | 2002-03-05 | Alcon Universal Ltd. | Phospholipids of hydroxyeicosatetraenoic acid-like derivatives and methods of use |
| TR200201249T2 (en) | 1999-11-09 | 2002-09-23 | Alcon, Inc. | The heteroatom intervening analogues of 15-hydroxyiecosatetraenoic acid and their methods of use. |
| MXPA02004700A (en) | 1999-11-09 | 2004-09-10 | Alcon Inc | 15-hydroxyeicosatetraenoic acid-related compounds and methods of use. |
| TR200201250T2 (en) | 1999-11-09 | 2002-09-23 | Alcon, Inc | Hydroxyiecosatetraenoate salts, their compositions and methods for their use in the treatment of dry eye disorders. |
| AU776146B2 (en) | 1999-11-09 | 2004-08-26 | Alcon Inc. | 3-heteroatom substituted and two carbon homologs of 15-HETE and methods of use |
| AU1101301A (en) | 1999-11-09 | 2001-06-06 | Alcon Universal Limited | 2,2-difluoro 15-hydroxyeicosatetraenoic acid analogs and methods of use |
| US6320062B1 (en) | 1999-11-09 | 2001-11-20 | Alcon Universal Ltd. | 15-hydroxyeicosatetraenoic acid analogs with enhanced metabolic stability and methods of their use in treating dry eye disorders |
| US6803385B2 (en) | 1999-11-09 | 2004-10-12 | Alcon, Inc. | Hydroxyeicosatetraenoic acid analogs and methods of their use in treating dry eye disorders |
| US6565861B1 (en) | 2000-02-11 | 2003-05-20 | Isis Innovation Limited | Artificial tear formulation |
| EP1517673A1 (en) * | 2002-06-20 | 2005-03-30 | Novartis Consumer Health S.A. | Nasal composition comprising a mucopolysaccharide and propylene glycol |
| US20050196370A1 (en) * | 2003-03-18 | 2005-09-08 | Zhi-Jian Yu | Stable ophthalmic oil-in-water emulsions with sodium hyaluronate for alleviating dry eye |
| AR062046A1 (en) | 2006-07-25 | 2008-08-10 | Osmotica Pharmaceutical Argentina S A | OPHTHALMIC SOLUTIONS |
| IT1394223B1 (en) | 2009-05-15 | 2012-06-01 | Thea Sas Lab | KIT FOR ASSESSMENT AND CUSTOMIZED SELECTION OF ARTIFICIAL TEARS |
| WO2011138228A1 (en) * | 2010-05-04 | 2011-11-10 | Trb Chemedica Ag | Aqueous composition for ophthalmic or dermal use |
| DE102010023949A1 (en) * | 2010-06-16 | 2011-12-22 | F. Holzer Gmbh | In-situ lecithin microemulsion gel formulation |
| CA3016688A1 (en) * | 2016-03-08 | 2017-09-14 | University Of Utah Research Foundation | Ophthalmic cross-linking agents and associated methods |
| EP3484497A4 (en) * | 2016-07-18 | 2020-01-01 | Regentree, LLC | Methods of treating dry eye syndrome |
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| PH17800A (en) * | 1980-03-21 | 1984-12-13 | Wellcome Found | Stabilized ophthalmic formulation |
| US4421748A (en) * | 1982-07-13 | 1983-12-20 | Trager Seymour F | Artificial tear aid |
| DE3316012A1 (en) * | 1983-05-03 | 1984-11-08 | Rainer Richard Otto Dr.med. 3104 Unterlüß Reifenrath | Pharmaceutical product for the treatment and prophylaxis of infections and of coughs and obstructive airway disorders and process for the preparation thereof |
| US4804539A (en) * | 1986-07-28 | 1989-02-14 | Liposome Technology, Inc. | Ophthalmic liposomes |
| US4839175A (en) * | 1986-07-28 | 1989-06-13 | Liposome Technology, Inc. | Liposomes with enhanced retention on mucosal tissue |
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| US4818537A (en) * | 1986-10-21 | 1989-04-04 | Liposome Technology, Inc. | Liposome composition for treating dry eye |
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| US5403592A (en) * | 1987-08-25 | 1995-04-04 | Macnaught Pty Limited | Lubricant composition for rheumatism |
| AU633078B2 (en) * | 1989-04-04 | 1993-01-21 | Alcon Laboratories, Inc. | The use of liposomes for the delivery of therapeutic agents to wounds, cuts and abrasions |
| US5174988A (en) * | 1989-07-27 | 1992-12-29 | Scientific Development & Research, Inc. | Phospholipid delivery system |
-
1991
- 1991-02-22 JP JP3504155A patent/JPH05503527A/en active Pending
- 1991-02-22 AU AU73076/91A patent/AU655919B2/en not_active Ceased
- 1991-02-22 EP EP19910904702 patent/EP0516685A4/en not_active Withdrawn
- 1991-02-22 WO PCT/AU1991/000063 patent/WO1991012808A1/en not_active Application Discontinuation
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008517043A (en) * | 2004-10-20 | 2008-05-22 | インターファーム ディベロップメント エスエー | Bioadhesive composition by release programming |
| US10646435B2 (en) | 2004-10-20 | 2020-05-12 | Care & Pharma Perspectives Sa | Pasty bio-adhesive sustained release compositions |
Also Published As
| Publication number | Publication date |
|---|---|
| EP0516685A4 (en) | 1993-03-17 |
| AU7307691A (en) | 1991-09-18 |
| WO1991012808A1 (en) | 1991-09-05 |
| EP0516685A1 (en) | 1992-12-09 |
| AU655919B2 (en) | 1995-01-19 |
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