[go: up one dir, main page]

WO2010107069A1 - Composition ophtalmique contenant des acides aminés - Google Patents

Composition ophtalmique contenant des acides aminés Download PDF

Info

Publication number
WO2010107069A1
WO2010107069A1 PCT/JP2010/054571 JP2010054571W WO2010107069A1 WO 2010107069 A1 WO2010107069 A1 WO 2010107069A1 JP 2010054571 W JP2010054571 W JP 2010054571W WO 2010107069 A1 WO2010107069 A1 WO 2010107069A1
Authority
WO
WIPO (PCT)
Prior art keywords
amino acid
glutamine
ophthalmic composition
asparagine
arginine
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.)
Ceased
Application number
PCT/JP2010/054571
Other languages
English (en)
Japanese (ja)
Inventor
茂 木下
千恵 外園
淳爾 羽室
明 岡野
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Ajinomoto Co Inc
Senju Pharmaceutical Co Ltd
Original Assignee
Ajinomoto Co Inc
Senju Pharmaceutical Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Ajinomoto Co Inc, Senju Pharmaceutical Co Ltd filed Critical Ajinomoto Co Inc
Priority to JP2011504870A priority Critical patent/JPWO2010107069A1/ja
Publication of WO2010107069A1 publication Critical patent/WO2010107069A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to an ophthalmic composition, and particularly to an ophthalmic composition useful for the prevention and treatment of ocular surface diseases associated with dry eye.
  • the lacrimal fluid covers the eyeball surface consisting of the cornea and conjunctiva to maintain the wetness of the cornea and prevent it from drying.
  • various kinds of sensations such as fatigue and foreign body sensation have occurred due to dryness of the keratoconjunctiva surface associated with tear reduction, dryness of the eyes when wearing contact lenses, or dryness of the eyes that occurs during the operation of OA equipment.
  • An increasing number of people complain of symptoms, ie dry eye symptoms. Dry eye is often accompanied by corneal epithelial damage or corneal epithelial fistula due to damage of corneal epithelial cells, and in severe cases, it may cause corneal ulcers and eye infections.
  • the first choice for dry eye treatment is artificial eye drops.
  • Various artificial tears have been proposed so far, and artificial tears mainly composed of salts such as sodium chloride, eye drops containing hydroxyethyl cellulose, chondroitin sulfate or hyaluronic acid, and the like are conventionally known.
  • these artificial tears alone do not improve symptoms.
  • dry eye is largely associated not only with dryness (decrease in tear volume) but also with abnormal tear composition (ie, tear quality).
  • eye drops in which specific amino acids are added to conventional eye drops have been developed (Patent Documents 1 to 3), but for dry eyes, particularly dry eyes associated with serious epithelial disorders, There is still no artificial tear that can provide a satisfactory therapeutic effect.
  • An object of the present invention is to provide an ophthalmic composition useful for the prevention and treatment of dry eye, particularly dry eye associated with severe epithelial disorder.
  • an ophthalmic composition comprising at least one amino acid selected from the group consisting of alanine, asparagine, glutamine and arginine.
  • the amino acid is 2 or 3 amino acids selected from alanine, asparagine and glutamine.
  • the amino acids are three kinds of alanine, asparagine and glutamine.
  • the ophthalmic composition according to the above [1], wherein the amino acids are arginine, asparagine and glutamine.
  • the present invention not only mild dry eye as a symptom, but also dry eye in which improvement of the symptom was not observed even when conventional artificial tears were frequently instilled, particularly dry eye associated with severe epithelial disorder. It has a therapeutic effect on. Furthermore, the preventive effect which prevents the onset of dry eye can be expected.
  • the present invention contains an ophthalmic composition containing at least one amino acid selected from alanine, asparagine, glutamine, and arginine (hereinafter sometimes abbreviated as the ophthalmic composition of the present invention).
  • an ophthalmic composition useful for the prevention and treatment of ocular surface diseases associated with dry eye is provided.
  • dry eye refers to keratoconjunctival epithelial disorder caused by a qualitative or quantitative abnormality in tears (layer).
  • Alanine, asparagine, glutamine and arginine, which are active ingredients of the ophthalmic composition of the present invention, may be free forms or pharmacologically acceptable salts.
  • a salt for example, a salt with a physiologically acceptable acid (eg, inorganic acid, organic acid) or a base (eg, alkali metal, alkaline earth metal) is used, and an alkali metal salt ( Examples: sodium salts, potassium salts), alkaline earth metal salts (eg, calcium salts, magnesium salts) and the like are preferably exemplified.
  • a peptide known to exhibit an effect equivalent to that of an amino acid that is an active ingredient of the ophthalmic composition of the present invention on cells, such as L-alanylglutamine, can also be used.
  • Alanine, asparagine, glutamine and arginine (hereinafter also referred to as effective amino acids), which are active ingredients of the ophthalmic composition of the present invention, may be used alone or in combination of two or more. This is highly effective and preferable. As such a preferable combination, asparagine and alanine, asparagine and glutamine, asparagine and arginine, alanine and glutamine, alanine and arginine, a combination of glutamine and arginine, and asparagine and alanine in the case of three combinations.
  • Combinations of alanine and glutamine, asparagine and alanine and arginine, alanine and glutamine and arginine, arginine and asparagine and glutamine, and combinations of four types include combinations of asparagine, alanine, glutamine and arginine.
  • the effective amino acid combination of the ophthalmic composition of the present invention is a combination consisting of 2 or 3 amino acids selected from alanine, asparagine and glutamine.
  • Another preferred combination is a combination of alanine and glutamine, glutamine and arginine, alanine and glutamine and arginine, asparagine and glutamine and arginine, alanine, asparagine, glutamine and arginine.
  • the concentration of the effective amino acid in the ophthalmic composition of the present invention is not particularly limited as long as the effect of promoting the proliferation of the keratoconjunctival epithelial cells and / or the wound healing effect is obtained and the cytotoxicity does not occur. Is a total of 0.05 mM to 1000 mM, preferably 0.1 mM to 800 mM, more preferably 0.3 mM to 200 mM, and particularly preferably 0.5 mM to 100 mM. Each effective amino acid concentration is not particularly limited as long as a desired effect is exhibited.
  • each effective amino acid concentration can be appropriately selected from the range of 0.1 ⁇ M to 800 mM, preferably 0.5 ⁇ M to 100 mM, more preferably 1 ⁇ M to 600 ⁇ M, and particularly preferably 1 ⁇ M to 500 ⁇ M.
  • alanine for example, 0.5 ⁇ M to 600 mM, preferably 1 ⁇ M to 500 mM, more preferably 8 ⁇ M to 150 mM, especially 10 ⁇ M to 100 mM, and in the case of asparagine, for example, 1 ⁇ M to 300 mM, preferably 5 ⁇ M to 150 mM, more preferably 10 ⁇ M to 100 mM, in the case of arginine, for example, 0.1 ⁇ M to 200 mM, preferably 0.5 ⁇ M to 100 mM, more preferably 3 ⁇ M to 50 mM, in the case of glutamine, for example, 1 ⁇ M to 600 mM It is preferably 5 ⁇ M to 500 mM, more preferably 10 ⁇ M to 200 mM, especially 12 to 150 ⁇ M.
  • the ophthalmic composition of the present invention may be any preparation that can be administered to the local tissue of the eye, and examples thereof include eye drops, patches, ointments, lotions, creams, etc. It is an eye drop.
  • a substrate may be used as appropriate.
  • Base materials used in eye drops include phosphate buffer, Hanks buffer, physiological saline, perfusate (eg, BS Plus (Nippon Alcon Co., Ltd.), Opeguard Neo Kit (Senju Pharmaceutical Co., Ltd.)), artificial For example, lacrimal fluid.
  • BS Plus is used as a base material, it is possible to use only the diluted solution without adding the oxyglutathione solution.
  • the ophthalmic composition of the present invention may further contain another drug having an effect of preventing or treating keratoconjunctival epithelial disorder.
  • a concomitant drug include, but are not limited to, a corneal protective agent (eg, hyaluronic acid, chondroitin sulfate or a salt thereof), an immunosuppressive / anti-inflammatory agent (eg, cyclosporine, steroid) and the like.
  • the ophthalmic composition of the present invention includes any other active ingredient such as an antiallergic or antihistamine ingredient, a decongestant ingredient, a local anesthetic ingredient, a vitamin ingredient, and an amino acid ingredient other than an effective amino acid (eg, valine, Leucine, isoleucine, serine, threonine, methionine, proline, phenylalanine, tyrosine, tryptophan, aspartic acid, glutamic acid, lysine, histidine, citrulline, ornithine, cystine, taurine, glycine) and the like.
  • an effective amino acid eg, valine, Leucine, isoleucine, serine, threonine, methionine, proline, phenylalanine, tyrosine, tryptophan
  • an effective amino acid eg, valine, Leucine, isoleucine, serine, threonine, methionine, proline,
  • the ophthalmic composition of the present invention may be appropriately mixed with various additives such as a buffer, an isotonic agent, a preservative, a solubilizer, a stabilizer, a chelating agent, a thickener, and a pH adjuster. it can.
  • the buffer examples include boric acid or a salt thereof (borax, etc.), citric acid or a salt thereof (sodium citrate, etc.), tartaric acid or a salt thereof (sodium tartrate, etc.), gluconic acid or a salt thereof (sodium gluconate, etc.) ), Acetic acid or a salt thereof (sodium acetate, etc.), phosphoric acid or a salt thereof (sodium monohydrogen phosphate, sodium dihydrogen phosphate, etc.), various amino acids such as glutamic acid or epsilon aminocaproic acid, and a tris buffer, etc. Combinations are listed.
  • isotonic agent examples include sorbitol, mannitol, glycerin, propylene glycol, sodium chloride, potassium chloride and the like.
  • preservative examples include paraoxybenzoates, benzalkonium chloride, benzethonium chloride, benzyl alcohol, sorbic acid or a salt thereof, chlorhexidine gluconate, sodium dehydroacetate, cetylpyridinium chloride, alkyldiaminoethylglycine hydrochloride, chlorobutanol Etc.
  • solubilizer examples include polyvinyl pyrrolidone, polyethylene glycol, propylene glycol, polyoxyethylene hydrogenated castor oil 60, polyoxyl 40 stearate, polysorbate 80 (trade name: Tween 80), and the like.
  • the stabilizer examples include sodium edetate, sodium thiosulfate, ascorbic acid, cyclodextrin, condensed phosphoric acid or a salt thereof, sulfite, citric acid or a salt thereof, and dibutylhydroxytoluene.
  • chelating agent examples include sodium edetate, sodium citrate, condensed phosphoric acid or a salt thereof (such as condensed sodium phosphate).
  • thickener examples include methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose sodium, polyvinyl pyrrolidone, polyvinyl alcohol, polyethylene glycol, hyaluronic acid and the like.
  • Examples of the pH adjuster include sodium hydroxide, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate, boric acid or a salt thereof (borax), hydrochloric acid, citric acid or a salt thereof (sodium citrate, sodium dihydrogen citrate). Etc.), phosphoric acid or a salt thereof (disodium hydrogen phosphate, potassium dihydrogen phosphate, etc.), acetic acid or a salt thereof (sodium acetate, ammonium acetate, etc.), tartaric acid or a salt thereof (sodium tartrate, etc.), and the like.
  • the pH of the ophthalmic composition of the present invention is adjusted to 3 to 10, preferably 5 to 8.
  • the ophthalmic composition of the present invention exhibits excellent effects such as reduction of eye pain, difficulty in opening the eye, foreign body sensation, fatigue, etc., as well as improvement in visual acuity, conjunctival hyperemia, corneal epithelial state, and the like. Therefore, the ophthalmic composition of the present invention is useful as a prophylactic / therapeutic agent for ocular surface diseases, particularly keratoconjunctival epithelial disorders.
  • keratoconjunctival epithelial disorders include corneal epithelial disorders caused by desiccation (eg, tear reduction, dry eye, meibomian gland dysfunction, Sjogren's syndrome, dry keratoconjunctivitis, blepharitis, Stevens-Johnson syndrome, VDT) Dry eye syndrome such as dry eye associated with work, or keratoconjunctival epithelial disorder associated with dry eye, scarring keratoconjunctivitis, corneal epithelial fistula, corneal ulcer, blepharitis, pemphigoid, spring catarrh, allergy Conjunctivitis, etc.), corneal epithelial damage caused by ultraviolet rays (eg, keratitis, snow eyes, etc.), chemical trauma caused by chemicals, drugs contained in eye drops (eg, preservatives, eye anesthetics, prostaglandins, Corneal epithelial disorder (for example, punctate superficial keratitis,
  • the ophthalmic composition of the present invention can also be used as an ophthalmic composition for preventing or improving eye fatigue, eye irritation, blurred vision, itchy eyes, conjunctival hyperemia, and discomfort when wearing contact lenses. Can be used.
  • the ophthalmic composition of the present invention is used for preventing or treating the above-mentioned diseases or conditions in humans and animals other than humans (for example, mammals other than humans (domestic animals such as pigs, cows, horses, dogs, and pets)). Can be used.
  • the dosage of the ophthalmic composition of the present invention may vary depending on the dosage form, target disease, animal species to be administered, age, sex, weight, symptoms, etc., for example, adult (for example, 60 kg body weight) In this case, it is usually in the range of 0.1 ⁇ g to 2.0 g, preferably 0.5 ⁇ g to 1.8 g, more preferably 1.0 ⁇ g to 1.g in terms of the total amount of amino acids in the composition per day. The range is 5 g.
  • the daily dose of the ophthalmic composition of the present invention can be administered once or divided into several times.
  • the ophthalmic composition of the present invention is used 5 to 20 times, preferably 16 to 18 times per day (generally once an hour) for severe dry eye patients. ), 2 to 10 times, preferably 3 to 7 times a day for patients with mild dry eye.
  • the dose per administration is 1 to 3 drops (50 to 150 ⁇ L), preferably 1 to 2 drops (50 to 100 ⁇ L) per eye.
  • the administration period is not particularly limited.
  • amino acids and the like are represented by abbreviations based on abbreviations by IUPAC-IUB Commission on Biochemical Nomenclature or conventional abbreviations in the field, examples of which are described below.
  • optical isomer with respect to an amino acid the L form is shown unless otherwise specified.
  • Gly Glycine Ala: Alanine Val: Valine Leu: Leucine Ile: Isoleucine Ser: Serine Thr: Threonine Cys: Cysteine Met: Methionine Glu: Glutamic acid Asp: Aspartic acid Lys Argin P : Tryptophan Pro: Proline Asn: Asparagine Gln: Glutamine Orn: Ornithine Cit: Citrulline (Cys) 2 : Cystine Tau: Taurine
  • the target amino acids were glycine, alanine, valine, leucine, isoleucine, phenylalanine, proline, serine, threonine, tyrosine, asparagine, glutamine, lysine, arginine, tryptophan, histidine, methionine, aspartic acid, glutamic acid, ornithine, citrulline. Cystine, taurine. Assuming that the total amount of amino acids to be measured in tears of each subject of healthy subjects and dry eye patients was 100, the composition ratio of each amino acid was calculated. The results are shown in Table 1. In addition, a 2-hour VDT operation was carried out with a resting tear fluid of a healthy person, and each amino acid concentration ( ⁇ M) in the tear fluid when a temporary dry eye state was obtained was measured. The results are shown in Table 2.
  • Zero medium powder in double distilled water 400mL [CaCl 2 (anhyd) 200mg , Fe (NO 3) 3 ⁇ 9H 2 O 0.1mg, KCl 400mg, MgSO 4 (anhyd) 97.67mg, NaCl 6400mg, NaHPO 4 ⁇ H 2 O 125 mg, Sodium pyruvate 110 mg, D-Capantheneate 4 mg, Choline Chloride 4 mg, Folic acid 4 mg, I-inositol 7.2 mg, Niacinide 4 mg, Riboflavin 4 mg, Riboflavin 4 NaHCO 3 3.7 g and Glucose 1 g were added and dissolved.
  • the medium was adjusted to pH 7.4 with HCl (hydrochloric acid) and diluted to 500 mL with double distilled water. Then, after sterilizing filtration with a 0.22 ⁇ m sterilizing filter, it was stored at 4 ° C.
  • HCl hydrochloric acid
  • Amino acid powder was appropriately added to the 2 ⁇ Zero medium and dissolved, and then sterilized with a 0.22 ⁇ m sterilizing filter and stored at 4 ° C.
  • 2 ⁇ Zero medium 50 mL is filled with Full medium powder [Glycine 3.0 mg, L-Aline 3.56 mg, L-Series 4 .2 mg, L-Throneine 9.5 mg, L-Cystein 2HCl 6.3 mg, L-Methionine 3.0 mg, L-Glutamine 58.4 mg, L-Asparagine 5.28 mg, L-Glutamate Acid-Asp.
  • amino acid-containing medium lacking some amino acids was also prepared by dissolving the necessary amino acid powder in 2 ⁇ Zero medium in the same manner as described above, or by aseptically adding a previously prepared amino acid solution.
  • For the supplemented medium containing essential amino acids and 1 to 4 non-essential amino acids dissolve the necessary amino acid powder in 2 ⁇ Zero medium in the same manner as above, or aseptically add a prepared amino acid solution. Adjusted.
  • the cultured cells were collected using 0.25% trypsin, seeded in a 96-well plate (Corning) at 2 ⁇ 10 4 cells / well, and EpiLife medium was used in a 5% CO 2 atmosphere.
  • the cells were cultured at 37 ° C. for 2 days. Thereafter, the medium was replaced with Zero medium, and cultured at 37 ° C. for 1 day in a 5% CO 2 atmosphere. Subsequently, the medium was changed again to each specimen medium, and the culture was continued for 3 days (5% CO 2 , 37 ° C.).
  • the amino acid composition of each specimen medium is shown in Table 3 for the deficient medium and Table 4 for the supplemented medium.
  • the essential amino acid medium contains glutamine and arginine, asparagine and alanine, asparagine and alanine and glutamine, asparagine and alanine and arginine, alanine and glutamine and arginine, arginine and asparagine and glutamine, and asparagine and alanine, glutamine and arginine.
  • the total concentration of amino acids contained in the medium is preferably less than about 18 mM.
  • cytotoxicity tends to be expressed more strongly than the effect of amino acid addition.
  • the cultured cells were collected using 0.25% trypsin, seeded in a 6-well plate (Corning) at 5 ⁇ 10 4 cells / well, and EpiLife medium was used in a 5% CO 2 atmosphere.
  • the cells were cultured at 37 ° C. for 2 weeks. Thereafter, the medium was changed to Zero medium, and cultured at 37 ° C. for 1 day in a 5% CO 2 atmosphere.
  • the confluent state cells were scraped linearly with the tip of a micropipette tip (1000 ⁇ L) to prepare a wound model. After wound preparation, the specimen medium was replaced and cultured for 48 hours. The recovery state of the wound site was examined using a phase contrast microscope.
  • wound width was measured using ImageJ image analysis software (NIH). A total of 6 measurements were made for each group.
  • amino acid-containing ophthalmic solution 2 As a result of observation from day 1 to day 7 of administration, no abnormality was observed in the cornea, iris and conjunctiva. Moreover, the blink immediately after administration was never observed. The total score of this group was 0, and the evaluation category of eye irritation corresponded to non-irritating substances.
  • amino acid-free ophthalmic solution As a result of observation from the first day of administration to the seventh day of administration, no abnormality was observed in the cornea, iris and conjunctiva. In addition, no blinks were observed immediately after administration. The total score of this group was 0, and the evaluation category of eye irritation corresponded to non-irritating substances. From the above, it can be determined that both the amino acid-containing ophthalmic solutions 1 and 2 have no eye irritation.
  • Example 2 Production test of ophthalmic composition of the present invention as an eye drop As shown in Table 9 below, an eye drop containing each amino acid is prepared.
  • Example 2 Clinical test using amino acid-containing eye drops
  • the amino acid-containing eye drops of each of the production examples described in Example 2 were administered to subjects, and the subjective symptoms or objective findings of the subjects after the administration were measured between subjects. Compare with. Specifically, the eye drop of any one of Production Examples 1, 2, 4, and 5 is administered to one eye of each subject, and the eye drop of Production Example 10 is administered to the other eye as a control. Eye drops are administered to healthy subjects and severe dry eye patients once or twice (50 to 100 ⁇ L) / eye once an hour. The number of administrations per day is 16-18. For patients with mild dry eye and VDT workers, 1-2 drops (50-100 ⁇ L) / eye is administered 4-6 times / day.
  • the above severe dry eye patient means a patient having a Schirmer test I method value of 5 mm or less and a Rose Bengal staining score (Van Bijsterveld score) of 9 points. It means a patient having a method I value of 5 mm or less and a Rose Bengal staining score (Van Bijsterveld score) of 6 to 8 points.
  • Mild dry eye patient means a dry eye patient with a Schirmer test I method value greater than 5 mm and a Rose Bengal staining score (Van Bijsterveld score) of 3-5 points.
  • Subjective symptoms Dryness, foreign body, eye pain, fatigue
  • Objective findings Improvement of visual acuity, presence of abnormalities of each conjunctiva by slit slit microscope, keratoconjunctival disorder caused by fluorescein staining Presence or absence (especially conjunctival punctuate staining (CPS) between ruptures), presence or absence of degenerated or damaged cells of the keratoconjunctival epithelium by rose bengal or Lissami green staining, BUT Time), observation of tear oil layer distribution (by dry eye observation device DR-1 TM (manufactured by Kowa))
  • Example 3 Clinical test using an eye drop containing an amino acid
  • the amino acid-containing eye drop prepared in Example 3 was administered to a subject, and the subjective symptoms or objective findings of the subject after the administration were evaluated.
  • amino acid-containing ophthalmic solution 3 or amino acid-containing ophthalmic solution 4 was administered once to 1-2 drops (50 to 100 ⁇ L) / eye and 6 times / day to each subject.
  • the subject has a normal tear volume with a Schirmer test I value of 5 mm or more, but the BUT (tear film breakage time) is significantly shorter than 5 seconds, and is there no keratoconjunctival epithelial disorder? It was a minor case and a BUT shortened dry eye patient with very strong subjective symptoms such as dryness.
  • SPK was improved from D2 to D1 at 8 weeks after administration in both the right eye of the subject 1 to which the amino acid-containing ophthalmic solution 3 was administered and the left eye of the subject 1 to which the amino acid-containing ophthalmic solution 4 was administered.
  • BUT was prolonged 8 weeks after administration in the left and right eyes of subject 2 and left and right eyes of subject 3 to which amino acid-containing ophthalmic solution 3 was administered.
  • the subjective symptom scores decreased in the left and right eyes of all subjects.
  • amino acid-containing ophthalmic solution 3 containing arginine and glutamine and the amino acid-containing ophthalmic solution 4 containing alanine, asparagine and glutamine are effective for the treatment of dry eye.
  • the therapeutic effect is acquired with respect to the dry eye in which the improvement of the symptom was not recognized even if the conventional artificial tears were instilled frequently, especially the dry eye accompanying a serious epithelial disorder. Specifically, it exhibits excellent effects in reducing subjective symptoms (eye pain, difficulty in opening the eye, foreign body sensation, fatigue, etc.) and improving objective findings (visual acuity, conjunctival hyperemia, corneal epithelial condition).
  • This application is based on Japanese Patent Application No. 2009-065284 filed in Japan (filing date: March 17, 2009), the contents of which are incorporated in full herein.

Landscapes

  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention concerne une composition ophtalmique qui est utile pour la prévention ou le traitement des conditions de sécheresse oculaire, notamment pour la prévention ou le traitement de conditions de sécheresse oculaire associées à de graves troubles épithéliaux. La présente invention décrit spécifiquement une composition ophtalmique qui est caractérisée par le fait qu'elle contient au moins un acide aminé choisi dans un groupe constitué par l'alanine, l'asparagine, la glutamine et l'arginine. La composition ophtalmique contient de préférence : deux ou trois acides aminés choisis parmi l'alanine, l'asparagine et la glutamine ; trois acides aminés, précisément l'arginine, l'asparagine et la glutamine ; ou deux acides aminés, précisément l'arginine et la glutamine. La présente invention concerne en outre une composition ophtalmique destinée à la prévention ou au traitement de troubles de la surface oculaire, notamment à la prévention ou au traitement de troubles de l'épithélium cornéen et conjonctival.
PCT/JP2010/054571 2009-03-17 2010-03-17 Composition ophtalmique contenant des acides aminés Ceased WO2010107069A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2011504870A JPWO2010107069A1 (ja) 2009-03-17 2010-03-17 アミノ酸含有眼科用組成物

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2009-065284 2009-03-17
JP2009065284 2009-03-17

Publications (1)

Publication Number Publication Date
WO2010107069A1 true WO2010107069A1 (fr) 2010-09-23

Family

ID=42739728

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2010/054571 Ceased WO2010107069A1 (fr) 2009-03-17 2010-03-17 Composition ophtalmique contenant des acides aminés

Country Status (2)

Country Link
JP (1) JPWO2010107069A1 (fr)
WO (1) WO2010107069A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017094506A1 (fr) * 2015-11-30 2017-06-08 ロート製薬株式会社 Composition ophtalmique
KR20200113243A (ko) * 2018-01-23 2020-10-06 세인다 파마슈티컬 코포레이션 안과용 약제학적 조성물 및 이의 제조 방법 및 용도
CN114869873A (zh) * 2022-05-05 2022-08-09 陈小鸟 谷氨酰胺在制备治疗干眼症的药物中的应用
RU2812316C2 (ru) * 2018-01-23 2024-01-29 Сэйнда Фармасьютикал Гуанчжоу Корпорейшн Офтальмологическая фармацевтическая композиция и способы ее получения и применения
CN120420344A (zh) * 2025-07-08 2025-08-05 中国人民解放军总医院第三医学中心 一种眼用药物组合物及其制备方法和应用

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2003160482A (ja) * 2001-09-17 2003-06-03 Menicon Co Ltd 眼科用液剤及びコンタクトレンズ用液剤
WO2006137469A1 (fr) * 2005-06-22 2006-12-28 Ajinomoto Co., Inc. Activateur du récepteur métabotropique du glutamate
ITRM20070202A1 (it) * 2007-04-10 2008-10-11 Finchlane Ltd Soluzione per uso esterno cicatrizzante le lesioni cutanee

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4605837B2 (ja) * 1999-06-17 2011-01-05 株式会社メニコンネクト 点眼剤
JP2001261552A (ja) * 2000-03-22 2001-09-26 Chisso Corp 点眼液用保存剤

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2003160482A (ja) * 2001-09-17 2003-06-03 Menicon Co Ltd 眼科用液剤及びコンタクトレンズ用液剤
WO2006137469A1 (fr) * 2005-06-22 2006-12-28 Ajinomoto Co., Inc. Activateur du récepteur métabotropique du glutamate
ITRM20070202A1 (it) * 2007-04-10 2008-10-11 Finchlane Ltd Soluzione per uso esterno cicatrizzante le lesioni cutanee

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DE BERARDINIS, E.: "The scar-producing action of amino acids in experimental corneal lesions and their influence on the metabolism of the cornea", AMERICAN JOURNAL OF OPHTHALMOLOGY, vol. 36, 1953, pages 138 - 139 *

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2021063133A (ja) * 2015-11-30 2021-04-22 ロート製薬株式会社 眼科組成物
JPWO2017094506A1 (ja) * 2015-11-30 2018-08-23 ロート製薬株式会社 眼科組成物
JP2019151661A (ja) * 2015-11-30 2019-09-12 ロート製薬株式会社 眼科組成物
WO2017094506A1 (fr) * 2015-11-30 2017-06-08 ロート製薬株式会社 Composition ophtalmique
JP7133048B2 (ja) 2015-11-30 2022-09-07 ロート製薬株式会社 眼科組成物
RU2812316C2 (ru) * 2018-01-23 2024-01-29 Сэйнда Фармасьютикал Гуанчжоу Корпорейшн Офтальмологическая фармацевтическая композиция и способы ее получения и применения
JP2021512172A (ja) * 2018-01-23 2021-05-13 セインダ ファーマシューティカル グアンジョウ コーポレイション 眼科的薬学的組成物、その調製方法、およびその適用
EP3744316A4 (fr) * 2018-01-23 2021-12-08 Seinda Pharmaceutical Guangzhou Corporation Composition pharmaceutique ophtalmique, son procédé de préparation et son application
CN112516080A (zh) * 2018-01-23 2021-03-19 盛元医药广州有限公司 一种眼用药物组合物及其制备方法和应用
CN112516080B (zh) * 2018-01-23 2023-09-19 盛元医药广州有限公司 一种眼用药物组合物及其制备方法和应用
JP7418351B2 (ja) 2018-01-23 2024-01-19 セインダ ファーマシューティカル グアンジョウ コーポレイション 眼科的薬学的組成物、その調製方法、およびその適用
KR20200113243A (ko) * 2018-01-23 2020-10-06 세인다 파마슈티컬 코포레이션 안과용 약제학적 조성물 및 이의 제조 방법 및 용도
EP4279063A3 (fr) * 2018-01-23 2024-02-14 Seinda Pharmaceutical Guangzhou Corporation Composition pharmaceutique ophtalmique, son procédé de préparation et son application
AU2019212565B2 (en) * 2018-01-23 2024-06-06 Seinda Pharmaceutical Guangzhou Corporation Ophthalmic pharmaceutical composition, preparation method therefor and application thereof
IL276244B1 (en) * 2018-01-23 2024-08-01 Seinda Pharmaceutical Guangzhou Corp A pharmaceutical preparation for the eyes, a method for its preparation and its application
KR102696573B1 (ko) 2018-01-23 2024-08-19 세인다 파마슈티컬 코포레이션 안과용 약제학적 조성물 및 이의 제조 방법 및 용도
CN114869873A (zh) * 2022-05-05 2022-08-09 陈小鸟 谷氨酰胺在制备治疗干眼症的药物中的应用
CN120420344A (zh) * 2025-07-08 2025-08-05 中国人民解放军总医院第三医学中心 一种眼用药物组合物及其制备方法和应用

Also Published As

Publication number Publication date
JPWO2010107069A1 (ja) 2012-09-20

Similar Documents

Publication Publication Date Title
CN101405009B (zh) 包含黄原胶和葡萄糖的眼科组合物
US6569903B2 (en) Ophthalmic compositions
JP6994061B2 (ja) ４－（７－ヒドロキシ－２－イソプロピル－４－オキソ－４ｈ－キナゾリン－３－イル）－ベンゾニトリルの製剤
JP2006176499A (ja) 眼疾患治療剤
RU2700927C2 (ru) Офтальмологическая композиция, содержащая циклоспорин и трегалозу
JP2018203792A (ja) 眼の異物感改善剤
CN103945846A (zh) 包含瑞巴派特和泪液保持剂的用于治疗眼前段疾病的药物
JP2025513090A (ja) 眼疾患の治療のためのミコフェノール酸及び／又はベタメタゾンの医薬組成物
JP2025004186A (ja) 眼表面疼痛を治療する方法
US20210213103A1 (en) Methods of treating dry eye syndrome
EP1408929B1 (fr) Contenant de la n-acetyle-cysteine pour le traitement du syndrome de la keratoconjonctivite seche
JP3175742B1 (ja) コンタクトレンズ用眼科用組成物
WO2010107069A1 (fr) Composition ophtalmique contenant des acides aminés
CN118510520A (zh) 用于治疗眼部疾病的霉酚酸和/或倍他米松的药物组合物
WO2018202783A1 (fr) Solution ophtalmique aqueuse stérile contenant du n-(n-acétylcystéinyl)-chitosane pour le traitement de troubles de la cornée non infectieux
EP1797888A1 (fr) Composition ophtalmique contenant de la gomme xanthane et un acide amine
JP2020075918A (ja) 角膜上皮創傷治癒促進用の眼科用組成物
WO2024135837A1 (fr) Composition aqueuse contenant de l'épinastine pour améliorer la transférabilité à un tissu et l'effet conservateur
HK40012612A (en) Methods of treating dry eye syndrome
JPWO2001041806A1 (ja) 眼科用組成物

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 10753560

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 2011504870

Country of ref document: JP

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 10753560

Country of ref document: EP

Kind code of ref document: A1