WO2005079809A1 - Gouttes pour les yeux transparentes au latanoprost - Google Patents

Gouttes pour les yeux transparentes au latanoprost Download PDF

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Publication number
WO2005079809A1
WO2005079809A1 PCT/JP2005/002552 JP2005002552W WO2005079809A1 WO 2005079809 A1 WO2005079809 A1 WO 2005079809A1 JP 2005002552 W JP2005002552 W JP 2005002552W WO 2005079809 A1 WO2005079809 A1 WO 2005079809A1
Authority
WO
WIPO (PCT)
Prior art keywords
ophthalmic solution
latanoprost
eye drops
sodium
transparent
Prior art date
Application number
PCT/JP2005/002552
Other languages
English (en)
Japanese (ja)
Inventor
Nanoko Tsuchimoto
Hiroyuki Asada
Akio Kimura
Original Assignee
Santen 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 Santen Pharmaceutical Co., Ltd. filed Critical Santen Pharmaceutical Co., Ltd.
Publication of WO2005079809A1 publication Critical patent/WO2005079809A1/fr

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Classifications

    • 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
    • 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
    • A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
    • A61K31/5575—Eicosanoids, e.g. leukotrienes or prostaglandins having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
    • 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
    • A61P27/06—Antiglaucoma agents or miotics

Definitions

  • the present invention relates to a clear and stable ophthalmic solution containing latanoprost, which is useful as a therapeutic agent for glaucoma, as an active ingredient.
  • Latanoprost has the chemical name isopropyl (Z) -7 [(1R, 2R, 3R, 5S) 3,5-dihydroxy-2-[(3R) -3-hydroxy-5-phenylpentyl] cyclopentyl]- It is a prostaglandin-based glaucoma treatment represented by 5-heptanate.
  • Latanoprost is a selective FP receptor agonist and exerts an intraocular pressure-lowering effect by promoting outflow of aqueous humor (for example, see Patent Document 1).
  • an ophthalmic solution containing 0.005% latanobrost (trade name: xalatan ophthalmic solution) is commercially available.
  • Patent Document 1 Japanese Patent No. 2721414
  • Ophthalmic solutions are generally compounded with isotonic agents and buffers as additives.
  • the tonicity agent is blended in order to maintain isotonicity, and typical examples thereof include inorganic salts of alkali metal salts such as sodium salt sodium and alkaline earth metal salts such as magnesium salt of sodium salt.
  • Latanoprost ophthalmic solution contains sodium salt. Buffering agents are added to prevent fluctuations in pH.Typical examples are inorganic salts such as sodium phosphate and sodium borate, and organic salts such as sodium acetate, sodium citrate, and sodium carbonate.
  • the rattanoblost ophthalmic solution contains sodium dihydrogen phosphate monohydrate and anhydrous sodium monohydrogen phosphate.
  • BAK benzalco-dum chloride
  • BAK has excellent preservative properties, it can cause corneal damage when used at high concentrations.
  • latanoprost ophthalmic solution containing a general-purpose additive was prepared and subjected to various studies. It was found that when the concentration of BAK was 0.01% or less, turbidity occurred. did. This is because the latanoprost BAK complex with highly hydrophobic latanobrost forms a complex, and the latanoprost BAK complex is precipitated by the salting-out effect of the salts, which are the added carotenoids. It is a surprising finding that precipitation occurs only when the concentration is increased. Therefore, in latanoblost ophthalmic solution, it is beneficial to search for a new preservative to replace BAK in order to prevent such clouding due to such a change in the composition. Means for solving the problem
  • the present inventors have studied various preservatives compatible with latanoblost ophthalmic solution, and found that the following preservatives can be used if at least one of the following preservatives is added. It was found that, while maintaining the above, white turbidity due to a change in the composition was prevented, and a clear and stable ophthalmic solution was obtained.
  • the concentration of latanobrost which is an active ingredient of the ophthalmic solution in the present invention, is preferably 0.001 to 0.1% (wZv), particularly preferably about 0.005% (WZV).
  • preservatives that can maintain a clear and stable ophthalmic solution without causing turbidity due to compounding even when added to an ophthalmic solution containing latanoprost as an active ingredient include: The following four can be mentioned.
  • the concentration of benzenium chloride is preferably 0.001-0.i% (wZv).
  • chlorhexidines examples include chlorhexidine dalconate, chlorhexidine acetate, chlorhexidine hydrochloride, and the like, and chlorhexidine dalconate is preferable.
  • concentration of chlorhexidines is preferably 0.001-0.1% (wZv).
  • nonoxybenzoic acid esters include, for example, ethyl ethyl paraoxybenzoate, methyl ethyl paraoxybenzoate, and noroxybenzoic acid.
  • the concentration of the paraoxybenzoic acid esters is preferably 0.001 to 0.1% (WZV).
  • the sorbic acid salt whose concentration of sorbic acid or a salt thereof is preferably 0.01-1% (W / V) is, for example, sorbic acid potassium rim.
  • the ophthalmic solution of the present invention can be prepared by a widely used method, and if necessary, an isotonic agent, a PH buffer, a pH adjuster, a solubilizing agent, a thickener and the like may be added. Can be.
  • tonicity agent examples include glycerin, propylene glycol, polyethylene glycol, trihalose, sucrose, sorbitol, mannitol, sodium chloride, lithium chloride, calcium chloride, magnesium chloride, and the like. be able to.
  • pH buffer examples include phosphates such as sodium phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, potassium phosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate; sodium borate And borates such as potassium borate; citrates such as sodium citrate and sodium citrate; acetates such as sodium acetate and potassium acetate; carbonates such as sodium carbonate and sodium hydrogen carbonate. it can.
  • phosphates such as sodium phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, potassium phosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate
  • sodium borate And borates such as potassium borate
  • citrates such as sodium citrate and sodium citrate
  • acetates such as sodium acetate and potassium acetate
  • carbonates such as sodium carbonate and sodium hydrogen carbonate. it can.
  • Examples of the pH adjuster include hydrochloric acid, citric acid, phosphoric acid, acetic acid, sodium hydroxide, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate and the like.
  • solubilizer examples include polysorbate 80, polyexylene-ethylene hydrogenated castor oil 60, Macrogol 4000 and the like.
  • thickener examples include hydroxypropylmethylcellulose, hydroxypropylcellulose, polyvinyl alcohol, carboxyvinyl polymer, polyvinylpyrrolidone and the like.
  • the pH of the ophthalmic solution of the present invention is preferably 3-8, particularly preferably 417.
  • An ophthalmic solution was obtained by performing the same operation as in Formulation 1 except that no preservative (Shiidai Benzetonium) was used. This ophthalmic solution was returned to room temperature, and it was confirmed that the pH was 6.7.

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

Abstract

Gouttes pour les yeux transparentes et stables qui contiennent du latanoprost comme ingrédient actif et sont utiles comme agent thérapeutique pour le glaucome. On ajoute au moins un antiseptique choisi parmi les antiseptiques 1) à 4) suivants à des gouttes pour les yeux contenant du latanoprost comme ingrédient actif. Ainsi, on peut obtenir des gouttes pour les yeux qu'on empêche de devenir troubles à cause d'un changement de composition et qui sont transparentes et stables, tout en conservant un effet antiseptique. 1) Chlorure de benzéthonium, 2) composés de chlorohexidine, 3) esters de l'acide p-hydroxybenzoïque et 4) acide sorbique et sels de celui-ci.
PCT/JP2005/002552 2004-02-19 2005-02-18 Gouttes pour les yeux transparentes au latanoprost WO2005079809A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2004043175 2004-02-19
JP2004-043175 2004-02-19

Publications (1)

Publication Number Publication Date
WO2005079809A1 true WO2005079809A1 (fr) 2005-09-01

Family

ID=34879286

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2005/002552 WO2005079809A1 (fr) 2004-02-19 2005-02-18 Gouttes pour les yeux transparentes au latanoprost

Country Status (1)

Country Link
WO (1) WO2005079809A1 (fr)

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10182465A (ja) * 1993-08-03 1998-07-07 Alcon Lab Inc 緑内障及び高眼圧治療用局所眼薬組成物
WO1999038533A1 (fr) * 1998-01-28 1999-08-05 Senju Pharmaceutical Co., Ltd. Mesures prophylactiques ou remedes contre les troubles de la vision
JP2001335511A (ja) * 1999-12-01 2001-12-04 Sankyo Co Ltd 緑内障を治療するための併用剤
WO2002011734A1 (fr) * 2000-08-08 2002-02-14 Wakamoto Pharmaceutical Co., Ltd. Compositions pharmaceutiques aqueuses
JP2002234851A (ja) * 2000-12-05 2002-08-23 Sankyo Co Ltd 局所投与のための眼圧低下組成物
JP2003206241A (ja) * 2002-01-11 2003-07-22 Teika Seiyaku Kk 眼科用剤
JP2004182719A (ja) * 2002-08-23 2004-07-02 Santen Pharmaceut Co Ltd ラタノプロストを有効成分とする安定な点眼液

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10182465A (ja) * 1993-08-03 1998-07-07 Alcon Lab Inc 緑内障及び高眼圧治療用局所眼薬組成物
WO1999038533A1 (fr) * 1998-01-28 1999-08-05 Senju Pharmaceutical Co., Ltd. Mesures prophylactiques ou remedes contre les troubles de la vision
JP2001335511A (ja) * 1999-12-01 2001-12-04 Sankyo Co Ltd 緑内障を治療するための併用剤
WO2002011734A1 (fr) * 2000-08-08 2002-02-14 Wakamoto Pharmaceutical Co., Ltd. Compositions pharmaceutiques aqueuses
JP2002234851A (ja) * 2000-12-05 2002-08-23 Sankyo Co Ltd 局所投与のための眼圧低下組成物
JP2003206241A (ja) * 2002-01-11 2003-07-22 Teika Seiyaku Kk 眼科用剤
JP2004182719A (ja) * 2002-08-23 2004-07-02 Santen Pharmaceut Co Ltd ラタノプロストを有効成分とする安定な点眼液

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