WO2000043015A1 - Gouttes ophtalmologiques - Google Patents

Gouttes ophtalmologiques Download PDF

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Publication number
WO2000043015A1
WO2000043015A1 PCT/JP2000/000286 JP0000286W WO0043015A1 WO 2000043015 A1 WO2000043015 A1 WO 2000043015A1 JP 0000286 W JP0000286 W JP 0000286W WO 0043015 A1 WO0043015 A1 WO 0043015A1
Authority
WO
WIPO (PCT)
Prior art keywords
ophthalmic solution
solution according
sodium edetate
eye drops
sodium
Prior art date
Application number
PCT/JP2000/000286
Other languages
English (en)
Japanese (ja)
Inventor
Yasuto Koyama
Nobuto Kanagawa
Original Assignee
Fujisawa 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 Fujisawa Pharmaceutical Co., Ltd. filed Critical Fujisawa Pharmaceutical Co., Ltd.
Priority to AU21295/00A priority Critical patent/AU2129500A/en
Publication of WO2000043015A1 publication Critical patent/WO2000043015A1/fr

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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • 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
    • 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
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/12—Ophthalmic agents for cataracts

Definitions

  • the present invention relates to an ophthalmic solution of a quinazoline derivative represented by the following chemical structural formula (I) or a pharmaceutically acceptable salt thereof, and is used in the medical field.
  • a and B each represent a lower alkylene group, and X, Y, and ⁇ each represent a halogen atom.
  • the quinazoline derivative (I) or a pharmaceutically acceptable salt thereof used in the present invention is a known compound, for example, the method described in Japanese Patent Application Laid-Open No. 62-96476. It can be manufactured by a method according to this, such as diabetic neuropathy [eg, diabetic peripheral neuropathy (eg, neuralgia, etc.), diabetic autonomic neuropathy (eg, impotence, etc.)], diabetic kidney Is useful for the treatment and prevention of diabetic complications such as diabetic retinopathy, diabetic retinopathy, diabetic corneal disorder and diabetic cataract.
  • Compound (II) described below is currently in clinical trials for use in diabetic neuropathy, etc. Is being promoted. Problems to be solved by the invention
  • an ophthalmic solution of a quinazoline derivative (I) or a pharmaceutically acceptable salt thereof can be introduced into a body sufficient for attaining drug efficacy even at a very low drug concentration.
  • the present inventors have found that the present invention exhibits migration, particularly intraocular migration, and completed the present invention.
  • a and B each represent a lower alkylene group.
  • the lower alkylene group is a linear or branched alkylene group having 1 to 6 carbon atoms, and preferably has 1 to 4 carbon atoms. Specific examples include a methylene group, an ethylene group, a trimethylene group, a propylene group and the like, and a methylene group and an ethylene group are particularly preferred.
  • X, ⁇ , and ⁇ ⁇ ⁇ ⁇ each represent a halogen (chlorine, bromine, fluorine, iodine) atom, and particularly preferably, X is a chlorine atom, ⁇ is a bromine atom, and ⁇ is a fluorine atom.
  • ⁇ and ⁇ are a methylene group
  • X is a chlorine atom
  • Y is a bromine atom
  • Z is a fluorine atom.
  • Ie A compound represented by the following formula: [3- (4-bromo-1-2-fluorobenzyl) -1 7-chloro-1,2,4-dioxo-1,2,3,4—tetrahydroquinazolin-1-yl Acetic acid is particularly preferred [hereinafter referred to as compound (II)].
  • Pharmaceutically acceptable salts of the compound include, for example, inorganic bases (eg, sodium, potassium, calcium, magnesium, aluminum, ammonium, etc.), organic bases (eg, ethanol Primary amines such as amino, acetylamine, diethanolamine, dicyclohexylamine, N, N'-secondary amines such as dibenzylethylenediamin, trimethylamine, Salts with basic substances such as triethylamine, pyridine, picolin, and tertiary amines such as triethanolamine.
  • inorganic bases eg, sodium, potassium, calcium, magnesium, aluminum, ammonium, etc.
  • organic bases eg, ethanol Primary amines such as amino, acetylamine, diethanolamine, dicyclohexylamine, N, N'-secondary amines such as dibenzylethylenediamin, trimethylamine
  • Salts with basic substances such as triethylamine, pyridine, picolin, and tertiary
  • Diluents such as distilled water and physiological saline are used as diluents for non-aqueous solutions or suspensions for use in preparing eye drops.
  • examples include vegetable oil, liquid paraffin, mineral oil, propylene glycol, and p-octyldodecanol.
  • eye drops include buffering agents, tonicity agents, preservatives, preservatives, thickeners, stabilizers, antioxidants, pH regulators, chelating agents that are ordinarily incorporated into eye drops. And various additives can be appropriately compounded.
  • the buffer is added for the purpose of keeping the pH constant at, for example, about 5.0 to 8.0, and includes a borate buffer, a citrate buffer, a tartrate flame buffer, and a phosphate buffer. Salt buffer, acetate buffer, etc. are used .
  • the amount of these buffers to be added is such that the buffer is added for the purpose of addition, that is, within a range that can keep pH constant within the above range, for example.
  • the tonicity agent is added for the purpose of making it isotonic with tears, and sugars such as budose sugar, mannitol, sorbitol, glycerin, concentrated glycerin, polyethylene glycol, and propylene glycol Polyhydric alcohols such as coal, and salts such as sodium chloride and sodium citrate are used. These isotonic agents are added in such an amount that the osmotic pressure of the eye drops becomes the same as that of tears.
  • parabens such as benzalkonium chloride, methyl paraoxybenzoate, propyl parahydroxybenzoate, and chlorobutanol are used. Parabens can also be used as a mixture. The above preservatives can also be used as preservatives.
  • Glycerin, carboxymethylcellulose, and hydroxypropyl polymer are used as thickeners, sodium sulfite, propylene glycol, etc. are used as stabilizers, and acetic acid is used as antioxidants.
  • Corbic acid, sodium ascorbate, tocopherol, sodium thiosulfate, etc. are used as pH regulators, such as hydrochloric acid, citric acid, phosphoric acid, acetic acid, tartaric acid, and sodium hydroxide.
  • Sodium hydroxide, sodium carbonate, sodium hydrogen carbonate, etc., and examples of the chelating agent include sodium edetate, sodium citrate, etc. .
  • the above chelating agents can be used as preservatives or stabilizers.
  • the preparation of the eye drops is performed by a conventional method, or by a sterilizing operation at an appropriate stage or by a sterilization treatment at an appropriate stage.
  • the preparation of the present invention may appropriately contain a component having another kind of medicinal effect, as long as the object of the present invention is not violated.
  • the dose and frequency of administration of the active ingredient of the present invention depend on the symptom of the disease to be treated, age, weight, dosage form, treatment period, desired therapeutic effect, and the like. More usually, the quinazoline derivative (I) or a pharmaceutically acceptable salt thereof is preferably 0.001 to 10: owZv%, preferably 0.01 to: L. 0 WZV. %, Most preferably 0.1 to 0.5 W / V%, several times per eye per day, preferably 1 to 6 times, 1 drop, preferably 1 to 4 drops be able to.
  • the formulation of eye drops containing the quinazoline derivative (I), which is the active ingredient of the present invention, or a pharmaceutically acceptable salt thereof can be used to determine the solubility of the active ingredient, the stability of the preparation, and the ability of the drug to migrate into the lens. It is carried out with the optimal formulation in terms of the antiseptic and antiseptic effects.
  • preferred additives used in the formulation of the present invention include sodium edetate, concentrated glycerin, and phenol.
  • Ravens for example, methyl paraoxybenzoate, propyl parabenzoate and the like or a mixture thereof).
  • sodium edetate is used in the range of 0.001 to 0.5 V%, preferably 0.005 to 0.1 WZV%, and concentrated glycerin.
  • the ophthalmic solution of the present invention can be used, for example, for the treatment and prevention of diabetic complications such as cataract, retinopathy, corneal disorder and dry eye.

Abstract

L'invention concerne des gouttes ophtalmologiques qui se caractérisent en ce qu'elles contiennent un dérivé de la quinazoline représenté par la formule (I), (dans laquelle A et B représentent chacun alkylène inférieur et X, Y et Z représentent chacun halogéno), et un sel dudit dérivé, acceptable au plan pharmacologique, à raison de 0,001 à 10,0 % en P/V.
PCT/JP2000/000286 1999-01-25 2000-01-21 Gouttes ophtalmologiques WO2000043015A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU21295/00A AU2129500A (en) 1999-01-25 2000-01-21 Eye drops

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP11/16087 1999-01-25
JP1608799 1999-01-25

Publications (1)

Publication Number Publication Date
WO2000043015A1 true WO2000043015A1 (fr) 2000-07-27

Family

ID=11906765

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2000/000286 WO2000043015A1 (fr) 1999-01-25 2000-01-21 Gouttes ophtalmologiques

Country Status (2)

Country Link
AU (1) AU2129500A (fr)
WO (1) WO2000043015A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000048447A3 (fr) * 1999-02-18 2001-01-25 R Tech Ueno Ltd Composition pour le traitement de troubles de secretion externe a l'exception de l'hypolarmoiement

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0218999A2 (fr) * 1985-10-07 1987-04-22 Fujisawa Pharmaceutical Co., Ltd. Dérivés de quinazoline, leur procédé de production et compositions pharmaceutiques les comprenant
WO1999038497A2 (fr) * 1998-01-30 1999-08-05 R-Tech Ueno, Ltd. Composition ophtalmique

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0218999A2 (fr) * 1985-10-07 1987-04-22 Fujisawa Pharmaceutical Co., Ltd. Dérivés de quinazoline, leur procédé de production et compositions pharmaceutiques les comprenant
WO1999038497A2 (fr) * 1998-01-30 1999-08-05 R-Tech Ueno, Ltd. Composition ophtalmique

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
AO S. ET AL.: "Effect of instillation of aldose reductase inhibitor FR74366 on diabetic cataract", INVESTIGATIVE OPHTHALMOLOGY AND VISUAL SCIENCE, vol. 32, no. 12, 1991, pages 3078 - 3083, XP002924399 *
AO SHIZUO ET AL.: "Effect of a novel aldose reductase inhibitor FR74366 on diabetic cataract", INT. CONGR. SER. - EXCERPTA MED. (CURR. CONCEPTS. ALDOSE REDUCTASE ITSD INHIB.), vol. 913, 1990, pages 221 - 224, XP002924400 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000048447A3 (fr) * 1999-02-18 2001-01-25 R Tech Ueno Ltd Composition pour le traitement de troubles de secretion externe a l'exception de l'hypolarmoiement

Also Published As

Publication number Publication date
AU2129500A (en) 2000-08-07

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