EP0760663A1 - Use of a 2-(4-(azolylbutyl)-piperazinyl-methyl)-benzimidazole derivative for treating allergic conjunctivitis - Google Patents

Use of a 2-(4-(azolylbutyl)-piperazinyl-methyl)-benzimidazole derivative for treating allergic conjunctivitis

Info

Publication number
EP0760663A1
EP0760663A1 EP96908059A EP96908059A EP0760663A1 EP 0760663 A1 EP0760663 A1 EP 0760663A1 EP 96908059 A EP96908059 A EP 96908059A EP 96908059 A EP96908059 A EP 96908059A EP 0760663 A1 EP0760663 A1 EP 0760663A1
Authority
EP
European Patent Office
Prior art keywords
radical
atom
methyl
allergic conjunctivitis
values
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.)
Withdrawn
Application number
EP96908059A
Other languages
German (de)
French (fr)
Inventor
Maria-Rosa Cuberes-Altisent
Jordi Frigola-Constansa
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.)
Esteve Pharmaceuticals SA
Original Assignee
Laboratorios del Dr Esteve SA
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 Laboratorios del Dr Esteve SA filed Critical Laboratorios del Dr Esteve SA
Publication of EP0760663A1 publication Critical patent/EP0760663A1/en
Withdrawn legal-status Critical Current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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • 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
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
    • 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

Definitions

  • the present invention relates to the use of derivatives of 2- [4- (azolybutyl) piperazinyl (methyl)] benzimidazole and analogues, as well as their physiologically acceptable salts, for the manufacture of ophthalmic drugs for topical use, intended for the treatment of allergic conjunctivitis and other related diseases.
  • dem ies of 2 - [4- (azolylbutyl) piperazinyl (methyl)] benzimidazole and the like are useful for the treatment of allergic conjunctivitis and other related diseases.
  • the compounds which are the subject of the present invention are intended for ophthalmic treatments for topical use, preventive or curative in mammals, humans included.
  • X, Y, Z and W equal or different, represent a nitrogen atom or a carbon atom linked to a hydrogen atom, a halogen atom, a methyl radical, an ethyl carboxylate radical, a radical carboxylic or a sulfonic radical, and its pharmaceutically acceptable salts.
  • the halogen atoms are preferably selected from chlorine and bromine.
  • the present invention therefore relates to a topical ophthalmic composition
  • a topical ophthalmic composition comprising at least one compound of general form 1, as defined above. associated with an ophthalmically acceptable vehicle.
  • topical ophthalmic compositions respond to specific technical characteristics linked to their application at the eye level, with the use of ophthalmically acceptable vehicles which avoid causing various adverse reactions to ophthalmic treatment, such as eyelid eyelids, tearing, painful reactions or redness of the eyes.
  • the excipients must be selected so that the ophthalmic composition does not trigger a lacrimation which would instantly cause the active ingredient.
  • the ophthalmically acceptable excipients are well known to the person skilled in the art, who will be able to select them according to the formulation which he will choose.
  • the ophthalmic compositions according to the invention are in the form of eye drops, ophthalmic ointments, gels or ophthalmic inserts.
  • the present invention also relates to the use of the compounds of general formula I above, for the preparation of a medicament intended for the treatment of allergic conjunctivitis and other relative diseases in mammals, including humans.
  • topical antihistamine ocular effect of the products object of the present invention was evaluated through a model of microvascular permeability in the guinea pig conjunctiva, induced by histamine.
  • this animal model of ocular antiallergic activity we measure the power, the effective dose fifty and the duration of action.
  • VAF Dunkin / Hartley male guinea pigs (6 per group) are injected intravenously, through the marginal vein of the ear, with 1.0 ml of Evans blue (1.0 mg / ml).
  • 20 ⁇ ⁇ of the appropriate concentration of the compound of Example 1 or of the vehicle is applied topically to one eye of each of the animals.
  • the guinea pigs are anesthetized and they are administered histamine (300 ng / 10 ⁇ l) subconjunctively. Thirty minutes later, the animals are sacrificed by CO 2 inhalation and the surface area of Evans blue is measured.
  • the area of the blue dye is multiplied by the color intensity graduated from 1 to 6, to produce a permeability value for each animal (Yauni et al., Int. Arch. Allergy Immimol, 1 993, 101, 102-106) .
  • the valcurs obtained by the treated groups are then compared with those obtained with the group treated with the vehicle using the Dunnett "t" test (Dunnett CW "A multiple comparison procedure for comparing treatments with a control", J. A m. Stat. Assoc. 1955, 50, 1096-1 121).
  • Example 3 significantly and dose-dependent inhibits histamine-induced vascular permeability in the guinea pig conjunctiva after topical ocular administration. This inhibition is observed in a range of concentrations from 0.1% to 0.0001% weight / volume.
  • the data obtained are presented in Table 3.
  • the ED-50 defined as the concentration of compound which produces the 50% inhibition of vascular permeability in comparison with the values of the control group, was 0.0024 p / v at 2 minutes, 0.00035 p / v at 30 minutes and 0.00043 p / v at 8 hours.
  • the administration dose is of course a function of the severity of the condition to be treated, the derivatives of the invention will, for example, be administered in the form of a solution, dispersion or gel.

Abstract

A topical ophthalmic composition including at least one compound of general formula (I), wherein n may be 0 or 1, m may be 2 or 3, and Het is a heteroaromatic radical of formula (a), wherein each of X, Y, Z and W, which are the same or different, is a nitrogen atom or a carbon atom attached to a hydrogen atom, a halogen atom, a methyl radical, an ethyl carboxylate radical, a carboxylic radical or a sulphonic radical, and pharmaceutically acceptable salts thereof, combined with an ophthalmically acceptable carrier, in particular for treating allergic conjunctivitis.

Description

UTILISATION DES DERIVES DE 2-(4-(AZOLYLBUTYL) -PIPERAZINYL-METHYL) -BENZIMIDAZOL E POUR LE TRAITEMENT DE LA CONJONCTIVITE ALLERGIQUE  USE OF DERIVATIVES OF 2- (4- (AZOLYLBUTYL) -PIPERAZINYL-METHYL) -BENZIMIDAZOL E FOR THE TREATMENT OF ALLERGIC CONJUNCTIVITY
La présente invention concerne l 'utilisation des dérivés de 2-[4- (azolybutyl) piperazinyl (méthyl)]benzimidazole et analogues, ainsi que de leurs sels physiologiquement acceptables, pour la fabrication de médicaments ophtalmiques d'usage topique, destinés au traitement de la conjonctivite allergique et d'autres maladies relatives. The present invention relates to the use of derivatives of 2- [4- (azolybutyl) piperazinyl (methyl)] benzimidazole and analogues, as well as their physiologically acceptable salts, for the manufacture of ophthalmic drugs for topical use, intended for the treatment of allergic conjunctivitis and other related diseases.
Les composés auxquels se rapporte la présente invention ont été décrits dans les démarches de brevets européens EP 468884 et EP 507696 comme antihistaminique.  The compounds to which the present invention relates have been described in the procedures of European patents EP 468884 and EP 507696 as an antihistamine.
Nous avons maintenant découvert que les dém és de 2 - [ 4- (azolylbutyl)piperazinyl(méthyl)]benzimidazole et analogues sont utiles pour le traitement de la conjonctivite allergique et d'autres maladies relatives. En particulier les composés objet de la présente invention sont destinés à des traitements ophtalmiques d'usage topique, préventifs ou curatifs chez les mammifères, l 'homme inclus.  We have now found that the dem ies of 2 - [4- (azolylbutyl) piperazinyl (methyl)] benzimidazole and the like are useful for the treatment of allergic conjunctivitis and other related diseases. In particular, the compounds which are the subject of the present invention are intended for ophthalmic treatments for topical use, preventive or curative in mammals, humans included.
Les composés préconisés dans le cadre de la présente invention repondent à la formule générale I  The compounds recommended in the context of the present invention correspond to the general formula I
dans laquelle in which
X, Y, Z et W, égaux ou différents, représentent un atome d'azote ou un atome de carbone lié à un atome d'hydrogène, un atome d'halogène, un radical méthyle, un radical carboxylate d'éthyle, un radical carboxylique ou un radical sulfonique, et ses sels pharmaceutiquement acceptables.  X, Y, Z and W, equal or different, represent a nitrogen atom or a carbon atom linked to a hydrogen atom, a halogen atom, a methyl radical, an ethyl carboxylate radical, a radical carboxylic or a sulfonic radical, and its pharmaceutically acceptable salts.
Les composés identifiés par les exemples 1 à 19 sont obtenus par les procédures décrites dans les demandes de brevets européens EP 468884 et EP 507696, et les données pour leur identification sont exposées dans les tableaux 1 et 2 Les exemples illustrent les propriétés de quelques dérivés entrant dans ie cadre de la présente invention. The compounds identified by Examples 1 to 19 are obtained by the procedures described in European patent applications EP 468884 and EP 507696, and the data for their identification are set out in Tables 1 and 2 The examples illustrate the properties of some derivatives falling within the scope of the present invention.
Les symptômes et la conjonctivite allergique, relativement commune, sont le picotement et le rougissement des yeux, yeux humides et larmoyants, paupières boursouflées et oedème de la conjonctive. La thérapie conventionnelle consiste principalement en l'utilisation topique de cromoghcate sodique, de vasoconstricteurs topiques associées avec des antihistaminiques, et dans les cas sévères en l'utilisation de corticostéroides topiques. Cependant, l'efficacité de ces traitements est modérée. Les effets secondaires et le besoin d'une administration fréquente de ces thérapies mènent à la recherche d'autres alternatives plus satisfaisantes (Dechat, K.L. et Goa, K.L. "Levocabastine. A review of its pharmacological properties and therapeutic potential as a topical antihistamine in allergie rhinitis and conjunctivitis", Drugs, 1 991 , 41. 202-224)  The relatively common symptoms and allergic conjunctivitis are tingling and reddening of the eyes, watery, watery eyes, puffy eyelids and edema of the conjunctiva. Conventional therapy consists mainly of the topical use of sodium cromoghcate, topical vasoconstrictors associated with antihistamines, and in severe cases the use of topical corticosteroids. However, the effectiveness of these treatments is moderate. The side effects and the need for frequent administration of these therapies lead to the search for other more satisfactory alternatives (Dechat, KL and Goa, KL "Levocabastine. A review of its pharmacological properties and therapeutic potential as a topical antihistamine in allergy rhinitis and conjunctivitis ", Drugs, 1 991, 41. 202-224)
Nous avons main tenant découvert que les dérivés de 2-[4- (azoiylbuty l)piperaziny l (méthyl)]benzimidazole montrent une puissante activité antiallergique oculaire av ec une durée d'action exceptionnellement longue.  We have now discovered that the derivatives of 2- [4- (azoiylbuty l) piperaziny l (methyl)] benzimidazole show potent antiallergic ocular activity with an exceptionally long duration of action.
D'une manière avantageuse, Het représente un radical pyrolyle (X, Y, Z et W sont dif férents d'un atome d'azote), un radical pyrazolyle (X = N, Y, Z ct W sont différents d'un atome d'azote), un radical imidozolyle (Y = N, X, Z et W sont différents d'un atome d'azote) et un radical triazolyle (X = Z = N, Y et W sont différents d'un atome d'azote). Les atomes d'halogène sont de préf érence sélectionnés parmi le chlore et le brome.  Advantageously, Het represents a pyrolyl radical (X, Y, Z and W are different from a nitrogen atom), a pyrazolyl radical (X = N, Y, Z and W are different from an atom nitrogen), an imidozolyl radical (Y = N, X, Z and W are different from a nitrogen atom) and a triazolyl radical (X = Z = N, Y and W are different from an atom nitrogen). The halogen atoms are preferably selected from chlorine and bromine.
La presenic invention concerne donc une composition ophtalmique topique comprenant au moins un composé de f ormule générale 1, telle que déf inie ci-dessus. associé à un véhicule ophtalmiquement acceptable.  The present invention therefore relates to a topical ophthalmic composition comprising at least one compound of general form 1, as defined above. associated with an ophthalmically acceptable vehicle.
Contrairement aux autres formulations orales ou injectables décrites dans l 'état de la technique, les compositions ophtalmiques topiques répondent à des caractéristiques techniques spécifiques liées à leur application au niveau de l 'oeil, avec l 'emploi de véhicules ophtalmiquement acceptables qui évitent de provoquer diverses réactions néfastes au traitement ophtalmique, comme par exemple la lermeture des paupières, le larmoiement, les réactions douloureuses ou encore une rougeur de la conjontn e. En particulier, les excipients doivent être sélectionnés de manière que la composition ophtalmique ne déclenche pas un larmoiement qui entrainerait instantanément le principe actif. Les excipients ophtalmiquement acceptables sont bien connus de l'homme du métier, qui saura les sélectionner en fonction de la formulation qu'il choisira D'une manière avantageuse, les compositions ophtalmiques selon l'invention se présentent sous la forme de collyres, de pommades ophtalmiques, de gels ou d'inserts ophtalmiques. Unlike the other oral or injectable formulations described in the state of the art, topical ophthalmic compositions respond to specific technical characteristics linked to their application at the eye level, with the use of ophthalmically acceptable vehicles which avoid causing various adverse reactions to ophthalmic treatment, such as eyelid eyelids, tearing, painful reactions or redness of the eyes. In particular, the excipients must be selected so that the ophthalmic composition does not trigger a lacrimation which would instantly cause the active ingredient. The ophthalmically acceptable excipients are well known to the person skilled in the art, who will be able to select them according to the formulation which he will choose. Advantageously, the ophthalmic compositions according to the invention are in the form of eye drops, ophthalmic ointments, gels or ophthalmic inserts.
La présente invention concerne également l'utilisation des composés de formule générale I ci-dessus, pour la préparation d'un médicament destiné au traitement de la conjonctivite allergique et d'autres maladies relatives chez les mammifères, l'homme inclus. The present invention also relates to the use of the compounds of general formula I above, for the preparation of a medicament intended for the treatment of allergic conjunctivitis and other relative diseases in mammals, including humans.
Etude du traitement topique de la conjonctivite allergique l'effet topique antihistaminique oculaire des produits objet de la présente invention a été évalué à travers un modèle de perméabilité microvasculaire dans la conjonctive de cobaye, induite par l'histamine. Dans ce modèle animal d'activité antiallergique oculaire, on mesure la puissance, la dose efficace cinquante et la durée d'action. Study of the topical treatment of allergic conjunctivitis the topical antihistamine ocular effect of the products object of the present invention was evaluated through a model of microvascular permeability in the guinea pig conjunctiva, induced by histamine. In this animal model of ocular antiallergic activity, we measure the power, the effective dose fifty and the duration of action.
Perméabilité microvasculaire chez la conjonctive de cobave induite par l'histamine (extravassation du colorant bleu d'Evans) Microvascular permeability in histamine-induced guinea pig conjunctiva (extravassation of Evans blue dye)
Des cobayes mâles VAF Dunkin/Hartley (6 par groupe) sont injectés par voie intraveineuse, à travers la veine marginale de J 'oreille, av ec 1 ,0 ml de bleu d'Evans ( 1,0 mg/ml). Environ 15 minutes après l 'injection du colorant, on applique topiquement 20 μ\ de la concentration appropriée du composé de l 'exemple 1 ou du véhicule dans un oeil de chacun des animaux. Après 2 minutes, 30 minutes et 6 heures de l'application topique, les cobayes sont ancsthésiés et on leur adminitre par voie subconjonctive l'histamine (300 ng/10 μ l). Trente minutes plus tard les animaux sont sacrifiés par inhalation de CO2 et on mesure la surface d 'extravassation du bleu d'Evans. La surface du colorant bleu est multipliée par l 'intensité de couleur graduée de 1 à 6, pour produire une valeur de perméabilité pour chaque animal (Yauni et al., Int. Arch . Allergy Immimol, 1 993, 101, 102- 106). Les valcurs obtenues par les groupes traités sont alors comparées avec celles obtenues avec le groupe traité avec le véhicule en utilisant le test "t" de Dunnett (Dunnett C. W. "A multiple comparison procédure for comparing treatments with a control", J. A m. Stat. Assoc. 1955, 50, 1096-1 121). VAF Dunkin / Hartley male guinea pigs (6 per group) are injected intravenously, through the marginal vein of the ear, with 1.0 ml of Evans blue (1.0 mg / ml). Approximately 15 minutes after the injection of the dye, 20 μ \ of the appropriate concentration of the compound of Example 1 or of the vehicle is applied topically to one eye of each of the animals. After 2 minutes, 30 minutes and 6 hours of topical application, the guinea pigs are anesthetized and they are administered histamine (300 ng / 10 μl) subconjunctively. Thirty minutes later, the animals are sacrificed by CO 2 inhalation and the surface area of Evans blue is measured. The area of the blue dye is multiplied by the color intensity graduated from 1 to 6, to produce a permeability value for each animal (Yauni et al., Int. Arch. Allergy Immimol, 1 993, 101, 102-106) . The valcurs obtained by the treated groups are then compared with those obtained with the group treated with the vehicle using the Dunnett "t" test (Dunnett CW "A multiple comparison procedure for comparing treatments with a control", J. A m. Stat. Assoc. 1955, 50, 1096-1 121).
Le composé de l 'exemple 1 inhibe de façon significative et dose-dépendante la perméablilité vasculaire induite par l'histamine dans la conjonctive de cobaye après une adminstration topique oculaire. Cette inhibition s'observe dans un rang de concentrations de 0,1% à 0,0001% poids/volume. Les données obtenues sont présentées dans le tableau 3. La DE-50, définie comme la concentration de composé qui produit le 50% d'inhibition de la perméabilité vascuiaire en comparaison avec les valeurs du groupe contrôle, a été de 0,0024 p/v à 2 minutes, 0,00035 p/v à 30 minutes et 0,00043 p/v à 8 heures. Ces résultats (Tableau 3) démontrent une puissante activité antihistaminique accompagnée d'un durée d'action exceptionnellement longue. The compound of Example 1 significantly and dose-dependent inhibits histamine-induced vascular permeability in the guinea pig conjunctiva after topical ocular administration. This inhibition is observed in a range of concentrations from 0.1% to 0.0001% weight / volume. The data obtained are presented in Table 3. The ED-50, defined as the concentration of compound which produces the 50% inhibition of vascular permeability in comparison with the values of the control group, was 0.0024 p / v at 2 minutes, 0.00035 p / v at 30 minutes and 0.00043 p / v at 8 hours. These results (Table 3) demonstrate a powerful antihistamine activity accompanied by an exceptionally long duration of action.
En thérapeutique humaine, la dose d'administration est bien sûr fonction de la gravité de l'affection à traiter, les dérivés de l'invention seront, par exemple, administrés sous forme de solution, dispersion ou gel. In human therapy, the administration dose is of course a function of the severity of the condition to be treated, the derivatives of the invention will, for example, be administered in the form of a solution, dispersion or gel.
On indiquera ci-après, à titre d'exemple, des formules galéniques particulières pour un des dérivés objet de la présente invention. Bien entendu, les mêmes types de compositions pouvant être préparés en remplaçant le composé de l'exemple 1 par les composés des exemples 2 à 19, et les excipients par leur équivalents.  By way of example, specific galenical formulas for one of the derivatives which are the subject of the present invention will be indicated below. Of course, the same types of compositions can be prepared by replacing the compound of Example 1 with the compounds of Examples 2 to 19, and the excipients with their equivalents.

Claims

REVENDICATIONS
1. Composition ophtalmique topique, caractérisée en ce qu'elle comprend au moins un composé de formule générale I. 1. Topical ophthalmic composition, characterized in that it comprises at least one compound of general formula I.
dans laquelle  in which
n peut avoir les valeurs 0 ou 1,  n can have the values 0 or 1,
m peut avoir les valeurs 2 ou 3,  m can have the values 2 or 3,
et Het représente un radical hétéroaromatique de formule dans laquelle and Het represents a heteroaromatic radical of formula in which
X, Y, Z et W, égaux ou différents, représentent un atome d'azote ou un atome de carbone lié à un atome d'hydrogène, un atome d'halogène, un radical méthyle, un radical carboxylate d'éthyle, un radical carboxylique ou un radical sulfonique, et ses sels pharmaceutiquement acceptables, associés à un véhicule ophtalmiquement acceptable.  X, Y, Z and W, equal or different, represent a nitrogen atom or a carbon atom linked to a hydrogen atom, a halogen atom, a methyl radical, an ethyl carboxylate radical, a radical carboxylic or a sulfonic radical, and its pharmaceutically acceptable salts, associated with an ophthalmically acceptable vehicle.
2. Composition selon la revendication 1 , caractérisée en ce qu'elle se présente sous la forme 6 collyre, de pommade ophtalmique, de gel ou d 'insert optalmique.  2. Composition according to claim 1, characterized in that it is in the form 6 eye drops, ophthalmic ointment, gel or optalmic insert.
3. Utilisation d'un composé de formule générale I,  3. Use of a compound of general formula I,
dans laquelle in which
n peut avoir les valeurs 0 ou 1 , n can have the values 0 or 1,
m peut avoir les valeurs 2 ou 3, et Het représente un radical hétéroaromatique de formule m can have the values 2 or 3, and Het represents a heteroaromatic radical of formula
dans laquelle in which
X, Y, Z et W, égaux ou différents, représentent un atome d'azote ou un atome de carbone lié à un atome d'hydrogène, un atome d'halogène, un radical méthyle, un radical carboxylate d'éthyle, un radical carboxylique ou un radical sulfonique, et ses sels pharmaceutiquement acceptables, associés à un véhicule ophtalmiquement acceptable, pour la préparation d'un médicament destiné au traitement de la conjonctivite allergique et d'autres maladies relatives chez les mammilères l 'homme inclus.  X, Y, Z and W, equal or different, represent a nitrogen atom or a carbon atom linked to a hydrogen atom, a halogen atom, a methyl radical, an ethyl carboxylate radical, a radical carboxylic or a sulphonic radical, and its pharmaceutically acceptable salts, associated with an ophthalmically acceptable vehicle, for the preparation of a medicament intended for the treatment of allergic conjunctivitis and other related diseases in mammals including humans.
EP96908059A 1995-03-14 1996-03-13 Use of a 2-(4-(azolylbutyl)-piperazinyl-methyl)-benzimidazole derivative for treating allergic conjunctivitis Withdrawn EP0760663A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR9502910A FR2731618B1 (en) 1995-03-14 1995-03-14 TOPICAL OPHTHALMIC COMPOSITION COMPRISING A DERIVATIVE OF 2- (4- (AZOLYLBUTYL) -PIPERAZINYL-METHYL) -BENZIMIDAZOLE, IN PARTICULAR FOR THE TREATMENT OF ALLERGIC CONJUNCTIVITY
FR9502910 1995-03-14
PCT/EP1996/001148 WO1996028161A1 (en) 1995-03-14 1996-03-13 Use of a 2-(4-(azolylbutyl)-piperazinyl-methyl)-benzimidazole derivative for treating allergic conjunctivitis

Publications (1)

Publication Number Publication Date
EP0760663A1 true EP0760663A1 (en) 1997-03-12

Family

ID=9476989

Family Applications (1)

Application Number Title Priority Date Filing Date
EP96908059A Withdrawn EP0760663A1 (en) 1995-03-14 1996-03-13 Use of a 2-(4-(azolylbutyl)-piperazinyl-methyl)-benzimidazole derivative for treating allergic conjunctivitis

Country Status (9)

Country Link
US (1) US5641781A (en)
EP (1) EP0760663A1 (en)
JP (1) JPH10500427A (en)
AU (1) AU718008B2 (en)
CA (1) CA2190187A1 (en)
ES (1) ES2117558B1 (en)
FR (1) FR2731618B1 (en)
WO (1) WO1996028161A1 (en)
ZA (1) ZA962060B (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7355042B2 (en) * 2001-10-16 2008-04-08 Hypnion, Inc. Treatment of CNS disorders using CNS target modulators
US20060035811A1 (en) * 2002-10-18 2006-02-16 Luis Molina Methods of treating dry eye disease with lantibiotics
CA2565545A1 (en) * 2004-05-06 2005-12-08 Molichem Medicines, Inc. Treatment of ocular diseases and disorders using lantibiotic compositions
WO2005107787A1 (en) * 2004-05-06 2005-11-17 Molichem Medicines, Inc. Treatment of membrane-associated diseases and disorders using lantibiotic containing compositions

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2665161B1 (en) * 1990-07-26 1992-11-27 Esteve Labor Dr NOVEL BENZIMIDAZOLE DERIVATIVES, THEIR PREPARATION AND THEIR APPLICATION AS MEDICAMENTS.
FR2674856B1 (en) * 1991-04-05 1993-07-30 Esteve Labor Dr NOVEL NON - SEDATIVE ANTIHISTAMINS, DERIVATIVES OF BENZIMIDAZOLE, PROCESS FOR THEIR PREPARATION AND THEIR USE AS MEDICAMENTS.
JP3527256B2 (en) * 1992-12-09 2004-05-17 ロート製薬株式会社 Antiallergic eye drops

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9628161A1 *

Also Published As

Publication number Publication date
ZA962060B (en) 1996-12-31
WO1996028161A1 (en) 1996-09-19
FR2731618A1 (en) 1996-09-20
ES2117558B1 (en) 1999-09-16
ES2117558A1 (en) 1998-08-01
JPH10500427A (en) 1998-01-13
FR2731618B1 (en) 1997-08-01
AU718008B2 (en) 2000-04-06
US5641781A (en) 1997-06-24
AU5145296A (en) 1996-10-02
CA2190187A1 (en) 1996-09-19

Similar Documents

Publication Publication Date Title
HU197840B (en) Process for producing synergic pharmaceutical compositions comprising amantadin and selegilin
EP0402203A2 (en) Use of a statine derivative for treatment of ophthalmologic disorders
CA2521152A1 (en) Use of a topical medicament comprising riluzole
EP1351679B1 (en) Method and composition for the treatment of diabetic neuropathy
FR2608045A1 (en) USE OF XANTHINE OXIDASE INHIBITORS, OXYGEN FREE RADIAL TRAPERS AND IRON CHELATORS FOR THE MANUFACTURE OF A PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OF GLAUCOMA AND PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF GLAUCOMA
EP1283708A2 (en) Use of biguanide derivatives for making a medicine having a wound healing effect
EP0403360B1 (en) Use of phenylethanolamines for the preparation of a medicament for treating ophthalmologic disorders
EP0760663A1 (en) Use of a 2-(4-(azolylbutyl)-piperazinyl-methyl)-benzimidazole derivative for treating allergic conjunctivitis
EP3405197B1 (en) Use of delgocitinib for the treatment of chronic hand eczema
EP0771187B1 (en) Novel combination product comprising an antifungal agent and crotamiton as an antifungal activity enhancer and dermatological or cosmetic compositions comprising same
AU2004264332B2 (en) Method and composition for treating burned skin
EP3193883B1 (en) Composition comprising a compound from the family of avermectins and doxycycline for the treatment of rosacea
WO2007138233A2 (en) Use of zatosetron for the treatment of rosacea, and pharmaceutical compositions
US20080255238A1 (en) Composition containing a thiourea derivative for preventing or treating pruritic or irritant skin diseases
JP7257091B2 (en) Dementia treatment and preventive drug
WO2006087481A1 (en) Use of rimonabant for the preparation of medicaments that can be used in the prevention and treatment of type 2 diabetes
CA2782048A1 (en) Use of a dipyridyl compound for treating rosacea
KR20050108402A (en) Therapeutic and/or preventive agent for chronic skin disease
JP2000515865A (en) How to handle over-attack
WO2004092153A1 (en) Diamine derivative, production process, and antioxidizing drug
WO2007138232A2 (en) Use of granisetron for the treatment of sub-types of rosacea, and pharmaceutical compositions containing same
FR2648042A1 (en) Use of phenylethanolaminotetralins for the preparation of medicaments for the treatment of ocular disorders
JP2002138052A (en) Itching curative medicine
EP0465583A1 (en) Use of a potassic agonist in the treatment of glaucoma
BE888982A (en) WATER-SOLUBLE ETHERS OF HYDROXYFLAVONES, THEIR PREPARATION AND THEIR USE

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK FI FR GB GR IE IT LI LU MC NL PT SE

17P Request for examination filed

Effective date: 19970317

17Q First examination report despatched

Effective date: 20000619

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20001030