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 or sparfloxacin
• • 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.

Landscapes

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

Applications Claiming Priority (3)

Publications (1)

Family

ID=9476989

Family Applications (1)

Country Status (9)

Families Citing this family (4)

Family Cites Families (3)

• 1995
  • 1995-03-14 FR FR9502910A patent/FR2731618B1/fr not_active Expired - Fee Related
• 1996
  • 1996-03-11 US US08/613,843 patent/US5641781A/en not_active Expired - Fee Related
  • 1996-03-13 JP JP8527293A patent/JPH10500427A/ja active Pending
  • 1996-03-13 ES ES09600606A patent/ES2117558B1/es not_active Expired - Fee Related
  • 1996-03-13 CA CA002190187A patent/CA2190187A1/fr not_active Abandoned
  • 1996-03-13 WO PCT/EP1996/001148 patent/WO1996028161A1/fr not_active Ceased
  • 1996-03-13 AU AU51452/96A patent/AU718008B2/en not_active Ceased
  • 1996-03-13 EP EP96908059A patent/EP0760663A1/de not_active Withdrawn
  • 1996-03-14 ZA ZA962060A patent/ZA962060B/xx unknown

Non-Patent Citations (1)

Also Published As

Similar Documents

Legal Events