US20090239842A1 - Solutions containing epinastin - Google Patents

Solutions containing epinastin Download PDF

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US20090239842A1
US20090239842A1 US12/394,684 US39468409A US2009239842A1 US 20090239842 A1 US20090239842 A1 US 20090239842A1 US 39468409 A US39468409 A US 39468409A US 2009239842 A1 US2009239842 A1 US 2009239842A1
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aqueous solution
epinastine
solution
concentration
group
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US12/394,684
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Volker Trach
Gerold Duschler
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    • 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
    • A61K9/0043—Nose
    • 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
    • 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
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/02—Nasal agents, e.g. decongestants
    • 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
    • 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
    • A61P27/14—Decongestants or antiallergics
    • 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
    • A61P27/16—Otologicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic 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
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F01—MACHINES OR ENGINES IN GENERAL; ENGINE PLANTS IN GENERAL; STEAM ENGINES
    • F01L—CYCLICALLY OPERATING VALVES FOR MACHINES OR ENGINES
    • F01L9/00—Valve-gear or valve arrangements actuated non-mechanically
    • F01L9/20—Valve-gear or valve arrangements actuated non-mechanically by electric means
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T137/00—Fluid handling
    • Y10T137/0318—Processes

Definitions

  • the invention relates to topically administered aqueous solutions containing epinastin, optionally in the form of its racemates, its enantiomers and optionally in the form of the pharmacologically acceptable acid addition salts thereof.
  • Allergic reactions of the eye signifies a series of differently defined syndromes.
  • Examples of allergic reactions of the nose include seasonal allergic rhinitis and perennial allergic rhinitis, for example.
  • the immunological mechanism on which ocular and nasal allergic reactions are based comprises, inter alia, inflammatory processes caused by histamine.
  • the allergic reactions produced by the release of histamine occur at an early stage of the ocular and nasal allergic reactions mentioned above.
  • ocular and nasal allergic reactions may be due to the release of other mast cell mediators as well as toxic eosinophilic granule proteins and enzymes.
  • the influx of neutrophils and eosinopbils into the tissue of the ocular conjunctiva and the nasal mucous membrane leads to a late phase reaction, hereinafter referred to as LPR.
  • LPR normally occurs within a period of 3-6 hours after the initial histamine-mediated allergic reaction.
  • LPR is also characterized by the occurrence of vasodilation and chemosis and by the swelling of the conjunctiva and the nasal mucous membrane.
  • histamine-produced allergic reactions can be counteracted by administering antihistamines
  • the influx of neurophils and eosinophils into the tissue of the ocular conjunctiva and the nasal mucous membrane remains unaffected by administering pure antihistamines.
  • the problem of the present invention is therefore to provide topically administrable solutions which inhibit the influx of neutrophils and eosinophils into the tissue of the ocular conjunctiva and the nasal mucous membrane, thereby reducing or preventing the occurrence of LPR and are therefore characterized by a longer lasting duration of activity.
  • topically administrable aqueous solutions containing epinastin, optionally in the form of its racemate, its enantiomers and possibly in the form of the pharmacologically acceptable acid addition salts thereof may be used to solve the problem on which the invention is based, since they inhibit the influx of neutrophils and eosinophils into the tissue of the ocular conjunctiva and nasal mucous membrane, thereby reducing or preventing the occurrence of LPR and are accordingly characterized by a longer lasting duration of activity.
  • the animals pretreated with epinastin solution according to the invention (0.05-0.5%) had a significantly lower content of cosinophils in their conjunctiva.
  • the animals pretreated with epinastin solution according to the invention had a significantly lower content of lymphocytes in their conjunctiva (p ⁇ 0.01).
  • a roughly 35% inhibition of mast cell degranulation was determined (p ⁇ 0.01).
  • the invention relates to topically administered aqueous solutions containing epinastin, optionally in the form of its racemate, its enantiomers and optionally in the form of the pharmacologically acceptable addition salts thereof, in a concentration of 0.005 to 0.5, preferably 0.02 to 0.1, most preferably 0.03 to 0.07 mg/ml of solution.
  • topically administered aqueous solutions containing epinastin hydrochloride are preferred according to the invention.
  • Suitable aqueous solvents are physiologically acceptable aqueous solvents, physiologically acceptable saline solutions being particularly preferred.
  • topically administered solutions are preferably prepared which typically contain 0.005 to 0.5, preferably 0.02 to 0.1, most preferably 0.03 to 0.07 mg/ml of epinastin, optionally in the form of its racemate, its enantiomers and optionally in the form of the pharmacologically acceptable acid addition salts thereof, as well as physiological saline solutions as the main carriers.
  • the pH of the solutions according to the invention should preferably be maintained within the range from 6.5 to 7.2 by means of a suitable buffer system.
  • the preparations may also contain conventional, pharmaceutically acceptable excipients, preservatives, stabilizers and/or penetration promoters.
  • the preferred carrier which may be used in the solutions according to the invention is purified water and preferably a physiological saline solution.
  • the excipients which may be used according to the invention include viscosity agents such as polyvinyl alcohol, povidone, hydroxypropylmethylcellulose, poloxamers, carboxymethylcellulose, carbomers and hydroxyethylcellulose.
  • the preferred preservatives which may be used in the solutions according to the invention include benzalkonium chloride, chlorobutanol, thimerosal, phenyl mercury acetate and phenyl mercury nitrate.
  • the penetration promoters may be, for example, surfactants, specific organic solvents such as dimethylsulfoxide and other sulfoxides, dimethylacetamide and pyrrolidone, specific amides of heterocyclic amines, glycols such as propyleneglycol, propylene carbonate, oleic acid, alkylamines and derivatives thereof, various cationic, anionic, non-ionogenic and amphoteric surfactants and the like.
  • specific organic solvents such as dimethylsulfoxide and other sulfoxides, dimethylacetamide and pyrrolidone
  • specific amides of heterocyclic amines such as propyleneglycol, propylene carbonate, oleic acid, alkylamines and derivatives thereof
  • various cationic, anionic, non-ionogenic and amphoteric surfactants and the like.
  • Substances may be added as necessary or as desired in order to adjust the tonicity of the solution.
  • Such substances include salts and especially sodium chloride, potassium chloride, mannitol and glycerol or other suitable physiologically acceptable agents for adjusting tonicity, without restricting the invention to the above.
  • buffers and substances may be used to adjust the pH, provided that the preparation obtained is physiologically acceptable.
  • These buffers might include acetate buffers citrate buffer, phosphate buffer and borate buffer.
  • physiologically acceptable antioxidants which may be used according to the invention include sodium metabisulphite, sodium thiosulphate, acetylcysteine, butylated hydroxyanisole and butylated hydroxytoluene, without restricting the invention to this list.
  • carrier components which may be incorporated in the solutions according to the invention are chelating agents.
  • the preferred chelating agent is disodium edetate (Na-EDTA), although other chelating agents may also be used instead of or in conjunction with disodium edetate.
  • topically administered aqueous solutions according to the invention may be applied either to the conjunctiva or to the nasal mucous membrane. Solutions for ophthalmic use are of equal importance to solutions for nasal application for the purposes of the present invention.
  • the invention relates not only to the solutions according to the invention mentioned hereinbefore but also to the use of the above-mentioned topically administered aqueous solutions for inhibiting the influx of neutrophils and eosinophils into the tissue of the ocular conjunctiva or the tissue of the nasal mucous membrane.
  • the present invention also relates to the use of epinastin, optionally in the form of its racemate, its enantiomers and optionally in the form of the pharmacologically acceptable acid addition salts thereof, for producing the topically administered aqueous solutions according to the invention for treating disorders of the ocular conjunctiva or the nasal mucous membranes in which there is therapeutic value in inhibiting the influx of neutrophils and eosinophils into the tissue of the ocular conjunctiva or the nasal mucous membrane in allergic reactions.

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  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Pulmonology (AREA)
  • Otolaryngology (AREA)
  • Mechanical Engineering (AREA)
  • General Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Detergent Compositions (AREA)

Abstract

Topically administered aqueous solutions containing epinastin, optionally in the form of its racemate or its enantiomers and optionally in the form of the pharmacologically acceptable acid addition salts thereof.

Description

    RELATED APPLICATIONS
  • This application is a continuation of U.S. Ser. No. 09/706,650, filed Nov. 6, 2000.
    • FIELD OF THE INVENTION
  • The invention relates to topically administered aqueous solutions containing epinastin, optionally in the form of its racemates, its enantiomers and optionally in the form of the pharmacologically acceptable acid addition salts thereof.
    • BACKGROUND OF THE INVENTION
  • Allergic reactions of the eye (hereinafter referred to as ocular allergic reactions) signifies a series of differently defined syndromes. The following are examples of ocular allergic reactions, e.g., seasonal allergic conjunctivitis, perennial allergic conjunctivitis, giant cell conjunctivitis, vernal keratoconjunctivitis or atopic keratoconjunctivitis. Examples of allergic reactions of the nose (hereinafter referred to as nasal allergic reactions) include seasonal allergic rhinitis and perennial allergic rhinitis, for example.
  • The immunological mechanism on which ocular and nasal allergic reactions are based comprises, inter alia, inflammatory processes caused by histamine. The allergic reactions produced by the release of histamine occur at an early stage of the ocular and nasal allergic reactions mentioned above. Moreover, ocular and nasal allergic reactions may be due to the release of other mast cell mediators as well as toxic eosinophilic granule proteins and enzymes. The influx of neutrophils and eosinopbils into the tissue of the ocular conjunctiva and the nasal mucous membrane leads to a late phase reaction, hereinafter referred to as LPR. LPR normally occurs within a period of 3-6 hours after the initial histamine-mediated allergic reaction. LPR is also characterized by the occurrence of vasodilation and chemosis and by the swelling of the conjunctiva and the nasal mucous membrane.
  • Whereas histamine-produced allergic reactions can be counteracted by administering antihistamines, the influx of neurophils and eosinophils into the tissue of the ocular conjunctiva and the nasal mucous membrane remains unaffected by administering pure antihistamines.
    • Problem of the Invention
  • The problem of the present invention is therefore to provide topically administrable solutions which inhibit the influx of neutrophils and eosinophils into the tissue of the ocular conjunctiva and the nasal mucous membrane, thereby reducing or preventing the occurrence of LPR and are therefore characterized by a longer lasting duration of activity.
    • DETAILED DESCRIPTION OF THE INVENTION
  • It has been found, surprisingly, that topically administrable aqueous solutions containing epinastin, optionally in the form of its racemate, its enantiomers and possibly in the form of the pharmacologically acceptable acid addition salts thereof, may be used to solve the problem on which the invention is based, since they inhibit the influx of neutrophils and eosinophils into the tissue of the ocular conjunctiva and nasal mucous membrane, thereby reducing or preventing the occurrence of LPR and are accordingly characterized by a longer lasting duration of activity.
  • The compound epinastin (3-amino-9,13b-dihydro-1H-dibenz-[c,f]imidazol[1,5-a]azepine) and the acid addition salts thereof were described for the first time in German Patent Application P 30 08 944.2.
  • The effect of the topically administered solutions containing epinastin as inhibitors of the influx of eosinophils and neutrophils was demonstrated using the so-called passive ocular anaphylaxis model in rats.
    • Description of Experiment
  • 72 hours after the rats have been sensitized by injecting antiserum into the eyelids of the test animals, a fresh provocation was induced in them by intravenous administration of ovalbumin. Some of the experimental animals were pretreated by the administration of solution containing epinastin according to the invention into the conjunctival sac 15 minutes before the ovalbumin is administered. Two hours after the administration of ovalbumin the experimental animals were killed and the conjunctiva was investigated for its content of eosinophils and neutrophils and the mast cell granulation was determined.
    • Results
  • The animals pretreated with epinastin solution according to the invention (0.05-0.5%) had a significantly lower content of cosinophils in their conjunctiva. The animals pretreated with epinastin solution according to the invention had a significantly lower content of lymphocytes in their conjunctiva (p<0.01). In the animals pretreated with epinastin solution according to the invention, a roughly 35% inhibition of mast cell degranulation was determined (p<0.01).
  • Consequently, the invention relates to topically administered aqueous solutions containing epinastin, optionally in the form of its racemate, its enantiomers and optionally in the form of the pharmacologically acceptable addition salts thereof, in a concentration of 0.005 to 0.5, preferably 0.02 to 0.1, most preferably 0.03 to 0.07 mg/ml of solution.
  • The above-mentioned topically administered aqueous solutions containing epinastin hydrochloride are preferred according to the invention.
  • Suitable aqueous solvents are physiologically acceptable aqueous solvents, physiologically acceptable saline solutions being particularly preferred.
  • According to the invention, topically administered solutions are preferably prepared which typically contain 0.005 to 0.5, preferably 0.02 to 0.1, most preferably 0.03 to 0.07 mg/ml of epinastin, optionally in the form of its racemate, its enantiomers and optionally in the form of the pharmacologically acceptable acid addition salts thereof, as well as physiological saline solutions as the main carriers. The pH of the solutions according to the invention should preferably be maintained within the range from 6.5 to 7.2 by means of a suitable buffer system. The preparations may also contain conventional, pharmaceutically acceptable excipients, preservatives, stabilizers and/or penetration promoters.
  • The preferred carrier which may be used in the solutions according to the invention is purified water and preferably a physiological saline solution.
  • Without restricting the subject matter of the invention to the following, the excipients which may be used according to the invention include viscosity agents such as polyvinyl alcohol, povidone, hydroxypropylmethylcellulose, poloxamers, carboxymethylcellulose, carbomers and hydroxyethylcellulose.
  • Without restricting the subject matter of the invention to the following, the preferred preservatives which may be used in the solutions according to the invention include benzalkonium chloride, chlorobutanol, thimerosal, phenyl mercury acetate and phenyl mercury nitrate.
  • The penetration promoters may be, for example, surfactants, specific organic solvents such as dimethylsulfoxide and other sulfoxides, dimethylacetamide and pyrrolidone, specific amides of heterocyclic amines, glycols such as propyleneglycol, propylene carbonate, oleic acid, alkylamines and derivatives thereof, various cationic, anionic, non-ionogenic and amphoteric surfactants and the like.
  • Substances may be added as necessary or as desired in order to adjust the tonicity of the solution. Such substances include salts and especially sodium chloride, potassium chloride, mannitol and glycerol or other suitable physiologically acceptable agents for adjusting tonicity, without restricting the invention to the above.
  • Various buffers and substances may be used to adjust the pH, provided that the preparation obtained is physiologically acceptable. These buffers might include acetate buffers citrate buffer, phosphate buffer and borate buffer.
  • Similarly, physiologically acceptable antioxidants which may be used according to the invention include sodium metabisulphite, sodium thiosulphate, acetylcysteine, butylated hydroxyanisole and butylated hydroxytoluene, without restricting the invention to this list.
  • Other carrier components which may be incorporated in the solutions according to the invention are chelating agents. The preferred chelating agent is disodium edetate (Na-EDTA), although other chelating agents may also be used instead of or in conjunction with disodium edetate.
  • The above-mentioned topically administered aqueous solutions according to the invention may be applied either to the conjunctiva or to the nasal mucous membrane. Solutions for ophthalmic use are of equal importance to solutions for nasal application for the purposes of the present invention.
  • The invention relates not only to the solutions according to the invention mentioned hereinbefore but also to the use of the above-mentioned topically administered aqueous solutions for inhibiting the influx of neutrophils and eosinophils into the tissue of the ocular conjunctiva or the tissue of the nasal mucous membrane.
  • The present invention also relates to the use of epinastin, optionally in the form of its racemate, its enantiomers and optionally in the form of the pharmacologically acceptable acid addition salts thereof, for producing the topically administered aqueous solutions according to the invention for treating disorders of the ocular conjunctiva or the nasal mucous membranes in which there is therapeutic value in inhibiting the influx of neutrophils and eosinophils into the tissue of the ocular conjunctiva or the nasal mucous membrane in allergic reactions.
  • The above-mentioned use for inhibiting LPR is preferred, whilst it is particularly preferable to use the preparation to treat the diseases listed at the beginning.
  • The Examples shown in Table 1 illustrate the invention without restricting it.
  • TABLE 1
    Solution 1 Solution 2 Solution 3 Solution 4 Solution 5 Solution 6 Solution 7
    0.05% 0.01% 0.05% 0.10% 0.01% 0.05% 0.10%
    [g/100 ml] [g/100 ml] [g/100 ml] [g/100 ml] [g/100 ml] [g/100 ml] [g/100 ml]
    Epinastin-hydrochloride 0.0500 0.0100 0.0500 0.1000 0.0100 0.0500 0.1000
    Na-EDTA 0.0500 0.0500 0.0500 0.0500 — — —
    Sodium chloride 0.5000 0.5000 0.5000 0.5000 0.5000 0.5000 0.5000
    Sodium dihydrogen phosphate 0.7800 0.7800 0.7800 0.7800 0.4100 0.4100 0.4100
    dihydrate
    Benzalkonium chloride 0.0101 0.0101 0.0101 0.0101 0.0101 0.0101 0.0101
    Sodium hydroxide 0.0001 0.0001 0.0001 0.0001 — — —
    Sodium dihydrogen phosphate — — — — 0.6500 0.6500 0.6500
    dihydrate
    Hydroxyethylcellulose — — — — 0.1000 0.1000 0.1000
    Water 99.4198 99.4598 99.4198 99.3698 99.0749 99.0349 99.9849
    100.8100 100.8100 100.8100 100.8100 100.7550 100.7550 100.7550

Claims (11)

1. A method for inhibiting the influx of neutrophils and eosinophils into the tissue of the ocular conjunctiva or the nasal mucous membrane in a host, the method comprising topically administering to a host in need of such treatment an aqueous solution comprising epinastine, optionally in the form of its racemate, its enantiomers, or its pharmacologically acceptable acid addition salts thereof, in a concentration of 0.005 to 0.5 mg/ml of solution.
2. The method according to claim 1, wherein the concentration of epinastine in the aqueous solution is 0.02 to 0.1 mg/ml of solution.
3. The method according to claim 2, wherein the concentration of epinastine in the aqueous solution is 0.03 to 0.07 mg/ml of solution.
4. The method according to claim 1, wherein the aqueous solution comprises epinastine hydrochloride.
5. The method according to one of claims 1 or 2, wherein the aqueous solution is adjusted to a pH of between 6.5 and 7.2 by means of a physiologically acceptable buffer.
6. The method according to claim 5, wherein the aqueous solution further comprises a preservative.
7. The method according to claim 6, wherein the preservative is selected from the group consisting of: benzalkonium chloride, chlorobutanol, thimerosal, phenyl mercury acetate, and phenyl mercury nitrate.
8. The method according to claim 5, wherein the aqueous solution further comprises a viscosity agent.
9. The method according to claim 8, wherein the viscosity agent is selected from the group consisting of: polyvinyl alcohol, povidone, hydroxypropylmethylcellulose, poloxamers, carboxymethylcellulose, carbomers, and hydroxyethylcellulose.
10. The method according to claim 5, wherein the aqueous solution further comprises a penetration promoter.
11. The method according to claim 10, wherein the penetration promoter is selected from the group consisting of: cationic, anionic, non-ionogenic, and amphoteric surfactants; dimethylsulfoxide and other sulfoxides; dimethylacetamide and pyrrolidone; amides of heterocyclic amines; glycols; propylene carbonate; oleic acid; and alkylamines and derivatives thereof.
US12/394,684 1999-11-12 2009-02-27 Solutions containing epinastin Abandoned US20090239842A1 (en)

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Applications Claiming Priority (6)

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DE19954516A DE19954516A1 (en) 1999-11-12 1999-11-12 Solutions containing epinastine
DEDE19954516.2 1999-11-12
US16777199P 1999-11-29 1999-11-29
US70665000A 2000-11-06 2000-11-06
US10/271,180 US20030050303A1 (en) 1999-11-12 2002-10-15 Solutions containing epinastin
US12/394,684 US20090239842A1 (en) 1999-11-12 2009-02-27 Solutions containing epinastin

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US10/271,180 Abandoned US20030050303A1 (en) 1999-11-12 2002-10-15 Solutions containing epinastin
US11/215,165 Abandoned US20050288274A1 (en) 1999-11-12 2005-08-30 Treating rhinitis by topically administering an epinastine solution to the nasal mucous membrane
US11/734,512 Abandoned US20070185082A1 (en) 1999-11-12 2007-04-12 Treating rhinitis by topically administering an epinastine solution to the nasal mucous membrane
US11/734,507 Abandoned US20070197503A1 (en) 1999-11-12 2007-04-12 Solutions containing epinastin
US11/863,008 Expired - Lifetime US7429602B2 (en) 1999-11-12 2007-09-27 Treating conjunctivitis by topically administering an epinastine solution to the conjunctiva
US12/394,684 Abandoned US20090239842A1 (en) 1999-11-12 2009-02-27 Solutions containing epinastin

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US10/271,180 Abandoned US20030050303A1 (en) 1999-11-12 2002-10-15 Solutions containing epinastin
US11/215,165 Abandoned US20050288274A1 (en) 1999-11-12 2005-08-30 Treating rhinitis by topically administering an epinastine solution to the nasal mucous membrane
US11/734,512 Abandoned US20070185082A1 (en) 1999-11-12 2007-04-12 Treating rhinitis by topically administering an epinastine solution to the nasal mucous membrane
US11/734,507 Abandoned US20070197503A1 (en) 1999-11-12 2007-04-12 Solutions containing epinastin
US11/863,008 Expired - Lifetime US7429602B2 (en) 1999-11-12 2007-09-27 Treating conjunctivitis by topically administering an epinastine solution to the conjunctiva

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8791154B2 (en) 2011-05-19 2014-07-29 Alcon Research, Ltd. High concentration olopatadine ophthalmic composition

Families Citing this family (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19954516A1 (en) * 1999-11-12 2001-05-17 Boehringer Ingelheim Int Solutions containing epinastine
CA2494065A1 (en) * 2002-08-02 2004-02-19 Boehringer Ingelheim International Gmbh Pharmaceutical formulations comprising combinations of epinastine, pseudoephedrine and methylephedrine
US20040247686A1 (en) * 2003-04-04 2004-12-09 Boehringer Ingelheim International Gmbh Pharmaceutical compositions comprising epinastine for the treatment of skin diseases
EP1468696A1 (en) * 2003-04-17 2004-10-20 Boehringer Ingelheim International GmbH Combinations of epinastine and antiphlogisitcs as new pharmaceutical compositions for the treatment of skin diseases
US20060073172A1 (en) * 2004-10-01 2006-04-06 Schneider L W Stabilized ophthalmic solution for the treatment of glaucoma and lowering intraocular pressure
CN101217948A (en) * 2005-07-08 2008-07-09 千寿制药株式会社 Percutaneously absorptive ophthalmic preparation comprising epinastine
WO2008098122A2 (en) * 2007-02-08 2008-08-14 Inspire Pharmaceuticals, Inc. Method for treating allergic rhinitis without adverse effects
US20080194544A1 (en) * 2007-02-08 2008-08-14 Ramesh Krishnamoorthy Aqueous formulations of epinastine for treating allergic rhinitis
US7378082B1 (en) 2007-11-05 2008-05-27 Inspire Pharmaceuticals, Inc. Method for treating allergic rhinitis without adverse effects
EP2464387A4 (en) * 2009-08-12 2013-05-15 Seros Medical Llc Deuterated water and riboflavin solution for extending singlet oxygen lifetimes in treatment of ocular tissue and method for use
EP2630952A1 (en) * 2012-02-23 2013-08-28 Novagali Pharma S.A. Self-preserved oil dispersions comprising boric acid
BR112015014367B1 (en) * 2012-12-19 2022-11-22 Novartis Ag LFA-1-INHIBITOR COMPOSITION, METHOD FOR STABILIZING SAID COMPOSITION, AND USE THEREOF TO TREAT AN EYE DISEASE
CN104491876A (en) * 2014-12-23 2015-04-08 中国药科大学 Sodium hyaluronate-containing epinastine eye drops and preparation method thereof
ITUB20153950A1 (en) * 2015-09-28 2017-03-28 Tred Srl NASAL DEVICE ABLE TO ACTIVATE THE RINO-PALATHIC REFLEX FOR RINOFARINGEA HYGIENISATION
JP6134853B1 (en) * 2016-10-28 2017-05-24 参天製薬株式会社 Epinastine-containing ophthalmic solution
JP6635974B2 (en) * 2017-04-24 2020-01-29 参天製薬株式会社 Epinastine-containing ophthalmic solution
KR102582048B1 (en) * 2017-05-01 2023-09-21 산텐 세이야꾸 가부시키가이샤 eye drops
JP2019108320A (en) * 2018-10-31 2019-07-04 参天製薬株式会社 Ophthalmologic composition which suppresses deterioration of soft contact lens
JP6736752B2 (en) * 2019-12-17 2020-08-05 参天製薬株式会社 Eye drops containing epinastine
JP7118579B1 (en) 2020-04-16 2022-08-16 参天製薬株式会社 Aqueous composition containing epinastine or its salt
JP6963651B2 (en) * 2020-04-16 2021-11-10 参天製薬株式会社 Aqueous composition containing epinastine or a salt thereof
JP2020169213A (en) * 2020-07-15 2020-10-15 参天製薬株式会社 Epinastine-containing eye drops
CN115448927A (en) * 2022-10-20 2022-12-09 重庆瑞泊莱医药科技有限公司 Epinastine hydrobromide crystal form II and preparation method thereof

Citations (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4313931A (en) * 1980-03-08 1982-02-02 Boehringer Ingelheim Kg Fused dibenzo imidazolo compounds, compositions and use
US5312916A (en) * 1991-01-25 1994-05-17 Boehringer Ingelheim Kg Process for preparing 3-amino-9,13b-dihydro-1H-dibenz(c,f)imidazo(1,5-a)azepine-hydrochloride
US5668133A (en) * 1992-12-09 1997-09-16 Alcon Laboratories, Inc. Ophthalmic compositions comprising emedastine and methods for their use
US5942503A (en) * 1995-11-14 1999-08-24 Boehringer Indelheim Kg Use of Epinastine for the treatment of pain
US20010008632A1 (en) * 1996-12-20 2001-07-19 Bernhard Freund Aqueous medicament preparations for the production of propellent gas-free aerosols
US20020037297A1 (en) * 1997-09-22 2002-03-28 Crespo Maria Del Carmen Diez Process for the topical treatment of rhinitis, conjunctivitis cold, and cold-like and flu symptoms
US6403790B1 (en) * 1999-12-03 2002-06-11 Boehringer Ingelheim Pharma Kg Process for the production of epinastine hydrochloride in the high-melting crystal modification
US20020151541A1 (en) * 2000-10-31 2002-10-17 Michel Pairet Pharmaceutical compositions containing tiotropium salts and antihistamines and their use
US20030050303A1 (en) * 1999-11-12 2003-03-13 Boehringer Ingelheim Pharma Gmbh Solutions containing epinastin
US20030104017A1 (en) * 2001-10-26 2003-06-05 Boehringer Ingelheim International Gmbh Epinastine formulation for oral administration
US20030181478A1 (en) * 2000-10-31 2003-09-25 Boehringer Ingelheim Pharma Kg Inhalable formulation of a solution containing a tiotropium salt
US20030203021A1 (en) * 2000-10-06 2003-10-30 Boehringer Ingelheim International Gmbh Pharmaceutical compositions containing epinastine and pseudoephedrine
US6649602B1 (en) * 1999-11-18 2003-11-18 Alcon, Inc. Use of an H1 antagonist and a safe steroid to treat eye conditions
US20030215396A1 (en) * 1999-09-15 2003-11-20 Boehringer Ingelheim Pharma Kg Method for the production of propellant gas-free aerosols from aqueous medicament preparations
US20030228359A1 (en) * 2002-04-03 2003-12-11 Boehringer Ingelheim International Gmbh Pharmaceutical formulations containing epinastine, belladonna, and pseudoephedrine
US6863848B2 (en) * 2002-08-30 2005-03-08 Signet Armorlite, Inc. Methods for preparing composite photochromic ophthalmic lenses
US20070097503A1 (en) * 2005-10-27 2007-05-03 Nissan Motor Co., Ltd. Light blocking device
US7420602B2 (en) * 2001-05-29 2008-09-02 Samsung Semiconductor Israel R&D Center (Sirc) Cmos imager for cellular applications and methods of using such

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US104017A (en) * 1870-06-07 Improvement in embroidering attachment for sewing-machines
US181478A (en) * 1876-08-22 Improvement in water-wheels
US8632A (en) * 1852-01-06 George hess
US203021A (en) * 1878-04-30 Improvement in side-bar wagons
US215396A (en) * 1879-05-13 Improvement in loom-temples
US228359A (en) * 1880-06-01 jones
US151541A (en) * 1874-06-02 Improvement in hay-loaders
IL122752A (en) * 1995-06-27 2001-07-24 Boehringer Ingelheim Kg Stable compositions for generating propellant-free aerosols
JP3124041B2 (en) * 1996-08-30 2001-01-15 京都薬品工業株式会社 Allergic dermatitis treatment
FR2803520B1 (en) * 2000-01-12 2002-09-20 Ceva Sante Animale PROCESS FOR INCREASING THE PRODUCTION OF EGGS AND CONSOLIDATING THE EGG SHELL IN POULTRY
DE10119718A1 (en) * 2001-04-21 2002-10-31 Boehringer Ingelheim Pharma Process for the continuous production of inhalable medicinal substances, device for carrying out the process and medicinal substance produced by this process

Patent Citations (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4313931A (en) * 1980-03-08 1982-02-02 Boehringer Ingelheim Kg Fused dibenzo imidazolo compounds, compositions and use
US5312916A (en) * 1991-01-25 1994-05-17 Boehringer Ingelheim Kg Process for preparing 3-amino-9,13b-dihydro-1H-dibenz(c,f)imidazo(1,5-a)azepine-hydrochloride
US5668133A (en) * 1992-12-09 1997-09-16 Alcon Laboratories, Inc. Ophthalmic compositions comprising emedastine and methods for their use
US5942503A (en) * 1995-11-14 1999-08-24 Boehringer Indelheim Kg Use of Epinastine for the treatment of pain
US20010008632A1 (en) * 1996-12-20 2001-07-19 Bernhard Freund Aqueous medicament preparations for the production of propellent gas-free aerosols
US20020037297A1 (en) * 1997-09-22 2002-03-28 Crespo Maria Del Carmen Diez Process for the topical treatment of rhinitis, conjunctivitis cold, and cold-like and flu symptoms
US20030215396A1 (en) * 1999-09-15 2003-11-20 Boehringer Ingelheim Pharma Kg Method for the production of propellant gas-free aerosols from aqueous medicament preparations
US20050288274A1 (en) * 1999-11-12 2005-12-29 Boehringer Ingelheim Pharma Gmbh Treating rhinitis by topically administering an epinastine solution to the nasal mucous membrane
US20030050303A1 (en) * 1999-11-12 2003-03-13 Boehringer Ingelheim Pharma Gmbh Solutions containing epinastin
US20070185082A1 (en) * 1999-11-12 2007-08-09 Volker Trach Treating rhinitis by topically administering an epinastine solution to the nasal mucous membrane
US6649602B1 (en) * 1999-11-18 2003-11-18 Alcon, Inc. Use of an H1 antagonist and a safe steroid to treat eye conditions
US6403790B1 (en) * 1999-12-03 2002-06-11 Boehringer Ingelheim Pharma Kg Process for the production of epinastine hydrochloride in the high-melting crystal modification
US20030203021A1 (en) * 2000-10-06 2003-10-30 Boehringer Ingelheim International Gmbh Pharmaceutical compositions containing epinastine and pseudoephedrine
US20030181478A1 (en) * 2000-10-31 2003-09-25 Boehringer Ingelheim Pharma Kg Inhalable formulation of a solution containing a tiotropium salt
US20020151541A1 (en) * 2000-10-31 2002-10-17 Michel Pairet Pharmaceutical compositions containing tiotropium salts and antihistamines and their use
US7420602B2 (en) * 2001-05-29 2008-09-02 Samsung Semiconductor Israel R&D Center (Sirc) Cmos imager for cellular applications and methods of using such
US20030104017A1 (en) * 2001-10-26 2003-06-05 Boehringer Ingelheim International Gmbh Epinastine formulation for oral administration
US20030228359A1 (en) * 2002-04-03 2003-12-11 Boehringer Ingelheim International Gmbh Pharmaceutical formulations containing epinastine, belladonna, and pseudoephedrine
US6863848B2 (en) * 2002-08-30 2005-03-08 Signet Armorlite, Inc. Methods for preparing composite photochromic ophthalmic lenses
US20070097503A1 (en) * 2005-10-27 2007-05-03 Nissan Motor Co., Ltd. Light blocking device

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8791154B2 (en) 2011-05-19 2014-07-29 Alcon Research, Ltd. High concentration olopatadine ophthalmic composition
US9533053B2 (en) 2011-05-19 2017-01-03 Alcon Research, Ltd. High concentration olopatadine ophthalmic composition

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