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US20030050303A1 - Solutions containing epinastin - Google Patents

Solutions containing epinastin Download PDF

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Publication number
US20030050303A1
US20030050303A1 US10/271,180 US27118002A US2003050303A1 US 20030050303 A1 US20030050303 A1 US 20030050303A1 US 27118002 A US27118002 A US 27118002A US 2003050303 A1 US2003050303 A1 US 2003050303A1
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Prior art keywords
aqueous solution
epinastine
solution
concentration
group
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.)
Abandoned
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US10/271,180
Inventor
Volker Trach
Gerold Duschler
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.)
Boehringer Ingelheim International GmbH
Original Assignee
Boehringer Ingelheim Pharma GmbH and Co KG
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Filing date
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Application filed by Boehringer Ingelheim Pharma GmbH and Co KG filed Critical Boehringer Ingelheim Pharma GmbH and Co KG
Priority to US10/271,180 priority Critical patent/US20030050303A1/en
Publication of US20030050303A1 publication Critical patent/US20030050303A1/en
Priority to US11/215,165 priority patent/US20050288274A1/en
Priority to US11/734,512 priority patent/US20070185082A1/en
Priority to US11/734,507 priority patent/US20070197503A1/en
Assigned to BOEHRINGER INGELHEIM INTERNATIONAL GMBH reassignment BOEHRINGER INGELHEIM INTERNATIONAL GMBH ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: BOEHRINGER INGELHEIM PHARMA GMBH & CO. KG, FKA. BOEHRINGER INGELHEIM PHARMA GMBH
Priority to US11/863,008 priority patent/US7429602B2/en
Priority to US12/394,684 priority patent/US20090239842A1/en
Abandoned legal-status Critical Current

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Classifications

    • 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
    • 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
    • A61K9/0043—Nose
    • 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
    • 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 eosinophils 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.
  • 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 eosinophils 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.
  • 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 buffer, 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 cosinophils into the tissue of the ocular conjunctiva or the nasal mucous membrane in allergic reactions.

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  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (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.[0001]
    • 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. [0002]
    • 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. [0003]
  • 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 eosinophils 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. [0004]
  • 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. [0005]
    • 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.[0006]
    • 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. [0007]
  • 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. [0008]
  • 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. [0009]
    • 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. [0010]
  • Results [0011]
  • The animals pretreated with epinastin solution according to the invention (0.05-0.5%) had a significantly lower content of eosinophils 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). [0012]
  • 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. [0013]
  • The above-mentioned topically administered aqueous solutions containing epinastin hydrochloride are preferred according to the invention. [0014]
  • Suitable aqueous solvents are physiologically acceptable aqueous solvents, physiologically acceptable saline solutions being particularly preferred. [0015]
  • 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. [0016]
  • The preferred carrier which may be used in the solutions according to the invention is purified water and preferably a physiological saline solution. [0017]
  • 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. [0018]
  • 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. [0019]
  • 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. [0020]
  • 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. [0021]
  • Various buffers and substances may be used to adjust the pH, provided that the preparation obtained is physiologically acceptable. These buffers might include acetate buffer, citrate buffer, phosphate buffer and borate buffer. [0022]
  • 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. [0023]
  • 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. [0024]
  • 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. [0025]
  • 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. [0026]
  • 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 cosinophils into the tissue of the ocular conjunctiva or the nasal mucous membrane in allergic reactions. [0027]
  • 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. [0028]
  • The Examples shown in Table 1 illustrate the invention without restricting it. [0029]
    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)

We claim:
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.
US10/271,180 1999-11-12 2002-10-15 Solutions containing epinastin Abandoned US20030050303A1 (en)

Priority Applications (6)

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

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
DE19954516.2 1999-11-12
DE19954516A DE19954516A1 (en) 1999-11-12 1999-11-12 Solutions containing epinastine
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

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US70665000A Continuation 1999-11-12 2000-11-06

Related Child Applications (5)

Application Number Title Priority Date Filing Date
US11/215,165 Continuation US20050288274A1 (en) 1999-11-12 2005-08-30 Treating rhinitis by topically administering an epinastine solution to the nasal mucous membrane
US11/734,507 Continuation US20070197503A1 (en) 1999-11-12 2007-04-12 Solutions containing epinastin
US11/734,512 Continuation US20070185082A1 (en) 1999-11-12 2007-04-12 Treating rhinitis by topically administering an epinastine solution to the nasal mucous membrane
US11/863,008 Continuation US7429602B2 (en) 1999-11-12 2007-09-27 Treating conjunctivitis by topically administering an epinastine solution to the conjunctiva
US12/394,684 Continuation US20090239842A1 (en) 1999-11-12 2009-02-27 Solutions containing epinastin

Publications (1)

Publication Number Publication Date
US20030050303A1 true US20030050303A1 (en) 2003-03-13

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Family Applications (6)

Application Number Title Priority Date Filing Date
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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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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CN112969465A (en) * 2018-10-31 2021-06-15 参天制药株式会社 Ophthalmic composition for inhibiting deterioration of soft contact lens
CN115397430A (en) * 2020-04-16 2022-11-25 参天制药株式会社 Aqueous composition containing epinastine or its salt

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