CN-122005753-A - Ophthalmic composition for treating dry eye

Abstract

The present invention provides pharmaceutical compositions for the topical treatment of dry eye comprising about 0.05 to 0.1% (w/v) cyclosporin dissolved in 1-perfluorobutyl-pentane, and methods of administration and treatment thereof. The invention also provides kits comprising such compositions.

Inventors

• Marcus Bell
• Jorge Hessel
• Alice Medes
• Sonia Crossell
• Hartmut Worth
• FRANK LOSCHER
• Bernhard Kingt

Assignees

• 诺瓦利克有限责任公司

Dates

Publication Date

20260512

Application Date

20171220

Priority Date

20161223

Claims (10)

1. 1. A pharmaceutical composition for use in the topical treatment of dry eye in a subject having dry eye, wherein the composition comprises about 0.05% to 0.1% (w/v) cyclosporin dissolved in 1-perfluorobutyl-pentane, and wherein the amount of cyclosporin administered in a single dose per eye is about 4 μg to 12 μg.
2. 2. A pharmaceutical composition for use in treating ocular surface damage in a subject having dry eye, wherein the composition comprises about 0.05% to 0.1% (w/v) cyclosporin dissolved in 1-perfluorobutyl-pentane, and wherein the amount of cyclosporin administered in a single dose per eye is about 4 μg to 12 μg.
3. 3. A pharmaceutical composition for use in treating dyskinesia in a subject suffering from dry eye, wherein the composition comprises about 0.05% to 0.1% (w/v) cyclosporin dissolved in 1-perfluorobutyl-pentane, and wherein the amount of cyclosporin administered in a single dose per eye is about 4 μg to 12 μg.
4. 4. The pharmaceutical composition for use according to any one of the preceding claims, wherein the subject is a human subject.
5. 5. The pharmaceutical composition for use according to any one of the preceding claims, wherein the total daily dose administered per eye is less than about 28 μg.
6. 6. The pharmaceutical composition for use according to any one of the preceding claims, wherein the dose of the composition is administered as one single drop to the eye of a subject.
7. 7. The pharmaceutical composition for use according to any of the preceding claims, wherein the dry eye is moderate to severe dry eye, and optionally wherein the subject is non-responsive to an artificial tear treatment.
8. 8. The pharmaceutical composition for use according to any one of the preceding claims, wherein the composition comprises up to about 1.0% (w/w) ethanol.
9. 9. The pharmaceutical composition for use according to any one of the preceding claims, wherein the composition consists essentially of about 0.05% or 0.1% (w/v) cyclosporin dissolved in 1-perfluorobutyl-pentane and optionally about 1.0% (w/w) ethanol.
10. 10. The pharmaceutical composition for use according to any one of the preceding claims, wherein the composition is administered twice daily.

Description

Ophthalmic composition for treating dry eye The application is a divisional application of China patent application (application date: 2017, 12, 20, title of the application: an ophthalmic composition for treating xerophthalmia) with application number 201780079941.0. Background Keratoconjunctivitis sicca, also known as dry eye or dysfunctional tear syndrome, is now recognized as a multifunctional condition of the tear film and ocular surface that results in discomfort, vision impairment, and even often ocular surface damage caused by tear film instability. The estimated prevalence of dry eye varies greatly depending on the criteria used to define the disease, but in the united states, it is estimated that up to 320 and 170 tens of thousands of women over 50 years old suffer from dry eye, and it is expected that the number of affected patients will increase by 40% by 2030. The pharmacological treatment of choice for dry eye is cyclosporin. Cyclosporine is an approved drug in the form of an ophthalmic (o/w) emulsion (Restasis ®) available in at least the united states. The product is useful for increasing tear production in a patient who is presumed to be inhibited by ocular inflammation associated with keratoconjunctivitis sicca. WO2011/073134 A1 discloses pharmaceutical compositions in the form of solutions comprising cyclosporin and semifluorinated alkanes as liquid carrier, which may be administered to the eye of a patient, for example for the treatment of keratoconjunctivitis sicca, e.g. compositions comprising cyclosporin in semifluorinated alkanes 1-perfluorobutyl-pentane (F4H 5) in the presence of ethanol as co-solvent. However, WO2011/073134 A1 does not describe dosing and treatment regimens for the treatment of dry eye, particularly moderate to severe dry eye and related conditions. Gehlsen et al (INVESTIGATIVE OPHTHALMOLOGY & Visual Science June 2015, vol. 56, 319) describe a study to test the use of CsA in SFA (F4H 5) as a vehicle for local treatment in experimental dry eye mouse models. Gehlsen et al describe the topical treatment of mice with induced experimental dry eye for 3 x/day (5 μl/eye) in this study. However, gehlsen et al do not disclose a therapeutic or dosing regimen for treating dry eye in a human subject, particularly a subject suffering from moderate to severe dry eye and related disorders. It is therefore an object of the present invention to provide a pharmaceutical composition for the treatment of dry eye, in particular moderate to severe dry eye and related disorders, comprising cyclosporin and 1-perfluorobutyl-pentane. Other objects of the present invention will be apparent based on the following description, examples and claims of the present invention. Disclosure of Invention In a first aspect, the present invention relates to a pharmaceutical composition for use in the topical treatment of dry eye, wherein the composition comprises about 0.05 to 0.1% (w/v) cyclosporin dissolved in 1-perfluorobutyl-pentane, and wherein the amount of cyclosporin administered in a single dose to each eye is about 4 to 12 μg. In another aspect, the invention provides a pharmaceutical composition for treating ocular surface damage in a subject suffering from dry eye, and/or for treating dyskinesia in a subject suffering from dry eye, preferably wherein the pharmaceutical composition is topically administered to provide an amount of cyclosporin of about 4 μg to 12 μg per single dose per eye. In particular, the subject may suffer from moderate to severe dry eye. In a further aspect, the invention provides a kit comprising a pharmaceutical composition for such use, wherein the kit comprises a container for containing the pharmaceutical composition and a drop dispenser adapted for administration of the composition in a volume of about 8 μl to 12 μl per drop. Detailed Description In a first aspect, the present invention relates to a pharmaceutical composition for use in the topical treatment of dry eye, wherein the composition comprises about 0.05 to 0.1% (w/v) cyclosporin dissolved in 1-perfluorobutyl-pentane, and wherein the amount of cyclosporin administered in a single dose to each eye is about 4 to 12 μg. Dry eye (also referred to simply as DED, also known as keratoconjunctivitis sicca, dysfunctional tear syndrome or dry eye) is a complex disease that results in symptoms of discomfort, vision impairment and tear film instability and creates the potential for damage to the ocular surface. It may be accompanied by an increase in osmotic pressure of the tear film and ocular surface inflammation. Patients with keratoconjunctivitis sicca may experience any one or a combination of high tear osmotic pressure, tear film instability, or abnormalities in the lipid layer composition of the tear film. Currently, two major categories of keratoconjunctivitis sicca or Dry Eye (DED) are water deficient DED and evaporative DED. In the water deficient version of the DED type, two major subtypes can be distinguis