Pharmaceutical compositions comprising semifluorinated alkanes for the treatment of conditions associated with contact lenses
阅读说明：本技术 治疗与隐形眼镜有关病症的包含半氟化烷烃的药物组合物 (Pharmaceutical compositions comprising semifluorinated alkanes for the treatment of conditions associated with contact lenses ) 是由 伯恩哈德·金特 马库斯·贝尔 奥利弗·施吕特尔 于 2018-05-09 设计创作，主要内容包括：本发明提供了包含式(I)：F(CF<Sub>2</Sub>)<Sub>n</Sub>(CH<Sub>2</Sub>)<Sub>m</Sub>H的半氟化烷烃的药物组合物,其中n是4到6的整数,并且m是5到8的整数,其用于治疗或预防与个体的眼睛的眼表有关的疾病或病症,其中所述个体是隐形眼镜佩戴者,并且其中所述隐形眼镜是水凝胶隐形眼镜,并且在将所述隐形眼镜插入所述个体的眼睛之前和/或在隐形眼镜佩戴期间和/或在所述隐形眼镜已从个体的眼睛取出之后,将所述组合物局部施用于所述个体的眼睛的表面,或其中所述隐形眼镜是硅酮水凝胶隐形眼镜,并且在将所述隐形眼镜从所述个体的眼睛中取出之后,将所述组合物局部施用于所述个体的眼睛的表面。(The present invention provides a composition comprising formula (I): f (CF) 2 ) n (CH 2 ) m H, wherein n is an integer from 4 to 6, and m is an integer from 5 to 8, for use in the treatment or prevention of a disease or condition associated with the ocular surface of an eye of an individual, wherein the individual is a contact lens wearer, and wherein the contact lens is a hydrogel contact lens, and prior to insertion of the contact lens into the eye of the individual and/or during contact lens wear and/or after the contact lens has been removed from the eye of the individualTopically applying the composition to a surface of the eye of the subject after eye removal, or wherein the contact lens is a silicone hydrogel contact lens and the composition is topically applied to the surface of the eye of the subject after the contact lens is removed from the eye of the subject.)
1. A pharmaceutical composition consisting essentially of 1-perfluorohexyloctane (F6H8) for use in the treatment or prevention of a disease or disorder associated with the ocular surface of the eye of an individual, wherein the individual is a contact lens wearer, and wherein
The contact lens is a hydrogel contact lens or a silicone hydrogel contact lens, and the composition is topically applied to a surface of the eye of the subject after the contact lens is removed from the eye of the subject.
2. The pharmaceutical composition for use according to claim 1, wherein the contact lens is a hydrogel contact lens.
3. The pharmaceutical composition for use according to claim 1 or 2, wherein the hydrogel contact lens comprises a plastic material selected from the group consisting of: acoffekang a; acoffer B; alpha feikang A; aizhufekang (Aizhufukang); baffenkang a; clorfeikang; 1, Detafeikang A; delofiran a; zhuxofenikang A; ipimoxidenecrosin A; etafilkang a; fukefeikang a; haifeikang A & B; haifeikang C; halafilkang A; haixifeikang a; haixifeikang B; seaffersukang D; esfeikang; lidofiran a; lidofirang B; mafeikang A; metophilam A, B; neffekang A; niskoffen a; nevirakang A; okufekang a; okufekang B; okufekang C; orkufilkang D; okufekang E; okufekang F; orfeikang a; omafilkang a; bofelkang a; phenanthroline 1; phenanthrene users A; jumaikang (barley remedy); sikafeikang A; shufeikang A; tefeikang; tazhufekang A; tazhufekang B; van Shufeikang A; vefian kang A; and siloxan a.
4. The pharmaceutical composition for use according to claim 1, wherein the contact lens is a silicone hydrogel contact lens.
5. The pharmaceutical composition for use according to claim 1 or 4, wherein the silicone hydrogel contact lens comprises a silicone hydrogel selected from the group of silicone hydrogels consisting of Abafukan A, Cuffukan A, Afflofakang A, Inffukan, Coffeukan A, Rocafefinacifenca, Rocafefincb, Narafiencb, Spiroffuka, Soffienmca and serine-A.
6. The pharmaceutical composition for use according to any one of claims 1-5, wherein the disease or condition associated with the ocular surface of the eye of the subject is associated with contact lens wear.
7. The pharmaceutical composition for use according to any one of claims 1 to 6, wherein the disease or condition associated with the ocular surface of the eye of the subject is dryness associated with sustained contact lens wear.
8. The pharmaceutical composition for use according to any one of claims 1 to 7, wherein the disease or disorder associated with the ocular surface of the eye of the subject is EOD dryness.
9. The pharmaceutical composition for use according to claim 7 or 8, wherein said disease or condition is characterized by increased dryness from insertion to removal of said contact lens.
10. A kit comprising a pharmaceutical composition for use according to any one of claims 1 to 9, a container for containing the composition, a device for dispensing the composition to the eye of the individual or patient, and optionally instructions on how to use and apply the composition when wearing contact lenses.
Technical Field
The present invention is in the field of compositions comprising semifluorinated alkanes for the treatment or prevention of ocular diseases.
Background
For various reasons, contact lenses are becoming increasingly popular as an alternative to wearing eyeglasses. In many cases, contact lenses can provide better vision correction as well as functional advantages, especially in sports and outdoor activities. In addition, many users prefer contact lenses over spectacles for aesthetic reasons. Recently, soft contact lenses have become inexpensive and readily available, making use more comfortable, and the useful and wearing time can also vary from as short as one day to as long as several days. In particular, disposable contact lenses have become the standard today.
However, one of the common complications associated with contact lens wear is eye dryness during contact lens wear, particularly due to extended contact lens wear. In many cases, the use of aqueous artificial tears to alleviate the sensation of dryness is not sufficient, as this does not result in the formation of a stable and long-lasting relief of dryness.
WO 2011/073134 a1 discloses pharmaceutical compositions for the treatment of keratoconjunctivitis sicca (dry eye disease) comprising a liquid vehicle including one or more semifluorinated alkanes. The composition comprises an active ingredient selected from macrolide immunosuppressants and can be administered topically to the eye. Contact lens wear is one of the risk factors for developing keratoconjunctivitis sicca.
WO2014/041055 a1 refers to compositions comprising at least two or more semifluorinated alkanes. The compositions are useful as medicaments for topical application to the eye or ocular tissue, for example for the treatment of keratoconjunctivitis sicca (dry eye disease) and/or meibomian gland dysfunction and its associated symptoms. As a non-pharmaceutical method for treating keratoconjunctivitis sicca, avoidance of exacerbating factors such as dry air, wind and ventilation, tobacco smoke, change of working habits is mentioned; eyelid hygiene; tear supplementation; physical tears are maintained by punctal plugs or therapeutic contact lenses.
WO 2017/055453A 1 relates to compositions comprising compounds of the formula CF3-(CF2)n-CH(CH3)-(CH2)m-CH3An ophthalmic composition of a semifluorinated compound characterized in that n is an integer selected from 3 to 5 and m is an integer selected from 1 to 5, and the use of the composition as a medicament for topical administration to the eye. This document describes, among other studies, tear film analysis studies for dry eye disease, which exclude patients wearing contact lenses.
Furthermore, WO 2017/055454A 1 relates to compositions comprising CF3(CF2)5(CH2)7CH3 and CF3-(CF2)5-CH(CH3)-(CH2)5-CH3And their use as medicaments for topical administration to the eye. In this case, tear film analysis studies have also been described which exclude patients wearing contact lenses.
WO 2005/123035 a1 discloses hydrophobic ophthalmic compositions suitable for use on or in contact lenses inserted into the eyes of patients having viscosities of from 1 to 15,000 centistokes (centrostokes). The compositions include silicone polymers, fluorinated silicone polymers, fluorocarbon polymers, fluorinated alcohols or perfluorinated polyether compositions, alone or in combination, suitable for coating at least a portion of a contact lens for insertion into an eye of a patient.
Martin-Montanez et al (Cont Lens antioxidant eye. 2015; 38(3):148-51) mention end-of-day dryness (EOD dryness), a symptom of preferentially softer contact Lens wearers with a multifactorial etiology with prevalence in the range of 28-72%, with many contact Lens wearers having no clinical symptoms.
WO 2007/008666 a2 describes a method of improving vision in a patient, the method comprising providing a composition comprising at least one polymer selected from the group consisting of silicones, fluorinated silicones, perfluorocarbons, fluorinated alcohols and fluorinated polyethers; and applying the composition to at least one surface of a contact lens for insertion into an eye of a patient.
Thus, satisfactory relief is currently not achieved for contact lens wearers, particularly those who wear contact lenses on a regular and/or extended basis, for the treatment or prevention of adverse effects associated with the ocular surface of the eye, such as discomfort, dryness or pain that occurs during or particularly after contact lens wear.
It is therefore an object of the present invention to provide a composition which may avoid certain disadvantages of the prior art and which may be used for the treatment or prevention of a disease or condition associated with the ocular surface of the eye of an individual, wherein the individual is a contact lens wearer. Other objects of the invention will become apparent from the following description, embodiments and claims of the invention.
Furthermore, it is an object of the present invention to provide compositions suitable for treating, ameliorating, reducing eye dryness or diseases or conditions associated therewith resulting from soft contact lens wear.
Further objects of the invention will become apparent from the following description, embodiments and patent claims.
Disclosure of Invention
In a first aspect, the present invention provides a pharmaceutical composition comprising a semifluorinated alkane of formula (I)
F(CF2)n(CH2)mH (I)
Wherein n is an integer of 4 to 6, and
m is an integer of 5 to 8,
for use in the treatment or prevention of a disease or condition associated with the ocular surface of the eye of an individual, wherein the individual is a contact lens wearer, and
wherein the contact lens is a hydrogel contact lens and the composition is topically applied to the surface of the eye of the individual, or before the contact lens is inserted into the eye of the individual and/or during contact lens wear and/or after the contact lens has been removed from the eye of the individual
Wherein the contact lens is a silicone hydrogel contact lens and the composition is topically applied to the surface of the eye of the subject after the contact lens is removed from the eye of the subject.
More specifically, according to this aspect, the invention also provides a pharmaceutical composition consisting essentially of 1-perfluorohexyloctane (F6H8) for use in treating or preventing a disease or condition associated with the ocular surface of the eye of an individual, wherein the individual is a contact lens wearer, and wherein the contact lens is a hydrogel contact lens or a silicone hydrogel contact lens, and wherein the composition is topically applied to the surface of the eye of the individual after removal of the contact lens from the eye of the individual.
In a second aspect, the present invention provides a method for the treatment or prevention of a disease or condition associated with the ocular surface of the eye of a subject, wherein the subject is a contact lens wearer, comprising topically administering to the surface of the eye of the subject a pharmaceutical composition comprising a semifluorinated alkane of formula (I) as defined above,
wherein the contact lens is a hydrogel contact lens and the composition is topically applied to the surface of the eye of the individual, or before the contact lens is inserted into the eye of the individual and/or during contact lens wear and/or after the contact lens has been removed from the eye of the individual
Wherein the contact lens is a silicone hydrogel contact lens and the composition is topically applied to the surface of the eye of the subject after the contact lens is removed from the eye of the subject.
More specifically, according to this aspect, the invention also provides a method for treating or preventing a disease or condition associated with the ocular surface of an eye of an individual, wherein the individual is a contact lens wearer comprising topically administering a pharmaceutical composition consisting essentially of 1-perfluorohexyloctane (F6H8) for treating or preventing a disease or condition associated with the ocular surface of an eye of an individual, wherein the individual is a contact lens wearer, and wherein the contact lens is a hydrogel contact lens or a silicone hydrogel contact lens, and the composition is topically administered to the surface of the eye of the individual after removal of the contact lens from the eye of the individual.
In a third aspect, the present invention provides the use of a pharmaceutical composition comprising a semifluorinated alkane of formula (I) as defined above, in the manufacture of a medicament for the treatment or prevention of a disease or condition associated with the ocular surface of the eye of a subject, wherein the subject is a contact lens wearer, and
wherein the contact lens is a hydrogel contact lens and the composition is topically applied to the surface of the eye of the individual, or before the contact lens is inserted into the eye of the individual and/or during contact lens wear and/or after the contact lens has been removed from the eye of the individual
Wherein the contact lens is a silicone hydrogel contact lens and the composition is topically applied to the surface of the eye of the subject after the contact lens is removed from the eye of the subject.
More specifically, according to this aspect, the invention also provides the use of a pharmaceutical composition consisting essentially of 1-perfluorohexyloctane (F6H8) in the manufacture of a medicament for the treatment or prevention of a disease or condition associated with the ocular surface of the eye of an individual, wherein the individual is a contact lens wearer, and wherein the contact lens is a hydrogel contact lens or a silicone hydrogel contact lens, and the composition is topically applied to the surface of the eye of the individual after removal of the contact lens from the eye of the individual.
In a fourth aspect, the present invention relates to a kit comprising a pharmaceutical composition for use according to the first aspect of the invention, a container for containing the composition, means for dispensing the composition to the eye of the individual or patient and optionally instructions on how to use and apply the composition when wearing contact lenses.
Detailed Description
In a first aspect, the present invention provides a pharmaceutical composition comprising a semifluorinated alkane of formula (I)
F(CF2)n(CH2)mH (I)
Wherein n is an integer of 4 to 6, and m is an integer of 5 to 8,
for use in the treatment or prevention of a disease or condition associated with the ocular surface of the eye of an individual, wherein the individual is a contact lens wearer, and
wherein the contact lens is a hydrogel contact lens and the composition is topically applied to the surface of the eye of the individual, or before the contact lens is inserted into the eye of the individual and/or during contact lens wear and/or after the contact lens has been removed from the eye of the individual
Wherein the contact lens is a silicone hydrogel contact lens and the composition is topically applied to the surface of the eye of the subject after the contact lens is removed from the eye of the subject.
The pharmaceutical compositions for use according to the invention comprise semifluorinated alkanes (which may also be referred to simply as SFA), which may be defined as linear compounds consisting of at least one perfluorinated segment (F-segment) and at least one non-fluorinated hydrocarbon segment (H-segment).
Alternative designations for designated semifluorinated alkanes, as described in parentheses below and as may also be used herein, are based on the general formula FnHm, wherein F represents a linear perfluorinated hydrocarbon segment, H represents a linear non-fluorinated hydrocarbon segment, and n, m are the number of carbon atoms of each segment. For example, F4H5 may be used to represent 1-perfluorobutylpentane or CF3(CF2)3-(CH3)4CH3(it may alternatively be represented by formula F (CF)2)4(CH2)5H) Having a linear nature with four carbon atoms (n ═ 4)A perfluorinated segment F and a linear non-fluorinated hydrocarbon segment with five carbon atoms (m ═ 5). Furthermore, F6H8 may be used to represent 1-perfluorohexyloctane or CF3(CF2)5-(CH3)7CH3(may alternatively be represented by formula F (CF)2)6(CH2)8H) It has a linear perfluorinated segment F with six carbons (n-6) and a linear non-fluorinated hydrocarbon segment with eight carbons (m-8).
The pharmaceutical composition for use according to the invention comprises a semifluorinated alkane of formula (I):
F(CF2)n(CH2)mH (I)
wherein n is independently selected from an integer of 4 to 6, and m is independently selected from an integer of 5 to 8.
Thus, the semifluorinated alkane may be selected from CF3(CF2)3-(CH2)4CH3(F4H5)、CF3(CF2)3-(CH2)5CH3(F4H6)、CF3(CF2)3-(CH2)6CH3(F4H7)、CF3(CF2)3-(CH2)7CH3(F4H8)、CF3(CF2)4-(CH2)4CH3(F5H5)、CF3(CF2)4-(CH2)5CH3(F5H6)、CF3(CF2)4-(CH2)6CH3(F5H7)、CF3(CF2)4-(CH2)7CH3(F5H8)、CF3(CF2)5-(CH2)4CH3(F6H5)、CF3(CF2)5-(CH2)5CH3(F6H6)、CF3(CF2)5-(CH2)6CH3(F6H7) and CF3(CF2)5-(CH2)7CH3(F6H 8). More preferably, the semifluorinated alkane may be selected from CF3(CF2)3-(CH2)4CH3(F4H5) and CF3(CF2)5-(CH2)7CH3(F6H8)。
In a preferred embodiment, the pharmaceutical composition for use according to the invention comprises a semifluorinated alkane of formula (I) selected from 1-perfluorohexyloctane (CF)3(CF2)5-(CH2)7CH3(F6H8)) and 1-perfluorobutylpentane (CF)3(CF2)3-(CH2)4CH3(F4H5))。
The pharmaceutical composition of the invention comprising "one (a)" semifluorinated alkane is herein understood to comprise at least one semifluorinated alkane having formula (I) as described above. However, optionally, the composition may comprise more than one semifluorinated alkane, for example, a mixture of two or more semifluorinated alkanes of formula (I), i.e. any of the semifluorinated alkane species described above.
In a further embodiment, the pharmaceutical composition of the invention may consist of a semifluorinated alkane of formula (I) as described above. In the present context, the term "a" semifluorinated alkane is understood to mean at least one semifluorinated alkane, but may also include more than one semifluorinated alkane compound or a selection of semifluorinated alkane compounds. Thus, in one embodiment, the composition may consist of more than one semifluorinated alkane of formula (I) as described above.
As used herein, the term "consisting of … … (constraints)" and related terms "consisting of … … (constraints)" or "consisting of … … (constraints)" should be understood to mean that no feature is present other than the feature to which the term is prefixed. In the context of a composition, any other ingredient or component in the composition, if present in addition to the ingredient or component to which the term is prefixed, is present only in trace or residual amounts, so as not to confer a technical advantage or relevance for the purposes of the present invention, as may be further understood (e.g., "consisting essentially of") by the term "substantially" or "essentially" used in conjunction with such terms. Conversely, in the context of the compositions of the present invention, the term "comprising" or a related term "comprises" or "comprising" is understood to mean that other features may be present in the composition than the feature to which the term is prefaced.
In a further embodiment, the pharmaceutical composition for use according to the invention as defined in any of the previous embodiments above preferably comprises a semifluorinated alkane or optionally a mixture of semifluorinated alkanes in an amount of at least 70% (w/w), 75% (w/w), 85% (w/w), 90% (w/w), 95% (w/w), 98% (w/w), 98.5% (w/w), 99% (w/w), 99.5% (w/w), 99.8% (w/w) or at least 99.9% (w/w), relative to the total weight of the composition. In a preferred embodiment, the composition of the invention is 100% (w/w) semifluorinated alkane or mixture of semifluorinated alkanes.
The term "% (w/w)" as used herein refers to the weight percent of the amount of a component of the composition relative to the total weight of the composition (where "w" represents weight), unless otherwise specified. For example, a pharmaceutical composition according to the invention may comprise up to about 1.5% (w/w) of a co-solvent, such as ethanol, relative to the total weight of the composition.
In a particularly preferred embodiment, the pharmaceutical composition for use according to the invention comprises 1-perfluorohexyloctane (CF)3(CF2)5-(CH2)7CH3(F6H8)), preferably as the only semifluorinated alkane present in the pharmaceutical composition. In another preferred embodiment, the pharmaceutical composition of the present invention consists essentially of 1-perfluorohexyloctane (F6H 8). In relation to this preferred embodiment, the term "pharmaceutical composition essentially consisting of 1-perfluorohexyloctane (F6H 8)" is understood to mean a pharmaceutical composition based on 1-perfluorohexyloctane (F6H8) in an amount of at least 98% (w/w), 98.5% (w/w), 99% (w/w), 99.5% (w/w), 99.8% (w/w) or at least 99.9% (w/w) relative to the total weight of the final composition, while the content of only minor ingredients or impurities (e.g. isomers of F6H8 or unavoidable by-products and/or residual moisture in the production of F6H8) is at most, relative to the final composition2% (w/w), or at most 1.5% (w/w), or at most 1% (w/w), or at most 0.5% (w/w), or at most 0.2% (w/w), or at most 0.1% (w/w).
In a further preferred embodiment, the composition for use according to the invention may be substantially free of water. In a further embodiment, the composition for use according to the invention may be substantially free of preservatives. However, in optional embodiments, the composition may comprise other active ingredients and/or one or more excipients.
Preferred semifluorinated alkanes F4H5 (also known as 1-perfluorobutylpentane, formula F (CF)2)4(CH2)5H) Is a chemically and physiologically inert water-insoluble liquid having a density of 1.284g/cm at 25 deg.C3The refractive index at 20 ℃ was 1.3204. A particularly preferred semifluorinated alkane F6H8, also known as 1-perfluorohexyloctane, is also a chemically and physiologically inert water-insoluble liquid having a density of 1.35g/cm at 25 ℃3The refractive index at 20 ℃ was 1.3432 ℃.
The pharmaceutical composition according to the invention may be used for the treatment, cure, amelioration or prevention of a disease or disorder or any symptom associated with the ocular surface of the eye of a subject, wherein the subject is a contact lens wearer. The term "disorder" as used herein more specifically relates to pathological disorders that can be treated by using the compositions of the present invention.
As understood herein, the use of a composition of the invention in the context of the prevention of a disease or condition or in prophylactic treatment refers to the use of the composition to prevent the risk of the occurrence or exacerbation or occurrence (or reoccurrence) of the disease or condition in an individual.
The term "contact lens wearer" as used herein refers to an individual, or patient wearing a contact lens, i.e., an individual wearing a contact lens or a contact lens inserted in one or both eyes thereof. Preferably, the term "contact lens wearer" means an individual or individual who does not wear contact lenses only occasionally or regularly. For example, the term "contact lens wearer" according to the present invention includes individuals who wear one or two contact lenses at least once every two weeks, preferably at least once every seven days, or at least once every six days, every five days, every 4 days, every 3 days, or at least once every 2 days. Preferably, the term "contact lens wearer" means an individual wearing contact lenses daily or on 6, 5, 4, 3 or 2 of 7 days.
Furthermore, the term "contact lens wearer" as used herein includes individuals wearing contact lenses that may be inserted into one or both eyes of the individual for varying periods of time, such as, for example, for from 1 hour or several hours, e.g., 1 to 24 hours, up to several days, e.g., 2, 3, 4, 5 or 7 days, or even one to several weeks, depending on the particular type of contact lens.
In one embodiment of the invention, the contact lens is a hydrogel contact lens and the composition is topically applied to the surface of the eye of the individual prior to insertion of the contact lens into the eye of the individual and/or during wear of the contact lens and/or after removal of the contact lens from the eye of the individual.
The term "hydrogel contact lens" as used herein refers to a hydrogel contact lens that does not contain a significant amount of silicone-containing components, e.g., no more than about 5% (w/w), preferably no more than about 3% (w/w), even more preferably no more than about 1% (w/w), silicone-containing components such as silicones, silicone acrylates, t-butyl styrene silicone acrylates, and/or fluoro acrylates. Preferably, the "hydrogel contact lenses" according to the invention do not contain any silicone-containing components and may also be referred to as non-silicone hydrogels. Hydrogel contact lenses according to the present invention preferably belong to the class of soft hydrophilic plastic contact lenses, which can be classified into four categories according to the U.S. Food and Drug Administration (FDA) according to their plastic composition and water content, including in particular:
group 1: a non-ionic plastic material with a water content of < 50%;
group 2: a nonionic plastic material having a water content of not less than 50%;
group 3: an ionic plastic material with a water content of < 50%; and
group 4: an ionic plastic material with water content more than or equal to 50 percent.
For example, a hydrogel contact lens or hydrogel contact lens of interest in the context of the present invention may comprise or be manufactured from a hydrophilic plastic material selected from the group consisting of: acofekang a (acofilcon a); acofekang b (acofilcon b); alpha-phenanthrene kang A (alphafilcon A); argyrofilcon (altraficon a); baffenkang a (bufilcon a); crofelon (crofelcon); deltafilcon a; delphaekang a (dimefilcon a); zhuxifekang a (droxifilcon a); epifilcon a (epsifilcon a); etafilcon a (etafilcon a); focofilcon a (focofilcon a); HAIFIKANG A & B (HEFILCON A & B); haifenck C (hfilcon C); halafilkang a (hiafilcon b); cisifencan a (hioxifilcon a); cisifencon b (hioxifilcon b); seaffenkang d (hioxifilcon d); esfilcon (isofilcon); lidofiran a (lidofilcon a); lidofirancb (lidofilcon b); mafilcon a (mafilcon); metafilcon A, B (methafilcon a, B); neffekang a (nelfilcon a); niscoffekang a (nescofilcon a); nevirakang a (netrafilcon a); orkufilcon a (ocufilcon a); orkufilcon b (ocufilcon b); orkufilcon c (ocufilcon c); orkufilcon d (ocufilcon d); orkufilcon e (ocufilcon e); orkufilcon f (ocufilcon f); oxfekang a (ofilcon a); omafilkang a (omafilcon a); bofelkang a (perfilcon a); phenanthroline drug A (phemfilcon A); phenanthrenefferskang a (phenfilcon a); polymazen (polymacon); sabifencan a (scafilcon a); shufeikan A (surfilcon A); tefilcon; taflufakang a (tetrafilcon a); taflufaxicam b (tetrafilcon b); vasufilcon A (Vasurfilcon A); vefenac a (vifilcon a); and silofenicon a (xylofilcon a).
A contact lens according to group 1 as defined above may for example comprise or be made of a plastic material selected from the group consisting of: acofekang b (acofilcon b) (49%); crofelon (crofelcon) (39%); delphaekang a (dimefilcon a) (36%); HAIFIKANG A & B (HEFILCON A & B) (45%); cisifencon b (hioxifilcon b) (49%); esfilcon (isofilcon) (36%); mafilcon (33%); polymazene (Polymacon) (38%); tefilcon (38%) and tacafhenamid a (tetrafilcon a) (43%) (the water content is given in parentheses).
The contact lens according to group 2 defined above may for example comprise or be made of a plastic material selected from the group consisting of: aconficam a (acofilcon a) (58%), alphafilcon a (alphafilcon a) (66%), alphafilcon a (65%), hficam c (hefilcon c) (57%), halafilcon b (hiafilcon b) (59%), halazefilcon a (hiofilcon a) (59%), halazefilcon d (hiofilcon a) (54%), lidofilcon b (lidofilcon b) (79%), lidofilcon a (70%), neffenkam a (nelfilcon a) (69%), niscofilcon a (nescofilcon a) (78%), nefokon a (netrafilcon a) (65%), ofilcon a (ofilcon a) (74%), omafilcon a (omafilcon a) (59%), sikafilcon a (scafilcon a) (71%), sufilcon a (surffilcon a) (74%), vesufilcon a (vasilcon a) (74%) and seoflilcon a (xylofilcon a) (67%) (the water content is given in parentheses).
A contact lens according to group 3 defined above may for example comprise or be made of a plastic material selected from the group consisting of: bafferan a (bufilcon a) (45%), tadafeka (deltafilcon a) (43%), crevafenacin a (droxifilcon a) (47%), orkufilcon a (ocufilcon a) (44%), bennfeka a (phenfilcon a) (38%) (the water content is given in parentheses).
A contact lens according to group 4 defined above may for example comprise or be made of a plastic material selected from the group consisting of: bafferan a (bufilcon a) (55%), ipifferan a (epsilon filcon a) (60%), etafilcon a (etafilcon a) (58%), focofilcon a (focafilcon a) (55%), metafilcon A, B (methafilcon a, B) (55%), orkufilcon B (ocufilcon B) (53%), orkufilcon c (ocufilcon c) (55%), orkufilcon d (ocufilcon d) (55%), orkufilcon e (ocufilcon e) (65%), orkufilcon f (ocufilcon f) (60%), bofilcon a (percfilcon a) (71%), fifelcon a (phefilcon a) (55%), tacaffilcon B (tetrafilcon B) (58%), wifilcon a (vifilcon a) (55%), water (water) were given.
Exemplary hydrogel contact lenses that may be worn by contact lens wearing individuals according to the present invention include SofLens 38 contact lenses as hydrogel contact lenses (
In an alternative embodiment of the invention, the contact lens is a silicone hydrogel contact lens and the composition is topically applied to the surface of the eye of the subject after the contact lens is removed from the eye of the subject.
The silicone hydrogel contact lenses according to the present invention preferably belong to group II or III of the class of hydrophobic plastic contact lenses defined by the U.S. Food and Drug Administration (FDA). Related silicone hydrogel contact lenses in the context of the present invention may comprise or be made from a plastic silicone material (i.e., comprise silicone, silicone acrylate, t-butyl styrene silicone acrylate, and/or fluoro acrylate silicone ester). Exemplary silicone hydrogel contact lenses according to the present invention may comprise or be made from a plastic material selected from the group consisting of: abacavirenz a (balafilcon a) (36%), kunfeka (comfilcon a) (48%), eflufifufen a (efroffilcon a) (74%), infliximan (enfilcon) (46%), cafeka (galyfilcon a) (47%), rofafilcon a (lotrafilcon a) (24%), rofafilcon b (lotrafilcon b) (33%), naftificin b (narafilcon b) (48%), sfeka (senofilcon a) (37%), sofofufekang a (somomofilcon a) (56%) and sifekang a (silcon a) (32%) (water content is given in parenthesis).
Exemplary silicone hydrogel contact lenses that may be worn by contact lens wearing individuals according to the present invention include those that are silicone hydrogel contact lensesDaily polishing contact lens: (
In a preferred embodiment, the hydrogel or silicone hydrogel contact lenses worn by the contact lens wearers of the present invention are disposable soft contact lenses, more particularly single use disposable soft contact lenses. In another preferred embodiment, the hydrogel or silicone hydrogel contact lens worn by a contact lens wearer of the present invention is a daily wear or extended wear contact lens.
Furthermore, the contact lenses worn by the contact lens wearers of the invention may be corrective contact lenses and/or therapeutic contact lenses and/or cosmetic or decorative contact lenses. Preferably, however, the contact lens may be a corrective contact lens and/or a cosmetic or decorative contact lens. In a further embodiment, the contact lens worn by a contact lens wearer according to the invention is not a therapeutic contact lens. In other embodiments, the contact lens is a corrective contact lens that corrects for poor vision of the contact lens wearer. In further embodiments, the contact lens is a cosmetic or decorative contact lens that changes the appearance of the eye of the contact lens wearer.
According to the present invention, a pharmaceutical composition comprising a semifluorinated alkane is topically applied to the surface of an eye of an individual, regardless of whether the contact lens is a hydrogel contact lens or a silicone hydrogel contact lens. In a preferred embodiment, the pharmaceutical composition may be instilled onto the surface of the eye of the contact lens wearer, preferably onto the surface of the eye of the contact lens wearer. The term "surface of the eye" is understood to include all surfaces of the eye or portions thereof that may be instilled. In a broad sense, the term "surface of the eye" may also include a surface area of the eye that is covered by a contact lens that has been inserted prior to administration of the pharmaceutical composition, more specifically, by an inserted hydrogel contact lens.
Furthermore, the term "surface of the eye" as used herein may include surface areas of the eye as well as any such areas or tissues of the eye that may be topically administered, such as the cornea or conjunctiva, or the eyelid margin or canthus, the lower eyelid and/or the eye capsule of a contact lens wearer. In a preferred embodiment, the pharmaceutical composition for use according to the invention is applied to the surface of the eye, the lower eyelid or the eye capsule of the eye of the individual or patient by instillation.
In a first alternative embodiment of the pharmaceutical composition for use according to the invention, the contact lens is a hydrogel contact lens, or more specifically a non-silicone, or silicone-free hydrogel contact lens. In this alternative embodiment, the composition is topically applied to the surface of the eye of the individual prior to insertion of the contact lens into the eye of the individual and/or during wear of the contact lens and/or after removal of the contact lens from the eye of the individual. In one embodiment, the pharmaceutical composition is topically applied to the surface of the eye of the individual prior to inserting the contact lens into the eye of the individual. Where the composition is topically applied to the surface of the eye of an individual or patient prior to insertion of the contact lens into the eye of the individual, the pharmaceutical composition is applied to the surface of the eye by the individual itself or any other individual without insertion or presence of a hydrogel contact lens in the eye. However, it is to be understood that the above-described hydrogel contact lenses can be inserted within a period of time after the pharmaceutical composition is administered to the eye, for example, about 1 hour to 2 hours, or as short as about 10 minutes or about 1 minute or less after the pharmaceutical composition has been administered.
Furthermore, according to this embodiment, the pharmaceutical composition for use according to the invention can be applied to the surface of the eye after insertion of the contact lens into the eye and before removal of the contact lens from the eye, as long as the contact lens is a hydrogel contact lens, or more specifically a non-silicone or non-silicone-containing hydrogel contact lens. In this embodiment, the pharmaceutical composition may be topically applied to the surface of the eye of the individual during contact lens wear. The pharmaceutical composition may then be applied to the surface of the eye to areas that may or may not be covered by the inserted contact lens.
It should be noted, however, that the pharmaceutical composition may be repeatedly administered to the eye of a contact lens wearer, as described in more detail below. In one embodiment, the pharmaceutical composition may be administered prior to insertion of the hydrogel contact lens, and may continue or repeat during hydrogel contact lens wear. In a preferred embodiment of this aspect of the invention, the hydrogel contact lens and the pharmaceutical composition for use according to the invention are both present in the eye of the individual.
In another embodiment, wherein the contact lens is a hydrogel contact lens, i.e. a non-silicone hydrogel contact lens as defined above, the pharmaceutical composition for use according to the invention may also be applied to the surface of the eye of the contact lens wearer after removal of the contact lens from the eye of the individual. Again, it should be noted that the application of the composition to the surface of the eye may be performed after a period of several seconds to several hours after the removal of the hydrogel contact lens. In addition, as outlined further below, the application may be performed once or repeated multiple times after the contact lens is removed.
In a second alternative embodiment of the pharmaceutical composition for use according to the invention, the contact lens is a silicone hydrogel contact lens as described above. In this alternative embodiment, the composition is topically applied to the surface of the eye of the individual only after the contact lens has been removed from the eye of the individual. It should be noted that in a second alternative of the present invention relating to silicone hydrogel contact lenses, the contact lens (more particularly, the silicone hydrogel contact lens as defined above) and the pharmaceutical composition comprising a semifluorinated alkane for use according to the present invention do not occur simultaneously in the eye of the individual.
In such cases, once or repeatedly, once the silicone hydrogel contact lens has been removed from the contact lens wearer's eye, the contact lens may also be removed prior to one application or repeated applications, as further outlined below.
It should be noted that for one or both of the alternative embodiments, i.e., embodiments relating to hydrogel contact lenses and embodiments relating to silicone hydrogel contact lenses, the composition may be topically applied to the surface of the eye of the individual after removal of the contact lens from the eye of the contact lens wearer. This is particularly beneficial for regeneration of the eye or ocular surface overnight, respectively, after removal of the hydrogel contact lens or silicone hydrogel contact lens. Preferably, this is particularly beneficial for treating, reducing or ameliorating EOD dryness.
Accordingly, in a particular embodiment, the present invention provides a pharmaceutical composition consisting essentially of 1-perfluorohexyloctane (F6H8) for use in treating or preventing a disease or disorder associated with the ocular surface of the eye of an individual, wherein the individual is a contact lens wearer, and wherein the contact lens is a hydrogel contact lens or a silicone hydrogel contact lens, and the composition is topically applied to the surface of the eye of the individual after the contact lens is removed from the eye.
According to this particular embodiment, the composition for use according to the invention consists essentially of or consists of 1-perfluorohexyloctane (F6H8) as described above. In this particular embodiment, the contact lens may be a hydrogel contact lens as described above or a silicone hydrogel contact lens as described above, but preferably, is a hydrogel contact lens. Furthermore, in this particular embodiment, the composition for use according to the invention is also topically applied to the surface of the eye of the contact lens wearer, as described in connection with the more general embodiment of the invention. However, according to this particular embodiment, the composition for use according to the invention is topically applied to the surface of the eye of the individual after the contact lens has been removed from the eye of the individual.
Also in connection with this embodiment, it is noted that the application of the composition to the surface of the eye may be performed after a period of time ranging from seconds to hours, for example, from about 1 or 2 seconds to 1 or 2 hours, or from about 5 seconds to 1 hour or 45 minutes or 30 minutes, or from about 1 minute to about 15 or 20 minutes, after the removal of the hydrogel or silicone hydrogel contact lens. In addition, as outlined further below, the application may be performed once or repeated multiple times after the contact lens is removed.
In further embodiments, the application of the composition for use according to the present invention to the surface of the eye may be performed for a period of time prior to reinserting the same or another hydrogel or silicone hydrogel contact lens into the eye. In a particular embodiment, the composition used according to the invention is administered at least 0.5 to 10 hours, more preferably 1 to 10 hours, most preferably 2 to 8 hours before reinserting the same or another hydrogel or silicone hydrogel contact lens into the lens. Accordingly, in these embodiments, the final application of the composition used according to the invention is performed at least 0.5 to 10 hours, more preferably 1 to 10 hours, most preferably 2 to 8 hours before the same or another hydrogel or silicone hydrogel contact lens is reinserted into the eye.
In a further embodiment, the composition for use according to the present invention is administered at least 2 to 10 hours, more preferably 4 to 10 hours, most preferably 6 to 10 hours before reinserting the same or another silicone hydrogel contact lens into the eye. Accordingly, in these embodiments, the final application of the composition for use according to the present invention is performed at least 2 to 10 hours, more preferably 4 to 10 hours, most preferably 6 to 10 hours before the same or another silicone hydrogel contact lens is reinserted into the eye.
In a further particular embodiment, the composition for use according to the invention is administered at least 0.5 to 10 hours, more preferably 1 to 10 hours, most preferably 2 to 10 hours, before reinserting the same or another hydrogel contact lens into the eye. Accordingly, in these embodiments, the final application of the composition for use according to the present invention is performed at least 0.5 to 10 hours, more preferably 1 to 10 hours, most preferably 2 to 10 hours, before the same or another hydrogel contact lens is reinserted into the eye.
It should also be noted that in this particular embodiment, the composition is topically applied to the surface of the eye of the individual only after the contact lens is removed from the eye of the individual, and thus, the hydrogel contact lens or silicone hydrogel contact lens as defined above is not simultaneously present in the eye of the individual. Also in this case, once the hydrogel contact lens or silicone hydrogel contact lens has been removed from the contact lens wearer's eye, one application or multiple applications may be performed repeatedly after the contact lens is removed, as further outlined below.
As noted above, the compositions of the present invention comprising a semifluorinated alkane (or, in particular embodiments, consisting essentially of the preferred semifluorinated alkane 1-perfluorohexyloctane (F6H8)) are useful for treating or preventing a disease or condition associated with the ocular surface of the eye of a subject, wherein the subject is a contact lens wearer. The term "disease or condition associated with the ocular surface of the eye" is to be understood as including any disease or condition, more particularly pathological condition, associated with or caused by a lack or deficiency of dried or supplied tear fluid to or replenished the ocular surface of the eye of a contact lens wearer.
Typical symptoms associated therewith include discomfort, dryness or pain during or after contact lens wear. Thus, in one embodiment, the disease or condition associated with the ocular surface of the eye of the subject according to the present invention is discomfort, dryness or pain during or after wearing the contact lens. Furthermore, the disease or condition related to the ocular surface of the eye of the individual according to the invention is preferably associated with, or at least partly caused by, wear of contact lenses, in particular long-term or repeated wear of contact lenses. It should be noted, however, that the "disease or condition related to the ocular surface of the eye" of a contact lens wearer according to the invention does not necessarily have to be caused by the wearing of a contact lens, but may also have a different cause, for example, as described in further detail below.
In a preferred embodiment, the disease or condition associated with the ocular surface of the eye of the individual according to the present invention is dryness associated with sustained, prolonged, repeated and/or regular contact lens wear, as described in more detail above. Thus, in a preferred embodiment of the invention, the disease or condition associated with the ocular surface of the eye of the individual is dryness associated with sustained wear of the contact lens.
In another preferred embodiment, the disease or condition associated with the ocular surface of the eye of the subject according to the present invention is a pathological condition characterized by symptoms of dry eye sensation due to contact lens wear. This symptom, hereinafter referred to as "EOD dryness", is also commonly referred to as "end-of-day dryness" or "end-of-day contact lens discomfort" or "delayed subjective dryness" or "discomfort associated with contact lenses". In a further preferred embodiment, the disease or condition associated with the ocular surface of the eye of the individual is EOD dryness, preferably EOD dryness associated with contact lenses.
As used herein, EOD dryness involves a common and clinically well-described complication caused by wearing soft contact lenses. It is characterized by a feeling or sensation of dryness during contact lens wear, especially after extended wear, and also after extended wear of soft contact lenses. This common side effect of continuous contact lens wear is generally progressive in nature and results in reduced wear time and, ultimately, cessation of contact lens wear. Although contact lenses are stable and suitable, in many cases patients complain that the feeling of dryness gets worse over time, especially in the afternoon and evening, and immediate or emergency removal of the lenses is desirable. Since prevalence rates are as high as 77% and EOD dryness is the main reason for discontinuing lens wear, it appears necessary to develop strategies to treat or ameliorate the symptoms of EOD dryness. A large number of contact lens wearers with dry EOD have no clinical symptoms, but suffer from symptoms associated with EOD. Thus, an individual or patient with EOD dryness may or may not show signs of abnormal tear film, decreased tear film break-up time, abnormal meibomian secretions, and ocular surface damage. It should therefore be noted that EOD dryness and Dry Eye Disease (DED) are two distinct and unrelated clinical entities, and eventually some patients suffer from both EOD dryness and DED, as described, for example, by Martin-Montanez et al (Cont Lens antioxidant eye.2015; 38(3): 148-51).
Most importantly, however, it should be noted that EOD dryness is a non-chronic, acute syndrome that typically occurs during soft contact lens wear and that typically increases with the duration of wear time, particularly at the end of the day. Accordingly, the pharmaceutical compositions for use according to the present invention may be used for the treatment, amelioration or prevention of a disease or disorder, more particularly for the treatment, amelioration or prevention of EOD dryness, or EOD dryness associated with contact lenses, which may be characterized by increased dryness of the contact lens from insertion to removal.
Typically, the surface of the contact lens wearer's eye will recover before the next wear. However, it has proven advantageous to shorten and strengthen the recovery time to minimize discomfort and irritation of the eye. In order to effectively reduce the discomfort and eye irritation sensation, the recovery period after application of the composition after wear of the contact lens is preferably at least 1 hour or at least 2 hours. In a particular embodiment, the recovery period after application of the composition for use according to the invention is from 1 to 10 hours, preferably from 2 to 10 hours, most preferably from 4 to 10 hours. As a result, the tendency to stop contact lens wear due to discomfort associated with extended wear of the contact lens can be effectively reduced. Thus, treatment of diseases or conditions associated with the ocular surface of the eye (e.g., dryness associated with contact lens wear, particularly dryness associated with extended contact lens wear or EOD dryness) by topical administration of a composition consisting essentially of 1-perfluorohexyl-octane is effective in reducing discomfort associated with contact lens wear. Furthermore, the treatment of diseases or disorders associated with the ocular surface of the eye (e.g., dryness associated with contact lens wear, particularly dryness associated with extended contact lens wear or EOD dryness) by topical administration of a composition consisting essentially of 1-perfluorohexyl-octane is effective in ameliorating and/or reducing the sensation of dryness or dryness after, before, and during contact lens wear.
EOD dryness is a clinical symptom that is exacerbated throughout contact lens wear, i.e., during normal contact lens wear, for example, during periods of time from the day until afternoon or evening when the contact lens is removed from the eye, such as 2 hours or more, or 3 hours or more, or 6 hours or more, or even 8 or 10 or even 12 hours or more, as compared to Dry Eye Disease (DED) as described below, beginning with low-grade symptoms after contact lens insertion into the eye and aggravating as contact lens wear lasts longer.
In contrast to EOD as described above, keratoconjunctivitis sicca (dry eye disease, DED) as used herein is chronic bilateral drying of the conjunctiva and cornea due to insufficient tear film. Symptoms may include itching, burning, irritation, and photophobia. Signs of DED generally include decreased tear production, decreased tear film break-up time (TBUT), ocular surface damage, which can be assessed by tests (i.e., Schirmer test, tear break-up test, corneal/conjunctival staining).
Meibomian Gland Dysfunction (MGD) is considered to be one of the major sources of DED. MGD is generally characterized by obstruction of meibomian glands and plugging of meibomian glands by hyperkeratosis and increased viscosity of the meibomian glands. Resulting in decreased meibomian secretion, affecting the stability of the tear film, and ultimately, keratoconjunctivitis sicca (dry eye disease, DED).
In a further embodiment, the disease or condition associated with the ocular surface of the eye of a contact lens wearer according to the invention is selected from keratoconjunctivitis sicca (dry eye disease, DED) and/or Meibomian Gland Dysfunction (MGD) and/or symptoms associated therewith. As noted above, keratoconjunctivitis sicca (DED) and Meibomian Gland Dysfunction (MGD), and the possible symptoms associated therewith, may occur with diseases or disorders associated with the ocular surface of the eye of a contact lens wearer.
Thus, in a preferred embodiment of the invention, the contact lens wearer is suffering from both keratoconjunctivitis sicca (DED) and/or Meibomian Gland Dysfunction (MGD) and/or symptoms associated therewith, as well as diseases or disorders associated with EOD dryness.
The pharmaceutical composition for use according to the invention may be topically applied to the surface of the eye of an individual (i.e. a contact lens wearer as described above) by drop-wise application or instillation or application of drops of the composition to a topically administrable portion of the surface of the eye. The ocular surface of the eye may include, but is not limited to, the cornea and/or conjunctiva and/or the eyelids or any combination thereof.
Furthermore, the pharmaceutical compositions for use according to the invention may be administered according to different dosing regimens. For example, topical administration may be once daily, typically during contact lens wear (in the case where the contact lens is a hydrogel contact lens), or preferably, particularly in combination with embodiments in which the composition consists essentially of 1-perfluorohexyl-octane (F6H8), after removal of the contact lens, e.g., in the evening after extended contact lens wear during the day. Preferably, however, the dropwise administration of the pharmaceutical composition according to the present invention may be repeated at least once, twice, three times, four times or five times per day. In each case of topical application of a composition according to the invention, each eye of a contact lens wearer may be dosed, preferably with a quantity of from about 1 to about 5 drops, preferably from 1 to about 3 drops, most preferably 1 or 2 drops, most preferably only 1 drop, of said pharmaceutical composition per eye into which a contact lens has been inserted or in a broader aspect is inserted or will be inserted.
In a second aspect, the present invention relates to a method for treating or preventing a disease or disorder associated with the ocular surface of the eye of a subject, wherein the subject is a contact lens wearer, the method comprising topically administering to the surface of the eye of the subject a pharmaceutical composition comprising a semifluorinated alkane comprising formula (I)
F(CF2)n(CH2)mH (I)，
Wherein n is an integer of 4 to 6, and
m is an integer of 5 to 8,
wherein the contact lens is a hydrogel contact lens and the composition is topically applied to the surface of the eye of the individual, or before the contact lens is inserted into the eye of the individual and/or during contact lens wear and/or after the contact lens has been removed from the eye of the individual
Wherein the contact lens is a silicone hydrogel contact lens and the composition is topically applied to the surface of the eye of the subject after the contact lens is removed from the eye of the subject.
The method according to this aspect of the invention may or may not comprise a step selected from the following steps:
-topically applying the pharmaceutical composition of the invention to the surface of the eye of a contact lens wearer;
-inserting a contact lens into the eye of a contact lens wearer;
-wearing a contact lens;
-removing the contact lens from the eye of the contact lens wearer;
-repeated topical application of the pharmaceutical composition of the invention to the surface of the eye of a contact lens wearer;
-reinserting the contact lens into the eye of the contact lens wearer after removing the contact lens, optionally after waiting a period of time.
Depending on whether the contact lens used in the method according to this aspect of the invention is a hydrogel contact lens or a silicone hydrogel contact lens as defined above, the methods may be combined in different sequences and may be performed once or repeatedly. In an exemplary embodiment, where the contact lens is a hydrogel contact lens, the method according to this aspect of the invention may comprise the steps of:
a1) topically applying the pharmaceutical composition of the present invention to the surface of the eye of a contact lens wearer;
b1) inserting a contact lens into an eye of a contact lens wearer;
c1) wearing contact lenses;
d1) optionally repeatedly topically applying the pharmaceutical composition of the present invention to the surface of the eye of a contact lens wearer;
e1) removing the contact lens from the eye of the contact lens wearer; and/or
f1) Optionally, the pharmaceutical compositions of the present invention are repeatedly topically applied to the surface of the eye of a contact lens wearer.
In another exemplary embodiment, where the contact lens is a silicone hydrogel contact lens, the method according to this aspect of the invention may comprise the steps of:
a2) inserting a contact lens into an eye of a contact lens wearer;
b2) wearing contact lenses;
c2) removing the contact lens from the eye of the contact lens wearer; and/or
d2) Topically applying the pharmaceutical composition of the present invention to the surface of the eye of a contact lens wearer;
e2) optionally, the pharmaceutical compositions of the present invention are repeatedly topically applied to the surface of the eye of a contact lens wearer.
It should be noted, however, that the above-described method steps may be suitably combined and optionally repeated according to the embodiments and preferred embodiments described in detail above for the first aspect of the invention.
Thus, in connection with a particular embodiment of the present invention directed to a pharmaceutical composition consisting essentially of 1-perfluorohexyloctane (F6H8) for use in treating or preventing a disease or disorder associated with the ocular surface of the eye of an individual, wherein the individual is a contact lens wearer, and wherein the contact lens is a hydrogel contact lens or a silicone hydrogel contact lens, and the composition is topically applied to the surface of the eye of the individual after removal of the contact lens from the eye of the individual, a method according to this aspect of the invention may comprise the steps of:
a3) inserting a hydrogel or silicone hydrogel contact lens into the eye of a contact lens wearer;
b3) wearing contact lenses;
c3) removing the contact lens from the eye of the contact lens wearer;
d3) topically applying the pharmaceutical composition of the present invention to the surface of the eye of a contact lens wearer; and
e3) optionally, the pharmaceutical compositions of the present invention are repeatedly topically applied to the surface of the eye of a contact lens wearer.
Furthermore, the present invention relates to a method for regenerating the eye and/or ocular surface overnight after removal of a contact lens of an eye of a subject, wherein said subject is a contact lens wearer, comprising topically administering a pharmaceutical composition comprising a semifluorinated alkane of formula (I) as described above for the first aspect of the invention, or according to a specific embodiment consisting essentially of 1-perfluorohexyloctane (F6H 8).
In a third aspect, the present invention relates to the use of a pharmaceutical composition comprising a semifluorinated alkane of formula (I) for the preparation of a medicament for the treatment or prevention of a disease or condition associated with the ocular surface of the eye of a subject,
F(CF2)n(CH2)mH (I)
wherein
n is an integer of 4 to 6, and
m is an integer of 5 to 8,
wherein the individual is a contact lens wearer, and
wherein the contact lens is a hydrogel contact lens and the composition is topically applied to the surface of the eye of the individual, or before the contact lens is inserted into the eye of the individual and/or during contact lens wear and/or after the contact lens has been removed from the eye of the individual
Wherein the contact lens is a silicone hydrogel contact lens and the composition is topically applied to the surface of the eye of the subject after the contact lens is removed from the eye of the subject.
More specifically, according to this aspect, the invention also provides the use of a pharmaceutical composition consisting essentially of 1-perfluorohexyloctane (F6H8) as described above, in the manufacture of a medicament for the treatment or prevention of a disease or condition associated with the ocular surface of the eye of an individual, wherein the individual is a contact lens wearer, and wherein the contact lens is a hydrogel contact lens or a silicone hydrogel contact lens, and the composition is topically applied to the surface of the eye of the individual after removal of the contact lens from the eye of the individual.
In a fourth aspect, the present invention relates to a kit comprising
-a pharmaceutical composition for use according to the first aspect of the invention,
-a container for containing the composition,
-means for dispensing the composition to the eye of an individual or patient; and optionally
Instructions on how to use and apply the composition while wearing the contact lens.
In other words, according to this aspect, the invention relates to a kit for the treatment or prevention of a disease or condition associated with the ocular surface of the eye of an individual, comprising
-a pharmaceutical composition and a pharmaceutical composition for use according to the first aspect of the invention,
-a container for containing the composition,
-means for dispensing the composition to the eye of an individual or patient; and optionally
Instructions on how to use and apply the composition while wearing the contact lens.
It should be noted that all embodiments described above in connection with the first aspect of the invention may also form embodiments or preferred embodiments of the further aspect of the invention.
The following is a list of numbered clauses or embodiments of the present invention:
1. pharmaceutical compositions comprising semifluorinated alkanes of formula (I)
F(CF2)n(CH2)mH (I)
Wherein n is an integer of 4 to 6, and
m is an integer of 5 to 8,
for use in the treatment or prevention of a disease or condition associated with the ocular surface of the eye of an individual, wherein the individual is a contact lens wearer, and
wherein the contact lens is a hydrogel contact lens and the composition is topically applied to the surface of the eye of the individual, or before the contact lens is inserted into the eye of the individual and/or during contact lens wear and/or after the contact lens has been removed from the eye of the individual
Wherein the contact lens is a silicone hydrogel contact lens and the composition is topically applied to the surface of the eye of the subject after the contact lens is removed from the eye of the subject.
2. The pharmaceutical composition for use according to clause 1, wherein the semifluorinated alkane of formula (I) is selected from 1-perfluorohexyloctane (F6H8) and 1-perfluorobutylpentane (F4H 5).
3. The pharmaceutical composition for use according to clause 1 or 2, wherein the composition consists essentially of 1-perfluorohexyloctane (F6H 8).
4. The pharmaceutical composition for use of any of clauses 1 to 3, wherein the hydrogel contact lens comprises a plastic material selected from the group consisting of: acofekang a (acofilcon a); acofekang b (acofilcon b); alpha-phenanthrene kang A (alphafilcon A); argyrofilcon (altraficon a); baffenkang a (bufilcon a); crofelon (crofelcon); deltafilcon a; delphaekang a (dimefilcon a); zhuxifekang a (droxifilcon a); epifilcon a (epsifilcon a); etafilcon a (etafilcon a); focofilcon a (focofilcon a); HAIFIKANG A & B (HEFILCON A & B); haifenck C (hfilcon C); halafilkang a (hiafilcon b); cisifencan a (hioxifilcon a); cisifencon b (hioxifilcon b); seaffenkang d (hioxifilcon d); esfilcon (isofilcon); lidofiran a (lidofilcon a); lidofirancb (lidofilcon b); mafilcon a (mafilcon); metafilcon A, B (methafilcon a, B); neffekang a (nelfilcon a); niscoffekang a (nescofilcon a); nevirakang a (netrafilcon a); orkufilcon a (ocufilcon a); orkufilcon b (ocufilcon b); orkufilcon c (ocufilcon c); orkufilcon d (ocufilcon d); orkufilcon e (ocufilcon e); orkufilcon f (ocufilcon f); oxfekang a (ofilcon a); omafilkang a (omafilcon a); bofelkang a (perfilcon a); phenanthroline drug A (phemfilcon A); phenanthrenefferskang a (phenfilcon a); polymazen (polymacon); sabifencan a (scafilcon a); shufeikan A (surfilcon A); tefilcon; taflufakang a (tetrafilcon a); taflufenac b (tetrafilcon b); vasufilcon A (Vasurfilcon A); vefenac a (vifilcon a); and silofenicon a (xylofilcon a).
5. The pharmaceutical composition for use according to any of clauses 1 to 4, wherein the contact lens is a hydrogel contact lens and the composition is topically applied to the surface of the eye of the individual prior to insertion of the contact lens into the eye of the individual and/or during contact lens wear and/or after the contact lens has been removed from the eye of the individual.
6. The pharmaceutical composition for use according to item 5, wherein the composition and the contact lens are present in the eye of an individual at the same time.
7. The pharmaceutical composition for use according to any of clauses 1 to 5, wherein the composition is topically applied to the surface of the eye of the individual prior to insertion of the contact lens into the eye of the individual.
8. The pharmaceutical composition for use according to any of clauses 1-3, wherein the silicone hydrogel contact lens comprises a silicone hydrogel selected from the group of silicone hydrogels consisting of abacavir A (Balafilcon A), Cuffircon A (comfilcon A), Afflofilcon A (efrofilcon A), Enfafilcon (enfilcon), Fofukang A (galyfilcon A), Rotiffilcon A (lotrafilcon A), Roftafilcon B (lotrafilcon B), Narafilcon B (narafilcon B), Spirofilcon A (senofilcon A), Soffilcon A (somofilcon A), and serfafilcon A (silfilcon A).
9. The pharmaceutical composition for use of any of clauses 1-8, wherein the composition is topically applied to the surface of the eye of the subject after the contact lens is removed from the eye of the subject.
10. The pharmaceutical composition for use of any of clauses 1 to 9, wherein the disease or condition related to the ocular surface of the eye of the subject is related to contact lens wear.
11. The pharmaceutical composition for use according to any of clauses 1 to 10, wherein the disease or condition associated with the ocular surface of the eye of the subject is dryness associated with continued wear of the contact lens.
12. The pharmaceutical composition for use according to any of clauses 1 to 9, wherein the disease or disorder associated with the ocular surface of the eye of the individual is selected from keratoconjunctivitis sicca (DED) and/or Meibomian Gland Dysfunction (MGD) and/or symptoms associated therewith.
13. The pharmaceutical composition for use according to any of clauses 1 to 9, wherein the disease or condition associated with the ocular surface of the eye of the subject is EOD dryness.
14. The pharmaceutical composition for use according to clauses 1-13, wherein the disease or condition associated with the ocular surface of the eye of the subject is EOD dryness associated with contact lenses.
15. The pharmaceutical composition for use according to any of clauses 10-12, wherein the subject has both the disease or condition according to any of clauses 10-12 and the disease or condition defined by any of clauses 13-14.
16. A kit comprising a pharmaceutical composition according to any clause of claims 1 to 15, a container for containing the composition, a device for dispensing the composition to the eye of an individual or patient, and optionally instructions on how to use and apply the composition when wearing contact lenses.
17. A method for treating or preventing a disease or disorder associated with the ocular surface of an eye of an individual, wherein the individual is a contact lens wearer, the method comprising topically administering a pharmaceutical composition consisting essentially of 1-perfluorohexyloctane (F6H8) onto the surface of the eye of the individual after the contact lens has been removed from the eye; and
wherein the contact lens is a hydrogel contact lens or a silicone hydrogel contact lens.
18. The method of clause 17, wherein the contact lens is a hydrogel contact lens.
19. The method of clauses 17 or 18, wherein the hydrogel contact lens comprises a plastic material selected from the group consisting of: acofekang a (acofilcon a); acofekang b (acofilcon b); alpha-phenanthrene kang A (alphafilcon A); argyrofilcon (altraficon a); baffenkang a (bufilcon a); crofelon (crofelcon); deltafilcon a; delphaekang a (dimefilcon a); zhuxifekang a (droxifilcon a); epifilcon a (epsifilcon a); etafilcon a (etafilcon a); focofilcon a (focofilcon a); HAIFIKANG A & B (HEFILCON A & B); haifenck C (hfilcon C); halafilkang a (hiafilcon b); cisifencan a (hioxifilcon a); cisifencon b (hioxifilcon b); seaffenkang d (hioxifilcon d); esfilcon (isofilcon); lidofiran a (lidofilcon a); lidofirancb (lidofilcon b); mafilcon a (mafilcon); metafilcon A, B (methafilcon a, B); neffekang a (nelfilcon a); niscoffekang a (nescofilcon a); nevirakang a (netrafilcon a); orkufilcon a (ocufilcon a); orkufilcon b (ocufilcon b); orkufilcon c (ocufilcon c); orkufilcon d (ocufilcon d); orkufilcon e (ocufilcon e); orkufilcon f (ocufilcon f); oxfekang a (ofilcon a); omafilkang a (omafilcon a); bofelkang a (perfilcon a); phenanthroline drug A (phemfilcon A); phenanthrenefferskang a (phenfilcon a); polymazen (polymacon); sabifencan a (scafilcon a); shufeikan A (surfilcon A); tefilcon; taflufakang a (tetrafilcon a); taflufenac b (tetrafilcon b); vasufilcon A (Vasurfilcon A); vefenac a (vifilcon a); and silofenicon a (xylofilcon a).
20. The method of clause 17, wherein the contact lens is a silicone hydrogel contact lens.
21. The method of clause 17 or 20, wherein the silicone hydrogel contact lens comprises a silicone hydrogel selected from the group of silicone hydrogels consisting of abacavirenz a (balafilcon a), kuffien a (comfilcon a), efrofilcon a (efrofilcon a), infliximan (enfilcon), cafefavirenz a (galyfilcon a), roxafieldcon a (lotrafilcon a), roxafieldcon b (lotrafilcon b), nalafieldcon b (narafilcon b), sfluor a (senofilcon a), sofiflucenz a (somofilcon a), and silfilcon a (sillicocon a).
22. The method of any of clauses 17 to 21, wherein the disease or condition related to the ocular surface of the eye of the individual is related to contact lens wear.
23. The method of any of clauses 17 to 22, wherein the disease or condition related to the ocular surface of the eye of the individual is dryness associated with continued wear of a contact lens.
24. The method of any of clauses 17-23, wherein the disease or condition related to the ocular surface of the eye of the subject is EOD dryness.
25. The method of clauses 23 or 24, wherein the disease or condition is characterized by dryness that increases from insertion to removal of a contact lens.
26. The method of any of clauses 17 to 25, wherein the method is effective to reduce discomfort associated with contact lens wear, preferably prolonged contact lens wear.
27. The method of any of clauses 17 to 26, wherein the method is effective to improve and/or reduce drying after, before, and during contact lens wear.
28. The method of any of clauses 17-27, wherein the method is effective to improve and/or reduce drying after, before, and during contact lens wear.
The following examples are intended to illustrate the invention, but are not intended to limit the invention in any way.