JP-7855312-B2 - Ophthalmic composition containing tafluprost for the treatment of glaucoma

Inventors

• ルッシャー， フランク
• シュトレール， ディアナ
• アイクホフ， キルステン

Assignees

• ノバリック ゲーエムベーハー

Dates

Publication Date

20260508

Application Date

20190424

Priority Date

20180427

Claims (4)

1. A pharmaceutical composition for use in a method of treating glaucoma, elevated intraocular pressure, and/or ocular hypertension, comprising 0.0030% (w/v) tafluprost dissolved in a liquid vehicle essentially consisting of at least 99% (w/w) 1-perfluorohexyloctane and a solubilizer, wherein a single dose of 0.30 μg to 0.35 μg of tafluprost per eye is administered to the target eye once daily, the solubilizer being ethanol, and the pharmaceutical composition containing neither water nor preservatives.
2. The pharmaceutical composition for use according to claim 1, wherein the pharmaceutical composition is administered to the patient's eye in a single dose of 0.33 μg of tafluprost per eye.
3. The pharmaceutical composition for use according to claim 1 or 2, wherein the pharmaceutical composition is administered in a dose volume of 11 μl per eye.
4. A kit for use in a method of treating glaucoma, elevated intraocular pressure, and/or ocular hypertension, comprising a pharmaceutical composition according to any one of claims 1 to 3, the kit comprising a container for holding the pharmaceutical composition and a drop dispenser adapted for dispensing 9 to 14 μl of the pharmaceutical composition per drop.

Description

This invention relates to the field of pharmacotherapy. More specifically, it relates to the treatment of diseases and conditions affecting the eye, such as glaucoma, elevated intraocular pressure, ocular hypertension, and/or related conditions. Elevated intraocular pressure (IOP) is a common eye disorder often associated with optic nerve damage, resulting in glaucoma. When there is no optic nerve damage, the condition is called ocular hypertension. Normal IOP is generally defined as being in the range of 10 to 21 mmHg. IOP is primarily caused by the balance between the rate of aqueous humor production and drainage in the eye. It is also influenced by corneal thickness and hardness. IOP typically fluctuates around 15 to 16 mmHg with an amplitude of up to 6 mmHg. For example, IOP generally decreases at night due to decreased aqueous humor production. IOP also responds to various physiological factors such as exercise, heart rate, respiration, and fluid intake, as well as certain types of systemic or topical medications. Aqueous humor is produced by the ciliary body of the eye and flows into the posterior chamber. Its composition is very similar to that of plasma, but it differs in that it has a lower protein content. Its main components are water (99%), electrolytes (inorganic ions to maintain physiological pH), small amounts of albumin and β-globulin, ascorbate, glucose, lactate, and amino acids. Aqueous humor is distributed from the posterior chamber through the pupil of the iris to the anterior chamber. From there, the aqueous humor flows through the so-called trabecular meshwork. The trabecular meshwork is a spongy tissue region supported by trabecular meshwork cells, and its main function is to drain aqueous humor into a series of canals called Schlemm's canals. From there, the aqueous humor enters the blood circulation. The flow of aqueous humor from the trabecular meshwork to Schlemm's canals occurs via two different pathways: directly through the aqueous humor vein to the episcleral vein, or indirectly through the collecting duct to the episcleral vein via the intrascleral venous plexus. This trabecular outflow pathway accounts for the majority of drained aqueous humor. Furthermore, there is a second major drainage pathway, which is the uveoscleral pathway. This uveoscleral pathway is relatively independent of intraocular pressure and usually accounts for only 5 to 10% of aqueous humor drainage in healthy individuals. Various prostanoid receptors have been found in both the trabecular meshwork and the uveoscleral tissue. This indicates that prostanoids are involved in regulating aqueous humor production and/or drainage, thereby influencing intraocular pressure. While genes encoding the EP, FP, IP, DP, and TP receptor families are expressed in the trabecular meshwork, the EP and FP receptor families are dominant in the uveoscleral tissue (Toris et al., Surv Ophthalmol. 2008; 53, Appendix 1, S107-S120). Prostanoids are physiological fatty acid derivatives representing a subclass of eicosanoids. Prostanoids include prostaglandins, prostamides, thromboxanes, and prostacyclins, all of which are mediators involved in many physiological processes. Natural prostaglandins such as PGF2α , PGE2 , PGD2 , and PGI2 exhibit specific affinities to their respective receptors (FP, EP, DP, IP), but also have some non-selective affinities to other prostaglandin receptors (ibid.). Prostaglandins also directly affect matrix metalloproteinases, neutral proteinases expressed in the trabecular meshwork that play a role in regulating fluid efflux resistance by degrading the extracellular matrix. Several prostaglandin analogs, including latanoprost, bimatoprost, tafluprost, travoprost, and unoprostone, have been found to be effective as topical medications for lowering intraocular pressure. Some experts believe bimatoprost is understood as a prostaglandin, not a prostaglandin derivative. Latanoprost, travoprost, tafluprost, and possibly bimatoprost are also potent and selective PGF -2α agonists. Their net effect is a reduction in intraocular pressure, which is mainly caused by a substantial increase in aqueous humor outflow via the uveoscleral pathway. They also likely increase trabecular meshwork outflow to some extent. Various eye drop formulations containing prostaglandin analogs have been developed and are commercially available. Tafluprost is available as a preservative formulation and as a non-preservative formulation in single-dose containers. The strength of the tafluprost formulation is 15 μg/mL (0.0015%) and it also contains the surfactant polysorbate 80. Bimatoprost is also sold as a buffered, isotonic, preservative aqueous solution with a strength of 0.3 mg/mL (0.03%). The strength of commercially available unoprostone formulations is 1.5 mg/mL (0.15%). It contains a buffer, preservative, isotonic agent, and polysorbate 80. However, ophthalmic antiseptic aqueous formulations have a drawback in that they can cause i