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US-20260124305-A1 - TOPICAL OPHTHALMOLOGICAL COMPOSITIONS

US20260124305A1US 20260124305 A1US20260124305 A1US 20260124305A1US-20260124305-A1

Abstract

A topical ophthalmological composition includes a muscarinic receptor antagonist as an active pharmaceutical ingredient; and medium chain triglycerides (MCTs) or light liquid paraffin oil as liquid vehicle. The topical ophthalmological composition treats an ocular disease.

Inventors

  • Jinsong Ni
  • VAN DINH
  • Rong Yang

Assignees

  • ADS THERAPEUTICS LLC

Dates

Publication Date
20260507
Application Date
20251103

Claims (20)

  1. 1 .- 15 . (canceled)
  2. 16 . A topical ophthalmological composition comprising: about 0.01% to about 0.05% (w/w) atropine as an active pharmaceutical ingredient (API); about 5% to about 20% (w/w) medium chain triglyceride (MCT) liquid vehicle; and about 80% to about 95% (w/w) semi-fluorinated alkane compound selected from the group consisting of perfluorobutylheptane (F4H5), perfluorobutylhexane (F4H6), perfluorohexylbutane (F6H4), perfluorohexylhexane (F6H6), perfluorohexyloctane (F6H8), and perfluorohexyl decane (F6H10), wherein the topical ophthalmological composition is non-aqueous.
  3. 17 . The topical ophthalmological composition of claim 16 , wherein the MCT is present in a concentration of about 10% (w/w).
  4. 18 . The topical ophthalmological composition of claim 16 , wherein the MCT is present in a concentration of 10%.
  5. 19 . The topical ophthalmological composition of claim 16 , wherein the semi-fluorinated alkane compound is present in a concentration of about 90% (w/w).
  6. 20 . The topical ophthalmological composition of claim 16 , wherein the semi-fluorinated alkane compound is present in a concentration of 90% (w/w).
  7. 21 . The topical ophthalmological composition of claim 16 , wherein the MCT is present in a concentration of 10% (w/w) and wherein the semi-fluorinated alkane compound is present in a concentration of 90% (w/w).
  8. 22 . The topical ophthalmological composition of claim 16 , wherein the atropine is present in a concentration of 0.01%, 0.02%, 0.025%, or 0.04% (w/w).
  9. 23 . The topical ophthalmological composition of claim 22 , wherein the atropine is in a free base form.
  10. 24 . The topical ophthalmological composition of claim 16 , wherein the MCT is a triglyceride of fatty acids selected from the group consisting of hexanoic acid, octanoic acid, decanoic acid, and dodecanoic acid.
  11. 25 . The topical composition of claim 16 , wherein the semi-fluorinated alkane is perfluorohexyloctane (F6H8).
  12. 26 . The topical composition of claim 16 , wherein the MCT comprises octanoic acid, decanoic acid, or a combination thereof.
  13. 27 . The topical ophthalmological composition of claim 16 , wherein the atropine in the topical ophthalmological composition is chemically stable for at least 1 year.
  14. 28 . A topical ophthalmological composition comprising: 0.01%, 0.02%, 0.025%, or 0.04% (w/w) atropine in free base form as an active pharmaceutical ingredient (API); 10% (w/w) medium chain triglyceride (MCT) liquid vehicle; and 90% (w/w) semi-fluorinated alkane compound selected from the group consisting of perfluorobutylpentane (F4H5), perfluorobutylhexane (F4H6), perfluorohexylbutane (F6H4), perfluorohexylhexane (F6H6), perfluorohexyloctane (F6H8), and perfluorohexyl decane (F6H10), wherein the topical ophthalmological composition is non-aqueous.
  15. 29 . The topical ophthalmological composition of claim 28 , wherein the semi-fluorinated alkane compound is perfluorohexyloctane (F6H8).
  16. 30 . The topical ophthalmological composition of claim 28 , wherein the MCT is a triglyceride of fatty acids selected from the group consisting of hexanoic acid, octanoic acid, decanoic acid, and dodecanoic acid.
  17. 31 . The topical ophthalmological composition of claim 28 , wherein the semi-fluorinated alkane compound is perfluorohexyloctane (F6H8) and wherein the MCT is a triglyceride of fatty acids selected from the group consisting of hexanoic acid, octanoic acid, decanoic acid, and dodecanoic acid.
  18. 32 . A method for slowing myopia progression in a subject, comprising administering the topical ophthalmological composition of claim 16 to an eye of the subject.
  19. 33 . A method for slowing myopia progression in a subject, comprising administering the topical ophthalmological composition of claim 28 to an eye of the subject.
  20. 34 . A method for slowing myopia progression in a subject, comprising administering the topical ophthalmological composition of claim 31 to an eye of the subject.

Description

This application is a continuation of U.S. patent application Ser. No. 18/768,656, filed on Jul. 10, 2024, which is a continuation of U.S. patent application Ser. No. 17/976,660, issued as U.S. Pat. No. 12,070,501, filed on Oct. 28, 2022, which is a continuation of PCT/US2022/014811, filed on Feb. 2, 2022, which claims priority to U.S. Provisional Patent Application No. 63/145,091, filed on Feb. 3, 2021, each of which is incorporated by reference for all purposes as if fully set forth herein. FIELD OF THE INVENTION The present invention relates to topical ophthalmological compositions of a muscarinic receptor antagonist dissolved in medium chain triglycerides (MCTs) or light liquid paraffin oil as liquid vehicle, wherein, the formulation of atropine is used for treating myopia. BACKGROUND OF THE INVENTION Atropine is an anti-muscarinic compound and is a competitive antagonist of muscarinic receptors. It has anti-parasympathetic functions. It is used for several indications such as anticholinergic poisoning and bradycardia. In the eye, it is traditionally used for dilating pupil. Recently, low dose of atropine is shown be able to attenuate the progression of myopia in young adults (Li 2019). For the myopia indication, atropine is approved in only a few countries as of now. Myopia, or nearsightedness, is a condition in which people can see close objects clearly, but objects farther away appear blurred. Myopia occurs if the eyeball is too long or the cornea (the clear front cover of the eye) is too curved so that distant objects can't be focused correctly on retina. Myopia is the most common eye disorder worldwide. About 30 percent of the U.S. population has myopia. The etiology of myopia is unknown. Genetics is believed to have a role in myopia. Myopia development may be affected by how a person uses the eyes. It may occur in school-age children and progresses until about age 20. However, myopia may also develop in adults due to visual stress or health conditions such as diabetes. Myopia may increase the risk of other ocular diseases (Wu 2019). Atropine solution (water-based) formulations have been tested in multiple clinical trials and is proven to be able to slow down the progression of myopia (Cooper 2018, Li 2019, Yam 2020). In the water-based formulation, atropine is prone to degradation at neutral pH solution once the container is open to the air, therefore, the shelf life of the product at neutral pH is often less than 1 year. Low pH of 3-6 in the formulation is used to increase the stability of atropine in solution (Berton 2020; Saito 2019). However, low pH is also known to cause irritation and discomfort in the eye. This invention uses an organic liquid carrier to create a more stable and less irritating formulation of atropine for ocular, in particular myopia, indications. In addition, atropine solution was used for causing cycloplegic refraction in the eye of the subject, for causing mydriasis in the eye of the subject, for treating amblyopia or lazy eye in children, for relieving vitreous floater symptoms, for treating or preventing painful ciliary muscle spasm or for treating myopia progression in pediatric subjects. SUMMARY OF THE INVENTION In one embodiment, the present invention provides a topical ophthalmological composition. The topical ophthalmological composition includes a muscarinic receptor antagonist as an active pharmaceutical ingredient (API); and a liquid vehicle selected from the group consisting of a medium chain triglyceride (MCT) and a light liquid paraffin oil. The topical ophthalmological composition treats an ocular disease. In another embodiment, the muscarinic receptor antagonist is selected from the group consisting of atropine, pirenzepine, aclidinium bromide, benztropine, cyclopentolate, diphenhydramine, doxylamine, dimenhydrinate, dicyclomine, darifenacin, flavoxate, hydroxyzine, ipratropium, mebeverine, oxybutynin, procyclidine, scopolamine, solifenacin, tropicamide, tiotropium, trihexyphenidyl, and tolterodine. In another embodiment, the muscarinic receptor antagonist is atropine. In another embodiment, the atropine is in a free base form or a salt form. In another embodiment, a concentration of the atropine in the free base form is from about 0.001% to about 0.1% (w/w). In another embodiment, the atropine free base is formulated in the MCT or formulated in the light liquid paraffin. In another embodiment, the MCT is a triglyceride of fatty acids, and the fatty acids selected from the group consisting of hexanoic acid, octanoic acid, decanoic acid, and dodecanoic acid. In another embodiment, the topical ophthalmological composition further includes a semi-fluorinated alkane compound. The semi-fluorinated alkane compound has a formula of RFRH or a formula of RFRHRF; RF is a perfluorinated hydrocarbon with 1 to 15 carbon atoms, and wherein RH is a non-fluorinated hydrocarbon with 1 to 15 carbon atoms. In another embodiment, a weight ratio of the MCT or the light liquid