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US-20260124235-A1 - OPHTHALMIC SOLUTION CONTAINING QUATERNARY CHITOSAN DERIVATIVES FOR TREATING OCULAR DISEASES

US20260124235A1US 20260124235 A1US20260124235 A1US 20260124235A1US-20260124235-A1

Abstract

A pharmaceutical composition to be applied to an ocular surface is disclosed that includes a quaternized chitosan derivative to provide antimicrobial activity against gram-negative bacteria, gram-positive bacteria, fungi, and viruses as an active ingredient. This is combined with a cellulose compound acting as a viscosity agent and demulcent to protect and lubricate mucous membrane surfaces. This is further combined with a humectant and tonicity agent to retain moisture on the ocular surface and maintain a comfortable osmolarity for the eye. This is further combined with a buffer/pH adjuster system configured to support a physiologically tolerable pH of about 6.0 to 8.0. Finally, this is combined with purified water as a diluent.

Inventors

  • Suchismita Acharya
  • Nuria Jimenez
  • Patrick Smale

Assignees

  • ClearSight Therapeutics

Dates

Publication Date
20260507
Application Date
20251105

Claims (20)

  1. 1 . A pharmaceutical composition to be applied to an ocular surface comprising: a quaternary chitosan derivative as an active ingredient to provide antimicrobial activity against at least one of gram-negative bacteria, gram-positive bacteria, fungi, and viruses; a non-ionic cellulose compound acting as a viscosity agent and demulcent to protect and lubricate mucous membrane surfaces; a non-ionic humectant and tonicity agent to retain moisture on the ocular surface, and maintain a comfortable osmolarity for the eye within a range of 150-350 mOsm/Kg, preferably 220-320 mOsm/Kg; a low ionic strength buffer/pH adjuster system configured to maintain a physiologically tolerable pH of about 6.0 to 8.0; and purified water as a diluent.
  2. 2 . The pharmaceutical composition of claim 1 , wherein the quaternary chitosan derivative is trimethyl chitosan (TMC).
  3. 3 . The pharmaceutical composition of claim 1 , wherein the quaternary chitosan derivative is N-(2-hydroxy)propyl-3-trimethylammonium chitosan chloride (HTCC).
  4. 4 . The pharmaceutical composition of claim 1 , wherein the quaternary chitosan derivative is present at a concentration of 0.01% to 1% w/w, preferably 0.05% to 0.2% w/w.
  5. 5 . The pharmaceutical composition of claim 1 , wherein the cellulose compound is comprised of hydroxypropyl methylcellulose (HPMC).
  6. 6 . The pharmaceutical composition of claim 1 , wherein the cellulose compound is nonionic comprised of hydroxyethyl cellulose (HEC).
  7. 7 . The pharmaceutical composition of claim 1 , wherein the humectant and tonicity agent comprises polyethylene glycol 400.
  8. 8 . The pharmaceutical composition of claim 7 , wherein Polyethylene glycol 400 is incorporated at a 2.6% concentration, which is the maximum concentration to be used within the osmolality range 220-320 mOsm/Kg.
  9. 9 . The pharmaceutical composition of claim 8 , and further comprising mannitol as a tonicity agent to adjust the osmolarity.
  10. 10 . The pharmaceutical composition of claim 1 , wherein the tonicity agents comprise Polyols as tonicity agents selected from the group of Mannitol, Glycerol and Sorbitol and the maximum concentrations to be used within the osmolality range 220-320 mOsm/Kg are the following: Mannitol 5.4%, Glycerol 2.9% and Sorbitol 5.4%.
  11. 11 . The pharmaceutical composition of claim 1 , wherein the low ionic strength buffer/pH adjuster system incorporates boric acid as the buffer.
  12. 12 . The pharmaceutical composition of claim 11 , wherein low ionic strength buffer/pH adjuster system incorporates Hydrochloric Acid as a pH adjuster.
  13. 13 . The pharmaceutical composition of claim 11 , wherein low ionic strength buffer/pH adjuster system incorporates Sodium Hydroxide as a pH adjuster.
  14. 14 . A pharmaceutical composition to be applied to an ocular surface comprising: a quaternary chitosan derivative as an active ingredient to provide antimicrobial activity against at least one of gram-negative bacteria, gram-positive bacteria, fungi, and viruses in a concentration of 0.01% to 1% w/w; a non-ionic cellulose compound acting as a viscosity agent and demulcent to protect and lubricate mucous membrane surfaces in a concentration of 0.5-1.0% w/w; a non-ionic humectant and tonicity agent to retain moisture on the ocular surface, and maintain a comfortable osmolarity for the eye within 220-320 mOsm/Kg, the non-ionic humectant and tonicity agent comprising: polyethylene glycol 400 in a concentration of 0.5-1.5% w/w, and mannitol in a concentration of 1-3% w/w; a low ionic strength buffer/pH adjuster system configured to maintain a physiologically tolerable pH of about 6.0 to 8.0 comprised of boric acid with a concentration of 0.1-1.5% w/w; and purified water as a diluent q.s. to 100%.
  15. 15 . The pharmaceutical composition of claim 14 , wherein the quaternary chitosan derivative is trimethyl chitosan (TMC).
  16. 16 . The pharmaceutical composition of claim 14 , wherein the quaternary chitosan derivative is N-(2-hydroxy)propyl-3-trimethylammonium chitosan chloride (HTCC).
  17. 17 . The pharmaceutical composition of claim 14 , wherein the cellulose compound is comprised of hydroxypropyl methylcellulose (HPMC).
  18. 18 . The pharmaceutical composition of claim 14 , wherein the cellulose compound is nonionic comprised of hydroxyethyl cellulose (HEC).
  19. 19 . The pharmaceutical composition of claim 14 , wherein the humectant and tonicity agent comprises polyethylene glycol 400.
  20. 20 . The pharmaceutical composition of claim 14 , wherein the low ionic strength buffer/pH adjuster system incorporates boric acid as the buffer.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application No. 63/717,628, filed Nov. 7, 2024, entitled STERILE AQUEOUS OPHTHALMIC SOLUTION CONTAINING QUATERNARY CHITOSAN DERIVATIVES FOR TREATING ACUTE INFECTIOUS CONJUNCTIVITIS (Atty. Dkt. No. CLEA60-35991), the specifications of which are incorporated by reference herein in their entirety. TECHNICAL FIELD This disclosure relates to a sterile ophthalmic solution containing a quaternary chitosan derivative. BACKGROUND Conjunctivitis, or inflammation of the conjunctiva, is a general term that refers to a diverse group of diseases/disorders that affect primarily the conjunctiva. Most varieties of conjunctivitis are self-limited, but some progress and may cause serious ocular and extraocular complications. Conjunctivitis can be classified as noninfectious or infectious and as acute, chronic, or recurrent. Noninfectious types of conjunctivitis include allergic, mechanical/irritative/toxic, immune-mediated, and neoplastic, and these types may overlap. The causes of infectious conjunctivitis include viruses, fungi, and bacteria. Acute Conjunctivitis (“Pink Eye”) is the inflammation of the lining of the eyelids and eyeball caused by bacteria, viruses, allergic or immunological reactions, mechanical irritation, or medicines. Conjunctivitis is a diagnosis that encompasses a diverse group of diseases that occur worldwide and affect all ages, all social strata, and all genders. Although there are no reliable figures that document the incidence or prevalence of all forms of conjunctivitis, this condition has been recognized as one of the most frequent causes of patient self-referral. It represents four million annual cases in the US treated with antibiotic eyedrops as the standard of care, with $1.9 billion in estimated lost wages annually in the US due to 8.5 million missed workdays and 3.5 million missed school days. The current treatment practice for acute conjunctivitis includes topical mast cell stabilizers, antihistamines, and topical antibiotics. It is highly contagious and prevalent in children. Eighty percent or more of the acute infectious conjunctivitis cases have a viral cause, for which the current practice of using antibiotics is inefficient and requires a prescription from a physician. In addition, the overuse of antibiotics creates resistance, making the treatment even less effective. This acute infectious conjunctivitis, especially epidemic keratoconjunctivitis (EKC), additionally poses a serious and ongoing threat to force health protection and mission readiness in the U.S. military. As the condition is highly contagious, often caused by adenoviruses, it can spread quickly in communal and operational settings such as barracks, naval vessels, and field deployments. EKC alone accounts for 13.3% of all conjunctival issues and 47.7% of ocular medical encounters among active-duty personnel, significantly impairing unit readiness and increasing the need for isolation. The clinical course involves a seven-day incubation period, followed by weeks of contagiousness. During deployments or shipboard confinement, where isolation is impractical, outbreaks can compromise entire units. EKC is predominantly viral (˜80%), with adenovirus identified in 65-90% of cases. Despite the operational impact, there are no FDA-approved antiviral treatments for adenoviral conjunctivitis, and current care remains mostly palliative, failing to shorten the duration of the disease or its transmissibility. This creates a critical capability gap in the management of ocular infections during military operations. Currently, treatment for EKC and other acute infectious conjunctivitis relies on supportive care, including cold compresses, antibiotics, lubricating drops, and hygiene education. In severe or complicated cases, off-label therapies such as povidone-iodine rinses, corticosteroids, and antiviral gels (e.g., ganciclovir) may be used. However, there is limited evidence of their effectiveness against adenovirus, and potential risks of side effects exist. The complex causes of EKC, involving viral, bacterial (such as Methicillin-resistant Staphylococcus aureus or MRSA), inflammatory factors, and corneal damage, require a comprehensive treatment approach. Current therapies do not target all the main aspects of EKC: viral replication, bacterial superinfection, inflammation, and ongoing mucosal colonization. Moreover, the increasing prevalence of antibiotic resistance and the absence of any FDA-approved ophthalmic drugs in the U.S. exacerbate therapeutic challenges. Conjunctivitis rarely causes permanent visual loss or structural damage, but its economic impact is considerable, largely due to lost work or school time and the costs of medical visits, testing, and treatment. SUMMARY The present invention, disclosed in one aspect herein, comprises a pharmaceutical composition to be applied to an ocular surface that includes a quaternary chitos