Compositions for the treatment of meibomian gland dysfunction and uses thereof

Abstract

The present invention provides compositions for the treatment of meibomian gland dysfunction and uses thereof. Specifically, disclosed herein are ophthalmic compositions for the treatment of meibomian gland dysfunction (MGD) and related ocular conditions and uses thereof. The compositions include photosensitive microscale dispersed ophthalmic ointments containing photosensitive particles, such as graphene, dispersed in a pharmaceutically acceptable carrier. Upon exposure to radiation, such as near-infrared (NIR) radiation, the particles generate heat and / or reactive oxygen species (ROS), promoting the melting of solidified meibum, relief of gland obstruction, reduction of ocular surface inflammation, and improvement of meibum quality. The formulations are administered topically to the eyelids, with delivery methods including ophthalmic patches or gels. The compositions of the present invention and uses thereof provide a safe, effective, and non-invasive treatment for MGD and other ocular surface disorders.

Description

[0001] Cross-reference to related applications

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 790,848, filed April 18, 2025, the entire contents of which are incorporated herein by reference. Technical Field

[0003] The disclosed invention generally falls within the field of photosensitive particles for treating eye conditions. Specifically, the present invention relates to compositions and methods for treating meibomian gland dysfunction and their uses. Background Technology

[0004] Meibomian gland dysfunction (MGD) is a leading cause of evaporative dry eye and one of the most common conditions seen in ophthalmology clinics. The prevalence of MGD varies considerably in published studies, but is relatively high in Asian populations, ranging from 46.2% to 69.3%. MGD symptoms significantly impact quality of life, causing not only eye irritation and ocular surface inflammation, but ultimately leading to visual impairment. According to the International Workshop on Meibomian Gland Dysfunction (IWMGD), MGD is a chronic, diffuse abnormality of the meibomian glands (MG), typically characterized by ductal obstruction and qualitative and / or quantitative changes in glandular secretion.

[0005] The object of this invention is to provide compositions and uses thereof for treating meibomian gland dysfunction (MGD) in an effective, economical, safe and user-friendly manner.

[0006] Any discussion of documents, actions, materials, devices, articles, etc., already included in this specification is not to be construed as an admission that any or all of these matters constitute part of the prior art or common general knowledge in the field relating to the disclosure of this invention that existed prior to the priority date of each claim of this application.

[0007] Throughout this specification, the word “comprising” or variations thereof such as “including” or “containing” shall be understood to imply inclusion of the stated elements, integers or steps, or groups of elements, integers or steps, but not to exclude any other elements, integers or steps, or groups of elements, integers or steps. Summary of the Invention

[0008] One objective of this invention is to provide an ophthalmic composition for treating meibomian gland dysfunction (MGD) and related ocular conditions. This composition contains photosensitive particles (such as graphene) that can generate heat and / or reactive oxygen species under radiation. It can be applied topically to the eyelids to achieve effects such as melting and solidifying meibomian glands, relieving gland blockage, reducing inflammation, and improving meibomian gland quality.

[0009] Another object of the present invention is to provide the use of the composition in the preparation of a medicament for treating MGD, which achieves a safe, non-invasive, and effective ocular treatment by applying the composition to the eyelids in conjunction with radiation of an appropriate wavelength (especially near-infrared light).

[0010] The above-mentioned objective of the present invention is achieved through the following technical solution.

[0011] In a first aspect, the present invention provides an ophthalmic composition comprising:

[0012] (i) one or more photosensitive particles that, when exposed to radiation, can generate heat and / or reactive oxygen species; and

[0013] (ii) Any pharmaceutically acceptable ophthalmic carrier may be selected.

[0014] The ophthalmic composition is suitable for application to the eyelids.

[0015] Preferably, in the ophthalmic composition of the present invention, the photosensitive particles are micron-sized particles, nano-sized particles, or a combination thereof.

[0016] Preferably, in the ophthalmic composition of the present invention, the photosensitive particles are made of one or more metals selected from gold, silver and iron oxide.

[0017] Preferably, in the ophthalmic composition of the present invention, the photosensitive particles are carbon-based nanostructures, and the carbon-based nanostructures are made of one or more materials selected from graphene, graphene derivatives, fullerenes, or semiconductor materials.

[0018] Preferably, in the ophthalmic composition of the present invention, the photosensitive particles comprise one or more photoactive heterojunction materials, and the photoactive heterojunction material is selected from one or more of the following: graphene oxide / copper ferrite nanoparticles (GO / CFN), silver-titanium oxide (Ag-TiO2), TiO2 / AgVO3, Ag / TiO2 / cellulose, alginate / Au-TiO2, lithium titanate in a low-density polyethylene matrix (Li-TiO2 / LDPE), Cu-TiO2, TiO2 / -Fe2O3, Bi-doped TiO2 (Bi-TiO2), and TiO2 co-doped with urea and Bi (urea, Bi-TiO2; U, Bi-TiO2), chitosan film containing melamine / TiO2 (CTS / MTiO2), TiO2 nanoparticles and graphene sheets (TiO2 / GSs), graphene oxide and cuprous oxide (rGO-Cu2O), and zinc oxide-selenium oxide (ZnO-Se).

[0019] Preferably, in the ophthalmic composition of the present invention, the photoactive heterojunction material comprises GO / CFN and / or exhibits strong absorbance at 808 nm.

[0020] Preferably, in the ophthalmic composition of the present invention, the photosensitive particles comprise graphene at concentrations of about 0.001 μg / mg-5.0 μg / mg, 0.005 μg / mg-2.5 μg / mg, 0.01 μg / mg-1.0 μg / mg, 0.015 μg / mg-0.95 μg / mg, 0.02 μg / mg-0.9 μg / mg, 0.03 μg / mg-0.8 μg / mg, 0.04 μg / mg-0.7 μg / mg, 0.05 μg / mg-0.6 μg / mg, 0.06 μg / mg-0.5 μg / mg, 0.07 μg / mg-0.4 μg / mg, 0.08 μg / mg-0.3 μg / mg, or 0.09 μg / mg-0.2 μg / mg.

[0021] Preferably, in the ophthalmic composition of the present invention, the pharmaceutically acceptable ophthalmic carrier is selected from one or more of liposomes, liposome-like nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, lipid-polymer hybrid nanoparticles, encapsulated lipid-polymer hybrid nanoparticles, and exosomes.

[0022] Preferably, in the ophthalmic composition of the present invention, the carrier is selected from lanolin, petrolatum, mineral oil, wax, silicone oil, castor oil, coconut oil, synthetic ester, hydrogel, or a combination thereof.

[0023] Preferably, in the ophthalmic composition of the present invention, the ophthalmic composition further comprises one or more anti-inflammatory agents.

[0024] In a second aspect, the present invention provides a formulation comprising the ophthalmic composition described herein, the form of which is selected from ophthalmic gels, ophthalmic patches, soluble or bioadhesive ophthalmic films, ophthalmic wound bandages, atomized or fine mist formulations, or lipid-based ointments.

[0025] Thirdly, the present invention provides the use of the ophthalmic composition or the preparation in the preparation of a medicament for treating an eye condition, wherein the treatment comprises bringing the eye of a subject into contact with the ophthalmic composition or the preparation of the present invention and exposing the ophthalmic composition or preparation to radiation.

[0026] Preferably, in the use described in this invention, the eye condition is meibomian gland dysfunction.

[0027] Preferably, in the application described in this invention, the radiation source includes one or more of the following: a handheld device, a fixed optical transmission system, a wearable device, a light-emitting diode (LED) array, a laser system, a broadband light source, a filtered light source, and an intense pulsed light (IPL) device.

[0028] Preferably, in the application described in this invention, the radiation has a wavelength of about 380 nm-1200 nm, 400 nm-1000 nm, 500 nm-900 nm, 550 nm-800 nm, 600 nm-750 nm, 1000 nm-1200 nm, 800 nm-1100 nm, or 900 nm-1000 nm.

[0029] Preferably, in the use described in this invention, the radiation is near-infrared (NIR) radiation.

[0030] Preferably, in the use described in this invention, the radiation exposure to the ophthalmic composition or preparation on the eyelids is for about 1-20 minutes, 3-17 minutes, 5-15 minutes, 7-13 minutes, 8-12 minutes, 9-11 minutes, or 9-10 minutes, for 1 day, 1-2 days, 1-3 days, 1-4 days, 1-5 days, 1-6 days, or 1-7 days.

[0031] Preferably, in the use described in this invention, the ophthalmic composition or preparation in the eyelid is exposed to the radiation to generate heat and / or ROS at the eyelid.

[0032] Preferably, in the use described in this invention, the treatment causes one or more of the following: melting of solidified meibomian glands, relief of meibomian gland obstruction, reduction of ocular surface inflammation, improvement of meibomian gland quality, or control of microbial growth.

[0033] This invention discloses formulations and methods for treating meibomian gland dysfunction (MGD). The composition comprises an effective amount of one or more photosensitive particles in a pharmaceutically acceptable excipient, the photosensitive particles being capable of generating heat and / or reactive oxygen species (ROS) upon exposure to radiation, for administration to the eye followed by effective irradiation to treat one or more MGD symptoms.

[0034] The formulation is intended for topical administration to the eyelids. In some forms, the formulation is an ointment. In some forms, the formulation is a film or patch. In some forms, the formulation is a dosage form whose shape conforms to the size of the MGD site to be treated, for the purpose of concentrating and targeting graphene to the MGD site. The photosensitive particles can be micron-sized particles, nanoparticles, or combinations thereof, such as metal-based nanoparticles, non-metal-based particles such as graphene, semiconductor materials, or polymer particles.

[0035] A method of treating MGD in subjects with the need involves administering the disclosed formulation to the site of MGD, which is the site of the disease. Preferably, the formulation is applied to the subject's eyelid, followed by the application of an effective amount of irradiation, preferably near-infrared (NIR) light. The NIR can be provided by an NIR light source device including a probe capable of emitting an NIR laser beam; i.e., a portable probe connected to the light source, for example, an 808 nm light source can be used in the disclosed method. The probe is aligned with the formulation to perform the treatment. In some forms, the light source is a fixed instrument in a clinic. In some forms, the light source is a portable device, such as a handheld LED Infrared Light Therapy Pen®. In some forms, the treatment distance is approximately 3-4 cm. In some forms, the treatment duration is approximately 5 minutes to approximately 60 minutes, 1 to 5 times daily, for approximately 1 to 10 days, such as 2, 3, 4, 5, 6, 7, 8, 9, or 10 days, preferably approximately 3 to approximately 5 days. In some forms, the treatment lasts from approximately 10 to 40 minutes, 1 to 3 times daily for 3 days. In some forms, the treatment current is fixed at approximately 300 mA to achieve the desired treatment temperature of approximately 41.3°C.

[0036] The present invention has the following beneficial effects:

[0037] (1) Highly effective treatment for MGD: The photosensitive particles generate local thermal effects and reactive oxygen species under near-infrared light irradiation, which can effectively melt and solidify meibomian glands, unblock meibomian gland blockage, improve the quality of meibomian gland secretion, and significantly reduce meibomian gland function scores.

[0038] (2) Improve tear film stability: After treatment, tear secretion can be increased (Schirmer I test results are significantly improved) and corneal epithelial defects can be reduced (corneal fluorescein staining score is reduced), thereby relieving dry eye symptoms.

[0039] (3) High safety: In the mouse model, no obvious burns or irritation were observed in the eyelid skin, cornea and conjunctiva after treatment. The temperature can be precisely controlled at around 41.3℃ by current to avoid thermal damage.

[0040] (4) Simple and non-invasive operation: The eye ointment is applied locally and combined with a handheld or portable radiation source (such as an LED infrared pen). Patients can use it in the home environment without anesthesia or complicated equipment.

[0041] (5) Cost-effective: Compared with expensive equipment such as LipiFlow® and intense pulsed light, the composition and radiation device of the present invention have lower costs and are easier to promote.

[0042] (6) Potential for combined treatment: The composition can be enhanced with anti-inflammatory agents or by using carriers such as hydrogels to enhance anti-inflammatory and antibacterial effects, and is suitable for a variety of ocular surface diseases.

[0043] (7) Diverse mechanisms: In addition to photothermal melting of eyelid esters, the generated reactive oxygen species can also control microbial growth, reduce oxidative stress, and comprehensively improve the pathological state of MGD.

[0044] Further advantages of the disclosed methods and compositions will be set forth in part in the description which follows, and in part will be understood from the description, or may be learned by practice of the disclosed methods and compositions. The advantages of the disclosed methods and compositions will be realized and obtained by means of the elements and combinations particularly pointed out in the appended claims. It should be understood that the foregoing general description and the following detailed description are merely exemplary and explanatory, and do not limit the claimed invention. Attached Figure Description

[0045] The embodiments of the present invention will now be described in detail with reference to the accompanying drawings, wherein:

[0046] Figure 1 This is a schematic diagram illustrating the concept of treating MGD by applying heat to melt solidified lipids in the meibomian glands using NIR-responsive microparticles;

[0047] Figure 2 This shows solidified, granular meibomian gland secretions observed when the meibomian glands are compressed;

[0048] Figure 3 The current-temperature curve of the eyelid under NIR irradiation is shown.

[0049] Figure 4 This demonstrates an assessment of meibomian tissue quality after pressure.

[0050] Figure 5 Intergroup comparisons of meibomian gland function scores were shown (*p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001).

[0051] Figure 6 Showing intergroup comparisons of Schirmer I test results (*p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001).

[0052] Figure 7 Intergroup comparisons of corneal fluorescein staining scores are shown (*p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001). Detailed Implementation

[0053] The disclosed methods and compositions can be more readily understood by referring to the following detailed description of specific embodiments and examples included therein, as well as the accompanying drawings and the description preceding and following them.

[0054] It should be understood that, unless otherwise stated, the disclosed methods and compositions are not limited to specific synthetic methods, specific analytical techniques, or specific reagents, and therefore can be varied. It should also be understood that the terminology used herein is for the purpose of describing particular embodiments only and not for limitation.

[0055] A. Definition

[0056] Unless otherwise stated herein, the description of numerical ranges herein is intended only as a shorthand for individually referring to each individual value falling within the range, and each individual value is included in the specification as if it were described separately herein.

[0057] The term "about" is used to describe values ​​that are approximately + / - 10% above or below the stated value; in other embodiments, the value may vary within approximately + / - 5% above or below the stated value; in other embodiments, the value may vary within approximately + / - 2% above or below the stated value; in other embodiments, the value may vary within approximately + / - 1% above or below the stated value. The foregoing ranges are intended to be clear from the context and do not imply further limitations.

[0058] As used herein, “active agent” refers to a physiologically or pharmacologically active substance that acts locally and / or systemically in the body. An active agent is a substance given to a patient for the treatment (e.g., a therapeutic agent), prevention (e.g., a preventative agent), or diagnosis (e.g., a diagnostic agent) of a disease or disorder. As used herein, “ophthalmic medication” or “ophthalmic active agent” refers to an agent administered to a patient to relieve, delay, or prevent one or more symptoms of an eye disease or disorder, or a diagnostic agent used for eye imaging or other assessment.

[0059] "Effective amount," when referring to active agents such as self-assembled peptides or biomolecules, pharmaceuticals, etc., means the amount necessary to elicit a desired biological response. As understood by those skilled in the art, the effective amount of a pharmaceutical agent can vary depending on factors such as the desired biological endpoint, the drug to be delivered, the nature of the delivery site, and the nature of the application conditions. For example, the effective amount of a composition for treating a disease or disorder may be an amount sufficient to promote recovery to a greater extent than in the absence of the composition.

[0060] "Prevention" refers to the prevention of the worsening of a condition, state, disease, symptom, or manifestation thereof, or the severity thereof. Prevention includes reducing the risk of a condition, state, or disease, or its symptoms or manifestations, or the worsening of its severity.

[0061] The term "treatment" refers to the reduction or improvement of the progression, severity, and / or duration of one or more symptoms of an injury, disease, or disorder; the delay of the onset of the disease or disorder; or the improvement of one or more consequences, indications, or symptoms (preferably one or more identifiable symptoms) of the injury, disease, or disorder, produced by the administration of one or more therapies (e.g., one or more therapeutic agents, such as the compounds described). The term "treatment" also includes reducing the risk of developing a disease or disorder, and delaying or inhibiting the recurrence of a disease or disorder.

[0062] The terms “increase,” “enhance,” “stimulate,” and / or “induce” (and similar terms) generally refer to actions that directly or indirectly improve or increase function or behavior relative to natural, expected, or average conditions or relative to current conditions. For example, substances that increase, stimulate, induce, or enhance anti-inflammatory effects may induce the production and / or secretion of anti-inflammatory cytokines, and / or the infiltration of immune cells such as Treg or Th17 cells that mediate anti-inflammatory responses.

[0063] The terms “subject” or “individual” include humans, mammals (such as cats, dogs, horses, etc.), and other living species that require treatment for inflammatory and / or autoimmune conditions / diseases.

[0064] The terms "carrier" or "excipient" refer to an inactive, organic or inorganic, natural or synthetic ingredient in a formulation, in combination with one or more active ingredients. In some embodiments, the carrier or excipient is an inert substance added to a pharmaceutical composition to further facilitate the administration of the compound, and / or does not cause significant irritation to the organism and does not eliminate the biological activity and properties of the administered compound.

[0065] B. Composition

[0066] This document discloses an ophthalmic composition comprising one or more photosensitive particles that are capable of generating heat and / or reactive oxygen species (ROS) upon exposure to radiation; and optionally a pharmaceutically acceptable ophthalmic carrier, wherein the ophthalmic composition is suitable for application to the eyelid.

[0067] 1. Photosensitive particles

[0068] This document discloses a composition comprising photosensitive particles, such as, but not limited to, microparticles, nanoparticles, or combinations thereof.

[0069] In some forms, the photosensitive particles are micron-sized particles. In some forms, the photosensitive particles are made of graphene. In some forms, the micron-sized particles are made of graphene-related materials (e.g., graphene oxide, carbon microtubes, polydopamine-coated carbon micron-sized particles, carbon microgels), metal and metal oxide materials (e.g., copper sulfide micron-sized particles, iron oxide micron-sized particles), polypyrrole nanogels, transition metal dichalcogenides (e.g., molybdenum disulfide MoS2, tungsten diselenide WSe2). In some forms, the photosensitive particles include, but are not limited to, metal-based nanoparticles, such as gold nanoparticles, silver nanoparticles, iron oxide nanoparticles; carbon-based nanostructures, such as carbon nanotubes, graphene derivatives, and fullerenes; semiconductor materials, such as titanium dioxide, metal oxide semiconductors, and quantum dots; organic and polymer materials, such as indocyanine green, porphyrin derivatives, polymer nanoparticles, and photosensitive microspheres and microcapsules.

[0070] Graphene is a carbon allotrope, a single layer of carbon atoms arranged in a hexagonal honeycomb lattice, making it a two-dimensional material with high electrical conductivity, incredible strength, flexibility, and extreme lightness. Graphene originates from graphite, consisting of multiple layers stacked together. In some forms, graphene exists as micrometer-scale sheets. In other forms, graphene exists as fullerenes.

[0071] In some forms, the photosensitive particles in the composition have sizes of about 1 nm-1000 μm, 10 nm-500 μm, 50 nm-250 μm, 100 nm-150 μm, 200 nm-100 μm, 500 nm-50 μm or 1 μm-25 μm.

[0072] In some formulations, the photosensitizing particles are present in the composition at concentrations of about 0.001 μg / mg to 5.0 μg / mg, 0.005 μg / mg to 2.5 μg / mg, 0.01 μg / mg to 1.0 μg / mg, 0.015 μg / mg to 0.95 μg / mg, 0.02 μg / mg to 0.9 μg / mg, 0.03 μg / mg to 0.8 μg / mg, 0.04 μg / mg to 0.7 μg / mg, 0.05 μg / mg to 0.6 μg / mg, 0.06 μg / mg to 0.5 μg / mg, 0.07 μg / mg to 0.4 μg / mg, 0.08 μg / mg to 0.3 μg / mg, or 0.09 μg / mg to 0.2 μg / mg. In some formulations, the photosensitizing particles are present at a concentration of 0.1 μg / mg.

[0073] The photosensitive particles disclosed herein contribute to the generation of heat and / or reactive oxygen species (ROS) upon exposure to radiation, particularly near-infrared (NIR) light. The photothermal response of these particles facilitates the melting of solidified meibomian glands, alleviating meibomian gland obstruction and improving tear film stability. In some forms, these particles are dispersed in pharmaceutically acceptable carriers to promote uniform distribution and sustained retention at the treatment site.

[0074] In some forms, the photosensitive particles disclosed herein contribute to the generation of heat and / or reactive oxygen species (ROS) when exposed to radiation, and are photoactive heterojunction materials.

[0075] Photoactive heterojunction materials are known in the art and include, but are not limited to, materials containing titanium dioxide (TiO2), copper (Cu), and zinc oxide (ZnO). Heterojunction photocatalysts / photoactive heterojunction materials and their preparation methods are known in the art (reviewed in Mutalik et al. Nanomaterials, Vol. 10(6):643 (2020), doi:10.3390 / nano10040643 and Zhou et al., ACS Appl. Bio. Mater., Vol. 4, pages3909-3936 (2021) and Low, et al., (2017). Heterojunction photocatalysts. Advanced materials, 29(20), 1601694). Generally, a heterojunction is defined as the interface between two different semiconductors with unequal band structures, which can lead to band alignment. Typically, there are three types of conventional heterojunction photocatalysts: heterojunction photocatalysts with spanned gaps (Type I), heterojunction photocatalysts with staggered gaps (Type II), and heterojunction photocatalysts with fractured gaps (Type III) (see Low, et al., (2017). Heterojunction photocatalysts. Advanced materials, 29(20), 1601694). Figure 3 ).

[0076] Exemplary combinations of photoactive heterojunction materials include, but are not limited to, graphene oxide / copper ferrite nanoparticles (GO / CFN), silver-titanium oxide (Ag-TiO2), TiO2 / AgVO3, Ag / TiO2 / cellulose, alginate / Au-TiO2, lithium titanate in a low-density polyethylene matrix (Li-TiO2 / LDPE), Cu-TiO2, TiO2 / -Fe2O3, Bi-doped TiO2 (Bi-TiO2) and TiO2 co-doped with urea and Bi (urea, Bi-TiO2; U, Bi-TiO2), chitosan films containing melamine / TiO2 (CTS / MTiO2), TiO2 nanoparticles and graphene sheets (TiO2 / GSs), graphene oxide and cuprous oxide (rGO-Cu2O), and zinc oxide-selenium oxide (ZnO-Se). The amount of photoactive material that can be incorporated into the hydrogel is from about 50 µg to about 250 µg, preferably from about 80 µg to about 200 µg.

[0077] In a preferred embodiment, the photoactive heterojunction material is formed from graphene oxide (GO) and copper ferrite nanoparticles (CFN). The bio-heterojunction material of copper ferrite nanoparticles (CFN) and graphene oxide (GO) can disrupt pathogenic bacteria through a synergistic strategy of photothermal desorption (PDT) and photothermal ionization (PTT). Accompanied by multivalent copper (Cu) and iron (Fe), copper ferrite nanoparticles (CFN, CuFe2O4) exhibit excellent NIR absorption, contributing to photothermal effects and Fenton(-like) reactivity. GO, as a two-dimensional biocompatible material, provides binding sites for CFN to form a heterojunction interface. After hybridization into a GO / CFN bio-heterojunction, the heterojunction interface between GO and CFN can generate singlet oxygen upon NIR exposure. 1 O2) kills pathogens through PDT. At the same time, the released copper ions can promote corneal epithelial regeneration and accelerate the wound healing process.

[0078] Methods for manufacturing photoactive heterojunction materials are known. For example, heterojunction materials formed from graphene oxide (GO) and copper ferrite nanoparticles (CFN) (GO / CFN) can be synthesized via a hydrothermal reaction. As described in the non-limiting examples, a desired amount of GO nanosheets is dissolved in ethylene glycol. Then, a certain amount of ferric chloride hexahydrate, copper chloride dihydrate, sodium acetate, and polyvinylpyrrolidone are added to the GO-ethylene glycol solution. The mixture is then sonicated and transferred to a Teflon autoclave. The hydrothermal reaction is maintained at a suitable temperature for a predetermined time, for example, 180°C for 24 hours. Finally, the GO / CFN heterojunction powder is collected, washed with ethanol and deionized water (DI), and dried.

[0079] The bioactivity of the antibacterial hydrogel composition containing photoactive heterojunction materials depends on the photocatalytic principle.

[0080] Photocatalysis is primarily a process in which electrons generated by a photosensitizer (PS) are photoexcited, and the excited state subsequently undergoes a redox reaction with reactants (reviewed in Zhou et al., ACS Appl. Bio. Mater., Vol. 4, pages 3909-3936 (2021)). Photocatalytic antibacterial processes involve reactions between bacteria and reactive oxygen species (ROS). As intermediates, ROS mainly originate from the incomplete reduction reactions between photoexcited electrons / holes and oxygen (O2) or water during photocatalytic reactions, exhibiting high activity (Jia, et al. Rejuvenated Photodynamic Therapy for Bacterial Infections. Adv. Healthcare Mater. 2019, 8, 1900608; Wang, Y. et al. Construction of nanomaterials with targeting phototherapy properties to inhibit resistant bacteria and biofilm infections. Chem. Eng. J. 2019, 358, 74−90). ROS mainly include singlet oxygen (…). 1O2), superoxide anion (•O2), hydroxyl radical (•OH), etc. (Wang, L et al. Using porous magnetic iron oxide nanomaterials as a facile photoporation nanoplatform for macromolecular delivery. J. Mater. Chem. B 2018, 6, 4427−4436). For example, in an embodiment incorporating the metal oxide TiO2, when the light energy is higher than the band gap of TiO2, electrons can jump from the valence band (VB) to the conduction band (CB), forming electron-hole pairs (Mao, et al. Repeatable photodynamic therapy with triggered signaling pathways of fibroblast cell proliferation and differentiation to promote bacteria-accompanied wound healing. ACS Nano2018, 12, 1747−1759). Holes can interact with OH- or H2O to produce •OH. •OH is a highly reactive substance that can indiscriminately oxidize a variety of organic substances. Photogenerated electrons can also interact with O2 to generate other reactive oxygen species (ROS) such as O2. These reactive oxygen species can also participate in redox reactions. The reaction process is illustrated by the following equation:

[0081]

[0082] Therefore, photocatalytic therapy relies on a photosensitizing reaction that accompanies subsequent biological effects. The process involves laser radiation of a specific wavelength exciting a photosensitizer (PS) at the site of bacterial infection, and the resulting photogenerated electrons or holes react with surrounding oxygen or water to produce highly reactive oxygen free radicals (Sun, J. et al. Synergistic photodynamic and photothermal antibacterial nanocomposite membrane triggered by single NIRlight source. ACS Appl. Mater. Interfaces 2019, 11, 26581−26589).

[0083] 2. Carrier

[0084] In some forms, the disclosed compositions also include a carrier. Any suitable carrier for delivering lipophilic materials can be used. In some forms, the carrier is oil-based.

[0085] In some forms, the lipophilic or oil-based material includes lanolin and / or petrolatum. In some forms, the lipophilic or oil-based material includes, but is not limited to, mineral oil, vegetable oil, wax, silicone oil, castor oil, olive oil, coconut oil, jojoba oil, shea butter, cocoa butter, or synthetic esters.

[0086] In some forms, the carrier includes liposomes, liposome-like nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, absorbed lipid-polymer hybrid nanoparticles, encapsulated lipid-polymer hybrid nanoparticles, exosomes, natural lipoproteins, and synthetic lipoproteins.

[0087] The selection of pharmaceutically acceptable ophthalmic carriers is important to ensure effective delivery, stability, and patient comfort. The carrier acts as a medium in which active photosensitive particles (such as graphene) are dispersed, facilitating their application to the eyelids and their subsequent therapeutic effects during irradiation.

[0088] A suitable ophthalmic carrier should be non-toxic and well-tolerated by ocular tissues to prevent irritation or adverse reactions. It should maintain the stability of the active ingredient, preventing degradation or aggregation over time. The carrier's viscosity should facilitate application while ensuring sufficient residence time on the ocular surface. For photothermal therapy, the carrier should not obstruct or absorb the therapeutic light wavelength to ensure effective activation of the photosensitizing particles.

[0089] In some forms, the carrier material is a hydrogel configured for the delivery of lipophilic active agents. Hydrogels can be used as lipophilic carriers by incorporating lipid nanoparticles (LNPs) or nanostructured lipid carriers (NLCs) into a hydrogel matrix, allowing for controlled and enhanced delivery of lipophilic drugs. LNPs and NLCs, being lipid-based nanoparticles, can effectively encapsulate lipophilic drugs, improving their solubility and stability. By embedding LNPs / NLCs within a hydrogel matrix, a dual delivery system is created. The hydrogel provides a biocompatible and tunable matrix for controlled drug release, while LNPs / NLCs enhance the encapsulation and delivery of lipophilic drugs. Various hydrogel polymers, such as alginates and chitosans, and lipid nanoparticles, such as NLCs and liposomes, are used in these composite systems.

[0090] Hydrogels are three-dimensional (3D) cross-linked polymer networks that can absorb and retain large amounts of water. A hydrogel is a three-dimensional (3D) network of hydrophilic polymers that can swell and retain large amounts of water while maintaining its structure due to the chemical or physical cross-linking of individual polymer chains. Hydrogels are primarily formed from biopolymers and / or polyelectrolytes. Hydrogels that can be used in the disclosed compositions can be prepared using any polymeric material suitable for ocular application.

[0091] Materials used to prepare hydrogels are known in the art, including, for example, polymers having quaternary ammonium functional groups, natural peptides such as collagen, gelatin, polysaccharides such as starch, alginate and agarose, phosphate-derived and sulfonate-derived polymers, phenol-derived and benzoic acid-derived polymers, and polyelectrolyte multilayers (Ahmed, J Adv Res. 2015 Mar; 6(2): 105–121; Pierau and Versace, Materials (Basel), 14(4): 787(2021)). Other examples include covalently cross-linked hyaluronic acid, and the hyaluronic acid can be modified or unmodified. Unmodified hyaluronic acid can be covalently cross-linked by a variety of methods, including using 1,4-butanediol diglycidyl ether (BDDE), divinyl sulfone, and dihydrazide. Hyaluronic acid can be modified to change the charge of the molecule, alter its biological activity, or include groups that can be used for cross-linking purposes. Thiolized hyaluronic acid or thiolated carboxymethyl hyaluronic acid is particularly useful. Modified hyaluronic acid can be crosslinked with external molecules for crosslinking, or without external crosslinking agents. For crosslinking thiolized HA or CMHA, molecules with thiol-reactive sites, such as acrylates, methacrylates, haloacetic esters, haloacetamides, or maleimides, can be used as external crosslinking agents; examples include poly(ethylene glycol) diacrylates and poly(ethylene glycol) dibromoacetate. For crosslinking without external crosslinking agents, thiolized HA or CMHA can be crosslinked via disulfide crosslinking through an oxidative process. Such disulfide crosslinking can be assisted by using oxidants such as sodium hypochlorite or peroxides.

[0092] When modified HA is crosslinked through modification (e.g., crosslinking of thiolized HA with disulfides), the level of modification can be adjusted to control the amount of crosslinking in the hydrogel, such that higher levels of modification result in more crosslinking. Thiolized HA or thiolized CMHA is particularly useful for formulating the hydrogels of this invention, wherein the thiol modification is about 0.05 to about 1.0 μmol of thiol per milligram of HA or CMHA. Modification levels within this range are particularly suitable for forming crosslinked hydrogels with desired shear-thinning properties and viscosity.

[0093] In a preferred embodiment, the polymer used to form the hydrogel matrix is ​​polyε-lysine (PεK), resulting in an inherent antimicrobial activity in the hydrogel. Polyε-lysine (pεK) is a cationic peptide with inherent antimicrobial properties and broad-spectrum antimicrobial activity, resisting Gram-positive and Gram-negative bacteria, yeasts, and fungi. ε-polylysine is a natural polymeric material for forming hydrogels, obtained through microbial fermentation. The molecular weight of ε-polylysine is 3 kDa to 5 kDa. An ε-polylysine hydrogel has the following structural units:

[0094]

[0095] Where n is any natural number from 20 to 30. ε-polylysine is available from BOC Sciences, catalog number: B0001-011213, CAS number: 28211-04-3. The method used to prepare PεK hydrogels is known in the art (Aveyard et al. ACS Appl Mater Interfaces 2019;11(41):37491-50).

[0096] Hydrogels can be hydrogels with intrinsic antibacterial activity, such as Fmoc-diphenylalanine and short peptides with Fmoc-terminated groups rich in lysine or pyridinium (which have been found to have moderate antibacterial activity against Gram-positive and Gram-negative bacteria); self-assembled hydrogels formed based on diphenylalanine peptide mimics of anthranilamide; and hydrogels prepared by self-assembly of amino acid-based cationic peptide mimics with naphthyl anthranilamide (NaA) terminology (reviewed in Aldilla, et al., Scientific Reports volume 12, Article number: 22259(2022)).

[0097] For example, McCloskey et al. disclosed Fmoc-peptides (FmocFF(a), FmocFFKK(b), Fmoc-FFFKK(c), and FmoCFFOO(d), as shown below) that form surfactant-like soft gels at a concentration of 1% by weight / volume (McCloskey, AP, Draper, ER, Gilmore, BF & Laverty, G. Ultrashortself-assembling Fmoc-peptide gelators for anti-infective biomaterial applications. J. Pept. Sci. 23, 131–140 (2017)). Other exemplary peptides are disclosed in Debnath, et al., Phys. Chem. B 2010, 114, 13, 4407–4415.

[0098]

[0099] Liposomes are artificial "fat vesicles," characterized by having one or more bilayers, spontaneously obtained by dispersing natural or synthetic amphiphilic lipids in water. Liposomes are spherical vesicles comprising one or more phospholipid bilayers surrounding an aqueous core from which selected drugs can be encapsulated. They are made of materials having polar head (hydrophilic) groups and nonpolar tail (hydrophobic) groups. The interaction between these groups induces vesicle formation. (Pharmaceutics 13, 206 (2021)) https: / / doi.org / 10.3390 / pharmaceutics 13020206 .

[0100] Nanostructured lipid carriers (NLCs) are nanoscale colloidal drug delivery systems whose cores contain a mixture of solid and liquid lipids. Compared to polymer or metal nanoparticles, this lipid-based nanosystem is a biocompatible, non-toxic, and safe nanomedicine delivery system. As the name suggests, NLCs are nanoscale multi-particle systems with sizes ranging from 50 nm to 500 nm. The particle size distribution of NLCs depends on the manufacturing method and composition of the nanoparticles. These colloidal particles are structurally similar to SLNs, with the main difference being in the core of these nanoparticles. Unlike SLNs, which contain a solid lipid core arranged in a highly organized manner, NLCs contain a lipid liquid and a solid lipid core that forms an unorganized drug matrix. Due to this unorganized nature, not only can more drug be loaded into the core, but NLCs also overcome the stability problems encountered by SLNs during long-term storage due to crystallization and drug expulsion (reviewed in Khan, et al., Adv Pharm Bull. 2022 Sep 18;13(3):446–460).

[0101] Lipid-polymer hybrid nanoparticles (LPHNPs) are next-generation core-shell nanostructures, conceptually derived from liposomes and polymer nanoparticles (NPs), where the polymer core is still encapsulated by a lipid layer. As their name suggests, LPHNPs combine features of polymer NPs and liposomes. They consist of three structural units: 1) a polymer core encapsulating the drug, 2) a lipid monolayer surrounding the polymer core, and 3) an outer lipid-PEG layer, which acts as a steric stabilizer to prolong LPHNP circulation by evading immune destruction. The intermediate lipid monolayer acts as a molecular barrier, mitigating drug loss during LPHNP formulation and protecting the core from degradation by preventing water diffusion into it. A review of LPHNPs and their preparation methods is available in Mukherjee, et al., Int J Nanomedicine. 19;14:1937-1952.

[0102] 3. Combination therapy

[0103] In some forms, the ophthalmic compositions disclosed herein may be combined with one or more anti-inflammatory agents.

[0104] In some forms, ophthalmic compositions may be combined with one or more of corticosteroids, cyclosporine, and azithromycin.

[0105] Topical corticosteroids, such as dexamethasone, are effective in reducing inflammation on the ocular surface. Short-term use can relieve symptoms. Cyclosporine is an immunomodulator that reduces inflammation by inhibiting T-cell activation. Preparations like 0.05% cyclosporine have been used to improve tear secretion in dry eye and reduce inflammatory markers. In addition to its antimicrobial properties, azithromycin also exhibits anti-inflammatory effects by reducing pro-inflammatory cytokines and matrix metalloproteinases. Topical application has shown efficacy in improving meibomian gland function and reducing associated symptoms.

[0106] By addressing glandular congestion and ocular surface inflammation, combining the disclosed ocular composition with an anti-inflammatory agent enhances the treatment of conditions such as meibomian gland dysfunction (MGD). This dual approach facilitates the clearance of meibomian gland congestion and reduces the inflammatory processes that contribute to ocular conditions such as MGD pathology.

[0107] 4. Pharmaceutical preparations

[0108] The disclosed compositions can be formulated into various dosage forms suitable for ocular or eyelid application, including but not limited to ocular gels, ocular patches, soluble or bioadhesive ocular films, ocular wound bandages, or lipid-based ointments. In some forms, the formulation can be formulated as a sustained-release form, which allows for gradual diffusion of the active ingredient over an extended period of time.

[0109] eye gel

[0110] In some forms, the disclosed compositions are in the form of ophthalmic gels. Ophthalmic gels are semi-solid systems that prolong contact time with the ocular surface, improving the bioavailability of the drug. Their viscosity reduces the drainage rate, allowing for sustained release of the active ingredient. In some forms, polymers such as chitosan and xyloglucan are used to formulate these gels due to their biocompatibility and mucosal adhesion properties.

[0111] eye patches

[0112] In some forms, the disclosed compositions are in the form of ophthalmic patches. Ophthalmic patches are designed to adhere to the surface of the eye or eyelid, providing controlled and sustained release of a therapeutic agent. These patches may be manufactured using biodegradable polymers, ensuring prolonged residence time and gradual drug release. The design of ophthalmic patches takes into account factors such as permeability, adhesion, and patient comfort to ensure efficacy and compliance.

[0113] Soluble or bioadhesive ophthalmic films

[0114] In some forms, the disclosed compositions are in the form of soluble or bioadhesive ophthalmic films. These films are placed on the surface of the eye, where they dissolve or adhere to release the active ingredient over time. Materials such as hydroxypropyl pea starch can be used to manufacture films for ophthalmic drug delivery, offering potential as carriers for drugs like azelastine hydrochloride. Such films provide sustained release and are designed to minimize discomfort and visual disturbance.

[0115] Eye wound bandage

[0116] In some forms, the disclosed compositions are in the form of ophthalmic wound bandages. Ophthalmic wound bandages, as protective coverings, can deliver therapeutic agents while promoting healing. Incorporating ophthalmic compositions into biodegradable bandages can provide local treatment, maintaining the necessary concentration of active ingredients at the site of action. Materials such as polyethylene glycol (PEG)-based hydrogels have been explored due to their adhesive properties and ability to form stable biocompatible barriers. A review of pharmaceutical ophthalmic bandages is available in (Zidan, et al., . Pharm Dev Technol, 23(3):255-260 (2017)).

[0117] lipid-based ointments

[0118] In some forms, the disclosed compositions are in the form of lipid-based ointments. Lipid-based ointments provide a prolonged residence time on the ocular surface due to their viscosity, thereby improving the bioavailability of the drug. A common choice for the ointment base is white petrolatum, known for its suitable melting point, which results in reduced viscosity after administration.

[0119] atomized or sprayed formulations

[0120] In some forms, the composition can be formulated as an aerosol or fine mist to enhance distribution on the ocular surface, achieving uniform absorption and maximum therapeutic effect.

[0121] C. Usage Method

[0122] Methods for treating an eye disease, eye disorder, or eye condition in a subject are provided. The disclosed method includes administering a therapeutically effective amount of the disclosed composition to a subject in need. The method includes contacting the eye of the subject in need with an effective amount of the disclosed composition.

[0123] The method involves contacting a composition in the eye of a subject with radiation of a wavelength of 380-1200 nm. In some forms, the wavelength of the radiation is about 380 nm-1200 nm, 400 nm-1000 nm, 500 nm-900 nm, 550 nm-800 nm, 600 nm-750 nm, 1000 nm-1200 nm, 800 nm-1100 nm, or 900 nm-1000 nm. In some forms, the method involves contacting the composition in the eye of a subject with near-infrared radiation (NIR). In some forms, the radiation is emitted from a portable handheld device, such as a handheld LED. In some forms, the radiation source includes one or more of a handheld device, a fixed light transmission system, a wearable device, a light-emitting diode (LED) array, a laser system, a broadband light source, a filtered light source, an intense pulsed light (IPL) device, or any combination thereof.

[0124] In some forms, the radiation source is a fixed instrument in the clinic. In some forms, the treatment duration is approximately 1-20 minutes, 3-17 minutes, 5-15 minutes, 7-13 minutes, 8-12 minutes, 9-11 minutes, or 9-10 minutes, lasting 1 day, 1-2 days, 1-3 days, 1-4 days, 1-5 days, 1-6 days, or 1-7 days.

[0125] In some forms, light exposure to the target location causes heat generation. In some forms, the treatment temperature is maintained at 38°C, 39°C, 40°C, 41°C, 42°C, 43°C, 44°C, 45°C, or 46°C, preferably 41.3°C, which is sufficient to melt the solidified meibomian gland without causing damage to the eyelid or cornea.

[0126] The therapeutic effects disclosed in this article are attributed to the photothermal response of the photosensitive particles upon radiation exposure, which facilitates multiple key mechanisms. Local heat melts and solidifies the meibomian glands, restoring normal glandular function, while the increased temperature promotes glandular secretion and alleviates meibomian gland obstruction. Additionally, radiation generates reactive oxygen species (ROS), and the controlled high temperature helps reduce ocular surface inflammation by mitigating inflammatory mediators associated with meibomian gland degeneration (MGD). The photothermal process also improves meibomian quality by enhancing its consistency and fluidity, which is essential for tear film stability. Furthermore, the generation of heat and ROS contributes to microbial control, reducing bacterial overgrowth commonly associated with MGD, thus ensuring a comprehensive and effective treatment approach.

[0127] In some forms, treatment using the disclosed compositions described herein improved meibomian gland function, as shown in the Examples section, where meibomian gland function scores were lowered compared to the control group. In some forms, increased tear secretion was observed in the Schirmer I test, indicating improved ocular surface lubrication. Corneal fluorescein staining scores showed a significant reduction in corneal epithelial defects, indicating effective restoration of ocular surface integrity. No significant side effects, including burns or ocular irritation, were observed after treatment.

[0128] In some forms, Table 1 provides known treatments for MGD.

[0129] Table 1. Comparative Analysis of Known Treatment Methods for MGD

[0130]

[0131]

[0132] * $ < $100; $100 < $$ < $1000; $1000 < $$$ < $10000; $$$$ > $10000

[0133] 1. Disease / symptom awaiting treatment

[0134] In a preferred form, the formulation or composition described herein is applied to the eyelid of a subject to treat meibomian gland dysfunction (MGD).

[0135] MGD is a common ocular condition characterized by obstruction and dysfunction of the meibomian glands, leading to insufficient lipid secretion and evaporative dry eye. MGD causes tear film instability, ocular surface inflammation and discomfort, typically resulting in symptoms such as dryness, irritation, redness, blurred vision, and a foreign body sensation. The disclosed photothermal therapy effectively addresses these problems by restoring glandular function and improving lipid secretion, thereby enhancing tear film stability and overall ocular health.

[0136] In some forms, the formulations or compositions described herein can be used to treat other ocular surface conditions associated with meibomian gland dysfunction and lipid layer abnormalities, such as blepharitis, evaporative dry eye, and contact lens discomfort due to impaired tear film stability. In some forms, the antimicrobial effects of ROS generation and controlled-temperature thermodynamics can be used to control bacterial ocular infections, including anterior and posterior blepharitis. In some forms, the anti-inflammatory properties of the treatment are beneficial in reducing ocular surface inflammation associated with conditions such as allergic conjunctivitis and rosacea.

[0137] In some forms, the formulations or compositions described herein can also be used as adjunctive therapy for postoperative recovery, particularly for controlling inflammation and improving ocular surface healing after procedures such as laser eye surgery or cataract extraction.

[0138] 2. Route of administration

[0139] In some forms, methods of treating eye disorders include administering an effective amount of the disclosed composition to a subject. For example, a pharmaceutical composition comprising an effective amount of the disclosed composition and one or more therapeutic agents may be applied to the eyelids of a subject in need. Preferably, the composition is in a form suitable for direct application to the eyelids. In some forms, the composition is applied as a topical preparation.

[0140] In some forms, radiation of an appropriate wavelength is emitted from a portable or handheld probe connected to a lamp, and the doctor or patient simply needs to align the probe to administer the treatment, or the subject can use a handheld device at home. In some forms, the light source is a fixed instrument in a clinic. In some forms, the light source is a portable device, such as a handheld LED infrared lamp. In some forms, the distance during treatment is approximately 2 cm to approximately 8 cm, or approximately 3 cm to approximately 5 cm or 4 cm. In some forms, the treatment duration is approximately 1 minute to 20 minutes, 3 minutes to 17 minutes, 5 minutes to 15 minutes, 7 minutes to 13 minutes, 8 minutes to 12 minutes, 9 minutes to 11 minutes, or 9 minutes to 10 minutes, lasting for 1 day, 1-2 days, 1-3 days, 1-4 days, 1-5 days, 1-6 days, or 1-7 days.

[0141] In some forms, the radiation source is adjustable to control at least one of the following: radiation intensity, radiation wavelength, exposure duration, pulse frequency, or beam area.

[0142] 3. Effective dosage

[0143] The disclosed compositions can be administered therapeutically to the eye to obtain a therapeutic benefit, or preventively to obtain a preventive benefit, or both therapeutic and preventive benefits. A therapeutic benefit refers to treating an underlying disorder, including eradicating or improving one or more symptoms associated with the underlying disorder, resulting in a patient reporting an improvement in sensation or condition, although the patient may still have the underlying disorder. For example, administering the composition to a patient with a condition provides a therapeutic benefit when that patient reports a reduction in the severity or duration of symptoms associated with that condition. A therapeutic benefit also includes stopping or slowing the progression of the disease, regardless of whether the patient achieves improvement.

[0144] In a preferred embodiment, the disclosed composition is retained at the administration site (e.g., eyelid) for a sufficient time to produce a therapeutic effect.

[0145] It should be understood that, unless otherwise stated, the disclosed methods and formulations are not limited to specific synthetic methods, specific analytical techniques, or specific reagents, and therefore can be varied. It should also be understood that the terminology used herein is for the purpose of describing specific embodiments only and not for limitation.

[0146] In some formulations, the photosensitizing particles are present in the composition at concentrations of about 0.001 μg / mg to 5.0 μg / mg, 0.005 μg / mg to 2.5 μg / mg, 0.01 μg / mg to 1.0 μg / mg, 0.015 μg / mg to 0.95 μg / mg, 0.02 μg / mg to 0.9 μg / mg, 0.03 μg / mg to 0.8 μg / mg, 0.04 μg / mg to 0.7 μg / mg, 0.05 μg / mg to 0.6 μg / mg, 0.06 μg / mg to 0.5 μg / mg, 0.07 μg / mg to 0.4 μg / mg, 0.08 μg / mg to 0.3 μg / mg, or 0.09 μg / mg to 0.2 μg / mg. In some formulations, the photosensitizing particles are present at a concentration of 0.1 μg / mg.

[0147] Example

[0148] Example 1: Photosensitive microscale dispersible eye ointment for the treatment of meibomian gland dysfunction.

[0149] For the treatment of MGD, photothermal therapy was performed using a photosensitive microscale dispersion ointment, and its efficacy and safety were tested in a mouse model of MGD. Figure 1 As shown.

[0150] The MGD mouse model was established by feeding 10-week-old female ApoE knockout mice a high-fat diet for one month. When the meibomian glands of the mice were compressed, pathologically solidified meibomian secretions were observed (highlighted with a red circle). Figure 2 This indicates that the MGD mouse model has been successfully established.

[0151] The photosensitive microscale dispersion eye ointment is composed of graphene and excipients (lanolin + petrolatum), with a graphene concentration of 0.1 μg / mg. When treated with the graphene ointment under NIR irradiation at different currents, the eyelid temperature in mice showed a positive correlation with the current. Figure 3The treatment current was then fixed at 300 mA to achieve the expected treatment temperature of approximately 41.3°C for the graphene-near-infrared light group (G-NIR). Treatment of other experimental groups (excipient-near-infrared group (E-NIR) and near-infrared light group (NIR)) was also performed at this current for three days (10 minutes each day). Throughout the treatment, the temperature should be maintained within the optimal range to avoid overheating that could damage the eyelids or underheating that would reduce the therapeutic effect. In the disclosed photothermal therapy system, the treatment temperature can be adjusted by regulating the current to achieve the optimal range.

[0152] In a clinical setting, meibomian gland function, tear secretion function, and corneal epithelial defect healing associated with MGD are three important tests for assessing meibomian gland status. Therefore, these tests are used to evaluate the efficacy of the disclosed treatments. Meibomian gland function is assessed through qualitative and quantitative analysis of meibomian gland sebum. In cases of meibomian gland compression, the G-NIR and NC (normal control) groups exhibited clear and fluid meibomian gland sebum, while granular, solidified meibomian gland sebum was observed in the PC (positive control), E-NIR, and NIR groups. Figure 4 Quantitative analysis of meibomian gland function was based on the Meibomian Gland Function Scoring of Chinese expert consensus on meibomian gland dysfunction: definition and classification (2023), where a lower score represents better meibomian gland function. Three days after treatment, the G-NIR group showed a significant reduction in meibomian gland function score compared to the PC, E-NIR, and NIR groups. Figure 5 These results indicate that the disclosed photothermal therapy effectively improved meibomian gland function, while treatment with NIR alone or NIR + excipients did not show significant therapeutic effects. Furthermore, the better performance of the G-NIR group in the Schirmer I test compared to the PC, E-NIR, and NIR groups suggests improved tear secretion function. Figure 6 Corneal epithelial defect healing was scored according to the National Eye Institute / Industry (NEI) Grading Scale for Corneal Fluorescein Staining, where a lower score represents less corneal epithelial defect, indicating better meibomian gland status. The corneal fluorescein staining score of the G-NIR group was significantly lower than that of the PC, E-NIR, and NIR groups. Figure 7These results confirm the efficacy of the disclosed treatment for MGD, consistent with other findings. Furthermore, no significant burns were observed on the eyelid skin, cornea, or conjunctiva of mice after photothermal therapy, confirming its safety. Figure 4 ).also, Figure 4 It was also shown that the melting of meibomian lipids can be demonstrated by observing the lipids at the orifice after extrusion.

[0153] All these results demonstrate that the disclosed photosensitive microscale dispersible ointment can alleviate meibomian gland obstruction and improve meibomian gland function. It has the potential to be used in clinical settings as an effective, economical, safe, and user-friendly treatment for MGD.

[0154] It should be understood that the disclosed methods and compositions are not limited to the specific methods, schemes, and reagents described, as they can vary. It should also be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of the invention, which is defined only by the appended claims.

[0155] Those skilled in the art will recognize or be able to use conventional experiments to determine many equivalents of specific embodiments of the methods and compositions described herein. Such equivalents are intended to be included in the claims of this invention.

Claims

1. An ophthalmic composition comprising: (i) one or more photosensitive particles that, when exposed to radiation, can generate heat and / or reactive oxygen species; and (ii) Any pharmaceutically acceptable ophthalmic carrier may be selected. The ophthalmic composition is suitable for application to the eyelids.

2. The ophthalmic composition according to claim 1, wherein the photosensitive particles are micron-sized particles, nano-sized particles, or a combination thereof; Preferably, the photosensitive particles are made of one or more metals selected from gold, silver and iron oxide; Preferably, the photosensitive particles are carbon-based nanostructures, and the carbon-based nanostructures are made of one or more materials selected from graphene, graphene derivatives, fullerenes, or semiconductor materials; Preferably, the photosensitive particles comprise one or more photoactive heterojunction materials, and the photoactive heterojunction material is selected from one or more of the following: graphene oxide / copper ferrite nanoparticles (GO / CFN), silver-titanium oxide (Ag-TiO2), TiO2 / AgVO3, Ag / TiO2 / cellulose, alginate / Au-TiO2, lithium titanate in a low-density polyethylene matrix (Li-TiO2 / LDPE), Cu-TiO2, TiO2 / -Fe2O3, Bi-doped TiO2 (Bi-TiO2), and TiO2 co-doped with urea and Bi (urea, Bi-TiO2; U, Bi-TiO2), chitosan film containing melamine / TiO2 (CTS / MTiO2), TiO2 nanoparticles and graphene sheets (TiO2 / GSs), graphene oxide and cuprous oxide (rGO-Cu2O), and zinc oxide-selenium oxide (ZnO-Se). Preferably, the photoactive heterojunction material comprises GO / CFN and / or exhibits strong absorbance at 808 nm.

3. The ophthalmic composition according to claim 1, wherein the photosensitive particles comprise graphene at concentrations of about 0.001 μg / mg-5.0 μg / mg, 0.005 μg / mg-2.5 μg / mg, 0.01 μg / mg-1.0 μg / mg, 0.015 μg / mg-0.95 μg / mg, 0.02 μg / mg-0.9 μg / mg, 0.03 μg / mg-0.8 μg / mg, 0.04 μg / mg-0.7 μg / mg, 0.05 μg / mg-0.6 μg / mg, 0.06 μg / mg-0.5 μg / mg, 0.07 μg / mg-0.4 μg / mg, 0.08 μg / mg-0.3 μg / mg, or 0.09 μg / mg-0.2 μg / mg.

4. The ophthalmic composition according to claim 1, wherein the pharmaceutically acceptable ophthalmic carrier is selected from one or more of liposomes, liposome-like nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, lipid-polymer hybrid nanoparticles, encapsulated lipid-polymer hybrid nanoparticles, and exosomes.

5. The ophthalmic composition according to claim 1, wherein the carrier is selected from lanolin, petrolatum, mineral oil, wax, silicone oil, castor oil, coconut oil, synthetic esters, hydrogels, or combinations thereof.

6. The ophthalmic composition according to claim 1, further comprising one or more anti-inflammatory agents.

7. A formulation comprising the ophthalmic composition of any one of claims 1-6, wherein the form is selected from ophthalmic gels, ophthalmic patches, soluble or bioadhesive ophthalmic films, ophthalmic wound bandages, atomized or fine mist formulations, or lipid-based ointments.

8. Use of the ophthalmic composition of any one of claims 1-6 or the formulation of claim 7 in the preparation of a medicament for treating an eye condition, wherein the treatment comprises bringing the eye of a subject into contact with the ophthalmic composition of any one of claims 1-6 or the formulation of claim 7 and exposing the ophthalmic composition or formulation to radiation.

9. The use according to claim 8, wherein the ocular condition is meibomian gland dysfunction.

10. The use according to claim 8, wherein the radiation source comprises one or more of a handheld device, a fixed optical transmission system, a wearable device, a light-emitting diode (LED) array, a laser system, a broadband light source, a filtered light source, and an intense pulsed light (IPL) device; Preferably, the radiation has a wavelength of approximately 380 nm-1200 nm, 400 nm-1000 nm, 500 nm-900 nm, 550 nm-800 nm, 600 nm-750 nm, 1000 nm-1200 nm, 800 nm-1100 nm, or 900 nm-1000 nm. More preferably, the radiation is near-infrared (NIR) radiation; Preferably, the radiation exposure to the ophthalmic composition or preparation on the eyelids is for about 1-20 minutes, 3-17 minutes, 5-15 minutes, 7-13 minutes, 8-12 minutes, 9-11 minutes, or 9-10 minutes, for 1 day, 1-2 days, 1-3 days, 1-4 days, 1-5 days, 1-6 days, or 1-7 days. Preferably, the ophthalmic composition or formulation in the eyelid is exposed to the radiation to generate heat and / or ROS at the eyelid. Preferably, the treatment causes one or more of the following: melting of solidified meibomian glands, relief of meibomian gland obstruction, reduction of ocular surface inflammation, improvement of meibomian gland quality, or control of microbial growth.

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