Ophthalmic formulations and methods of use

Abstract

Provided herein are methods and compositions for eye drops and medicaments. Thus, the eye drops and medicaments have the potential for providing and pioneering non-surgical treatment of ocular conditions.

Description

Background Technology

[0001] This invention relates generally to therapies, and more specifically to ocular therapies.

[0002] According to the International Agency for the Prevention of Blindness (https: / / www.iapb.org / knowledge / what-is-avoidable-blindness / cataract / ), the World Health Organization (WHO) estimates that nearly 18 million people worldwide are blind due to cataracts, accounting for almost half of all blindness cases globally. Cataracts remain a leading cause of blindness worldwide and a significant cause of vision impairment.

[0003] To date, the only available treatment for cataracts is surgical removal of the cloudy lens and replacement with a clear artificial lens. To the best of our knowledge, the FDA has not approved any non-surgical pharmacological agents (including eye drops) to prevent, stop, or cure cataracts.

[0004] This invention attempts to solve these problems, as well as others. Summary of the Invention

[0005] This article provides methods and compositions for ophthalmic pharmaceuticals. Therefore, ophthalmic pharmaceuticals have the potential to provide and pioneer non-surgical treatments for eye conditions and diseases.

[0006] The methods, systems, and compositions are set forth in part in the description which follows, and will be apparent in part from the description, or may be learned by practice of the methods, compositions, and systems. The advantages of the methods, apparatus, and systems will be realized and obtained by means of the elements and combinations particularly pointed out in the appended claims. It should be understood that both the foregoing general description and the following detailed description are exemplary and illustrative only, and do not limit the claimed methods, compositions, and systems.

[0007] Therefore, the object of this invention is to exclude any previously known products, manufacturing processes, or methods of using the product from this invention, thereby reserving the right to disclose any previously known products, processes, or methods herein. It should also be noted that this invention is not intended to include, within the scope of this invention, any products, processes, or methods of manufacturing or using the product that do not meet the written description and enablement requirements of the USPTO (35 U.S. SC § 112, paragraph 1) or EPO (Section 83 of the EPC), thereby reserving the right to disclose any previously described products, manufacturing processes, or methods of using the product herein. In the practice of this invention, compliance with EPC Section 53(c) and EPC Rules 28(b) and (c) may be advantageous. All rights to any embodiment of any patented subject matter of this application are expressly waived by the applicant in any prior filing of any application in the family of this application or any other family or any third party. Nothing herein shall be construed as an undertaking. Attached Figure Description

[0008] In the accompanying drawings, similar elements are identified by similar reference numerals in several preferred embodiments of the invention.

[0009] Figure 1 This is a graph showing the ages of patients using an ophthalmic preparation according to one embodiment.

[0010] Figure 2 This is a diagram illustrating the effective treatment period using an ophthalmic preparation according to one embodiment.

[0011] Figure 3 This is a diagram illustrating effective treatment according to age using an ophthalmic preparation according to one embodiment. Detailed Implementation

[0012] The foregoing and other features and advantages of the invention will be apparent from the following detailed description of exemplary embodiments, which are read in conjunction with the accompanying drawings. The detailed description and drawings are merely illustrative and not limiting of the invention, the scope of which is defined by the appended claims and their equivalents.

[0013] Embodiments of the invention will now be described with reference to the accompanying drawings, wherein similar figures consistently reflect similar elements. The terminology used in the description presented herein is not intended to be interpreted in any limited or restrictive manner, but merely as it is used in conjunction with the detailed description of certain specific embodiments of the invention. Furthermore, embodiments of the invention may include several novel features, none of which alone is responsible for its desired properties or is essential for practicing the invention described herein.

[0014] In the context of describing this invention, the terms “a” and “an” and “the” and similar pronouns should be interpreted as including both the singular and plural, unless otherwise stated herein or the context clearly contradicts them. It will be further understood that, when used, the terms “comprises,” “comprising,” “includes,” and / or “including” specify the presence of the stated features, integers, steps, operations, elements, and / or components, but do not exclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and / or groups thereof.

[0015] Unless otherwise stated herein, the listing of value ranges herein is intended only as a shorthand method of individually referring to each individual value falling within that range, and each individual value is incorporated into the specification as if it were listed separately herein. When accompanied by numerical values, the word “about” should be interpreted as indicating a deviation from the stated value of up to and including 10%. The use of any and all exemplary language (“e.g.” or “such as”) provided herein is intended only to better illustrate the invention and, unless otherwise required, does not constitute a limitation on the scope of the invention. No language in the specification should be construed as indicating any unstated element essential to the practice of the invention.

[0016] References to “one embodiment,” “implementation,” “exemplary embodiment,” “various embodiments,” etc., may indicate that one or more embodiments of the invention thus described may include a particular feature, structure, or characteristic, but not every embodiment must include that particular feature, structure, or characteristic. Furthermore, the repeated use of the phrase “in one embodiment” or “in an exemplary embodiment,” does not necessarily refer to the same embodiment, although they may.

[0017] As used herein, the term "method" means the manner, means, technique, and procedure for accomplishing a given task, including but not limited to those known to practitioners in the fields of chemistry, pharmacology, biology, biochemistry, and medicine, or readily developed from known methods, means, techniques, and procedures. Unless expressly stated otherwise, it is never intended to interpret any method or aspect set forth herein as requiring its steps to be performed in a specific order. Therefore, in cases where the steps are limited to a specific order in a method claim not specifically stated in the claims or description, the order is never intended to be inferred in any way. This applies to any possible unexpressed fundamental principles of interpretation, including logical matters relative to the arrangement of steps or the flow of operations, clear meaning derived from grammatical structure or punctuation, or the number or type of aspects described in the description.

[0018] Example

[0019] The following embodiments are provided to provide those skilled in the art with a complete disclosure and description of how to manufacture and evaluate the compounds, compositions, articles, devices, and / or methods claimed herein, and are intended to be purely exemplary of the invention and not to limit the scope of what the inventors believe their invention to be. However, based on this disclosure, those skilled in the art will understand that many changes can be made to the specific embodiments disclosed, and similar or analogous results can be obtained without departing from the spirit and scope of the invention.

[0020] Efforts have been made to ensure the accuracy of figures (e.g., quantities, temperatures, etc.), but some errors and deviations should be taken into account. Unless otherwise stated, parts are by weight, temperatures are in °C or at ambient temperature, and pressures are at or near atmospheric pressure.

[0021] definition

[0022] As used herein, the term "therapeutic effective concentration" means an amount that will inhibit the progression or formation of cataracts in the eye or inhibit the progression or formation of an ophthalmic disease. "Therapeutic effective concentration" means an amount sufficient to achieve the intended therapeutic and / or preventive effect, such as an amount resulting in prevention or reduction of symptoms associated with an ophthalmic disease. The amount of composition administered to a subject will depend on the type and severity of the disease and individual characteristics such as general health, age, sex, weight, and tolerance. This will also depend on the stage, severity, and type of the disease. Those skilled in the art can determine an appropriate dosage based on these and other factors. The composition may also be administered in combination with one or more other therapeutic compounds. In the methods described herein, a zinc compound and an antihistamine are administered to a subject having one or more signs or symptoms of an ophthalmic disease. For example, a "therapeutic effective amount" of the zinc compound and the antihistamine means a concentration that at least improves the physiological effects of the ophthalmic disease or condition.

[0023] The "therapeutic effective amount" of the zinc compound and antihistamine will depend on a variety of factors known to those skilled in the art. Such factors include, but are not limited to, eye size, the number and progression of any fully developed or developing cataracts already present in the eye, and the route of administration. The "therapeutic effective amount" will also depend on whether the pharmaceutical composition is administered once or periodically over a period of time. The period can be any number of days, weeks, months, or years. In one embodiment, the "therapeutic effective amount" of the zinc compound is to scavenge reactive oxygen species, reduce the total content and imbalance of soluble proteins, alleviate the co-expression of cross-linked glycation and glycation product receptors, and downregulate polyol pathway enzymes to delay cataract development, or clear protein ashes.

[0024] As used herein, the terms “therapy” or “treatment” or “relief” refer to therapeutic treatments and preventative methods or measures aimed at preventing a target disease state or ailment. It is intended to suppress (reduce). Upon receiving therapeutically effective amounts of zinc compounds and antihistamines according to the methods described herein, the subject exhibits a reduction or disappearance of one or more observable and / or measurable signs or symptoms of an eye disease. If indicated, the subject has been successfully “treated” with an eye disease. It should also be understood that the treatment or prevention modalities for various medical conditions described are intended to mean “substantial” and include not only the overall treatment or prevention but also the overall achievement of some biologically or medically relevant outcome.

[0025] As used herein, the term "ophthalmic composition" refers to a pharmaceutically acceptable formulation, delivery device, mechanism, or system suitable for administration to the eye. The term "ophthalmic composition" includes, but is not limited to, solutions, suspensions, gels, ointments, sprays, reservoir devices, or any other type of formulation, device, or mechanism suitable for the short-term or long-term delivery of zinc compounds and antihistamines to the eye. Compared to oral formulations, ophthalmic compositions, for example, exhibit specific technical characteristics associated with their application to the eye, including the use of pharmaceutically acceptable ophthalmic loading bodies that avoid various reactions such as, for example, conjunctival and corneal irritation, eyelid closure, tear secretion, and pain. Certain ophthalmic compositions are advantageously presented in the form of ophthalmic solutions or suspensions (i.e., eye drops), ophthalmic ointments, or ophthalmic gels comprising zinc compounds and antihistamines.

[0026] As used herein, the term "load carrier" is intended to include carriers, diluents, or excipients suitable for ophthalmic use. "Excipient" refers to a component that provides one or more bulk components, imparts satisfactory processing characteristics, helps control the dissolution rate, and additionally provides other desired characteristics to the composition. In particular, excipients are selected so that the ophthalmic composition does not trigger tear secretion that would entrain the active ingredient. Acceptable excipients are well known to those skilled in the art, who will know how to select them according to the desired formulation.

[0027] "Ophthalmic diseases" or "eye disorders" refers to eye conditions, including cataracts, open-angle primary glaucoma, acute floaters (physiological floaters (Musca volitans)), acute and chronic glaucoma, optic neuritis, corneal edema, macular edema, optic disc edema or other edema, postoperative disorders, retinal hemorrhage, retinopathy, retinal detachment (especially in diabetic patients), acute and chronic conjunctivitis and tearing, other corneal disorders, presbyopia, computer vision syndrome, eye strain, eye inflammation, blurred vision or blurred vision, dry eye syndrome, retinal diseases, vitreous opacities and lesions, pus, lacrimal duct obstruction, eye twitching, diabetic complications, and other systemic or hereditary diseases affecting the eye.

[0028] As used in this article, cataracts are clouding of the eye's lens caused by altered protein interactions within the lens. Protein interactions include protein misfolding and protein-protein interactions such as aggregation. Presbyopia is vision impairment caused by aging. Symptoms of presbyopia include: decreased ability to focus on near objects, eye strain, difficulty reading fine print, fatigue when reading or looking at a lit screen, blurred vision at close range, reduced contrast when reading printed materials, need for brighter and more direct light to read, need to hold reading materials further away to see them clearly, and headaches, especially when using near vision. Individuals with presbyopia may have normal vision, but over time, their ability to focus on near objects is at least partially lost, and these individuals require glasses for tasks that require near vision, such as reading. Presbyopia affects almost all individuals over the age of 40 to some extent. Cataracts include all types and degrees (such as NI, NII, NIII, NIV, and mature cataracts), including both acute and chronic cases.

[0029] "Zinc compounds" means any zinc sulfate, zinc sulfate heptahydrate, zinc sulfate hexahydrate, zinc chloride, zinc pyrithione, zinc dibutyldithiocarbamate, zinc oxide, zinc acetate, zinc salicylate, zinc salts of all isomers of tocopherol hemisuccinic acid, zinc salts of straight-chain, branched-chain, saturated and unsaturated C2 to C20 aliphatic carboxylic acids, zinc pyruvate, zinc lactate, zinc ester complexes, and zinc acetylacetone or zinc acetoacetate complexes, and their N-acetylated and acyl derivative compounds. These compounds can be prepared by procedures well known to those skilled in the art.

[0030] The term "antihistamine" describes a class of drugs that counteract the activity of histamine receptors in the body. In this sense, antihistamines are subdivided according to the histamine receptors they act on. The two largest classes of antihistamines are H1-antihistamines and H2-antihistamines. H1-antihistamines exert their effects by binding to histamine H1 receptors in mast cells, smooth muscle, and endothelium in the body, as well as in the tuberous papillary nucleus in the brain. Antihistamines targeting histamine H1 receptors are used to treat allergic reactions in the nose (e.g., itching, runny nose, and sneezing). They can also be used to treat insomnia, motion sickness, or vertigo caused by inner ear problems. H2-antihistamines bind to histamine H2 receptors in the upper digestive tract (primarily the stomach). Antihistamines targeting histamine H2 receptors are used to treat stomach acid disorders (e.g., peptic ulcers and acid reflux). Antihistamines may include bromophenamine, chlorphenamine, dextrobromophenamine, dextrochlorphenamine, carbisamine, chlormastine, diphenhydramine, pyramine, tripiramine, triprolidine, methaqualone, bromophenhydramine, promethazine, atazatine, cyproheptadine, diphenhydramine, doxylamine, alimazine, benzydidine, and hydroxyzine; or antihistamines may include levocetirizine hydrochloride, fexofenadine, loratadine, descarboxyethoxyloratadine, norastemizole, desmethylastemizole, cetirizine, avastin, ketotifen, temestine, ebastine, epinastine, mizolastine, and statazine. Pharmacologically acceptable salts of antihistamines and their derivatives may be any pharmacologically compatible inorganic or organic salt. Furthermore, such salts can be prepared by those skilled in the art using well-known procedures.

[0031] overall

[0032] The subject matter of this invention generally relates to ophthalmic preparations comprising therapeutically effective amounts of a zinc compound and at least one antihistamine, for the treatment and prevention of ophthalmic diseases at therapeutically effective concentrations. More preferably, the ophthalmic preparations are manufactured at therapeutically effective concentrations for the treatment or prevention of signs or symptoms associated with cataracts.

[0033] The therapeutic effects of active zinc compounds and antihistamines are synergistic. For example, a combination of a zinc compound with an expected active concentration of at least 0.01%, at least 0.10%, at least 0.25%, at least 0.50%, or even at least 1.00% or higher, with an antihistamine with an active concentration of at least 0.001%, at least 0.01%, at least 0.1%, or even at least 1.00%, is more effective in treating or preventing signs or symptoms associated with cataracts or eye diseases than the combined total effect of using zinc and antihistamine components separately. It should also be recognized that synergistic effects can occur when two or more active ingredients are used at different concentrations and with different zinc compounds, different antihistamines, and combinations thereof (e.g., zinc derivatives and H1 and H2 antihistamines). In one embodiment, the use of zinc compounds alone can cause significant discomfort to the eyes; therefore, the addition of antihistamines provides a comfortable experience for the patient and allows them to avoid the negative irritant side effects of zinc.

[0034] This invention provides an ophthalmic drop formulation for topical administration of beneficial zinc compounds and antihistamines to the eye. Topical eye drops typically target the treatment of the anterior segment, which is the intended therapy for the formulation of this invention. The anterior segment includes the anterior chamber, iris, ciliary body, lens, and ocular surface. The ocular surface is composed of the cornea, conjunctiva, eyelids, lacrimal glands and meibomian glands, and interconnecting nerves. The topical eye drop formulation releases the zinc compound and antihistamines over a period of several days without interfering with vision.

[0035] This invention relates to novel ophthalmic formulations suitable for administration to the eye. In various aspects of the invention, these formulations are liquids, gels, ointments, or emulsion micelles (oil-in-water or water-in-oil). The formulations comprise at least one active zinc compound and an antihistamine compound, delivered as an ophthalmic formulation. The ophthalmic formulations of the present invention deliver therapeutic and non-toxic levels of the active agent over a period of time or a therapeutic duration. These formulations are both biocompatible and effectively deliver therapeutically effective amounts of the zinc compound and the antihistamine.

[0036] Therapeutic amounts of zinc compounds and antihistamines may be present in eye drops, ophthalmic implants, or other ophthalmic preparations in any suitable amounts, including, for example, about 0.00001%, about 0.001%, at least 0.01%, at least 0.05%, 0.01-0.05%, at least 0.1%, at least 0.2%, 0-0.2%, at least 0.25%, 0.00001-0.25%, at least 0.3%, at least 0.4%, etc. At least 0.5%, 0.3-0.5%, at least 1%, 0-1%, at least 0.29%, 0.0-0.29%, 0.1-0.3%, at least 0.35%, at least 0.45%, 0.1-0.5%, at least 1%, 0.5-1.0%, at least 0.75%, 0.15-0.75%, at least 0.50%, 0.25-0.50%, 0.50-0.60%, or even 0.90% or more. Generally and unless the context otherwise requires, all concentrations herein shall be interpreted as follows: (1) wt / wt% for solid components; (2) wt / vol% for solid components in liquids; and (3) vol / vol% for liquid components. Such concentrations can advantageously and effectively prevent or alleviate at least one sign or symptom associated with at least one of the following eye conditions: (a) cataracts (e.g., blurred or dizzy vision, decreased visual acuity, sensitivity to light or glare, decreased contrast sensitivity, poor night vision, darkening, color vision changes, graying or whitening of the pupil, etc.); (b) diabetic retinopathy (e.g., blurred vision, vision loss, macular edema, floaters, retinal and vitreous hemorrhage, exudates, etc.); (c) glaucoma (e.g., blurred vision and decreased visual acuity, peripheral vision loss, visual field defects, optic nerve damage, high intraocular pressure (IOP), retinal fiber defects, etc.); (d) macular degeneration (e.g., blurred vision, decreased visual acuity, linear distortion, central...). (e) Distorted vision, macular edema, macular drusen, macular degeneration, etc.; (f) Dry eye syndrome (e.g., eye irritation, gritty or gritty sensation, redness, burning sensation, poor vision, poor tear quality, shortened tear film breakup time, poor Schirmer test performance, increased sensitivity of the eye to wind and heat, etc.); (g) Protrusion (e.g., dryness, eye pain, redness of the eye, etc.); (h) Keratoconus (e.g., distorted vision, hallucinations, light sensitivity, eye fatigue, etc.); (i) Pterygium / pinholera (e.g., distorted vision, blurred vision, decreased vision, inflammation, irregular astigmatism, etc.); (i) Ocular allergies (e.g., eye irritation, blurred vision, decreased vision, etc.); or any other ocular disease and signs or symptoms.

[0037] Zinc and oxidative stress

[0038] Zinc compounds, and more particularly zinc sulfate, act as important astringents that dissolve oxidized proteins, making them extremely useful in all types and developmental stages of cataracts (such as NI, NII, NIII, NIV, and mature cataracts), including both acute and chronic cases. The use of zinc sulfate leads to the prevention or reduction of cataract progression, or the reversal of cataracts formed at different stages of their development, and significantly improves visual acuity and lens transparency in patients, particularly in older adults who develop cataracts due to aging.

[0039] Álvarez-Barrios et al. (2021) discussed how “oxidative stress affects all structures of the human eye, with particular emphasis on the ocular surface, lens, retina, and retinal pigment epithelium, which are considered natural barriers to antioxidant protection and contribute to the initiation and / or progression of eye diseases” (p. 1). Since oxidative stress plays a significant role in the initiation and progression of cataracts, the antioxidant properties of zinc compounds, and more particularly zinc sulfate, allow them to scavenge reactive oxygen species, thereby protecting the lens. In a recent study by Barman and Srinivasan (2019), they reported that “zinc supplementation alleviates the progression and maturation of diabetic cataracts. Zinc also effectively prevents a decrease in the total content and imbalance of soluble proteins in the lens.”

[0040] Zinc supplementation also reduced cross-linking glycation and the co-expression of glycation product receptors, as well as oxidative stress markers in the lens of the eye. Zinc supplementation further induced the concentration of heat shock proteins, particularly α-crystallin, in the lens of diabetic rats. Zinc supplementation counteracted the increased activity and expression of polyol pathway enzymes and molecules in the lens. The results of this animal study support the advantages of zinc supplementation in exerting anti-glycation effects and downregulating polyol pathway enzymes to delay the onset of cataracts in diabetic rats (p. 212).

[0041] In particular, it has been proposed that zinc sulfate slows down the progression of opacity and reduces the opacity score (Abdul-Hussein & Alzubaidy, 2014).

[0042] In one implementation, therapeutically effective amounts of zinc compounds and antihistamines are used as postoperative agents to remove side effects and unpleasant conditions following cataract surgery by dissolving protein ash and clearing the newly implanted lens. Therapeuticly effective amounts of zinc compounds and antihistamines can also provide postoperative support after corneal transplantation, in which the eye may reject the newly transplanted cornea.

[0043] Corneal edema following treatment with effective amounts of zinc compounds and antihistamines for clarifying laser-assisted corneal surgery (due to the prolonged surgery time). Epithelial damage leads to edema, which in turn causes deterioration of corneal clarity.

[0044] Therapeutic amounts of zinc compounds and antihistamines also act as important ocular astringents, which help clear the mucus buildup in the eyes, often associated with exposure to air allergens.

[0045] Treatment with effective amounts of zinc compounds and antihistamines for acute ocular floaters (physiological floaters).

[0046] This treatment uses high concentrations of zinc compounds and antihistamines to lower intraocular pressure, and is therefore used to treat acute and chronic glaucoma.

[0047] Therapeutic doses of zinc compounds and antihistamines are used to treat optic neuritis (activating the optic nerve).

[0048] Effective doses of zinc compounds and antihistamines can prevent any type of edema, macular edema, and optic disc edema.

[0049] Effective doses of zinc compounds and antihistamines are used to treat retinal hemorrhage, neovascularization, and diabetic retinopathy.

[0050] Effective doses of zinc compounds and antihistamines are used to treat retinal detachment, especially in diabetic patients or emergency cases.

[0051] Therapeutic amounts of zinc compounds and antihistamines contain potent antihistamines (such as chlorpheniramine maleate), thus they are of great value in symptom relief of allergic conditions (including conjunctivitis) and in the treatment of clinical manifestations of ocular allergies.

[0052] Therapeutic amounts of zinc compounds and antihistamines can be used as lubricants and preservatives.

[0053] Dosage and administration:

[0054] Dosage and dosing regimen will depend on the specific therapeutically effective amount of the zinc compound and antihistamine used, the nature of the antihistamine, such as the severity of the subject's eye disease, its therapeutic index, the subject's condition, and their medical history. A wide range of human dosage forms can be used for therapeutically effective amounts of zinc compounds and antihistamines. The dosage of the compound should appropriately fall within a wide concentration range, including the less toxic ED50. The dosage may vary within this range depending on the dosage form and route of administration used. For any compound used in the method, a therapeutically effective dose can be estimated.

[0055] Typically, therapeutically effective amounts of zinc compounds and antihistamines are sufficient to achieve therapeutic or preventative effects, ranging from about 0.15 mg / kg body weight to about 1.2 mg / kg body weight daily, and from about 0.03 mg / kg body weight to about 24 mg / kg body weight daily. In another embodiment, the therapeutic or preventative effect ranges from about 0.000001 mg / kg body weight / day to about 10,000 mg / kg body weight / day. Preferably, the dose ranges from about 0.00001 mg / kg body weight / day to about 1 mg / kg body weight / day. For example, the dose may be in the range of 1 mg / kg body weight or 10 mg / kg body weight every 2 or 3 days, or 1-10 mg / kg body weight weekly, every 2 or 3 weeks. In one embodiment, the single dose range of therapeutically effective amounts of zinc compounds and antihistamines is from 0.01 to 10,000 μg / kg body weight. In one embodiment, the concentration of the therapeutically effective zinc compound and antihistamine in the carrier ranges from 0.2 to 20,000 μg / (1 mL of the formulation to be delivered). Exemplary therapeutic dosing regimens require administration once daily, twice daily, three times daily, or four times daily. The intervals can be more irregular than indicated, depending on the patient's symptoms, by measuring the subject's blood glucose or insulin levels and adjusting the dose or administration accordingly. In therapeutic applications, relatively high doses are used at relatively short intervals until disease progression is suppressed or stopped, preferably until the subject shows partial or complete improvement in disease symptoms.

[0056] After that, preventative measures can be provided to the patient.

[0057] In some embodiments, the therapeutically effective amount of zinc compound and antihistamine can be defined as a concentration of zinc compound and antihistamine in the target tissue of 10⁻¹¹ to 10⁻⁶ mol, such as about 10⁻⁷ mol. This concentration can be delivered at a systemic dose of 0.001-100 mg / kg or an equivalent dose at body surface area.

[0058] The dosing regimen will be optimized to maintain therapeutic concentrations in the target tissue, preferably daily or weekly, but continuously (e.g., intravenous infusion or percutaneous application).

[0059] In some embodiments, the therapeutically effective doses of the zinc compound and the antihistamine are defined as "low," "medium," or "high" dose levels. In one embodiment, the low dose is about 0.0001 to about 0.5 mg / kg / h, preferably about 0.01 to about 0.1 mg / kg / h. In one embodiment, the medium dose is about 0.1 to about 1.0 mg / kg / h, preferably about 0.1 to about 0.5 mg / kg / h. In one embodiment, the high dose is about 0.5 to about 10 mg / kg / h, preferably about 0.5 to about 2 mg / kg / h.

[0060] Those skilled in the art will understand that specific severity, including but not limited to the severity of the disease or ailment, the subject's overall health and / or age, and the presence of other conditions, can affect the dosage and duration required for effective treatment. Furthermore, treating a subject with a therapeutically effective amount of the therapeutic composition described herein includes a single treatment or a series of treatments.

[0061] In one embodiment, the dose in one or more affected eyes is 2 drops, up to 4 times daily. In one embodiment, the maximum dosage is 2 drops / 4 times / day. The average droplet volume is equal to 0.05 ml, with a ZnSO4 concentration of 0.30% and an available dose of approximately 0.15 mg per drop. Additionally, 0.06% chlorpheniramine maleate is equivalent to approximately 0.03 mg of chlorpheniramine maleate per drop. The currently recommended maximum dose is 8 drops daily, equivalent to approximately 1.2 mg of zinc sulfate and approximately 0.24 mg of chlorpheniramine maleate daily. In another embodiment, the dose may be 1 drop / 4 times.

[0062] Example:

[0063] The eye drops were provided to 230 volunteers who were diagnosed with an eye disease or condition, primarily cataracts. Their diagnosis was primarily conducted at ophthalmology clinics and vision centers prior to initiating use of the eye drops. Nearly 207 participants (approximately 90% of the patients) showed positive results for the problems addressed by the eye drop formulation during treatment periods ranging from 2 to 60 days for cataract cases and 7 to 60 days for other resolution cases. Participants included 108 women (47%) and 122 men (53%), with an age range of 15 to 95 years (mean = 66.1, standard deviation = 11.8, median = 67). Patient ages are shown in... Figure 1 Participants included patients with other complications such as diabetes (28.3%), hypertension (17.8%), kidney failure (0.9%), and heart failure (8.7%). Treatment outcomes were reported centrally by physicians or by patients themselves when physician examination was unavailable. Effective treatment periods are shown in Table 1 and... Figure 2 middle. Figure 2 The effective treatment period is shown, with a mean of 12.4, a median of 10, a standard deviation of 8.2, a minimum of 2, and a maximum of 60. The range is 2 to 30 if two cases in the dataset showing improvement within 60 days are considered extreme values. At 1 week: 41.9% showed effective treatment. At 2 weeks: 28.4% showed effective treatment. At 3 weeks: 7.9% showed effective treatment. The graph of effective treatment by age is from... Figure 3 middle.

[0064] Table 1: Frequency of Effective Treatment Period (days)

[0065] level count % of the total accumulation% 2 2 0.9％ 0.9％ 3 7 3.1％ 3.9％ 4 3 1.3％ 5.2％ 5 4 1.7％ 7.0％ 7 96 41.9％ 48.9％ 10 7 3.1％ 52.0％ 12 1 0.4％ 52.4％ 14 65 28.4％ 28.4％ 15 7 3.1％ 83.8％ 21 18 7.9％ 91.7％ 28 2 0.9％ 92.6％ 30 15 6.6％ 99.1％ 60 2 0.9％ 100.0％

[0066] For cataracts, there were 171 volunteers (including 44 diabetic volunteers). NI: 4 volunteers; NII: 56 volunteers; NIII: 96 volunteers; mature: 57 volunteers. Eleven case reports showed partial or null results (estimated efficacy 93.6%). In some cases, elderly patient volunteers were informed by their doctors that they were not eligible for surgery due to their medical conditions, and the developed eye drops provided them with a safe alternative, resulting in positive treatment outcomes.

[0067] Postoperative complications were observed in 34 volunteers. Four case reports indicated partial or invalid outcomes (estimated validity 88.2%). Eye drops as a postoperative medication help manage potential surgical complications / side effects.

[0068] For the visually impaired, there were 30 volunteers. Seven cases reported partial or invalid results (estimated validity 76.7%). Several volunteers reported that their vision gradually recovered after using the eye drops.

[0069] For glaucoma, 20 volunteers were included. Four case reports showed partial or no results (estimated efficacy of 80%). Zinc's astringent properties play an important role in lowering intraocular pressure, thus it has potential efficacy in the treatment of acute and chronic glaucoma.

[0070] Table 2

[0071]

[0072] In one embodiment, the main active ingredient in the ophthalmic preparation is zinc sulfate, which can also be used as an astringent to help reduce redness and irritation. This embodiment of zinc sulfate for treating cataracts can occur in the following ways: preventing or reducing the progression of cataract formation, or reversing cataracts that have formed at different stages of their development, and significantly improving visual acuity and lens transparency in patients, particularly for older adults who develop cataracts due to aging.

[0073] In one embodiment, the primary active ingredient is zinc sulfate (ZnSO4). In one embodiment, the concentration of zinc sulfate is about 0.30%, however, concentrations higher or lower than 0.30% (e.g., 0.25%) can be used. In one embodiment, the ophthalmic composition has the following formulation: about 300 mg (0.30%) of zinc sulfate, about 60 mg (0.06%) of chlorpheniramine maleate, and about 100 ml of isotonic buffer solution.

[0074] In another implementation, chlorpheniramine maleate can be replaced with antihistamines while maintaining a synergistic therapeutic effect.

[0075] In addition, alternative embodiments, where the therapeutically effective zinc compound and antihistamine may be: approximately 250 mg of zinc sulfate, approximately 100 mg of naphazoline hydrochloride, and approximately 125 mg of diphenhydramine hydrochloride, in approximately 100 ml of isotonic buffer solution. While this embodiment may be effective for cataracts, it is contraindicated in patients with angle-closure glaucoma due to the presence of naphazoline, which causes vasoconstriction of conjunctival vessels and may exacerbate the effects of glaucoma.

[0076] In addition, other effective zinc compounds and antihistamines may include: about 280 mg of zinc sulfate and about 50 mg of tetrahydrozoline hydrochloride in about 100 ml of isotonic buffer solution.

[0077] In addition, other alternative treatments that are effective zinc compounds and antihistamines may include: about 290 mg of zinc sulfate and about 30 mg of feniramine maleate in about 100 ml of isotonic buffer solution.

[0078] Manufacturing method

[0079] For ophthalmic use, zinc compounds and antihistamines are formulated as solutions, suspensions, and ointments suitable for ophthalmic applications. For eye drop formulations, see the following references: Mitra (ed.), Ophthalmic Drug Delivery Systems, Marcel Dekker, Inc., New York, NY. (1993) or Havener, W. et al., Ocular Pharmacology, CV Mosby Co., St. Louis (1983). Eye drops are suitable for topical administration to the eye in the form of solutions, suspensions, ointments, creams, or solid implants. In the case of a single administration, 0.1 ng to 5000 μg, 1 ng to 500 μg, or 10 ng to 500 μg of zinc compounds and antihistamines may be instilled into the human eye.

[0080] In one embodiment, the zinc sulfate eye drops are a sterile solution containing 0.25% w / v zinc sulfate heptahydrate (ZnSO4,7H2O) in purified water. 5 mL of water and 5 mL of ammonia buffer (pH 10.9) are added to 5 mL of solution, and titration is performed with 0.01 M disodium edetate (VS) using Median Black 11 solution as an indicator. Each mL of 0.01 M disodium edetate (VS) is equivalent to 2.875 mg of ZnSO4,7H2O, providing a content of 0.22 to 0.28% w / v zinc sulfate heptahydrate (ZnSO4,7H2O).

[0081] In another embodiment, the zinc sulfate eye drops comprise about 0.27 w / v% to about 0.33 w / v% of zinc sulfate hydrate (ZnSO4, 7H2O: 287.55), prepared in a container by adding 3 g of zinc sulfate hydrate, 20 g of boric acid, 5 g of sodium chloride, 2 mL of anise oil, and sufficient purified water to make 1000 mL. The ophthalmic liquid and solution with the components are prepared, and 25 mL of the zinc sulfate ophthalmic solution is accurately pipetted and added to 100 mL of water and 2 mL of ammonia, then titrated.

[0082] In one embodiment, zinc sulfate (0.25% w / v) eye drops (pH 7.2±2) are prepared by dissolving zinc sulfate powder (250 mg) and 20 mg benzalkonium chloride in 100 ml of buffer solution (which already consists of 440 mg of phosphate powder in 100 ml of distilled water).

[0083] Useful buffers include, but are not limited to, borate buffers, phosphate buffers, carbonate buffers, and acetate buffers. The concentration of buffers in ophthalmic compositions can vary from about 1 mM to about 150 mM or greater, depending on the specific buffer chosen.

[0084] Depending on the specific form chosen, the composition may contain a variety of additives, such as buffers, isotonic agents, solubilizers, preservatives, thickeners, chelating agents, antioxidants, antibacterial agents, and pH adjusters.

[0085] Ophthalmic preparations may contain non-toxic substances, such as antibacterial agents that are harmless to use, such as thimerosal, benzalkonium chloride, methylparaben and propylparaben, benzyldodecylammonium bromide, benzyl alcohol or phenethyl alcohol; buffering components, such as sodium chloride, sodium borate, sodium acetate, sodium citrate or gluconate; sorbitol monolaurate, triethanolamine, polyoxyethylene sorbitol monopalmitate, ethylenediaminetetraacetic acid, etc. Other conventional components or preservatives may be added.

[0086] Examples of suitable preservatives include, but are not limited to, chlorobutanol, sodium dehydroacetate, benzalkonium chloride, cetylpyridine chloride, phenethyl alcohol, parabens, benzyl chloride, hydrophilic dehalogenated copolymers of ethylene oxide and dimethylethylene-imine, and mixtures thereof. Tackifiers may be selected from, for example, methylcellulose, hydroxyethylcellulose, carboxymethylcellulose, hydroxypropyl methylcellulose, polyvinyl alcohol, carboxymethyl cellulose, chondroitin sulfate, and their salts. Suitable solubilizers include, but are not limited to, polyoxyethylene hydrogenated castor oil, polyethylene glycol, polysorbate 80, and polyoxyethylene monostearate. Typical chelating agents include, but are not limited to, sodium edetate citric acid, salts of diethylenetriaminepentaacetic acid, diethylenetriaminepentamethylenephosphonic acid, and stabilizers such as sodium edetate and sodium bisulfite.

[0087] Alternative implementation methods

[0088] In one embodiment, the formulation further comprises an active agent selected from the group consisting of antioxidants, metal complexes, anti-inflammatory agents, antibiotics, and antihistamines. In one embodiment, the antioxidant is vitamin A, vitamin C, vitamin E, lycopene, selenium, alpha-lipoic acid, coenzyme Q, glutathione, carotenoids, or ginkgo biloba. In one embodiment, the formulation includes acecridine, acetazolamide, anecoltab, aclonidine, atropine, azapentacene, azelastine, bacitracin, befnolol, betamethasone, betalolol, bimatoprost, brimonidine, brinzolamide, carbacholine, carteolol, celecoxib, celecoxib, ramphenicol, chlortetracycline, ciprofloxacin, cromoglycate, cromoglycine, cyclopentate, cyclosporine, dapiprazole, dexamethasone, diclofenac, dichlorfenamide, dipifluridine, dazolamide, ecothiofete, emestin, epinastine, adrenaline, erynemycin. Etoxzolamide, Eucatropine, Fludrocortisone, Flurbiprofen, Fomivirzen, Flamycetin, Ganciclovir, Gatifloxacin, Gentamicin, Homatropine, Hydrocortisone, Iodidine, Indomethacin, Isoflurofeto, Ketoprost, Ketotifen, Latanoprost, Levobunocin, Levofloxacin, Rhodoxamide, Clotipronol, Medlizone, Metazolamide, Metipronol, Moxifloxacin, Nafazoline, Natamycin, Nedolomex, Neomycin, Norfloxacin, Ofloxacin, Olopatadine, Oxymetazoline, Pyriprexate, Pergatanib, Phenylephrine, Physostigmine, Pizostigmine, Polymyxin B, Prednisolone, Pu Paracaine, ranibizumab, limexolone, scopolamine, szodamine, squalamine, sulfacetamide, sulprofen, tetracaine, tetrahydrozoline, tetrizoline, timolol, tobramycin, travoprost, triamcinolone, trifluorometazolamide, trifluridine, trimethoprim, and active agents selected from the group consisting of xylometazoline, pharmaceutically acceptable salts thereof, and combinations thereof.

[0089] The preventive and therapeutic uses of zinc compounds and antihistamines are detailed below.

[0090] The zinc compounds and antihistamines described herein can be used for the prevention or treatment of eye diseases. In particular, this disclosure provides both preventative and therapeutic methods for treating subjects at risk of developing (or being susceptible to) eye diseases and medical conditions. Therefore, this method prevents and / or treats an ophthalmic disease in a subject by administering an effective amount of a zinc compound and an antihistamine to the subject in need. For example, the zinc compound and antihistamine may be administered to the subject for the purpose of improving one or more factors contributing to an eye disease or condition.

[0091] One aspect of this technology includes methods for reducing an eye disease in a subject for therapeutic purposes. For therapeutic use, the composition or medicine treats symptoms of the disease in a subject who has suspected or already has the disease, including complications and intermediate pathological phenotypes during disease progression. Alternatively, it may be administered in an amount sufficient to at least partially inhibit progression. Therefore, this disclosure provides a method for treating an individual suffering from an eye disease. In some embodiments, by administering a zinc compound and an antihistamine, this technology relates to diabetic retinopathy, cataracts, retinitis pigmentosa, glaucoma, choroidal neovascularization, retinal degeneration, and oxygen induction in mammals. Methods for treating or preventing certain eye diseases such as recurrent retinopathy are provided.

[0092] In one implementation, a zinc compound and an antihistamine are administered to the subject to treat or prevent diabetic retinopathy. Diabetic retinopathy is characterized by capillary aneurysms and punctate hemorrhages. Subsequently, cotton-cotton-like white spots form on the retina due to microvascular occlusion. Furthermore, individuals with diabetic retinopathy may develop retinal edema and / or hard white spots due to increased vascular permeability. Angiogenesis subsequently occurs, and retinal detachment is caused by friction from connective tissue growth in the vitreous humor. Iris reddening and neovascular glaucoma may also occur, which can turn and lead to blindness. Symptoms of diabetic retinopathy include poor reading ability, blurred vision, sudden blindness in one eye, halos around light, black spots, and / or flashes of light. These are not the only symptoms.

[0093] In one implementation, a zinc compound and an antihistamine are administered to a subject to treat or prevent cataracts. Cataracts are a congenital or acquired condition characterized by a decrease in the transparency of the natural lens. Individuals with cataracts may exhibit one or more symptoms, including but not limited to clouding of the lens surface, lens opacity, and / or lens swelling. Typical examples of congenital cataract-related diseases are pseudocataracts, intramembranous cataracts, coronal cataracts, laminar cataracts, punctate cataracts, and filamentous cataracts. Typical examples of acquired cataract-related diseases are senile cataracts, secondary cataracts, brown cataracts, complicated cataracts, diabetic cataracts, and traumatic cataracts. Acquired cataracts can also be caused by electric shock, radiation, ultrasound, drugs, systemic diseases, and nutritional imbalances. Acquired cataracts further include postoperative cataracts.

[0094] In one implementation, a zinc compound and an antihistamine are administered to the subject to treat or prevent retinitis pigmentosa. Retinitis pigmentosa is a disease characterized by damage to rod cells and / or cone cells. Dark lines in the retina are typical in individuals with retinitis pigmentosa. Individuals with retinitis pigmentosa also exhibit a variety of symptoms, including but not limited to headache, numbness or tingling in the extremities, flashes of light, and / or impaired vision. See, for example, the following reference: Heckenlively et al., Clinical findings and common symptoms in retinitis pigmentosa. Am J Ophthalmol. 105(5):504-511 (1988).

[0095] Treatment or prevention of glaucoma in subjects. Glaucoma is a hereditary disease characterized by elevated intraocular pressure, leading to decreased vision. Glaucoma can be caused by a variety of pre-existing eye conditions, such as trauma, surgery, and other structural malformations. Glaucoma can occur at any age but is most common in older individuals, leading to blindness. Patients with glaucoma typically have an intraocular pressure of 21 mmHg or higher. However, even without an increased intraocular pressure (i.e., 21 mmHg or higher), normal-pressure glaucoma can occur, where glaucoma-like distortions are observed in the visual field and optic nerve head. Symptoms of glaucoma include, but are not limited to, blurred vision, severe eye pain, headache, irritation, nausea, and / or vomiting.

[0096] In one implementation, a zinc compound and an antihistamine are administered to the subject to treat or prevent macular degeneration. Macular degeneration is a typical age-related disease. General classifications of macular degeneration include wet, dry, and age-independent macular degeneration. Dry macular degeneration accounts for approximately 80-90% of all cases and is also known as atrophic, non-exudative, or dorsenoid macular degeneration. In dry macular degeneration, drusen typically accumulates beneath the retinal pigment epithelium. If the drusen interferes with the function of photoreceptors in the macula, blindness occurs. Symptoms of dry macular degeneration include, but are not limited to, astigmatism, central visual distortion, dysphoria, and / or color vision changes. Dry macular degeneration can lead to progressive vision loss.

[0097] Wet macular degeneration (AMD) is also known as angiogenesis, subretinal neovascularization, exudation, or discoid degeneration. In wet AMD, blood vessels grow abnormally under the macula. Blood leaks from these vessels into the macula, damaging photoreceptors. Wet AMD progresses rapidly and can cause severe impairment of central vision. Wet and dry AMD share similar symptoms. However, age-related AMD is rare and may be associated with genetics, diabetes, malnutrition, injury, infection, or other factors. Symptoms of age-related AMD include, but are not limited to, astigmatism, distorted central vision, distorted light and dark vision, and / or changes in color vision.

[0098] In one implementation, a zinc compound and an antihistamine are administered to the subject to treat or prevent choroidal neovascularization (CNV). Choroidal neovascularization (CNV) is a disease characterized by the growth of new blood vessels in the choroidal layer of the eye. The newly formed vessels grow across the Bruch's membrane on the choroid and into the subretinal space. CNV can lead to visual impairment and complete blindness. Symptoms of CNV include, but are not limited to, flickering, flashing light or gray spots in the affected eye, blurred vision, astigmatism, and / or blindness.

[0099] In one implementation, a zinc compound and an antihistamine are administered to a subject to treat or prevent retinal degeneration. Retinal degeneration is a hereditary disorder associated with destruction of the retina. Retinal tissue can degenerate due to a variety of causes, including arterial and venous occlusion, diabetic retinopathy, retinopathy of prematurity, and / or retrolental fibrosis. Retinal degeneration typically includes retinal detachment and lattice-like degeneration and is associated with progressive macular degeneration. Symptoms of retinal degeneration include, but are not limited to, vision loss, blindness, night blindness, narrowed visual field, peripheral vision loss, retinal detachment, and / or light sensitivity.

[0100] In one implementation, a zinc compound and an antihistamine are administered to the subject to treat or prevent oxygen-induced retinopathy. Oxygen-induced retinopathy (OIR) is a disease characterized by microvascular degeneration. OIR is an established model for studying retinopathy of preterm infants. OIR is associated with damage to vascular cells that lead to abnormal angiogenesis. Microvascular degeneration results in ischemia, which causes the physical changes associated with OIR. Oxidative stress also plays an important role in vascular occlusion in OIR, in which endothelial cells are susceptible to oxidative damage. However, pericytes, smooth muscle cells, and perivascular astrocytes are generally resistant to oxidative damage. See, for example, the following reference: Beauchamp et al., Role of thromboxane in retina microvascular degeneration in oxygen-induced retinopathy, J Appl Physiol. 90:2279-2288 (2001). OIR, including retinopathy of preterm infants, is usually asymptomatic. However, abnormal eye movements, esotropia, high myopia, and / or leukocytosis may be signs of OIR or retinopathy of prematurity.

[0101] In one aspect, the present invention provides a method for preventing an ocular disease in a subject by administering a zinc compound and an antihistamine to the subject, which modulates signs or markers of one or more ocular diseases. For example, subjects at risk of developing an ocular disease can be identified by any or a combination of diagnostic or prognostic analyses as described herein. For prophylactic use, the zinc compound and antihistamine are administered to a subject suspected of or at risk of a disease or symptom, biochemical, histological, and / or behavioral symptoms of the disease, or a combination thereof. The dosage is sufficient to eliminate or reduce the risk of the disease, reduce its severity, or delay its development (including the disease and metastatic pathological phenotypes in disease progression). Administration of the prophylactic aromatic cationic drug can occur before the onset of abnormal symptom characteristics, thereby preventing the disease or lesion or delaying its progression. Depending on the type of abnormality, the zinc compound and antihistamine may be used to treat the subject, acting to enhance or improve mitochondrial function or reduce oxidative damage. Suitable compounds can be determined based on the screening tests described herein.

[0102] The biological effects of treatments based on zinc compounds and antihistamines are measured. In various embodiments, appropriate in vitro or in vivo tests are performed to determine the effectiveness of the therapy based on a specific zinc compound and antihistamine, and whether its administration is appropriate as a therapy. In various embodiments, representative cells of the type associated with the subject's disease are used to determine whether the therapy based on a specific zinc compound and antihistamine has the desired effect on the cell type. In vitro testing can be performed. Therapeutic compounds can be tested in suitable animal model systems, such as rats, mice, chickens, cattle, monkeys, rabbits, etc., prior to testing in human subjects. Similarly, for in vivo testing, any animal model system known in the art can be used prior to administration to human subjects. In one embodiment, administration of a zinc compound and antihistamine to a subject exhibiting symptoms associated with an eye disease resulted in improvement in one or more of these symptoms.

[0103] Zinc compounds and antihistamines are typically formulated to be compatible with their intended route of administration. Examples of routes of administration include parenteral (e.g., intravenous, intradermal, intracavitary, or subcutaneous), oral, inhalation, transdermal (topical), intraocular, iontophoresis, and transmucosal administration.

[0104] Solutions or suspensions intended for parenteral, intradermal, or subcutaneous administration may contain the following components: water for injection, saline solution, non-volatile oil, polyethylene glycol, glycerin, propylene glycol, or other synthetic compounds; sterile diluents, such as solvents; antimicrobial agents, such as benzyl alcohol or metal parabens; antioxidants, such as ascorbic acid or sodium bisulfite; chelating agents, such as ethylenediaminetetraacetic acid; buffers, such as acetates, citrates, and phosphates; and tonic modifiers, such as sodium chloride or dextrose. pH can be adjusted using acids or bases, such as hydrochloric acid or sodium hydroxide. Parenteral formulations may be packaged in glass or plastic ampoules, disposable syringes, or multi-dose vials. For the convenience of patients or treating physicians, dosage formulations may be provided in kits containing all the necessary equipment for the treatment unit, such as drug vials, diluent vials, syringes, and needles.

[0105] Example

[0106] The preceding embodiments are presented to provide those skilled in the art with a complete disclosure and illustration of how to manufacture and evaluate the compounds, compositions, articles, apparatuses, and / or methods claimed herein, and are intended to be purely exemplary of the invention and not to limit the scope of what the inventors believe their invention to be. However, based on this disclosure, those skilled in the art will understand that many changes can be made to the specific embodiments disclosed, and similar or analogous results can be obtained without departing from the spirit and scope of the invention.

[0107] Efforts have been made to ensure the accuracy of figures (e.g., quantities, temperatures, etc.), but some errors and deviations should be taken into account. Unless otherwise stated, parts are by weight, temperatures are in °C or at ambient temperature, and pressures are at or near atmospheric pressure.

[0108] All publications and patent applications mentioned in this specification are incorporated herein by reference to the same extent that each individual publication or patent application is explicitly and separately cited by reference.

[0109] While the invention has been described in conjunction with various embodiments, it should be understood that modifications can be made to the invention. This application is intended to cover any variations, uses, or alterations of the invention that generally follow the principles of the invention and include such deviations from this disclosure within the scope of known and customary practice in the field to which this invention pertains.

Claims

1. Use of a formulation in the manufacture of a medicament for treating an eye condition selected from the group consisting of: cataracts, postoperative disorders, blindness, glaucoma, blurred vision, floaters, edema, retinal hemorrhage, optic neuritis, conjunctivitis, lacrimation, retinal detachment, or purulent discharge, wherein the formulation comprises a therapeutically effective concentration of a zinc compound and at least one antihistamine, said zinc compound being zinc sulfate at a concentration of 0.30% in a buffer solution, and said antihistamine being chlorpheniramine maleate at a concentration of 0.06% in a buffer solution.

2. The use according to claim 1, wherein, The drug is 93.6% effective for cataracts at all stages.

3. The use according to claim 1, wherein, The drug is 80% effective against glaucoma.

4. The use according to claim 1, wherein, The medication is formulated for a treatment duration of 2 to 60 days.

5. The use according to claim 1, wherein, The drug is formulated for a 2-day effective treatment period.

6. The use according to claim 1, wherein, The drug improved the subjects' eye symptoms one week after delivery of therapeutically effective concentrations.

7. The use according to claim 1, wherein, The drug was 88.2% effective against postoperative complications.

8. The use according to claim 1, wherein, The drug is 76.7% effective in treating blindness.

9. The use according to claim 1, wherein, The eye condition is glaucoma, and the drug delivery therapy effectively lowers intraocular pressure to treat acute and chronic glaucoma.

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