Refamycin ophthalmic composition and its use

Abstract

An ophthalmic composition comprising an effective amount of one or more rifamycin compounds or a pharmaceutically acceptable salt thereof, a method for preparing said composition, and a method for using said composition in the treatment of various disorders are provided herein.

Description

【Technical Field】 【0001】 The present technology relates to an ophthalmic composition comprising an effective amount of one or more rifamycin compounds or pharmaceutically acceptable salts thereof, a method for preparing said composition, and a method for the use of said composition in the treatment of various disorders. 【Background Art】 【0002】 The following description of the background of the present technology is provided merely to assist in understanding the present technology and does not admit to describing or constituting prior art to the present technology. 【0003】 Loss of vision is a common problem associated with aging or various eye diseases such as age-related macular degeneration, ocular histoplasmosis syndrome, myopia, diabetic retinopathy, and inflammatory diseases, all of which are caused by neovascularization in the cornea, retina, or choroid. 【0004】 Age-related macular degeneration (AMD) is a common eye disease that typically affects the elderly and causes vision loss in the center of the visual field (macula) due to retinal damage. Some peripheral vision remains, but it is difficult or impossible to read or recognize faces. There are two main forms of macular degeneration, namely, atrophic (dry) and exudative (wet). In the dry (non-exudative) form, cellular debris called "drusen" accumulates between the retina and the choroid. In the more severe wet (exudative) form, blood vessels grow from the choroid behind the retina. AMD is the leading cause of blindness in people over 65 years old and is caused by abnormal development of blood vessels behind the retina. The advanced AMD population is increasing by 11% and reaching 3.3 million due to aging. Intravitreal injection with anti-vascular endothelial growth factor (anti-VEGF) therapy has become the standard of care for the treatment of choroidal neovascular membranes (CNV) associated with AMD. 【0005】 Treatment options for wet AMD include bevacizumab (Avastin, Genentech, San Francisco, CA), a full-length anti-VEGF antibody; ranibizumab (Lucentis, Genentech), an affinity-matured fragment; pegaptanib sodium (Macugen, OSI / Eyetech Inc.); and aflibercept (Eylea, Regeneron, Tarrytown, NY), as well as other anti-VEGF drugs. However, such intravitreal injections are a process that requires high precision because they are performed under local anesthesia with the aid of a needle. In this process, a needle must be inserted into the vitreous humor that fills the cavity between the lens and the retina, and thus the surgery must be performed very carefully so as not to damage the retina. Therefore, there is an urgent need for improved treatment methods, administration routes, and methods for treating eye disorders such as AMD. The present disclosure addresses this urgent need by providing a formulation capable of efficiently delivering one or more rifamycin compounds to the eye, particularly subretinally and sub-sclerally. 【Summary of the Invention】 【0006】 The present disclosure generally relates to an ophthalmic composition comprising, consisting essentially of, or consisting of an effective amount of one or more rifamycin compounds or pharmaceutically acceptable salts thereof, and one or more viscosity-increasing agents. The present disclosure also provides a method for preparing the composition. The compositions and methods of the present disclosure are useful for the treatment of various disorders, particularly various disorders of the eye. 【0007】 Thus, in one aspect, the present disclosure provides an ophthalmic composition having a viscosity of at least 1 mPaS at 25° C., the composition comprising, consisting essentially of, or consisting of: a) an effective amount of one or more rifamycin compounds or pharmaceutically acceptable salts thereof; b) a buffer; and c) one or more viscosity-increasing agents. 【0008】 In certain embodiments, one or more rifamycin compounds are selected from the group consisting of rifamycin SV, 3-formylrifamycin SV, rifampicin, rifabutin, rifapentine, or rifaximin. In further embodiments, the one or more rifamycin compounds are rifampicin. In some embodiments, the effective amount of the one or more rifamycin compounds comprises, consists essentially of, or consists of a final concentration in the composition of at least 0.001 to at least 0.01% w / w, or at least 0.01 to at least 0.25% w / w, or at least 0.25 to at least 0.5% w / w, or 0.5 to at least 1.5% w / w, or at least 0.75 to at least 1.5% w / w, or at least 1 to at least 1.5% w / w. 【0009】 In certain embodiments, the buffer is acetic acid, boric acid, citric acid, phosphoric acid, hydrochloric acid, glycine, citrate phosphate, succinic acid, phthalic acid, cacodylic acid, tris (tris hydroxymethyl aminomethane), barbituric acid, 2-amino-1,3-propanediol (amethiol), sodium bicarbonate, HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), ACES (N-(2-acetamido)iminodiacetic acid), BES (N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid), bis(N,N-bis(2-hydroxyethyl)glycine), bistris(bis(2-hydroxyethyl)iminotris)(hydroxymethyl)methane), CAPS (N-cyclohexyl-3-aminopropanesulfonic acid)(N-cyclohexyl-2-hydroxy-3-aminopropanesulfonic acid), CHES (3-[N,N-bis(2-hydroxyethyl)amino]-2-hydroxypropanesulfonic acid), EPPS (3-[4-(2-hydroxyethyl)-1-piperazinyl]propanesulfonic acid), HEPES-Na (2-[4-(2-hydroxyethyl)-1-piperazinyl]ethanesulfonic acid sodium), HEPPS (2-hydroxy-3-[4-(2-hydroxyethyl)-1-piperazinyl]propanesulfonic acid monohydrate), MES (2-morpholinopropanesulfonic acid), MOPSO (2-hydroxy-3-morpholinopropanesulfonic acid), PIPES (piperazine-1,4-bis(2-ethanesulfonic acid)), POPSO 1,4-bis(2-hydroxy-3-propanesulfonic acid), TAPSO (2-hydroxy-N-tris(hydroxymethyl)methyl-3-aminopropanesulfonic acid, TES (N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid), tricine (N-[tris(hydroxymethyl)methyl]glycine), hydrochloric acid, sodium hydroxide, sodium phosphate, sodium borate, sodium citrate, sodium acetate, and sodium lactate; and buffers such as citrate / dextrose, sodium bicarbonate, and ammonium chloride, and citrate, phosphate, boric acid, bicarbonate, sodium salts, or potassium. 【0010】 In certain embodiments, one or more viscosity modifiers are selected from the group consisting of petrolatum, liquid paraffin, light liquid paraffin, castor oil, mineral oil, cotton. Seed oil, soybean oil, sesame oil, corn oil, macrogol, butene, polyvinyl alcohol, polystyrene, polyacrylic acid, propylene glycol, propylene butoxide, hypromellose, talc, gelatin, hydrogenated rosin glycerol ester, aliphatic hydrocarbon resin, benzyl acetate, silicone, dimethylpolysiloxane, magnesium aluminum silicate, xanthan gum, sodium chondroitin sulfate, cyclodextrin, sodium alginate, propylene glycol alginate, carrageenan, glucono-lactone, squalene, stearyl alcohol, lanolin, gelatin, sorbitol, dextran, tragacanth, palmitic acid, hyaluronic acid, hydroxyethyl cellulose, hydroxypropyl cellulose, butylene glycol, polyoxyethylene polyoxypropylene glycol, polysorbate, sodium metaphosphate, methyl vinyl ester maleic anhydride copolymer gum, or a cellulose-based polymer. In some further embodiments, one or more viscosity modifiers are petrolatum or liquid paraffin. 【0011】 In certain embodiments, the composition comprises, consists essentially of, or consists of a final viscosity of at least about 1 mPaS to at least about 4000 mPaS, at least about 1 mPaS to at least about 1 mPaS, at least about 1 mPaS to at least about 5 mS, at least about 5 mPaS to at least about 50 mPaS, at least about 50 mPaS to at least about 100 mPaS, or at least about 100 mPaS to at least about 200 mPaS, or optionally about 100 mPaS, or about 150 mPaS, or about 160 mPaS, or about 170 mPaS, or about 180 mPaS, or about 190 mPaS, or about 200 mPaS at 25°C. In some further embodiments, the composition comprises, consists essentially of, or consists of a final viscosity of at least about 161 mPaS at 25°C. 【0012】 In certain embodiments, the composition has a final viscosity at 25 °C of at least about 500 mPaS to at least about 900 mPaS, or optionally about 500 mPaS, about 600 mPaS, about 700 mPaS, about 800 mPaS, about 850 mPaS, about 860 mPaS, about 870 mPaS, about 880 mPaS, about 890 mPaS, or about 900 mPaS, or consists essentially of or consists of the same. In some further embodiments, the composition has a final viscosity at 25 °C of at least about 867 mPaS, or consists essentially of or consists of the same. 【0013】 In certain embodiments, the composition has a final viscosity at 25 °C of at least about 1000 mPaS to at least about 2500 mPaS, or optionally at 25 °C about 1000 mPaS, about 1500 mPaS, about 2000 mPaS, about 2100 mPaS, about 2200 mPaS, about 2300 mPaS, about 2400 mPaS, or about 2500 mPaS, or is composed of or consists essentially of these. In some further embodiments, the composition has a final viscosity at 25 °C of at least about 2145 mPaS, or consists essentially of or consists of the same. 【0014】 In certain embodiments, the composition has a viscosity at 25 °C of at least about 3000 mPaS to at least about 4000 mPaS, or optionally about 3000 mPaS, about 3500 mPaS, about 3600 mPaS, about 3700 mPaS, about 3800 mPaS, about 3900 mPaS, or about 4000 mPaS, or consists essentially of or consists of the same. In some further embodiments, the composition has a viscosity at 25 °C of at least about 3815 mPaS, or consists essentially of or consists of the same. 【0015】 In certain embodiments, the one or more rifampicin compounds are rifampicin, the one or more viscosity modifiers are petrolatum, and the effective amount of rifampicin comprises, consists essentially of, or consists of a final concentration in the composition of at least about 0.001% w / w. In some embodiments, the one or more rifampicin compounds are rifampicin, the one or more viscosity modifiers are liquid paraffin, and the effective amount of rifampicin comprises a final concentration in the composition of at least about 0.001% w / w to about 1% w / w. In some embodiments, one or more rifamycin compounds are rifampicin, one or more viscosity modifiers are petrolatum, and the effective amount of rifampicin comprises a final concentration in the composition of at least about 0.001% w / w to about 1% w / w. In some embodiments, the one or more rifampicin compounds are rifampicin, the one or more viscosity modifiers are liquid paraffin, and the effective amount of rifampicin comprises a final concentration in the composition of at least about 0.001% w / w to about 1% w / w. 【0016】 In one embodiment, the effective amount of one or more rifamycin compounds or a pharmaceutically acceptable salt thereof is the only therapeutically active compound in the composition. 【0017】 In certain embodiments, the present disclosure provides a method for delivering one or more rifamycin compounds to the subretinal, scleral, retinal, and / or vitreous tissues, the method comprising, consisting essentially of, or consisting of topically administering to the eye any one of the compositions disclosed herein. 【0018】 In certain embodiments, the present disclosure provides a method for treating an angiogenesis eye disease, the method comprising, consisting essentially of, or consisting of topically administering to the eye any one of the compositions disclosed herein. In some embodiments of the method, the angiogenesis eye disease is selected from the group consisting of macular degeneration, diabetic retinopathy, chronic glaucoma, retinal detachment, sickle cell retinopathy, age-related macular degeneration (AMD), retinal ganglion cell damage, iris neovascularization, inflammatory diseases, chronic uveitis, neoplasms, Fuchs heterochromic iridocyclitis, neovascular glaucoma, corneal angiogenesis, choroidal angiogenesis, retinal angiogenesis, retinal vascular tumor proliferation, glaucoma, glaucoma surgery, tissue adhesion, scarring, tissue fibrosis, and brain injury. In some further embodiments, the angiogenesis eye disease is AMD. In some further embodiments, the angiogenesis eye disease is dry AMD. In some further embodiments, the angiogenesis eye disease is wet AMD. In some further embodiments, the angiogenesis eye disease is diabetic retinopathy. 【0019】 In some further embodiments, administration of the composition results in delivery of one or more rifamycin compounds to the subretinal, scleral, retinal, and / or vitreous tissues. In some further embodiments, administration of the composition results in delivery of one or more rifamycin compounds to the subretinal and scleral. In some further embodiments, administration of the composition inhibits angiogenesis in the subretinal tissue. 【0020】 In some further embodiments, topical administration of the composition results in at least about 5-fold, 10-fold, 50-fold, or 100-fold decrease in plasma exposure of one or more rifamycin compounds compared to oral administration at 300 mg. In some embodiments, topical administration of the composition results in at least about 100-fold decrease in plasma exposure of one or more rifamycin compounds compared to oral administration at 300 mg. BRIEF DESCRIPTION OF THE DRAWINGS 【0021】 【Figure 1-1】Figures 1A - 1H are histological sections of the retina treated with rifampicin topical eye drops, rifampicin SC injection, and vehicle - only controls with oxygen - induced retinopathy induced in the retina, and histological sections of the retina without induced retinopathy; and histological sections of the retina treated with rifampicin topical eye drops, rifampicin SC injection, and vehicle - only controls with oxygen - induced retinopathy induced in the retina, and histological sections of the retina without induced retinopathy. Figure 1A shows a 200x histological section of the retina treated with vehicle - only control. Figure 1B shows a 400x histological section of the retina treated with vehicle - only control. 【Figure 1-2】 Figure 1C shows a 200x histological section of the retina treated with rifampicin topical preparation. Figure 1D shows a 400x histological section of the retina treated with rifampicin topical preparation. 【Figure 1-3】 Figure 1E shows a 200x histological section of the retina treated with rifampicin SC injection. Figure 1F shows a 400x histological section of the retina treated with rifampicin SC injection. 【Figure 1-4】 Figure 1G shows a 200 - fold histological section of the retina without induced retinopathy. Figure 1H shows a 400 - fold histological section of the retina without induced retinopathy. 【Figure 2】 Figures 2A and 2B are graphs showing representative AUC (X - Fold AUC) vs viscosity data (mPaS). The AUC values evaluated in the sub - retinal and retinal tissues in the pharmacokinetic study were analyzed to determine the AUC correlation with the viscosity of Formulations A - F as described in Example 12. AUC (as X - fold AUC) was plotted against viscosity (mPaS) for each dose administered. Figure 2A shows AUC vs viscosity data for delivery to the sub - retinal tissue. Figure 2B shows AUC vs viscosity data for delivery to the retinal tissue. 【Figure 3-1】Figures 3A and 3B are diagrams showing the relationship between the viscosity and shear rate of oily formulations (A - F) and aqueous formulations (G, H, RK32) at 25°C. The relationship between the viscosity (mPaS) and shear rate (s-1) for each formulation is shown in the viscosity ranges of 0 mPaS to 200,000 mPaS (Figure 3A) and 0 mPaS to 100,000 mPaS (Figure 3B). The oily formulations A - E showed a shear rate of 200 s-1. The aqueous formulations G, H, and RK32 showed a shear rate of 200 s-1. 【Figure 3-2】 Figures 3A and 3B are diagrams showing the relationship between the viscosity and shear rate of oily formulations (A - F) and aqueous formulations (G, H, RK32) at 25°C. The relationship between the viscosity (mPaS) and shear rate (s-1) for each formulation is shown in the viscosity ranges of 0 mPaS to 200,000 mPaS (Figure 3A) and 0 mPaS to 100,000 mPaS (Figure 3B). The oily formulations A - E showed a shear rate of 200 s-1. The aqueous formulations G, H, and RK32 showed a shear rate of 200 s-1. 【Figure 4】 Figure 4 shows the chemical structures of exemplary suitable rifamycin compounds of the present disclosure. Two diagrams of rifamycin SV are provided. 【Mode for Carrying Out the Invention】 【0022】 To provide a substantial understanding of the present technology, it should be understood that specific aspects, modes, embodiments, variations, and features of the present method are described below in various levels of detail. 【0023】 This disclosure should not be limited to the specific embodiments described in this application, which are intended as a single illustration of individual aspects of this disclosure. Not all of the various embodiments of this disclosure are described herein. As will be apparent to those skilled in the art, many modifications and changes can be made to this disclosure without departing from the spirit and scope thereof. In addition to those listed herein, functionally equivalent methods and apparatuses within the scope of this disclosure will be apparent to those skilled in the art from the foregoing description. Such modifications and changes are intended to fall within the scope of the appended claims. This disclosure should be limited only by the terms of the appended claims, along with the full scope of equivalents to which such claims are entitled. 【0024】 It is to be understood that this disclosure is not limited to specific uses, methods, reagents, compounds, compositions, or biological systems, which can of course vary. Similarly, the terminology used herein is for the purpose of describing particular aspects only and is not to be construed as limiting. 【0025】 This disclosure demonstrates that administration of the ophthalmic compositions and formulations described herein delivers one or more rifamycin compounds to the posterior segment of the eye more efficiently than previous formulations. As demonstrated in the examples herein, administration of the ophthalmic compositions and formulations of this disclosure results in delivery of one or more rifamycin compounds to the posterior segment of the eye at a concentration effective to inhibit neovascularization. Accordingly, this disclosure provides improved compositions and formulations that can achieve more efficient delivery of one or more rifamycin compounds to the eye. The improved compositions and formulations of this technology are useful in methods for treating various eye diseases. 【0026】 Definitions Unless otherwise defined, all technical and scientific terms used herein have the meaning commonly understood by one of ordinary skill in the art to which this disclosure belongs. As used herein, the following terms have the meanings set forth below unless otherwise specified. The terms used herein are for the purpose of describing particular embodiments only and are not intended to be limiting of the disclosure. 【0027】 As used herein, the singular forms “a,” “an,” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. 【0028】 Unless otherwise indicated, all numbers expressing amounts of ingredients, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about.” As used herein, the term “about” or “approximately” means within an acceptable error range for a particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, i.e., the limitations of the measurement system. For example, “about” can mean within 3 or more standard deviations, per the practice in the art. Alternatively, “about” can mean within 20%, 10%, 5%, or 1% of a given value. Alternatively, especially with respect to biological systems or processes, the term can mean within an order of magnitude, within 5-fold, or within 2-fold of a value. 【0029】 Combinations of substituents and variables are only those that result in the formation of stable compounds. The term “stable” as used herein refers to compounds that have sufficient stability to permit their formation and maintain their integrity for a sufficient period of time so that the compounds are useful for the purposes detailed herein (e.g., 2 hours, 5 hours, 10 hours, 1 day and night, 1 day, 2 days, 3 days, 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 6 months, 1 year, 2 years, and 3 years). 【0030】 As used herein, "control" is an alternative sample used in an experiment for comparison purposes. A control can be "positive" or "negative". For example, if the purpose of the experiment is to determine the correlation of the efficacy of a therapeutic agent for the treatment of a particular type of disease, a positive control (a composition known to exhibit the desired therapeutic effect) and a negative control (a subject or sample that has not received treatment or has received a placebo) are typically used. 【0031】 As used herein, the terms "effective amount" or "therapeutically effective amount" refer to an amount of an agent sufficient to achieve the desired therapeutic effect. In the context of therapeutic applications, the amount of a therapeutic agent administered to a subject can depend on the type and severity of the infection, as well as individual characteristics such as general health, age, sex, weight, and drug tolerance. It can also depend on the degree, severity, and type of the disease. One of ordinary skill in the art can determine the appropriate dosage according to these and other factors. 【0032】 The terms "carrier" and "vehicle" as used herein refer to a relatively non-toxic chemical compound or agent that facilitates the incorporation of a compound into cells, such as cells of the eye or tissue. Carriers and vehicles useful herein include any given material known in the art that is non-toxic and does not interact with other components of the formulation in a detrimental manner. As used herein, the term "pharmaceutically acceptable carrier" includes any given excipient, as well as all solvents, dispersion media, coatings, wetting agents (e.g., sodium lauryl sulfate), isotonic and absorption delaying agents, disintegrating agents (e.g., potato starch or sodium starch glycolate), and tonicity adjusting agents. 【0033】 Examples of excipients of the present disclosure include one or more "viscosity modifiers". As used herein, "viscosity modifier" refers to one or more relatively non-toxic chemical compounds or agents that change the viscosity of a pharmaceutical ingredient and / or formulation. Representative examples of viscosity modifiers include petrolatum, liquid paraffin, light liquid paraffin, castor oil, mineral oil, cottonseed oil, soybean oil, sesame oil, corn oil, macrogol, butene, polyvinyl alcohol, polystyrene, polyacrylic acid, propylene glycol, propylene butoxide, hypromellose, talc, gelatin, hydrogenated rosin glycerol ester, aliphatic hydrocarbon resin, benzyl acetate, silicone, dimethylpolysiloxane, magnesium aluminum silicate, xanthan gum, sodium chondroitin sulfate, cyclodextrin, sodium alginate, propylene glycol alginate, carrageenan, glucono-lactone, squalene, stearyl alcohol, lanolin, gelatin, sorbitol, dextran, tragacanth, palmitic acid, hyaluronic acid, hydroxyethyl cellulose, hydroxypropyl cellulose, butylene glycol, polyoxyethylene polyoxypropylene glycol, polysorbate, sodium metaphosphate, methyl vinyl ester maleic anhydride copolymer, locust bean gum, cellulose-based polymers, and the like. 【0034】 Other representative examples of excipients of the present disclosure include antioxidants (such as thiosulfate, sodium thiosulfate, sodium formaldehyde sulfoxylate, sodium formaldehyde sulfoxylate dihydrate, etc.) and tonicity modifiers (such as sodium chloride, etc.). 【0035】 As used herein, the term "surfactant" refers to any given molecule having both a polar head group that is energetically favorable for solvation by water and a hydrophobic tail that is not sufficiently solvated by water. The surfactant can be an ionic or non-ionic surfactant. The term "ionic surfactant" includes cationic, anionic, and zwitterionic surfactants. The term "cationic surfactant" refers to a surfactant having a cationic head group. The term "anionic surfactant" refers to a surfactant having an anionic head group. 【0036】 As used herein, the terms "pharmaceutically acceptable" or "pharmacologically acceptable" when used herein, when administered to a host (e.g., an animal or a human), generally refer to a composition that is safe, non-toxic, not biologically or otherwise undesirable, and that does not substantially produce harmful allergic or immune reactions. Such formulations include any pharmaceutically acceptable dosage form. 【0037】 As used herein, the terms "pharmaceutically acceptable salt" or "a salt thereof" mean a salt that is pharmaceutically acceptable as defined above and has the desired pharmacological activity. Such salts include acid addition salts formed with organic and inorganic acids such as hydrogen chloride, hydrogen bromide, hydrogen iodide, sulfuric acid, phosphoric acid, acetic acid, glycolic acid, maleic acid, malonic acid, oxalic acid, methanesulfonic acid, trifluoroacetic acid, fumaric acid, succinic acid, tartaric acid, citric acid, benzoic acid, and ascorbic acid. Base addition salts are formed with organic and inorganic bases such as sodium, ammonia, potassium, calcium, ethanolamine, diethanolamine, N-methylglucamine, and choline. All pharmaceutically acceptable salts or compounds represented by the formulas used herein are included. 【0038】 As used herein, the term "pharmaceutically acceptable salt" refers to salts of the compounds with pharmaceutically acceptable organic or inorganic acids or bases, depending on their structure. Representative examples of such pharmaceutically acceptable salts include alkali metal salts (4,4-diaminostilbene-2-disulfonate), ammonium salts, alkaline earth salts, ammonium salts, benzoates, bisulfates, bicarbonates, bicarbonates, calcium acetate, acetates, citrates, clubranates, dihydrochlorides, edisylates, esylates, fumarates, gluconates, glutamates, glycolylarsanilic acid salts, hexafluorophosphates, hexylresorcinates, hydrobromides, hydroxynaphthoates, isothionates, lactates, laurates, maleates, maleates, mesylates, methyl bromide, methyl sulfate, mucates, napsylates, N-methylglucamine ammonium salts, 3-hydroxy-2-carboxylic acid, oleic acid, palmitic acid, palmitic acid, polygalacturonic acid, propionic acid, p-toluenesulfonic acid, salicylic acid, stearic acid, subsalicylates, succinates, sulfates, subsalicylates, tannates, tartrates, theoclinates, tosylates, triethyl iodide, valerates. 【0039】 As used herein, the term "hydrate" means a form of a compound in which water molecules are combined in specific ratios as an essential part of the structural complex of the compound. 【0040】 As used herein, the term "solvate" means a form of a compound in which solvent molecules are combined in specific ratios as an essential part of the structural complex of the compound. 【0041】 As used herein, the term "prodrug" means a compound that, upon administration, is metabolized or otherwise converted to an active or more active form with respect to at least one property. To produce a prodrug, a pharmaceutically active compound is chemically modified so as to render it less active or inactive, but such chemical modification is such that the active form of the compound is produced by metabolism or other biological processes. A prodrug may have altered metabolic stability or transport properties, fewer side effects, or lower toxicity compared to the drug (Nogrady, 1985, Medicinal Chemistry A Biochemical Approach, Oxford University Press, New York, pages 388-392). A prodrug can also be prepared using a compound that is not a drug. 【0042】 The term "ophthalmically acceptable" with respect to a formulation, composition, or component of the present disclosure indicates that the formulation, composition, or component does not have a persistent adverse effect on the eye being treated or its function, or on the overall health of the subject being treated, and exhibits transient effects such as mild irritation or a "stinging" sensation. 【0043】 The term "active agent" or "active ingredient" is used herein to refer to a chemical substance or compound that induces a desired beneficial effect when administered to a patient. Also included are salts, derivatives, and analogs of specifically recited compounds or classes of compounds (e.g., rifamycin compounds) that also induce the desired effect. For example, the term "rifampicin" as used herein includes its pharmaceutically acceptable salts and its derivatives. 【0044】 The term "buffer solution" or "buffer" refers to a material that, when added to a solution, causes the solution to resist changes in its pH value. 【0045】 The term "dilution" refers to the dilution of the formulations of the present invention or those derived from the formulations of the present invention, using an aqueous system composed of, for example, physiologically balanced physiological saline (PBS), for example, phosphate buffered saline, or water, or other water-soluble components, to a desired final concentration. 【0046】 As used herein, the terms "final concentration" and "final concentration in a composition" refer to the concentration of the indicated component in a complete composition, formulation, pharmaceutical composition, or any other medium thereof. The final concentration is relative to the final amount of the complete composition, formulation, pharmaceutical composition, or any other medium thereof, and includes, but is not limited to, pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solutions, dispersions, suspensions, emulsions, or sterile powders for use in the methods and compositions provided herein. The final concentration can be expressed in any concentration unit known in the art, including, but not limited to, weight % or mass % of the composition, % w / w, % w / v, M, g / 100 mL, etc. 【0047】 As used herein, the terms "increasing" or "enhancing" have the meaning of a positive change of at least about 5%, for example, but not limited to, about 5%, about 10%, about 25%, about 30%, about 50%, about 75%, or about 100%. 【0048】 As used herein, the term "ligand" refers to a molecule that binds to a receptor. In particular, a ligand binds to a receptor on another cell, enabling cell-cell recognition and / or interaction. 【0049】 The terms "polypeptide", "peptide", and "protein" are used interchangeably herein to refer to a polymer of amino acid residues. This term applies to naturally occurring amino acid polymers, as well as amino acid polymers in which one or more amino acid residues are non-naturally occurring amino acids, for example, amino acid analogs. This term encompasses amino acid chains of any length, including full-length proteins, in which the amino acid residues are linked by covalent peptide bonds. 【0050】 As used herein, the term "reduce" has the meaning of causing a negative change of at least about 5%, such as, but not limited to, about 5%, about 10%, about 25%, about 30%, about 50%, about 75%, or about 100%. 【0051】 As used herein, the terms "subject", "individual", or "patient" are used interchangeably and refer to an individual organism, vertebrate, or mammal, including a human, non-human primate, rodent, domestic animal species, wild animal, etc. (e.g., a subject that should be the recipient of a particular treatment or from which cells are to be harvested). In certain embodiments, the individual, patient, or subject is human. 【0052】 As used herein, the term "administration" of an agent to a subject includes any route by which the agent is introduced or delivered to the subject to perform its intended function. Administration can be by any suitable route, including, but not limited to, ocular, topical, intravenous, intramuscular, intraperitoneal, subcutaneous, and other suitable routes described herein. The methods and compositions of the present disclosure preferably include intravitreal administration, administration to the eye, or topical administration to the eye. As used herein, both intravitreal administration and intraocular administration refer to the introduction or delivery of the agent to the subject that is effected by the introduction or delivery of the agent to the eye. Administration includes self-administration and administration by another person. 【0053】 As used herein, the terms "treat", "treating", or "treatment" include alleviating, reducing, or ameliorating a disease or condition, or preventing one or more of its symptoms, preventing additional symptoms, ameliorating or preventing the underlying metabolic cause of the symptoms, inhibiting a disease or condition, e.g., arresting or suppressing the onset of a disease or condition, reducing a disease or condition, causing regression of a disease or condition, alleviating a condition caused by a disease or condition, or suppressing the symptoms of a disease or condition, and are intended to include prevention. The term also includes reducing a disease or condition, e.g., causing regression of clinical symptoms. The term further includes achieving a therapeutic and / or prophylactic benefit. Such a therapeutic benefit is intended to mean eradication or amelioration of the underlying disease being treated. Also, such a therapeutic benefit is achieved by eradication or amelioration of one or more physiological symptoms associated with the underlying disease such that improvement is observed in the individual, even though the individual still suffers from the underlying disease. For prophylactic benefit, the composition is administered to an individual at risk of developing a particular disease or to an individual reporting one or more of the physiological symptoms of a disease, even though the disease has not yet been diagnosed in the individual. As used herein, "treating" or "treatment" in a subject such as a human encompasses treatment of a disease or disorder described herein, including (i) inhibiting the disease or disorder, i.e., arresting its onset; (ii) reducing the disease or disorder, i.e., causing regression of the disorder; (iii) retarding the progression of the disorder; and / or (iv) inhibiting, reducing, or retarding the progression of one or more symptoms of the disease or disorder. The therapeutic effects of treatment include, but are not limited to, inhibiting recurrence of the disease, alleviating symptoms, reducing any direct or indirect pathological consequence of the disease, preventing metastasis, reducing the rate of disease progression, improving or alleviating the disease state, and improving remission or prognosis.Also, the various treatment modalities for the diseases described herein are intended to mean "substantial", which includes, although not entirely, less than total treatment, and it should be understood that some biologically or medically relevant results are achieved. In certain embodiments, the treatment is a continuous long-term treatment of a chronic disease, or a single or multiple administrations for the treatment of an acute condition. 【0054】 The terms "prevent" or "prevention" refer to reducing the risk of acquiring a disease or disorder (i.e., in a subject who is exposed to the disease or has a predisposition thereto but has not yet experienced or presented with symptoms of the disease, not developing at least one of the clinical symptoms of the disease). The term further includes not developing clinical symptoms, for example, in a subject at risk of developing such a disease or disorder, thereby substantially avoiding the onset of the disease or disorder. 【0055】 The term "macular degeneration" refers to various degenerative conditions characterized by loss of central vision due to deterioration of the macula. One of these conditions is age-related macular degeneration (AMD), which exists in both "dry" and "wet" forms. 【0056】 The term "ocular angiogenesis" refers to the abnormal development, proliferation, and / or growth of blood vessels on or in the eye, for example, on the surface of the retina. 【0057】 Ophthalmic composition Rifamycin compound In certain embodiments, the present disclosure provides an ophthalmic composition comprising, consisting essentially of, or further comprising an effective amount of one or more rifamycin compounds or a pharmaceutically acceptable salt thereof. The rifamycin class of antibiotics was originally isolated from cultures of Streptomyces mediterranei. Due to the large number of synthetically generated available analogs and derivatives, rifamycins are widely used in the elimination of pathogenic bacteria that have become resistant to commonly used antibiotics. Rifamycins are effective against mycobacteria and are therefore used in the treatment of chronic infections including tuberculosis (TB), leprosy, and Mycobacterium avium complex (MAC) infections. Tuberculosis is known to affect other organs including eye tissues in addition to its effects on the lungs. Therefore, the effect of rifamycins on ocular tuberculosis and other eye disorders is a targeted area of research of interest in the art. Rifampicin has been shown to exhibit a potent anti-angiogenic effect, strongly inhibiting major angiogenic genes such as VEGF and HGF. 【0058】 Examples of suitable rifamycin compounds of the present disclosure include rifampicin (rifampin), rifabutin, rifapentine, rifalazil, rifaximin, rifamycin SV, 3-formylrifamycin, rifamycin B, or a pharmaceutically acceptable salt or derivative thereof. Suitable rifamycin compounds of the present disclosure are commercially available, for example, from Sigma-Aldrich or can be prepared by known procedures. The chemical structures of exemplary suitable rifamycin compounds of the present disclosure are shown in FIG. 4. The synthesis of simple rifamycin derivatives is well known in the art. For example, the syntheses of rifampin (U.S. Patent No. 3,342,810), rifabutin (U.S. Patent No. 4,219,478), and rifalazil (U.S. Patent No. 4,983,602) are known in the art and are incorporated herein by reference. 【0059】 In one aspect, the present disclosure provides an ophthalmic composition comprising, consisting essentially of, or further comprising an effective amount of one or more rifamycin compounds or a pharmaceutically acceptable salt thereof. In some embodiments, the one or more rifamycin compounds are selected from the group consisting of rifamycin SV, 3-formylrifamycin SV, rifampicin, rifabutin, rifapentine, and rifaximin. In some embodiments, the one or more rifamycin compounds are rifamycin SV. In some embodiments, the one or more rifamycin compounds are 3-formylrifamycin SV. In some embodiments, the one or more rifamycin compounds are rifampicin. In some embodiments, the one or more rifamycin compounds are rifabutin. In some embodiments, the one or more rifamycin compounds are rifapentine. In some embodiments, the one or more rifamycin compounds are rifaximin. 【0060】 In some embodiments, the concentration of one or more rifamycin compounds is suitably determined in the range of about 0.00001% w / w to about 50% w / w. As used herein, “% w / w” indicates the proportion or weight concentration of a substance within a mixture, measured by weight or mass. In some embodiments, the effective amount of one or more rifamycin compounds includes a final concentration in the composition of at least about 0.05% w / w, at least about 0.1% w / w, at least about 2% w / w, at least about 0.25% w / w, at least about 0.3% w / w, at least about 0.35% w / w, at least about 0.4% w / w, at least about 0.45% w / w, at least about 0.5% w / w, at least about 0.55% w / w, at least about 0.6% w / w, at least about 0.65% w / w, at least about 0.7% w / w, at least about 0.75% w / w, at least about 0.8% w / w, at least about 0.85% w / w, at least about 0.9% w / w, at least about 0.95% w / w, at least about 1% w / w, at least about 1.05% w / w, at least about 1.1% w / w, at least about 1.15% w / w, at least about 1.2% w / w, at least about 1.25% w / w, at least about 1.3% w / w, at least about 1.35% w / w, at least about 1.4% w / w, at least about 1.45% w / w, or at least about 1.5% w / w. In some embodiments, the effective amount of one or more rifamycin compounds is such that the final concentration in the composition is at least 0.25 to at least 1.5% w / w, or at least 0.5 to at least 1.5% w / w, or at least 0.75 to at least 1.5% w / w, or at least 1 to at least 1.5% w / w, or at least 1.5 to at least 3% w / w, or at least 3 to at least 5% w / w, or at least 5% w / w. 【0061】 In some embodiments, the effective amount of one or more rifamycin compounds is such that the final concentration in the composition is from about 0.00001% w / w to 0.0001% w / w, from about 0.0001% w / w to about 0.0005% w / w, from about 0.0005% w / w to about 0.001% w / w, from about 0.001% w / w to about 0.005% w / w, from about 0.005% w / w to about 0.01% w / w, from about 0.01% w / w to about 50% w / w, from about 0.01% w / w to about 0.05% w / w to about 0.1% w / w, from about 0.05% w / w to about 40% w / w, from about 0.1% w / w to about 0.25% w / w to about 30% w / w, from about 0.5% w / w to about 20% w / w, from about 0.5% w / w to about 1.0% w / w, from about 1.0% w / w to about 2.0% w / w, from about 2.0% w / w to about 5.0% w / w, from about 1.0% w / w to about 10% w / w, from about 1.5% w / w to about 5% w / w, from about 2.0% w / w to about 3.0% w / w, from about 5.0% w / w to about 10.0% w / w. In some embodiments, the effective amount of one or more rifamycin compounds is about 50% w / w, 30% w / w, 20% w / w, 10% w / w, about 8% w / w, about 7% w / w, about 5% w / w, about 4% w / w, about 3.5% w / w, about 3% w / w, about 2.5% w / w, about 2% w / w, about 1.5% w / w, about 1% w / w, about 0.25% w / w, about 0.1% w / w, about 0.05% w / w, about 0.01% w / w, about 0.005% w / w, about 0.002% w / w, about 0.001 w / w, about 0.0001% w / w, or about 0.00001%. 【0062】 In some embodiments, the lower limit of the effective amount of one or more rifamycin compounds includes the final concentration in a composition selected from the range of about 0.00001% w / w to about 50% w / w, and can be set, for example, at about 0.00001% w / w, 0.0001% w / w, 0.0005% w / w, 0.001% w / w, or 0.005% w / w (however, it is not limited to such % w / w). In some embodiments, the upper limit of the effective amount of one or more rifamycin compounds includes the final concentration in a composition selected from the above range, and can be, for example, about 50% w / w, 40% w / w, 30% w / w, or 20% w / w. 【0063】 In some embodiments, the concentration of one or more rifamycin compounds can be appropriately determined in the range of about 0.0001% by weight to about 50% by weight. As used herein, "weight %" can be expressed as "g / 100 mL of composition" or "weight / volume (w / v)". 【0064】 In some embodiments, the lower limit of the effective amount of one or more rifamycin compounds includes the final concentration in a composition selected from the range of about 0.00001% by weight to about 50% by weight, and can be set, for example, at about 0.00001% by weight, 0.0001% by weight, 0.0005% by weight, 0.001% by weight, or 0.005% by weight (however, it is not limited thereto). In some embodiments, the upper limit of the effective amount of one or more rifamycin compounds includes the final concentration in a composition selected from the above range, and can be, for example, about 50% by weight, 40% by weight, 30% by weight, or 20% by weight. 【0065】 In some embodiments, the effective amount of one or more rifamycin compounds is from about 0.00001 wt% to about 0.0001 wt%, from about 0.0001 wt% to about 0.0005 wt%, from about 0.0005 wt% to about 0.001 wt%, from about 0.001 wt% to about 0.005 wt%, from about 0.005 wt% to about 0.01 wt%, from about 0.01 wt% to about 50 wt%, from about 0.01 wt% to about 0.05 wt%, from about 0.05 wt% to about 0.1 wt%, from about 0.05 wt% to about 40 wt%, from about 0.1 wt% to about 0.25 wt%, from about 0.1 wt% to about 30 wt%, including the final concentration in a composition of from 0.5 wt% to about 20 wt%, from 0.5 wt% to about 20 wt%, from 0.5 wt% to about 1.0 wt%, from 1.0 wt% to about 2.0 wt%, from 2.0 wt% to about 5.0 wt%, from 1.0 wt% to about 10 wt%, from 1.5 wt% to about 5 wt%, from 2.0 wt% to about 3.0 wt%, from 5.0 wt% to about 10.0 wt%, and ranges between any given two of these values, or values lower than any given value from these values. In some embodiments, the effective amount of one or more rifamycin compounds in the composition is at a final concentration of about 50 wt%, 30 wt%, 20 wt%, 10 wt%, about 8 wt%, about 7 wt%, about 5 wt%, about 4 wt%, about 3.5 wt%, about 3 wt%, about 2.5 wt%, about 2 wt%, about 1.5 wt%, about 1 wt%, about 0.5 wt%, about 0.25 wt%, about 0.1 wt%, about 0.05 wt%, about 0.01 wt%, about 0.005 wt%, about 0.002 wt%, about 0.001 wt%, about 0.0005 wt%, about 0.0001 wt%, or about 0.00001%. 【0066】 Buffer In one aspect, the ophthalmic composition of the present disclosure includes one or more buffering agents. The buffering agent can be a weak acid or a weak base present in the composition to maintain the pH of the composition. In some embodiments, the ophthalmic composition of the present disclosure comprises, consists essentially of, or consists of one or more buffering agents for maintaining the pH of the composition. In some embodiments, the pH of the ophthalmic composition of the present disclosure is, for example, a pH value of about 1 to 12, a pH value of about 2 to 12, a pH value of about 3 to 9, or a pH value of about 3 to 7.5. The pH value of the ophthalmic composition of the present disclosure can be adjusted to the first, second, or third decimal place. For example, when adjusting the pH to the third decimal place, the lower limit value is, for example, 1.000, 2.000, 3.000, 4.000, 5.000, etc., and the upper limit value is, for example, 12.000, 11.000, 10.000, 9.000, 8.000, etc. 【0067】 In some embodiments, the ophthalmic composition of the present disclosure further comprises, consists essentially of, or consists of one or more buffering agents.In some embodiments, one or more buffers are selected from the group consisting of acetic acid, boric acid, citric acid, phosphoric acid, hydrochloric acid, glycine, citrate phosphate, succinic acid, maleic acid, cacodylic acid, tris (tris hydroxymethyl aminomethane), barbituric acid, 2-amino-2-methyl-1,3-propanediol (ammediol), sodium bicarbonate, HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), ACES (N-(2-acetamido)iminodiacetic acid), BES (N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid), bis(N,N-bis(2-hydroxyethyl)glycine), bistris(bis(2-hydroxyethyl)iminotris)(hydroxymethyl)methane, CAPS (N-cyclohexyl-3-aminopropanesulfonic acid)), CAPSO (N-cyclohexyl-2-aminopropanesulfonic acid), CHES (N-cyclohexyl-2-aminoethanesulfonic acid), DIPSO (3-[4-(2-hydroxyethyl)-1-piperazinyl]propanesulfonic acid), HEPES-Na (2-[4-(2-hydroxyethyl)-1-piperazinyl]ethanesulfonic acid sodium), HEPPSO (2-hydroxy-3-[4-(2-hydroxyethyl)-1-piperazinyl]propanesulfonic acid, monohydrate), MES (2-morpholinoethanesulfonic acid), MOPSO (2-hydroxy-3-morpholinopropanesulfonic acid), PIPES (piperazine-1,4-bis(2-ethanesulfonic acid)), POPSO (piperazine-1,4-bis(2-hydroxy-3-propanesulfonic acid), TAPSO (2-hydroxy-N-tris)hydroxymethyl)methyl-3-aminopropanesulfonic acid, TES (N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid), tricine (N-[tris(hydroxymethyl)methyl]glycine), and hydrochloric acid; bases such as sodium hydroxide, sodium phosphate, sodium borate, sodium citrate, sodium acetate, and sodium lactate; and buffers such as citrate / dextrose, sodium bicarbonate, and ammonium chloride, and combinations thereof including citrate, phosphate, borate, bicarbonate, sodium salts and potassium salts. 【0068】 In some embodiments, the ophthalmic composition of the present disclosure comprises, consists essentially of, or consists of one or more buffering agents. In some embodiments, the one or more buffering agents are Tris. Examples of representative Tris buffers used in the present disclosure include Tris-HCl buffer, TE buffer (e.g., having a composition of 10 mM Tris / Tris-HCl and 1 mM EDTA), TAE buffer (e.g., having a composition of 40 mM Tris / Tris-acetate and 1 mM EDTA), TBE buffer (e.g., having a composition of 89 mM Tris / Tris-borate and 2 mM EDTA), and TBS (e.g., having a composition of 10 mM Tris / Tris-HCl and 150 mM NaCl), but are not limited thereto. 【0069】 In some embodiments, the ophthalmic composition of the present disclosure comprises, consists essentially of, or consists of one or more buffering agents. In some embodiments, the buffering agent is present in the composition at a final concentration of from about 1 mM to about 100 mM. In some embodiments, the buffering agent is present in the composition at a final concentration of from about 10 mM to about 100 mM. In some embodiments, the buffering agent is present in the composition at a final concentration of from about 20 mM to about 100 mM. In some embodiments, the buffering agent is present in the composition at a final concentration of from about 30 mM to about 100 mM. In some embodiments, the buffering agent is present in the composition at a final concentration of from about 40 mM to about 100 mM. In some embodiments, the buffering agent is present in the composition at a final concentration of from about 50 mM to about 100 mM. In some embodiments, the buffering agent is present in the composition at a final concentration of from about 60 mM to about 100 mM. In some embodiments, the buffering agent is present in the composition at a final concentration of from about 70 mM to about 100 mM. In some embodiments, the buffering agent is present in the composition at a final concentration of from about 80 mM to about 100 mM. In some embodiments, the buffering agent is present in the composition at a final concentration of from about 90 mM to about 100 mM. In some embodiments, the buffering agent is present in the composition at a final concentration of about 1 mM, about 2 mM, about 3 mM, about 4 mM, about 5 mM, about 6 mM, about 7 mM, about 8 mM, about 9 mM, about 10 mM, about 15 mM, about 20 mM, about 25 mM, about 30 mM, about 40 mM, about 50 mM, about 60 mM, about 70 mM, about 80 mM, about 90 mM, or about 100 mM. 【0070】 Pharmaceutically acceptable carrier In some embodiments, the ophthalmic composition of the present disclosure comprises, consists essentially of, or further consists of a pharmaceutically acceptable carrier. The pharmaceutically acceptable carriers for the compositions of the present invention are not limited, but can include amino acids, peptides, biological polymers, non-biological polymers, monosaccharides or starches, inorganic salts, and gums, which can be present alone or in combinations thereof. Peptides used in acceptable carriers can include, for example, gelatin and / or albumin. Cellulose or its derivatives can be used in pharmaceutically acceptable carriers. The sugars used in acceptable carriers can be lactose and / or glucose. Other useful sugars that can be utilized in pharmaceutical compositions include, but are not limited to, fructose, galactose, lactitol, maltitol, maltose, mannitol, melibiose, myo-inositol, palatinose, raffinose, stachyose, sucrose, trehalose, xylitol, hydrates thereof, and combinations thereof. Binders can be included in pharmaceutically acceptable carriers. Examples of binders include, but are not limited to, starches (e.g., corn starch or potato starch), gelatin; natural or synthetic gums such as acacia, sodium alginate, powdered tragacanth, guar gum, cellulose or cellulose derivatives (e.g., methylcellulose, ethylcellulose, cellulose acetate); microcrystalline cellulose, polyvinylpyrrolidone, and mixtures thereof. The inorganic salts used in acceptable carriers can be magnesium salts, for example, magnesium chloride or magnesium sulfate. Other inorganic salts, such as calcium salts, can be used. Examples of calcium salts include, but are not limited to, calcium chloride, calcium sulfate.Other examples of substances that can be used as pharmaceutically acceptable carriers include vegetable oils such as peanut oil, cottonseed oil, olive oil, corn oil; polyols such as glycerin, propylene glycol, polyethylene glycol; water free of pyrogens, isotonic saline, phosphate buffer solutions; emulsifiers such as Tweens®; wetting agents, lubricants, coloring agents, flavoring agents, preservatives, but are not limited thereto. 【0071】 In some embodiments, the pharmaceutically acceptable carrier is greater than 90%, greater than 80%, greater than 70%, greater than 60%, greater than 50%, greater than 40%, greater than 30%, greater than 10%, greater than 9%, greater than 8%, greater than 6%, greater than 5%, greater than 4%, greater than 3%, greater than 2%, greater than 1%, greater than 0.5%, greater than 0.4%, greater than 0.3%, greater than 0.2%, greater than 0.1%, greater than 0.09%, greater than 0.08%, greater than 0.07%, greater than 0.06%, greater than 0.05%, greater than 0.04%, greater than 0.03%, greater than 0.008%, greater than 0.007%, greater than 0.006%, greater than 0.005%, greater than 0.004%, greater than 0.003%, greater than 0.002%, greater than 0.001%, greater than 0.0009%, greater than 0.0008%, greater than 0.0007%, greater than 0.0006%, greater than 0.0005%, greater than 0.0004%, greater than 0.0003%, greater than 0.0002%, or greater than 0.0001% of the pharmaceutical composition (w / w, w / v or v / v). 【0072】 Surfactant In some embodiments, the ophthalmic composition of the present disclosure comprises, consists essentially of, or consists of one or more surfactants. Surfactants that can be used to form the pharmaceutical compositions and dosage forms of the present application include, but are not limited to, hydrophilic surfactants, lipophilic surfactants, and mixtures thereof. That is, mixtures of hydrophilic surfactants can be used, mixtures of lipophilic surfactants can be used, or mixtures of at least one hydrophilic surfactant and at least one lipophilic surfactant can be used. 【0073】 Suitable surfactants are known in the art and include, but are not limited to, sorbitan ether esters of oleic acid (e.g., polysorbate 80 or Tween 20 and 80), polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, Cremophor, sodium alkylbenzene sulfonate, glycerol, lecithin, sucrose ester, polyoxyethylene alkyl ether, polyoxyl stearate, polyoxyl 40 stearate, ethylene glycol stearate, ethylene glycol monostearate, polyethylene glycol monostearate, oxyethylated octylphenol (tyloxapol), propylene glycol, benzyl alcohol, macrogol, cyclodextrin, dibutylhydroxytoluene, sorbitol, tromethamine, propylene glycol, mannitol, and polyoxyethylene polyoxypropylene glycol (e.g., polyoxyethylene (160) polyoxypropylene (30) glycol, or polyoxyethylene (200) polyoxypropylene (70) glycol), or combinations thereof. In some embodiments, the ophthalmic composition comprises, consists essentially of, or consists of polysorbate 80, polyoxyethylene hydrogenated castor oil, lecithin, or combinations thereof. 【0074】 Suitable hydrophilic surfactants can generally have an HLB value of at least 10, while suitable lipophilic surfactants can generally have an HLB value of about 10 or less. A useful parameter that can be used to characterize the relative hydrophilicity and hydrophobicity of nonionic amphiphilic compounds is the hydrophilic-lipophilic balance (the "HLB" value). Surfactants with lower HLB values are more hydrophobic and have higher solubility in oil, while surfactants with higher HLB values are more hydrophilic and have higher solubility in aqueous solutions. Hydrophilic surfactants are generally considered to be compounds with an HLB value exceeding about 10, as well as anionic, cationic, or zwitterionic compounds for which the HLB scale is generally not applicable. Similarly, lipophilic (i.e., hydrophobic) surfactants are generally considered to be compounds with an HLB value of about 10 or less. However, the HLB value of a surfactant only provides a rough guide that is generally used to enable the formulation of industrial, pharmaceutical, and cosmetic emulsions. 【0075】 Hydrophilic surfactants can be either ionic or nonionic. Suitable ionic surfactants include alkylammonium salts, fatty acid derivatives of amino acids, glyceride derivatives of amino acids, fusidate salts, oligopeptides, and polypeptides, oligopeptides, and polypeptides, lecithin and hydrogenated lecithin, lysophosphatidylcholine and hydrogenated lysophosphatidylcholine, phospholipids and their derivatives, fatty acid salts, lysophospholipids and their derivatives, carnitine fatty acid ester salts, salts of alkyl sulfates, sodium docecyl sulfate, acyl lactylates, mono- and diacetyl tartrate esters of mono- and diglycerides, succinylated mono- and diglycerides, mono- and diacetyl tartrate esters of mono- and diglycerides, citrate esters of mono- and diglycerides, and mixtures thereof, but are not limited thereto. 【0076】 Among the aforementioned groups, examples of the ionic surfactant include, but are not limited to, lecithin, lysolecithin, phospholipids, lysophospholipids and their derivatives, carnitine fatty acid ester salts, fatty acid salts, salts of alkyl sulfates, sodium dobesilate, acyl lactylates, mono- and diacetyl tartrate esters of mono- and diglycerides, succinylated mono- and diglycerides, citrate esters of mono- and diglycerides, and mixtures thereof. The ionic surfactant can also include, but is not limited to, alkyl diaminoethyl glycine hydrochloride solution, benzododecinium bromide, benzalkonium chloride, benzethonium chloride, sodium polystyrene sulfonate, benzoic acid (benzoate), ethylenediaminetetraacetic acid, thimerosal, sodium thiosulfate, citric acid (citrate), glutamic acid (glutamate), sorbic acid, sodium dehydroacetate, and acetate. 【0077】 The ionic surfactant is a lactic acid ester of fatty acid, lecithin, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylserine, lysophosphatidylserine, lysophosphatidylserine, lysophosphatidylglycerol, lysophosphatidylglycerol, PEG-phosphatidylethanolamine, stearoyl-2-lactylate, stearoyl lactylate, mono / diacetyl tartrate esters of mono / diglycerides, citrate esters of mono / diglycerides, cocoyl sarcosine, caprylate, caprylate, laurate, myristate, palmitate, oleate, linoleate, stearate, ricinoleate, lauryl sulfate, docetate, lauroyl carnitine, palmitoyl carnitine, myristoyl carnitine, and their salts and mixtures. 【0078】 Hydrophilic nonionic surfactants include alkyl glucosides, alkyl thioglucosides, alkyl maltosides, lauryl macrogol glycerides, polyoxyalkylene alkyl ethers, polyethylene glycol alkyl ethers such as polyethylene glycol alkyl phenols, polyethylene glycol fatty acid esters, polyoxyalkylene alkyl phenol fatty acid monoesters and polyethylene glycol fatty acid diesters, polyoxyethylene polyoxypropylene block copolymers and mixtures thereof, polyoxyalkylene fatty acid esters such as polyethylene glycol sorbitan fatty acid esters, hydrophilic transesterification products of polyols, glycerides, vegetable oils, hydrogenated vegetable oils, fatty acids and sterols, polyoxyethylene sterols and their derivatives, polyoxyethylated vitamins and their derivatives, polyethylene glycol sorbitan fatty acid esters and at least one hydrophilic transesterification product composed of polyols, triglycerides, vegetable oils, hydrogenated vegetable oils are included, but not limited thereto. The polyol can be glycerol, ethylene glycol, polyethylene glycol, sorbitol, propylene glycol, pentaerythritol, or a sugar. 【0079】 Examples of other hydrophilic nonionic surfactants include, but are not limited to, PEG-10 laurate, PEG-12 laurate, PEG-12 oleate, PEG-20 laurate, PEG-32 laurate, PEG-20 dioleate, PEG-32 oleate, PEG-200 oleate, PEG-400 stearate, PEG-32 distearate, PEG-40 stearate, PEG-100 dilaurate, PEG-25 glyceryl trioleate, PEG-32 dioleate, PEG-20 glyceryl laurate, PEG-30 glyceryl laurate. PEG-40 glyceryl laurate, PEG-50 hydrogenated castor oil, PEG-40 castor oil, PEG-35 castor oil, PEG-60 castor oil, PEG-40 hydrogenated castor oil, PEG-60 corn oil, PEG-6 caprylate glyceride, PEG-8 caprylate glyceride, polyglyceryl-10 laurate, PEG-30 phytosterol, PEG-30 sorbitan oleate, PEG-80 sorbitan laurate, polysorbate 20, POE-9 lauryl ether, POE-10 oleyl ether, POE-20 stearyl ether, tocopheryl PEG-100 succinate, PEG-24 cholesterol, Tween 40, sucrose monolaurate, sucrose monopalmitate, PEG 10-100 nonylphenol series, PEG 15-100 octylphenol series, and poloxamer. 【0080】 Suitable lipophilic surfactants include at least one selected from the group consisting of fatty alcohols, glycerol fatty acid esters, acetylated glycerol fatty acid esters, lower alcohol fatty acid esters, propylene glycol fatty acid esters, sorbitan fatty acid esters, polyethylene glycol sorbitan fatty acid esters, sterols and sterol derivatives, polyoxyethylated sterols and sterol derivatives, polyethylene glycol alkyl ethers, sugar ethers, sugar esters, glycerides, vegetable oils, hydrogenated vegetable oils, fatty acids and sterols, oil-soluble vitamins / vitamin derivatives, lactic acid derivatives of monoglycerides and diglycerides, and hydrophobic transesterification products of polyols with mixtures thereof, but are not limited thereto. Among this group, preferred lipophilic surfactants include glycerol fatty acid esters, propylene glycol fatty acid esters, and mixtures thereof, or hydrophobic transesterification products of polyols with at least one member of the group consisting of vegetable oils, hydrogenated vegetable oils, and triglycerides. 【0081】 In some preferred embodiments of the present disclosure, the ophthalmic composition comprises, consists essentially of, or further consists of a surfactant selected from polysorbate 80, Tween 80, Tween 20, polyoxyethylene hydrogenated castor oil, polyoxyethylene alkyl ether, and lecithin, or combinations thereof. 【0082】 In some embodiments, the ophthalmic composition of the present disclosure does not contain any ionic surfactant. In some embodiments, the ophthalmic composition of the present disclosure comprises, consists essentially of, or further consists of an ionic surfactant having a final concentration in the composition of at least about 0.00001 wt% to at least about 50 wt%. In some embodiments, the ionic surfactant has a final concentration in the composition of about 0.00005 wt% or less. In some embodiments, the ionic surfactant has a final concentration in the composition of at least about 0.00005 wt%. 【0083】 In some embodiments, the ophthalmic composition of the present disclosure includes a surfactant having a lower limit concentration of about 0.00001 wt%, about 0.0001 wt%, or about 0.001 wt% in the composition. In some embodiments, the ophthalmic composition of the present disclosure includes a surfactant having a final concentration in the composition of about 50 wt%, about 40 wt%, about 30 wt%, about 20 wt%, or about 10 wt% (but not limited thereto). A suitable range of surfactant concentration is set from these upper and lower limit values. For example, the amount of surfactant in the present composition can be from about 0.00001 wt% to about 50 wt%, from about 0.0001 wt% to about 50 wt%, from about 0.001 wt% to about 50 wt%, from about 0.01 wt% to about 50 wt%, from about 0.1 wt% to about 50 wt%, from about 0.1 wt% to about 40 wt%, from about 0.1 wt% to about 30 wt%, from about 1 wt% to about 20 wt%, or from about 2 wt% to about 10 wt%. 【0084】 In some embodiments, the ophthalmic composition of the present disclosure is from about 0.00001 wt% to about 50 wt%, from about 0.00005 wt% to about 50 wt%, from about 0.0001 wt% to about 50 wt%, from about 0.001 wt% to about 50 wt%, from about 0.01 wt% to about 20 wt%, from about 0.01 wt% to about 15 wt%, from about 0.15 wt% to 10 wt%, from about 0.2 wt% to about 5 wt%, from about 0.25 wt% to about 3 wt%, from about 0.3 wt% to about 2 wt%, from about 0.1 wt% to about 20 wt%, from about 1 wt% to about 10 wt%, from about 2 wt% to 8 wt%, from about 2 wt% to 5 wt%, from about 5 wt% to 10 wt%, from about 5 wt% to 20 wt%, and ranges between any given two of these values, or values lower than any given one of these values. 【0085】 In the present disclosure, the final concentration of the surfactant in the composition can be adjusted in the range up to the first, second, third, fourth, or fifth decimal place. For example, the concentration of the surfactant can be appropriately set in the range of 0.00001 - 50.00 wt%, 0.0001 - 50.00 wt%, 0.001 - 50.00 wt%, 0.01 - 50.00 wt%, 0.10 - 50.00 wt%. 【0086】 Examples of lubricants that can be used in the ophthalmic compositions disclosed herein include, but are not limited to, agar, calcium stearate, magnesium stearate, mineral oil, light mineral oil, glycerin, sorbitol, mannitol, polyethylene glycol, other glycols, stearic acid, sodium lauryl sulfate, talc, hydrogenated vegetable oils (e.g., peanut oil, cottonseed oil, sunflower oil, sesame oil, olive oil, corn oil, and soybean oil), zinc stearate, ethyl oleate, ethyl laurate, or mixtures thereof. Further examples of lubricants include, by way of example, syloid silica gel, coagulated aerosol of synthetic silica, or mixtures thereof. The lubricant is optionally added in an amount of less than about 1 weight percent of the pharmaceutical composition. 【0087】 The composition can include one or more pharmaceutically acceptable additives including, but not limited to, anti-adhesives, anti-foaming agents, buffers, antioxidants, polymers, preservatives, chelating agents, odorants, opacifiers, suspending agents, fillers, plasticizers, and mixtures thereof. 【0088】 Viscosity increasing agent In some embodiments of the present disclosure, the ophthalmic composition further comprises, consists essentially of, or consists of one or more viscosity - enhancing agents. The viscosity - enhancing agent can function to increase the viscosity of the ophthalmic composition of the present disclosure, as a result of which the contact time with the eye is increased, mucosal adhesion is increased, and drainage is reduced. In some embodiments, the viscosity - enhancing agent increases the viscosity of the composition or ophthalmic solution, ointment, or suspension. In some embodiments, the viscosity - enhancing agent increases the contact time with the eye, thereby reducing the drainage rate. In some embodiments, the viscosity - enhancing agent increases mucosal adhesiveness and ocular bioavailability and / or imparts a lubricating effect. Examples of suitable viscosity - enhancing agents include, but are not limited to, petrolatum, liquid paraffin, light liquid paraffin, carboxyvinyl polymer (e.g., Carbopol 934P or 974P), cellulose polymers (e.g., carboxymethyl cellulose, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, etc.), polysaccharides (e.g., xanthan gum), polyvinylpyrrolidone, polyvinyl alcohol, chondroitin sulfate, lanolin, hyaluronic acid, propylene glycol, and combinations thereof. 【0089】 In some preferred embodiments of the present disclosure, the one or more viscosity - enhancing agents comprise, consist essentially of, or consist of petrolatum or liquid paraffin. In a preferred embodiment of the present disclosure, the one or more viscosity - enhancing agents comprise, consist essentially of, or consist of petrolatum. In another preferred embodiment of the present disclosure, the one or more viscosity - enhancing agents comprise, consist essentially of, or consist of liquid paraffin. 【0090】 In some embodiments, the ophthalmic composition comprises, consists essentially of, or consists of a viscosity modifier having a final concentration in the composition of from about 0.00001 wt% to about 50 wt%, from about 0.00005 wt% to about 50 wt%, from about 0.0001 wt% to about 50 wt%, from about 0.001 wt% to about 50 wt%, from about 0.01 wt% to about 20 wt%, from about 0.1 wt% to about 15 wt%, from about 0.15 wt% to about 10 wt%, from about 0.2 wt% to about 5 wt%, from about 0.25 wt% to about 3 wt%, from about 0.3 wt% to about 2 wt%, from about 0.5 wt% to about 2 wt%, from about 0.1 wt% to about 20 wt%, from about 1 wt% to about 10 wt%, from about 2 wt% to 10 wt%, from about 2 wt% to 5 wt%, from about 2 wt% to 5 wt%, from about 5 wt% to 10 wt%, from about 5 wt% to 20 wt%, from about 5 wt% to 20 wt%, from 10 wt% to 40 wt%, from 20 wt% to 50 wt%, from 30 wt% to 60 wt%, from 40 wt% to 70 wt%, from 50 wt% to 80 wt%, from 60 wt% to 90 wt%, from 70 wt% to 100 wt%, from 80 wt% to 100 wt%, from 90 wt% to 100 wt%, about 100%, about 90%, about 80%, about 70%, about 60%, about 50%, about 40%, about 30%, about 20%, about 10%, about 5%, and ranges between any two given values from these values or values lower than the specified value from these values. In some embodiments, the ophthalmic composition comprises, consists essentially of, or consists of a viscosity modifier having a final concentration in the composition of from about 0.01 wt% to 100 wt%. 【0091】 The viscosity of a solution can be measured in units of Pa·s (Pascal seconds; hereinafter, "PaS") or mPa·s (millipascal seconds; hereinafter, "mPaS"). Viscosity can also be measured in cP (centipoise), where 0.001 PaS is equivalent to 1 mPaS, which is further equivalent to 1 cP. The viscosity of a solution strongly depends on temperature and typically decreases with increasing temperature. Viscosity can be measured using a rheometer or viscometer. Viscosity can be measured using a rheometer or viscometer that includes a temperature control unit that maintains and controls the temperature in the range of at least 0.0 ± 0.1 °C, 5.0 ± 0.1 °C, 10.0 ± 0.1 °C, 15.0 ± 0.1 °C, 20.0 ± 0.1 °C, 25.0 ± 0.1 °C, 37.0 ± 0.1 °C, 50.0 ± 0.1 °C, 75.0 ± 0.1 °C, 95.0 ± 0.1 °C, 98.0 ± 0.1 °C, or 100 ± 0.1 °C. 【0092】 Shear rate can also be determined using a rheometer that includes a temperature control unit that maintains and controls the temperature in the range of at least 0.0 ± 0.1 °C, 5.0 ± 0.1 °C, 10.0 ± 0.1 °C, 15.0 ± 0.1 °C, 20.0 ± 0.1 °C, 25.0 ± 0.1 °C, 37.0 ± 0.1 °C, 50.0 ± 0.1 °C, 75.0 ± 0.1 °C, 95.0 ± 0.1 °C, 98.0 ± 0.1 °C, or 100 ± 0.1 °C. Shear is the relative motion between adjacent layers of a fluid. Shear rate is the rate of change of the velocity at which a fluid layer passes through another adjacent fluid layer. In some embodiments, the ophthalmic composition of the present disclosure includes a shear rate in the following ranges. -1 s 0s 200s -1 s 200s, -1 s 20s, or -1 s 20s -1 200s, or -1 s 200s -1 or -1 200s -1 75s 100s or -1 200s, or 150s -1 or 175s -1 190s -1 s 400s -1 or 210s -1400 s -1 or 230 s -1 or 240 s, 325 s -1 350 s -1 to 400 s -1 or 275 s -1 to 400 s, or 380 s -1 to 400 s -1 or 0 s -1 -1 to 600 s, or 0 s -1 to 800 s -1 or 0 s -1 to 1,000 s -1 。In some further embodiments, the ophthalmic composition of the present disclosure comprises a shear rate measured at a temperature in the range of at least 0.0 ± 0.1 °C, or 5.0 ± 0.1 °C, or 10.0 ± 0.1 °C, or 15.0 ± 0.1 °C, or 20.0 ± 0.1 °C, or 25.0 ± 0.1 °C, or 37.0 ± 0.1 °C, or 50.0 ± 0.1 °C, or 75.0 ± 0.1 °C, or 95.0 ± 0.1 °C, or 98.0 ± 0.1 °C, or 100 ± 0.1 °C. 【0093】 In some embodiments, the ophthalmic composition of the present disclosure comprises a final viscosity at 0 °C in the range of 1 mS to 5 PamS, or 5 PamS to 25 PamS, or 25 PamS to 100 PamS, or 100 PamS to 200 PamS, or 150 PamS to 300 PamS, or 200 PamS to 500 PamS, or 300 PamS to 800 PamS, or 500 PamS to 1000 PamS, or 800 PamS to 1500 PamS, or 1000 PamS to 2000 PamS, or 1500 PamS to 3000 PamS, or 2000 PamS to 4000 PamS, or 3000 PamS to 6000 PamS, or 4000 PamS to 8000 PamS. In some embodiments, the viscosity is measured using a rheometer. In some embodiments, the viscosity is measured using a viscometer. In some embodiments, the rheometer comprises a temperature control unit that maintains and controls a temperature in the range of at least 0.0 ± 0.1 °C. 【0094】 In some embodiments, the ophthalmic composition of the present disclosure includes a final viscosity in the range of 1 mS to 5 Pa·mS, or 5 Pa·mS to 25 Pa·mS, or 25 Pa·mS to 100 Pa·mS, or 100 Pa·mS to 200 Pa·mS, or 150 Pa·mS to 300 Pa·mS, or 200 Pa·mS to 500 Pa·mS, or 300 Pa·mS to 800 Pa·mS, or 500 Pa·mS to 1000 Pa·mS, or 800 Pa·mS to 1500 Pa·mS, or 1000 Pa·mS to 2000 Pa·mS, or 1500 Pa·mS to 3000 Pa·mS, or 2000 Pa·mS to 4000 Pa·mS, or 3000 Pa·mS to 6000 Pa·mS, or 4000 Pa·mS to 8000 Pa·mS at 5°C. In some embodiments, the viscosity is measured using a rheometer. In some embodiments, the viscosity is measured using a viscosimeter. In some embodiments, the rheometer comprises a temperature control unit that maintains and controls a temperature in the range of at least 5.0 ± 0.1°C. 【0095】 In some embodiments, the ophthalmic composition of the present disclosure includes a final viscosity in the range of 1 mS to 5 Pa·mS, or 5 Pa·mS to 25 Pa·mS, or 25 Pa·mS to 100 Pa·mS, or 100 Pa·mS to 200 Pa·mS, or 150 Pa·mS to 300 Pa·mS, or 200 Pa·mS to 500 Pa·mS, or 300 Pa·mS to 800 Pa·mS, or 500 Pa·mS to 1000 Pa·mS, or 800 Pa·mS to 1500 Pa·mS, or 1000 Pa·mS to 2000 Pa·mS, or 1500 Pa·mS to 3000 Pa·mS, or 2000 Pa·mS to 4000 Pa·mS, or 3000 Pa·mS to 6000 Pa·mS, or 4000 Pa·mS to 8000 Pa·mS at 10°C. In some embodiments, the viscosity is measured using a rheometer. In some embodiments, the viscosity is measured using a viscosimeter. In some embodiments, the rheometer comprises a temperature control unit that maintains and controls a temperature in the range of at least 10.0 ± 0.1°C. 【0096】 In some embodiments, the ophthalmic composition of the present disclosure includes a final viscosity in the range of 1 mS to 5 Pa·mS, or 5 Pa·mS to 25 Pa·mS, or 25 Pa·mS to 100 Pa·mS, or 100 Pa·mS to 200 Pa·mS, or 150 Pa·mS to 300 Pa·mS, or 200 Pa·mS to 500 Pa·mS, or 300 Pa·mS to 800 Pa·mS, or 500 Pa·mS to 1000 Pa·mS, or 800 Pa·mS to 1500 Pa·mS, or 1000 Pa·mS to 2000 Pa·mS, or 1500 Pa·mS to 3000 Pa·mS, or 2000 Pa·mS to 4000 Pa·mS, or 3000 Pa·mS to 6000 Pa·mS, or 4000 Pa·mS to 8000 Pa·mS at 15°C. In some embodiments, the viscosity is measured using a rheometer. In some embodiments, the viscosity is measured using a viscosimeter. In some embodiments, the rheometer comprises a temperature control unit that maintains and controls a temperature in the range of at least 15.0 ± 0.1°C. 【0097】 In some embodiments, the ophthalmic composition of the present disclosure includes a final viscosity in the range of 1 mS to 5 Pa·mS, or 5 Pa·mS to 25 Pa·mS, or 25 Pa·mS to 100 Pa·mS, or 100 Pa·mS to 200 Pa·mS, or 150 Pa·mS to 300 Pa·mS, or 200 Pa·mS to 500 Pa·mS, or 300 Pa·mS to 800 Pa·mS, or 500 Pa·mS to 1000 Pa·mS, or 800 Pa·mS to 1,5000 Pa·mS, or 1000 Pa·mS to 2000 Pa·mS, or 1,5000 Pa·mS to 3000 Pa·mS, or 2000 Pa·mS to 4000 Pa·mS, or 30000 Pa·mS to 6000 Pa·mS, or 4000 Pa·mS to 8000 Pa·mS at 20°C. In some embodiments, the viscosity is measured using a rheometer. In some embodiments, the viscosity is measured using a viscosimeter. In some embodiments, the rheometer comprises a temperature control unit that maintains and controls a temperature in the range of at least 20.0 ± 0.1°C. 【0098】 In some embodiments, the ophthalmic composition of the present disclosure has a viscosity of 1 mS to 5 Pa·mS, or 5 Pa·mS to 25 Pa·mS, or 25 Pa·mS to 100 Pa·mS, or 100 Pa·mS to 200 Pa·mS, or 150 Pa·mS to 300 Pa·mS, or 200 Pa·mS to 500 Pa·mS, or 300 Pa·mS to 800 Pa·mS, or 500 Pa·mS to 1000 Pa·mS, or 800 Pa·mS to 1500 Pa·mS, or 1000 Pa·mS to 2000 Pa·mS, or 1500 Pa·mS to 3000 Pa·mS, or 2000 Pa·mS to 4000 Pa·mS, or 3000 Pa·mS to 6000 Pa·mS, or 4. In some embodiments, the viscosity is measured using a rheometer. In some embodiments, the viscosity is measured using a viscometer. In some embodiments, the rheometer comprises a temperature control unit that maintains and controls a temperature in the range of at least 25.0 ± 0.1 °C. 【0099】 In some embodiments, the ophthalmic composition of the present disclosure has a final viscosity in the range of 1 mS to 5 Pa·mS, or 5 Pa·mS to 25 Pa·mS, or 25 Pa·mS to 100 Pa·mS, or 100 Pa·mS to 200 Pa·mS, or 150 Pa·mS to 300 Pa·mS, or 200 Pa·mS to 500 Pa·mS, or 300 Pa·mS to 800 Pa·mS, or 500 Pa·mS to 1000 Pa·mS, or 800 Pa·mS to 1500 Pa·mS, or 1000 Pa·mS to 2000 Pa·mS, or 1500 Pa·mS to 3000 Pa·mS, or 2000 Pa·mS to 4000 Pa·mS, or 3000 Pa·mS to 6000 Pa·mS, or 4000 Pa·mS to 8000 Pa·mS at 37 °C. In some embodiments, the viscosity is measured using a rheometer. In some embodiments, the viscosity is measured using a viscometer. In some embodiments, the rheometer comprises a temperature control unit that maintains and controls a temperature in the range of at least 37.0 ± 0.1 °C. 【0100】 In some embodiments, the ophthalmic composition of the present disclosure has a viscosity of 1 mS to 5 Pa·mS, or 5 Pa·mS to 25 Pa·mS, or 25 Pa·mS to 100 Pa·mS, or 100 Pa·mS to 200 Pa·mS, or 150 Pa·mS to 300 Pa·mS, or 200 Pa·mS to 500 Pa·mS, or 300 Pa·mS to 800 Pa·mS, or 500 Pa·mS to 1000 Pa·mS, or 800 Pa·mS to 1500 Pa·mS, or 1000 Pa·mS to 2000 Pa·mS, or 1500 Pa·mS to 3000 Pa·mS, or 2000 Pa·mS to 4. In some embodiments, the viscosity is measured using a rheometer. In some embodiments, the viscosity is measured using a viscometer. In some embodiments, the rheometer comprises a temperature control unit that maintains and controls a temperature in the range of at least 50.0 ± 0.1 °C. 【0101】 In some embodiments, the ophthalmic composition of the present disclosure has a final viscosity in the range of 1 mS to 5 Pa·mS, or 5 Pa·mS to 25 Pa·mS, or 25 Pa·mS to 100 Pa·mS, or 100 Pa·mS to 200 Pa·mS, or 150 Pa·mS to 300 Pa·mS, or 200 Pa·mS to 500 Pa·mS, or 300 Pa·mS to 800 Pa·mS, or 500 Pa·mS to 1000 Pa·mS, or 800 Pa·mS to 1500 Pa·mS, or 1000 Pa·mS to 2000 Pa·mS, or 1500 Pa·mS to 3000 Pa·mS, or 2000 Pa·mS to 4000 Pa·mS, or 3000 Pa·mS to 6000 Pa·mS, or 4000 Pa·mS to 8000 Pa·mS at 75 °C. In some embodiments, the viscosity is measured using a rheometer. In some embodiments, the viscosity is measured using a viscometer. In some embodiments, the rheometer comprises a temperature control unit that maintains and controls a temperature in the range of at least 75.0 ± 0.1 °C. 【0102】 In some embodiments, the ophthalmic composition of the present disclosure includes a final viscosity in the range of 1 mS to 5 Pa·mS, or 5 Pa·mS to 25 Pa·mS, or 25 Pa·mS to 100 Pa·mS, or 100 Pa·mS to 200 Pa·mS, or 150 Pa·mS to 300 Pa·mS, or 200 Pa·mS to 500 Pa·mS, or 300 Pa·mS to 800 Pa·mS, or 500 Pa·mS to 1000 Pa·mS, or 800 Pa·mS to 1500 Pa·mS, or 1000 Pa·mS to 2000 Pa·mS, or 1500 Pa·mS to 3000 Pa·mS, or 2000 Pa·mS to 4000 Pa·mS, or 3000 Pa·mS to 6000 Pa·mS, or 4000 Pa·mS to 8000 Pa·mS at 95°C. In some embodiments, the viscosity is measured using a rheometer. In some embodiments, the viscosity is measured using a viscometer. In some embodiments, the rheometer comprises a temperature control unit that maintains and controls a temperature in the range of at least 95.0 ± 0.1°C. 【0103】 In some embodiments, the ophthalmic composition of the present disclosure includes a final viscosity in the range of 1 mS to 5 Pa·mS, or 5 Pa·mS to 25 Pa·mS, or 25 Pa·mS to 100 Pa·mS, or 100 Pa·mS to 200 Pa·mS, or 150 Pa·mS to 300 Pa·mS, or 200 Pa·mS to 500 Pa·mS, or 300 Pa·mS to 800 Pa·mS, or 500 Pa·mS to 1000 Pa·mS, or 800 Pa·mS to 1500 Pa·mS, or 1000 Pa·mS to 2000 Pa·mS, or 1500 Pa·mS to 3000 Pa·mS, or 2000 Pa·mS to 4000 Pa·mS, or 3000 Pa·mS to 6000 Pa·mS, or 4000 Pa·mS to 8000 Pa·mS at 98°C. In some embodiments, the viscosity is measured using a rheometer. In some embodiments, the viscosity is measured using a viscometer. In some embodiments, the rheometer comprises a temperature control unit that maintains and controls a temperature in the range of at least 98.0 ± 0.1°C. 【0104】 In some embodiments, the ophthalmic composition of the present disclosure includes a final viscosity in the range of 1 mS to 5 Pa·mS, or 5 Pa·mS to 25 Pa·mS, or 25 Pa·mS to 100 Pa·mS, or 100 Pa·mS to 200 Pa·mS, or 150 Pa·mS to 300 Pa·mS, or 200 Pa·mS to 500 Pa·mS, or 300 Pa·mS to 800 Pa·mS, or 500 Pa·mS to 1,000 Pa·mS, or 800 Pa·mS to 1,500 Pa·mS, or 1,000 Pa·mS to 2000 Pa·mS, or 1,500 Pa·mS to 3000 Pa·mS, or 2000 Pa·mS to 4000 Pa·mS, or 3000 Pa·mS to 6000 Pa·mS, or 4000 Pa·mS to 8000 Pa·mS at 100 °C. In some embodiments, the viscosity is measured using a rheometer. In some embodiments, the viscosity is measured using a viscosimeter. In some embodiments, the rheometer comprises a temperature control unit that maintains and controls a temperature in the range of at least 100.0 ± 0.1 °C. 【0105】 In some embodiments, the ophthalmic composition has a final viscosity of at least about 1 mPa·s to 5 Pa·mS at 25 °C, or 5 mS to 25 Pa·mS at 25 °C, or 25 Pa·mS to 100 Pa·mS at 25 °C, or at least about 200 mPa·s to 100 Pa·mS at 25 °C, or optionally about 1 mPa·s, about 5 Pa·mS, about 25 Pa·mS, about 100 Pa·mS, or about 150 Pa·mS, or about 160 Pa·mS, or about 170 Pa·mS, or about 180 Pa·mS. 【0106】 In a preferred embodiment, the ophthalmic composition comprises, consists essentially of, or consists of a final viscosity of at least about 5 mPa·s at 25 °C. 【0107】 In some embodiments, the ophthalmic composition has a final viscosity at 25 °C of at least about 500 mPaS to at least about 900 mPaS, or optionally about 500 mPaS, or about 600 mPaS, or about 700 mPaS, or about 800 mPaS, or about 850 mPaS, or about 860 mPaS, or about 870 mPaS, or about 880 mPaS, or about 890 mPaS, or about 900 mPaS. In a preferred embodiment, the ophthalmic composition comprises, consists essentially of, or consists of a final viscosity at 25 °C of at least about 867 mPaS. 【0108】 In some embodiments, the ophthalmic composition has a final viscosity at 25 °C of at least about 1000 mPaS to at least about 2500 mPaS, or optionally about 1000 mPaS, or about 1500 mPaS, or about 2000 mPaS, or about 2100 mPaS, or about 2200 mPaS, or about 2300 mPaS, or about 2400 mPaS, or about 250 mPaS. In a preferred embodiment, the ophthalmic composition comprises, consists essentially of, or consists of a final viscosity at 25 °C of at least about 2145 mPaS. 【0109】 In some embodiments, the ophthalmic composition consists of, or consists of a viscosity at 25 °C of at least about 3000 mPaS to at least about 4000 mPaS, or optionally about 3000 mPaS, or about 3500 mPaS, or about 3600 mPaS, about 3700 mPaS, or about 3800 mPaS, or about 3900 mPaS, or about 4000 mPaS. In a preferred embodiment, the ophthalmic composition comprises, consists essentially of, or consists of a viscosity at 25 °C of at least about 3815 mPaS. 【0110】 In some embodiments, the ophthalmic composition of the present disclosure has a viscosity of at least 1 mPaS at 25 ° C and comprises, consists essentially of, or further consists of a) an effective amount of one or more rifamycin compounds or pharmaceutically acceptable salts thereof, b) a buffer, and c) one or more viscosity modifiers. In some preferred embodiments, the one or more rifamycin compounds are rifampicin and the one or more viscosity modifiers are petrolatum. In some preferred embodiments, the one or more rifamycin compounds are rifampicin and the one or more viscosity modifiers are liquid paraffin. 【0111】 In some embodiments, one or more rifampicin compounds are rifampicin, one or more viscosity modifiers are petrolatum, and the effective amount of rifampicin comprises a final concentration of at least about 0.001% w / w in the composition. In some embodiments, one or more rifampicin compounds are rifampicin, one or more viscosity modifiers are liquid paraffin, and the effective amount of rifampicin comprises a final concentration of at least about 0.01% w / w in the composition. In some embodiments, one or more rifampicin compounds are rifampicin, one or more viscosity modifiers are liquid paraffin, and the effective amount of rifampicin comprises a final concentration of at least about 0.1% w / w in the composition. In some embodiments, one or more rifampicin compounds are rifampicin, one or more viscosity modifiers are liquid paraffin, and the effective amount of rifampicin comprises a final concentration of at least about 0.001% w / w in the composition. In some embodiments, one or more rifampicin compounds are rifampicin, one or more viscosity modifiers are petrolatum, and the effective amount of rifampicin comprises a final concentration of at least about 1% w / w in the composition. In some embodiments, one or more rifampicin compounds are rifampicin, one or more viscosity modifiers are liquid paraffin, and the effective amount of rifampicin comprises a final concentration of at least about 1% w / w in the composition. In a further embodiment, one or more rifamycin compounds are rifampicin, one or more viscosity modifiers are petrolatum, the effective amount of rifampicin comprises a final concentration of at least about 0.001% w / w in the composition, and the composition comprises a final viscosity of at least about 1 mPaS, about 5 mPaS, about 9 mPaS, about 55 mPaS, about 146 mPaS, about 161 mPaS, at least about 867 mPaS, at least about 2145 mPaS, or at least about 3815 mPaS at 25°C.In a further embodiment, the one or more rifamycin compounds are rifampicin, the one or more viscosity modifiers are petrolatum, the effective amount of rifampicin comprises a final concentration of at least about 1% w / w in the composition, and the composition comprises a final viscosity of at least about 5 mPaS, about 9 mPaS, about 55 mPaS, about 146 mPaS, about 161 mPaS, at least about 867 mPaS, at least about 2145 mPaS, or at least about 3815 mPaS at 25°C. In a further embodiment, the one or more rifamycin compounds are rifampicin, the one or more viscosity modifiers are liquid paraffin, the effective amount of rifampicin comprises a final concentration of at least about 0.001% w / w in the composition, and the composition comprises a final viscosity of at least about 1 mPaS, about 5 mPaS, about 9 mPaS, about 55 mPaS, about 146 mPaS, about 161 mPaS, at least about 867 mPaS, at least about 2145 mPaS, or at least about 3815 mPaS at 25°C. In a further embodiment, the one or more rifamycin compounds are rifampicin, the one or more viscosity modifiers are liquid paraffin, the effective amount of rifampicin comprises a final concentration of at least about 1% w / w in the composition, and the composition comprises a final viscosity of at least about 5 mPaS, about 9 mPaS, about 55 mPaS, about 146 mPaS, about 161 mPaS, at least about 867 mPaS, at least about 2145 mPaS, or at least about 3815 mPaS at 25°C. 【0112】 Phospholipid compound and preservative In some embodiments, the ophthalmic composition disclosed herein comprises, consists essentially of, or further comprises one or more phospholipid compounds. Suitable phospholipids in the art include, but are not limited to, small alkyl chain phospholipids, phosphatidylcholine, soy phosphatidylcholine, dipalmitoyl phosphatidylglycerol, egg phosphatidylglycerol, distearoyl phosphatidylcholine, dilauroyl phosphatidylcholine, 1-myristoyl-2-palmitoyl phosphatidylcholine, 1-palmitoyl-2-stearoyl phosphatidylcholine, l-palmitoyl phosphatidylcholine, l-oleoyl-2-palmitoyl phosphatidylcholine. Dioleoyl phosphatidylethanolamine, dilauroyl phosphatidylglycerol, phosphatidylserine, phosphatidylinositol, phosphatidylglycerol, dimyristoyl phosphatidylglycerol, distearoyl phosphatidylglycerol, dioleoyl phosphatidylglycerol, phosphatidic acid, dimyristoyl phosphatidic acid, dimyristoyl phosphatidylethanolamine, dipalmitoyl phosphatidylethanolamine, dimyristoyl phosphatidylethanolamine, dimyristoyl phosphatidylserine, dipalmitoyl phosphatidylserine, brain phosphatidylserine, sphingomyelin, sphingolipid, brain sphingomyelin, dipalmitoyl sphingomyelin, distearoyl sphingomyelin, galactosylceramide, ganglioside, cerebroside, phosphatidylglycerol, phosphatidic acid, lysophosphatidylcholine, lysophosphatidylethanolamine, cephalin, cardiolipin, dicetyl phosphate, distearoyl phosphatidylethanolamine, or combinations thereof. The phospholipid may also be a derivative or analog of any of the above phospholipids.In some embodiments, the ophthalmic composition is from about 0.00001 wt% to about 50 wt%, from about 0.00005 wt% to about 50 wt%, from about 0.0001 wt% to about 50 wt%, from about 0.001 wt% to about 50 wt%, from about 0.01 wt% to about 20 wt%, from about 0.1 wt% to about 15 wt%, from about 0.15 wt% to 10 wt%, from about 0.2 wt% to about 5 wt%, from about 0.25 wt% to about 3 wt%, from about 0.3 wt% to about 2 wt%, from about 0.2 wt% to 8 wt%, from about 2 wt% to 5 wt%, from about 5 wt% to 10 wt%, or from about 5 wt% to 20 wt%. In some embodiments, the ophthalmic composition comprises, consists essentially of, or consists of from about 0.01 wt% to 10 wt% of a phospholipid compound. 【0113】 In some embodiments, the ophthalmic composition of the present disclosure optionally comprises, consists essentially of, or consists of a preservative. Examples of preservatives include, but are not limited to, imidazolidinyl urea, methylparaben, propylparaben, phenoxyethanol, disodium EDTA, benzalkonium chloride, thimerosal, chlorobutanol, sorbic acid, and combinations thereof. In some embodiments, the ophthalmic composition comprises, consists essentially of, or consists of a preservative having a final concentration in the composition of from about 0.00001 wt% to about 50 wt%, from about 0.00005 wt% to about 50 wt%, from about 0.0001 wt% to about 50 wt%, from about 0.001 wt% to about 50 wt%, from about 0.01 wt% to about 20 wt%, from about 0.1 wt% to about 15 wt%, from about 0.15 wt% to 10 wt%, from about 0.2 wt% to about 5 wt%, from about 0.25 wt% to about 3 wt%, from about 0.3 wt% to about 2 wt%, from about 0.1 wt% to about 20 wt%, from about 1 wt% to about 10 wt%, from about 2 wt% to about 10 wt%, from about 2 wt% to 8 wt%, from about 2 wt% to 5 wt%, from about 5 wt% to 10 wt%, or from about 5 wt% to 20 wt%. In some embodiments, the ophthalmic composition comprises, consists essentially of, or consists of from about 0.01 wt% to 10 wt% of a preservative in the composition. 【0114】 Pharmaceutical composition In certain embodiments, the ophthalmic compositions of the present disclosure can be administered alone or as a component of a pharmaceutical formulation (also referred to as a therapeutic or pharmaceutical composition). A pharmaceutical formulation is in a form that enables the biological activity of the active ingredient(s) contained therein (e.g., one or more rifamycin compounds) to be effective and refers to a formulation that does not contain additional ingredients that are unacceptably toxic to the subject to which the formulation is administered. The compounds of the subject matter can be formulated for administration by any convenient method for use in human or veterinary medicine. For example, one or more agents of the present disclosure can be formulated with a pharmaceutically acceptable carrier. A pharmaceutically acceptable carrier refers to a component in a pharmaceutical formulation that is generally non-toxic to the subject and other than the active ingredient. Pharmaceutically acceptable carriers include, but are not limited to, buffers, excipients, stabilizers, and / or preservatives. Generally, pharmaceutical formulations for use in the present disclosure are in a physiologically acceptable form that does not contain pyrogens when administered to a subject. Therapeutically useful agents other than those described herein can be included in the above formulations as needed and can be administered in combination with the agents of the subject matter in the methods of the present disclosure. 【0115】 Typically, the compound is administered to the eye, for example, by topical administration, intravitreal (e.g., intracameral) injection, or by an implant or device. Intravitreal injection can be performed, for example, through the pars plana 3 mm to 4 mm posterior to the limbus. Pharmaceutical compositions for administration to the eye can be formulated in a variety of ways, including, for example, eye drops, eye solutions, ophthalmic suspensions, ophthalmic emulsions, intravitreal injections, sub-Tenon's injections, bioerodible ophthalmic implants, and non-bioerodible ophthalmic inserts or depots. 【0116】 In some embodiments, the compound is administered parenterally [e.g., by intravenous (IV) injection, intraarterial injection, intraosseous injection, intramuscular injection, intrathecal injection, subcutaneous injection, or intradermal injection]. 【0117】 In some embodiments, the ophthalmic composition of the present composition is formulated into a pharmaceutical composition suitable for ocular or parenteral administration and comprises, consists essentially of, or consists of one or more rifamycin compounds in combination with one or more viscosity modifiers. In some embodiments, the pharmaceutical composition can be a pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solution, dispersion, suspension or emulsion, or sterile powder that can be reconstituted into a sterile solution or dispersion immediately prior to use. The solution or dispersion contains antioxidants, buffers, bacteriostatic agents, suspending agents, thickening agents, or solutes that make the formulation isotonic with the blood of the intended recipient. Examples of suitable aqueous and non-aqueous carriers used in the pharmaceutical formulations of the present disclosure include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, etc.), vegetable oils (such as olive oil), injectable organic esters (such as ethyl oleate), and suitable mixtures thereof. Suitable fluidity is maintained, for example, by the use of coating materials (such as lecithin), by maintaining the required particle size in the case of dispersions, and by the use of surfactants. 【0118】 In some embodiments, the treatment method of the present disclosure includes systemically or locally administering a pharmaceutical composition from an implant or device. Further, the pharmaceutical composition is encapsulated or injected in a form for delivery to a target tissue site (such as bone marrow or muscle). In certain embodiments, the composition of the present disclosure can deliver one or more of the agents of the present disclosure to a target tissue site (such as bone marrow or muscle), provides a structure for the developing tissue, and includes a matrix that can be optimally resorbed in the body. For example, the matrix provides sustained release of one or more agents of the present disclosure. Such matrices are currently formed from materials used in other implant medical applications. 【0119】 The selection of the matrix material is based on one or more of biocompatibility, biodegradability, mechanical properties, aesthetic appearance, and interfacial properties. The particular use of the subject composition defines the appropriate formulation. Potential matrices for the composition are biodegradable and chemically defined calcium sulfate, tricalcium phosphate, hydroxyapatite, polylactic acid, and polyanhydrides. Other possible materials are biodegradable and biologically well-defined, for example, including bone or skin collagen. Further matrices comprise, consist essentially of, or consist of pure proteins or extracellular matrix components. Other potential matrices are non-biodegradable and chemically defined, for example, including sintered hydroxyapatite, bioglass, aluminates, or other ceramics. The matrix consists of a combination of any of the above types of materials, for example, including polylactic acid and hydroxyapatite or collagen and tricalcium phosphate. The bioceramics are modified in composition (e.g., calcium aluminate phosphate) and processing to vary one or more of pore size, particle size, particle shape, and biodegradability. 【0120】 In certain embodiments, the pharmaceutical compositions of the present disclosure are administered orally in the form of, for example, capsules, cachets, pills, tablets, lozenges (using flavoring bases such as sucrose and acacia or tragacanth), powders, granules, solutions or suspensions in aqueous or non-aqueous liquids, oil-in-water or water-in-oil liquid emulsions, or elixirs or syrups, or troches (using inert bases such as gelatin and glycerin, or sucrose and acacia), and / or mouthwashes, each containing a predetermined amount of a compound of the present disclosure and optionally one or more other active ingredients. The compounds of the present disclosure, and optionally one or more other active ingredients, are also administered as a bolus, electuary, or paste. 【0121】 In solid dosage forms for oral administration (e.g., capsules, tablets, dragees, powders, and granules), the present disclosure relates to, for example, sodium citrate, dicalcium phosphate, fillers or diluents (e.g., starch, lactose, sucrose, mannitol, and silicic acid), binders (e.g., carboxymethylcellulose, alginates, polyvinylpyrrolidone, sucrose, and acacia), wetting agents (e.g., agar, calcium carbonate, potato or tapioca starch, alginic acid, silicates, and sodium carbonate), solution retarders (e.g., paraffin), absorption promoters (e.g., quaternary ammonium compounds), wetting agents (e.g., cetyl alcohol and glycerol monostearate), absorbents (e.g., kaolin and bentonite), clays, lubricants (e.g., talc, calcium stearate, magnesium stearate, solid polyethylene glycol, sodium lauryl sulfate), coloring agents, and mixtures thereof. In the case of capsules, tablets, and pills, the pharmaceutical formulation (composition) also contains, consists essentially of, or consists of a buffering agent. Solid compositions of the same type are also used as fillers in soft and hard gelatin capsules using one or more excipients including, for example, lactose or milk sugar and high molecular weight polyethylene glycol. 【0122】 Liquid dosage forms for oral administration of pharmaceutical compositions include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups, and elixirs. In addition to the active ingredient, the liquid dosage forms can contain inert diluents commonly used in the art, such as, for example, water or other solvents, solubilizing agents and / or emulsifying agents [e.g., ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, or 1,3-butylene glycol, oils (e.g., cottonseed oil, peanut oil, corn oil, germ oil, olive oil, castor oil, and sesame oil), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycol, fatty acid esters of sorbitan, and mixtures thereof]. In addition to the inert diluent, oral formulations can also contain adjuvants, such as, for example, wetting agents, emulsifying and suspending agents, sweetening agents, flavoring agents, coloring agents, perfuming agents, preservatives, and combinations thereof. 【0123】 Suspensions can contain suspending agents, such as, for example, ethoxylated isostearyl alcohol, polyoxyethylene sorbitol, sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar, tragacanth, and combinations thereof, in addition to the active compound. 【0124】 Prevention of the action and / or growth of microorganisms is ensured, for example, by including various antibacterial and antifungal agents, such as parabens, chlorobutanol, and phenolsorbic acid. 【0125】 In certain embodiments, it is desirable to include in the composition, for example, isotonic agents, such as sugars or sodium chloride. In addition, sustained absorption of injectable pharmaceutical forms is brought about, for example, by including agents that delay absorption, such as aluminum monostearate and gelatin. 【0126】 It is understood that the dosing regimen is determined by the attending physician, taking into account various factors that modify the action of one or more of the agents of the present disclosure. Such factors include, but are not limited to, the patient's red blood cell count, hemoglobin level, desired target red blood cell count, patient age, patient gender, patient diet, severity of any disease that may contribute to decreased red blood cell levels, administration time, and other clinical factors. The addition of other known active agents to the final composition also affects the dosage. Progression is monitored by periodic evaluation of one or more of the red blood cell level, hemoglobin level, reticulocyte level, and other indicators of the hematopoietic process. 【0127】 In certain embodiments, the dosing frequency is, for example, once a day, twice a day, three times a day, four, five, six, seven, eight, nine, or ten times a day. In certain embodiments, once every two days, once every three days, every four, five, six, seven, eight, nine, or ten days can be used. In certain embodiments, once a week, every two weeks, every three weeks, or every four weeks can be used. The amount of eye drops or ointment is, for example, 3 μL / application, 5 μL / application, 10 μL / application, 20 μL / application, 30 μL / application, 50 μL / application, 60 μL / application, or 70 μL / application. 【0128】 Another target delivery system for one or more of the agents of the present disclosure is a colloidal dispersion system. Colloidal dispersion systems include, for example, polymer conjugates, nanocapsules, microspheres, beads, and lipid-based systems including oil-in-water emulsions, micelles, mixed micelles, and liposomes. In certain embodiments, a preferred colloidal system of the present disclosure is a liposome. Liposomes are artificial membrane vesicles useful as delivery vehicles in vitro and in vivo. For example, RNA, DNA, and intact virions have been shown to be encapsulated within the aqueous interior and delivered to cells in a biologically active form [see, for example, Fraley, et al. (1981) Trends Biochem. Sci., 6:77]. 【0129】 Liposomal compositions are typically a combination of phospholipids that include a steroid (e.g., cholesterol). The physical properties of liposomes depend on pH, ionic strength, and the presence of divalent cations. For example, other phospholipids or other lipids are also used, including phosphatidyl compounds (e.g., phosphatidylglycerol, phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine, sphingolipids, cerebrosides, or gangliosides), egg phosphatidylcholine, dipalmitoyl phosphatidylcholine, and distearoyl phosphatidylcholine. Targeting of liposomes is also possible, for example, based on organ specificity, cell specificity, and organelle specificity, and is known in the art. 【0130】 In certain embodiments, the present disclosure provides a pharmaceutical preparation comprising, consisting essentially of, or further comprising one or more rifamycin compounds of the present disclosure and a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical formulation also comprises, consists essentially of, or further consists of one or more additional active agents, such as a compound used to treat an eye disorder such as those described herein. Preferably, the pharmaceutical preparation of the present disclosure is substantially free of pyrogens. In certain embodiments, the present disclosure provides a packaged pharmaceutical labeled for use in one or more of the increase, treatment, or prevention of one or more of the following eye disorders: [e.g., age-related macular degeneration, wet macular degeneration, dry macular degeneration, Stargardt's disease, and Best's disease), retinal vein occlusion (e.g., central retinal vein occlusion, retinal vein branch occlusion, and ischemic retinal vein occlusion), retinal artery occlusion (e.g., central retinal artery occlusion, retinal artery branch occlusion, and ischemic retinal artery occlusion)] diabetic optic neuropathy [e.g., anterior ischemic optic neuropathy (arteritic and non-arteritic) and posterior ischemic optic neuropathy], macular telangiectasia (type I or II), retinal ischemia (e.g., acute retinal ischemia or chronic retinal ischemia). 【0131】 The ophthalmic composition disclosed in this specification is manufactured by methods known in the art. For example, the active ingredient, i.e., one or more rifamycin compounds, is dissolved in purified water, oil, or physiological saline. Then, a surfactant is added and mixed. Further additives, such as isotonic agents like sodium chloride or glycerin, buffering agents like sodium phosphate or sodium borate, pH adjusters like dilute hydrochloric acid or sodium hydroxide, preservatives like potassium sorbate, and antioxidants like tocopherol or ascorbic acid, are optionally added to the mixture to obtain the ophthalmic composition. 【0132】 The ophthalmic composition of the present disclosure is tested for various physicochemical properties, in vitro properties, and in vivo properties. Transparency is measured, for example, using microscopy based on vision and / or fluorescence. Further, the presence of particulate matter is determined to ensure that the ophthalmic solution does not contain foreign particles. Light obscuration methods and / or microscopy are used to count and / or measure particle size. The isotonicity and pH of the composition are also tested. 【0133】 The drug content in the ophthalmic composition of the present disclosure is evaluated by appropriate analytical methods such as UV-vis spectroscopy and HPLC. Further, the composition is also tested for the effectiveness, stability, and effective shelf life of the preservative according to standard guidelines. The composition of the present invention is further sterilized using various sterilization methods known in the art. 【0134】 The rifamycin compound or its pharmaceutically acceptable salt present in the ophthalmic composition of the present disclosure is stably dissolved in the aqueous formulation. 【0135】 The term "stable" means that one or more rifamycin compounds or pharmaceutically acceptable salts thereof are dissolved in an aqueous formulation and after a period of time, no precipitate or particulate matter is present. Examples of said period include 2 hours, 5 hours, 10 hours, throughout the day and night, 1 day, 2 days, 3 days, 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 6 months, 1 year, 2 years, and 3 years. Also, the temperature for maintaining stability is for example, 0°C to 40°C (upper limit: 40°C, lower limit: 0°C), and can be appropriately set within the above temperature range. The temperature is for example, a constant temperature, or a constant temperature range. Specific examples of the temperature (range) for maintaining stability include 0°C, 4°C, 10°C, 15°C, 20°C, 25°C, 30°C, 35°C, 37°C, 35°C, 40°C to 40°C, 4°C to 37°C, 4°C to 30°C, 4°C to 30°C, 4°C to 25°C, 4°C to 20°C, 4°C to 10°C, 10°C to 37°C, 10°C to 30°C, 10°C to 25°C, 10°C to 20°C, 20°C to 25°C, 20°C to 37°C, 25°C to 37°C, 25°C to 30°C. 【0136】 The ophthalmic composition of the present disclosure is expected to exhibit high affinity for mucosal tissues including the eye. Some embodiments described herein relate to compositions that deliver a therapeutically effective amount of a drug (e.g., one or more rifamycin compounds) to systemic circulation via the mucosa. In some embodiments, the compositions of the present invention offer advantages over other forms of administration routes (e.g., oral or intravitreal administration, etc.), including but not limited to, avoidance of first-pass metabolism of the drug, avoidance of irritation of the GI mucosa, avoidance of fluctuations in drug levels, avoidance of a predictable and extended active period, minimization of undesirable side effects, compatibility with drugs having a short half-life and a narrow therapeutic index, maintenance of a steady-state plasma concentration of a potent drug, greater patient compliance due to elimination of multiple doses and dosage forms (oral and systemic), no need for local anesthesia, no pain associated with injection, ease of administration, compatibility with self-administration, and ease of termination of treatment at any point. 【0137】 In some embodiments, the pharmaceutical composition is formulated for parenteral administration. "Parenteral administration" generally refers to an administration route other than the gastrointestinal tract. Examples of parenteral administration include, but are not limited to, intravenous injection, intraarterial injection, intrathecal injection (into the spinal cord), intratonsillar injection, subcutaneous injection, intramuscular injection, infusion, or transplantation. Infusion can be by intradermal, or subcutaneous, or transdermal implant. Exemplary pharmaceutical compositions for parenteral administration are the following references incorporated herein by reference: U.S. Patent Application Pub. No. 2006 / 0287221. Nos. 5,244,925, 4,309,421, 4,158,707, and 5,164,405 (all of which are incorporated herein by reference). 【0138】 Compositions formulated for parenteral administration include aqueous solutions and / or buffered solutions commonly used for injection and / or infusion. Commonly used aqueous buffers and / or solutions include, but are not limited to, about 0.9% sodium chloride solution, phosphate buffer, lactated Ringer's solution, acetate Ringer's solution, phosphate buffered saline, citrate buffer, Tris buffer, histidine buffer, HEPES buffer, glycine buffer, N-glycylglycine buffer, and the like. Other pharmaceutically acceptable carriers for parenteral administration include ethanol, glycerol, propylene glycol, cyclodextrin and cyclodextrin derivatives, vegetable oils, and the like. 【0139】 In some embodiments, the pharmaceutical composition for injection and / or infusion contains a preservative present in an amount that effectively prevents or reduces microbial contamination or degradation. Various agents, such as phenol, m-cresol, benzyl alcohol, parabens, chlorobutanol, methotrexate, sorbic acid, thimerosal, ethyl hydroxybenzoate, bismuth tribromophenate, methyl hydroxybenzoate, bacitracin, propyl hydroxybenzoate, erythromycin, 5-fluorouracil, doxorubicin, mitoxantrone, rifamycin, chlorocresol, benzalkonium chloride, can be used to prevent or reduce contamination. 【0140】 In some embodiments, a sterile solution is prepared by incorporating the crystalline form of the ophthalmic composition disclosed herein, optionally together with various other ingredients as described herein, in a suitable solvent in the required amounts and subsequently filter sterilizing. Generally, a dispersion is prepared by incorporating various sterilized active ingredients into a sterile medium containing a basic dispersion medium and the required other ingredients from those listed above. In the case of sterile powders for the preparation of sterile injection solutions, specific preparation methods include, but are not limited to, vacuum drying and lyophilization techniques that yield any additional desired ingredients from a pre-sterilized filtered solution thereof in addition to the powder of the active ingredient. 【0141】 In some embodiments, the pharmaceutical composition is formulated for topical and / or transdermal delivery. The compositions of the present application are formulated into formulations in liquid, semi-solid, or solid forms suitable for topical or local administration. Examples of forms suitable for topical or local administration include, but are not limited to, gels, water-soluble jellies, creams, lotions, suspensions, foams, powders, slurries, ointments, oils, pastes, suppositories, solutions, sprays, emulsions, saline solutions, dimethyl sulfoxide (DMSO)-based solutions. Generally, carriers with higher densities can provide regions with long-term exposure to the active ingredient. In contrast, solution formulations provide more immediate exposure of the active ingredient to the selected region. 【0142】 The pharmaceutical composition comprises, consists essentially of, or consists of a suitable solid or gel phase carrier with a compound that enables or aids the enhanced penetration of therapeutic molecules across the stratum corneum barrier of the skin. Many of these penetration enhancing molecules are known to those skilled in the art of topical formulations. Examples of such carriers and excipients include, but are not limited to, alcohols (e.g., ethanol), fatty acids (e.g., oleic acid), humectants (e.g., urea), glycols (e.g., propylene glycol), surfactants (e.g., isopropyl myristate and sodium lauryl sulfate), glycerol monolaurate, sulfoxides, pyrrolidones, terpenes (e.g., menthol), amines, amides, alkanes, alkanols, water, calcium carbonate, calcium phosphate, various sugars, starches, cellulose derivatives, gelatin, and polymers such as polyethylene glycol. 【0143】 Another exemplary formulation for use in the methods of the present application uses a transdermal delivery device (“patch”). Such transdermal patches are used to provide a continuous or discontinuous infusion of the ophthalmic compositions of the present disclosure described herein, in a controlled amount, with or without additional agents. The construction and use of transdermal patches for the delivery of pharmaceutical agents are well known in the art. For example, U.S. Pat. Nos. 5,023,252; 4,992,445; and 5,001,139; which are hereby incorporated by reference herein. 【0144】 In some embodiments, the present application provides a pharmaceutical composition comprising an effective amount of the ophthalmic composition described herein for transdermal delivery and a pharmaceutical excipient suitable for delivery by inhalation. Compositions for inhalation include solutions and suspensions in pharmaceutically acceptable aqueous or organic solvents, or mixtures thereof, as well as powders. Liquid or solid compositions contain suitable pharmaceutically acceptable excipients as described herein. The compositions are administered by oral or nasal respiratory routes for systemic effect. In some embodiments, preferably the composition in a pharmaceutically acceptable solvent is nebulized by use of an inert gas. In some embodiments, the nebulized solution is inhaled directly from the nebulizing device. In other embodiments, the nebulizing device is attached to a face mask tent or intermittent positive pressure breathing apparatus. The solution, suspension, or powder composition is preferably administered orally or nasally from a device that delivers the formulation in a suitable manner. 【0145】 The pharmaceutical compositions used in the present disclosure are formulated for intraocular (eye), rectal, sublingual, buccal, or intranasal (e.g., intrapulmonary) administration. Formulations suitable for intraocular administration include eye drops in which the active ingredient is dissolved or suspended in a suitable carrier, particularly an aqueous solvent for the active ingredient. The active ingredient is preferably present in such formulations at a concentration of 0.5 to 20%, conveniently 0.5 to 10%, particularly about 1.5% w / w. Formulations suitable for sublingual administration are typically formulated to dissolve rapidly when placed in the mouth, allowing absorption of the active ingredient through the blood vessels under the tongue. Exemplary sublingual formulations include, for example, lozenges containing the active ingredient in a flavoring base, usually sucrose and acacia or tragacanth; troches containing the active ingredient in an inert base such as gelatin and glycerin, or sucrose and acacia; mouthwashes containing the active ingredient in a suitable liquid carrier; for example, orally disintegrating tablets that can disintegrate in less than 90 seconds when placed in the mouth; and thin films. Such disintegration can be measured by an in vitro dissolution test. Formulations for oral administration can include, for example, oral tablets, bioadhesive particles, wafers, lozenges, medicated chewing gums, adhesive gels, patches, films, which can be delivered, by way of several examples, as aqueous solutions, pastes, ointments, or aerosols. Formulations for rectal administration are provided, for example, as suppositories having a suitable base containing cocoa butter or salicylate. Formulations suitable for intrapulmonary or nasal administration can have a particle size in the range of 0.1 to 500 microns (including particle sizes in the range of 0.1 to 500 microns such as 0.5, 1, 30 microns, 35 microns, etc.), which are administered by rapid inhalation through the nasal cavity or inhalation through the mouth so as to reach the alveolar sacs. Suitable formulations include aqueous or oily solutions of the active ingredient. Formulations suitable for aerosol or dry powder administration are prepared according to conventional methods and are delivered together with other therapeutic agents such as compounds previously used for the treatment or prevention of cancerous infections, as described below.The pharmacological formulations of the present application are administered to patients as injectable formulations containing any suitable carrier such as various vehicles, adjuvants, additives, and diluents; or mesopimazine mesylate utilized in the present application is parenterally administered to patients in the form of sustained-release subcutaneous implants or targeted delivery systems such as monoclonal antibodies, vectorized delivery, iontophoresis, polymer matrices, liposomes, and microspheres. Examples of delivery systems useful in the present application include the following. Numbers. 5,225,182; 5,169,383; 5,167,616; 4,959,217; 4,925,678; 4,487,603; 4,486,194; 4,447,233; 4,447,224; 4,439,196; and 4,475,196. Many other such implants, delivery systems, and modules are well known to those skilled in the art. 【0146】 The formulations can be provided in unit-dose or multi-dose sealed containers, for example, ampoules and vials, and can be stored in a lyophilized (freeze-dried) state that requires only the addition of a sterile liquid excipient, for example, water, immediately prior to use. Immediate injection solutions and suspensions can be prepared from sterile powders, granules, and tablets of the type described herein. 【0147】 The compositions and formulations are provided, if desired, in vials, containers, packs, or dispenser devices containing one or more unit dosage forms containing the active ingredient. The vials, containers, packs, or dispenser devices include, consist essentially of, or further consist of, for example, a metal or plastic foil such as a blister pack. The vials, containers, packs, or dispenser devices or dispenser devices are accompanied by instructions for administration. 【0148】 Furthermore, the composition is encapsulated or injected in a form for delivery to a target tissue site. In certain embodiments, the compositions of the present disclosure can deliver one or more therapeutic compounds to a target tissue site and include a matrix that provides a structure for the developing tissue and that can be optimally resorbed in the body. For example, the matrix provides a sustained release of the active ingredient. Such matrices are currently formed from materials used in other implant medical applications. 【0149】 The selection of the matrix material is based on biocompatibility, biodegradability, mechanical properties, cosmetic appearance, and interfacial properties. The particular use of the subject composition dictates the appropriate formulation. Potential matrices for the composition are biodegradable and chemically defined calcium sulfate, tricalcium phosphate, hydroxyapatite, polylactic acid, and polyanhydrides. Other possible materials are biodegradable and are well defined biologically, such as bone or skin collagen. Further matrices are composed of pure proteins or extracellular matrix components. 【0150】 Other potential matrices are non - biodegradable and chemically defined, such as sintered hydroxyapatite, bioglass, aluminates, or other ceramics. The matrix consists of any combination of materials of the types described above, such as polylactic acid and hydroxyapatite or collagen and tricalcium phosphate. The bioceramics are compositionally altered, for example, in processing to alter calcium aluminate phosphate, and pore size, particle size, particle shape, and biodegradability. The suspension contains suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol, and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar and tragacanth, and mixtures thereof, in addition to the active compound. 【0151】 In certain embodiments, the compositions of the present disclosure also contain adjuvants such as preservatives, wetting agents, emulsifying agents, and dispersing agents. Prevention of the action of microorganisms is ensured by including various antibacterial and antifungal agents, such as parabens, chlorobutanol, phenolsorbic acid, and the like. It is also desirable to include isotonic agents such as sugars, sodium chloride, etc. in the composition. Further, sustained absorption of the injectable pharmaceutical form is brought about by including agents that delay absorption, such as aluminum monostearate and gelatin. 【0152】 The preparation of such pharmaceutical compositions is described, for example, in Anderson, Philip O.; Knoben, James E.; Troutman, William G., eds., Handbook of Clinical Drug Data, Tenth Edition, McGraw-Hill, 2002; Pratt and Taylor, eds., Principles of Drug Action, Third Edition, Churchill Livingston, N.Y., 1990; Katzung, ed., Basic and Clinical Pharmacology, The Pharmacological Basis of Therapeutics, Tenth Edition, McGraw Hill, 2001; Remingtons Pharmaceutical Sciences, 20th Ed., Lippincott Williams & Wilkins., 2000; Martindale, The Extra Pharmacopoeia, Thirty-Second Edition(The Pharmaceutical Press, London, 1999); all of which are incorporated by reference herein in their entirety, and these are incorporated herein in their entirety. 【0153】 Exemplary Therapeutic Uses As described herein, the Applicant has surprisingly discovered that administration of the ophthalmic compositions of the present disclosure to the eye results in efficient delivery of one or more rifamycin compounds to the posterior part of the eye (including subretinal, scleral, retinal, and / or vitreous tissues) at a concentration sufficient to inhibit neovascularization. Further, the data of the present disclosure suggest that said ophthalmic compositions also have a positive effect in the treatment or prevention of ocular (eye) disorders, particularly vascular eye disorders including those associated with, for example, ischemia and / or vascular insufficiency. 【0154】 The structural and functional integrity of the eye depends on a regular supply of oxygen and nutrients. The retina, one of the most metabolically active tissues, consumes oxygen more rapidly than other tissues in the body [Cohen et al. (1965) Retina. Orlando, Fla.: Academic Press Inc.; pp. 36-50; Anderson et al. (1964) Arch Ophthalmol 72:792-795; and Ames A. (1992) Can J Physiol Pharmacol. 70(Suppl): S158-64]. The presence of a dual circulatory system makes retinal oxygenation unique [Osborne et al. (2004) Prog Retin Eye Res.23:91-147]. Most of the photoreceptors and the outer plexiform layer receive nutrients indirectly from the choroidal capillaries, while the inner retinal layers are supplied by the superficial and deep capillary plexuses formed by the branches of the central artery of the retina. The inner layer of the retina is known to be the most sensitive to hypoxia challenge [Janaky et al. (2007) Doc Ophthalmol. 114:45-51], while the outer retina is more resistant to hypoxia stress [Tinjust et al. (2002) Aviat Space Environ Med. 73:1189-94]. 【0155】 Many systemic and cellular responses, such as glycolysis, angiogenesis, vasodilation, and erythropoiesis, enable organisms to respond to hypoxia [Harris et al. (2002) Nat Rev Cancer. 2:38-47]. Many tissues can induce protective mechanisms under hypoxic-ischemic conditions, which are typically induced within minutes of onset and are extremely important for limiting damage [Kitagawa et al. (1990) Brain Res. 528:21-4]. However, during long-term hypoxia, these protective mechanisms generally decrease / disappear within hours of hypoxic-ischemic injury, leading to cell death and tissue damage [Prass et al. (2003) Stroke. 34:1981-6]. The transcriptional activator hypoxia-inducible factor-1α (HIF-1α) is the master regulator of cellular O2 homeostasis [Iyer et al. (1998) Genes Dev. 12:149-62]. Hypoxia is known to induce HIF-1α and its target genes, such as vascular endothelial growth factor (VEGF) and nitric oxide synthase (NOS), in many tissues. Interestingly, overproduction of these factors, e.g., during long-term hypoxia, is involved in cell death in the hypoxic-ischemic state. Furthermore, enhanced extracellular accumulation of glutamate and inflammatory cytokines that occurs during long-term hypoxia can damage cells and tissues. Increased expression of various isoforms of HIF-1α, VEGF, and NOS has been reported in the retina after hypoxic injury [Kaur et al. (2006) Invest Ophthalmol Vis Sci. 47:1126-41; and Tezel et al. (2004) Curr Opin Ophthalmol. 15:80-4]. 【0156】 Retinal ganglion cells (RGCs) are particularly sensitive to acute, transient, and mild systemic hypoxia stress [Kergoat et al. (2006) Invest Ophthalmol Vis Sci. 47:5423-7]. Loss of RGCs occurs in many eye conditions such as glaucoma and diabetes (Sucher et al. (1997) Vision Res. 37:3483-93; Abu-El-Asrar et al. (2004) Invest Ophthalmol Vis Sci. 45:2760-6), and oxygen and substrate deprivation-induced ischemia is partially mediated by the accumulation of free oxygen radicals [Block et al. (1997) Exp Eye Res. 64:559-64; Muller et al. (1997) Exp Eye Res. 64:637-43; and Szabo et al. (1997) Clin Neurosci. 4:240-5], glutamate excitotoxicity [Kuroiwa Tet al. (1985) Acta Neuropathol (Berl) 68:122-9; Osborne et al. (2004) Prog Retin Eye Res. 23:91-147; and Kaur et al. (2006) Invest Ophthalmol Vis Sci. 47:1126-41], inflammation and disruption of the blood-retinal barrier [Kuroiwa et al. (1985) Acta Neuropathol (Berl) 68:122-9; and Kaur et al. (2007) J Pathol. 【0157】 Hypoxia-ischemia also results in retinal vascular damage associated with fluid accumulation in the extracellular space (angiogenic edema) or intracellular space (cytotoxic edema) [Marmor et al. (1999) Doc Ophthalmol. 97:239-49]. The extracellular space of the inner retina consists of narrow slits between densely packed cellular elements. Fluid leaking from damaged capillaries in the inner retina accumulates in the extracellular space, displacing retinal cellular elements, disrupting the normal anatomical structure of neuronal connections, and resulting in macular edema [Hamann et al. (2005) Acta Ophthalmol Scand. 83:523-5]. Macular edema can further exacerbate retinal ischemia and promote increased oxidative stress and inflammation (Guex-Crosier Y. (1999) Doc Ophthalmol. 97:297-309; van Dam PS. (2002) Diabetes Metab Res Rev. 18:176-84; and Miyake et al. (2002) Sury Ophthalmol. 47:S203-8.). An increase in the permeability of the blood-retinal barrier (BRB) resulting in fluid accumulation has been reported to contribute to compressive retinal neurodegeneration [Antcliff et al. (1999) Semin Ophthalmol. 14:223-32; Marumo T et al. (1999) J Vasc Res. 36:510-15; and Reichenbach et al. (2007) Graefes Arch Clin Exp Ophthalmol. 245:627-36). Although initially protective, excessive and / or chronic production of VEGF, nitric oxide (NO), and aquaporin-4 during hypoxia-ischemic injury can cause neovascularization and dysfunction of the BRB in the retina, leading to serum leakage into the retinal tissue and retinal edema. In addition to increased vascular permeability, ocular hypoxia has also been correlated with endothelial cell death, leukocyte plugging of blood vessels, and microaneurysms [Linsenmeier et al. (1998) Invest Ophthalmol Vis Sci. 39:1647-57]. 【0158】 Hypoxia-ischemia occurs in various eye conditions, such as retinal artery / vein occlusion or thrombosis, ocular ischemic syndrome, ischemic optic neuropathy, and retinal ischemia. Hypoxia-ischemia is also involved in the development of glaucoma [Flammer J. (1994) 'Sury Ophthalmol. 38(Suppl): S3-6; Chung et al. (1999) Sury Ophthalmol. 43(Suppl 1): S43-50; and Tezel et al. (2004) Curr Opin Ophthalmol. 15:80-4], complications that threaten vision in diabetic eye diseases, including retinal and optic nerve head neovascularization [Linsenmeier et al. (1998) Invest Ophthalmol Vis Sci. 39:1647-57], and plays a role in age-related macular degeneration [Tso et al. (1982) Ophthalmology. 89:902-15; Yanoff et al. (1984) Sury Ophthalmol. 28(Suppl):505-11; and Bressler et al. (2001) In: Schachat AP, editor. Retina. St. Louis, Mo. Systemic causes of ocular hypoxia include cardiovascular effects, chronic obstructive airway disease, arterial / venous occlusive states, [Brown et al. (1988) Int Ophthalmol. 11:239-51] Takayasu's arteritis [Shelhamer et al. (1985) Ann Intern Med. 103:121-6], hyperviscosity syndrome [Ashton et al. (1963) J Pathol Bacteriol. 86:453-61], and trauma (such as surgery or accidental injury) [Purtscher's retinopathy; Buckley et al. (1996) Postgrad Med J. 72:409-12]. Hypoxia associated with the above conditions is a common cause of visual impairment and blindness [Osborne, et al. (2004) Prog Retin Eye Res. 23:91-147]. 【0159】 Accordingly, in certain embodiments, the present disclosure provides a method for treating or preventing ocular vascular disorders (diseases) in a patient (subject) in need thereof (especially mammals such as rodents, cats, dogs, primates, and humans) by administering to the patient an ophthalmic composition comprising, consisting essentially of, or further comprising a therapeutically effective amount of one or more rifamycin compounds, a buffer, and a viscosity enhancer. Ocular vascular disorders include, but are not limited to, macular degeneration, diabetic retinopathy, chronic glaucoma, retinal detachment, sickle cell retinopathy, age-related macular degeneration (AMD), retinal ganglion cell damage, iris neovascularization, inflammatory diseases, chronic uveitis, neoplasms, Fuchs heterochromic iridocyclitis, neovascular glaucoma, corneal neovascularization, choroidal neovascularization, retinal neovascularization, retinal vascular tumor proliferation, glaucoma, glaucoma surgery, tissue adhesion, scarring, tissue fibrosis, and brain injury. 【0160】 In some embodiments, provided is a method for using an ophthalmic composition comprising, consisting essentially of, or further comprising one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent for treating or preventing ocular vascular disorders associated with ischemia. In some embodiments, provided is a method for using an ophthalmic composition comprising, consisting essentially of, or further comprising one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent for treating or preventing ischemic eye diseases. In some embodiments, provided is a method for using an ophthalmic composition comprising, consisting essentially of, or further comprising one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent for treating or preventing ocular vascular disorders associated with microvascular insufficiency. In some embodiments, provided is a method for using an ophthalmic composition comprising, consisting essentially of, or further comprising one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent for treating or preventing ocular microvascular insufficiency diseases. In some embodiments, provided is a method for using an ophthalmic composition comprising, consisting essentially of, or further comprising one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent for treating or preventing ocular vascular disorders associated with retinopathy. In some embodiments, provided is a method for using an ophthalmic composition comprising, consisting essentially of, or further comprising one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent for treating or preventing ocular vascular disorders associated with neuropathy. In some embodiments, provided is a method for using an ophthalmic composition comprising, consisting essentially of, or further comprising one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent for treating or preventing ischemic retinopathy. In some embodiments, provided is a method for using an ophthalmic composition comprising, consisting essentially of, or further comprising one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent for treating or preventing ischemic neuropathy.In some embodiments, provided are methods for using an ophthalmic composition comprising, consisting essentially of, or further comprising one or more rifamycin compounds, a buffer, and a viscosity enhancer to treat or prevent retinopathies associated with microvascular insufficiency. In some embodiments, provided are methods for using an ophthalmic composition comprising, consisting essentially of, or further comprising one or more rifamycin compounds, a buffer, and a viscosity enhancer to treat or prevent optic neuropathies associated with microvascular insufficiency. In particular, the present disclosure provides methods of using an ophthalmic composition consisting essentially of one or more rifamycin compounds, a buffer, and a viscosity enhancer to treat or prevent one or more diseases selected from age-related macular degeneration (e.g., age-related macular degeneration, juvenile macular degeneration, dry macular degeneration, Stargardt disease, and Best disease), retinal vein occlusion (e.g., central retinal vein occlusion, branch retinal vein occlusion, and ischemic retinal vein occlusion), retinal artery occlusion (e.g., central retinal artery occlusion, branch retinal artery occlusion, and ischemic retinal artery occlusion), diabetic retinopathy, anterior ischemic optic neuropathy (arteritic and non-arteritic), posterior ischemic optic neuropathy, macular telangiectasia (type I or type II), retinal ischemia (acute retinal ischemia or chronic retinal ischemia), ocular ischemia syndrome, retinal vasculitis, and retinopathy of prematurity. In some embodiments, the methods and compositions disclosed herein for treating an eye disease result in improving the vision of a patient's eye. In some embodiments, the methods and compositions disclosed herein for treating an eye disease increase the vision of a patient's eye. In some embodiments, the methods and compositions disclosed herein for treating an eye disease increase the visual field of a patient's eye. Optionally, the methods of the present disclosure for treating or preventing ocular vascular disorders further comprise, consist essentially of, or further consist of: one or more rifamycin compounds, a buffer, and a viscosity enhancer [e.g., photocoagulation], anti-angiogenic therapy [e.g., bevacizumab (Avastin®), ranibizumab (Lucentis®), and aflibercept (Eylea®)], Ca. 2+Inhibitors (e.g., flunarizine and nifedipine), cryotherapy, hyperbaric oxygenation, Na + channel blockers (e.g., topiramate), iGluR antagonists (e.g., MK-801, dextromethorphan, eliprodil, and flupirtine), antioxidants (e.g., dimethylthiourea, vitamin E, alpha-lipoic acid, superoxide dismutase, catalase, desferrioxamine, mannitol, allopurinol, calcium besylate, flupirtine, trimetazidine, and EGB-761), anti-inflammatory agents, cyclodiathermy, eye filtration procedures, drainage valve implantation, antiplatelet therapy (e.g., aspirin, ticlopidine, and clopidogrel), anticoagulant therapy (e.g., warfarin and heparin), steroids, systemic or local corticosteroids (e.g., prednisone triamcinolone (Triesence®), and dexamethasone (Ozurdex®), steroid-sparing immunosuppressants (e.g., cyclosporine, azathioprine, cyclophosphamide, mycophenolic acid, mofetil, infliximab, and etanercept), nutritional supplements (e.g., vitamin C, vitamin E, lutein, zeaxanthin, folic acid, vitamin B6, and zeaxanthin), vitrectomy, scleral buckle surgery, and pneumatic retinopexy. In a preferred embodiment, the above methods and compositions for treating or preventing ocular vascular disorders in a patient in need thereof comprise, consist essentially of, or further comprise an ophthalmic composition having a viscosity of at least 1 mPaS at 25°C. In a more preferred embodiment, the one or more rifampicin compounds are rifampicin, the one or more viscosity agents are petrolatum or liquid paraffin, and the effective amount of rifampicin comprises a final concentration of at least about 0.001% w / w to about 1% w / w in the composition. 【0161】 In certain embodiments, the present disclosure provides methods and compositions for improving vision (e.g., increasing visual acuity and / or visual field) in a patient in need thereof by administering to the patient a therapeutically effective amount of an ophthalmic composition comprising, consisting essentially of, or further consisting of one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent. In some embodiments, the present disclosure provides methods for using an ophthalmic composition comprising, consisting essentially of, or further consisting of one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent to improve vision (e.g., increasing visual acuity and / or visual field) in a patient having a vascular disorder of the eye. In some embodiments, the present disclosure provides methods for using an ophthalmic composition comprising, consisting essentially of, or further consisting of one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent to improve vision (e.g., increasing visual acuity and / or visual field) in a patient having a vascular disorder of the eye associated with an ischemic eye disease. In some embodiments, the present disclosure provides methods for using an ophthalmic composition comprising, consisting essentially of, or further consisting of one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent to improve vision (e.g., increasing visual acuity and / or visual field) in a patient having a vascular disorder of the eye associated with microvascular insufficiency. In some embodiments, the present disclosure provides methods for using an ophthalmic composition comprising, consisting essentially of, or further consisting of one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent to improve vision (e.g., increasing visual acuity and / or visual field) in a patient having a microvascular insufficiency disorder of the eye. In some embodiments, the present disclosure provides methods for using an ophthalmic composition comprising, consisting essentially of, or further consisting of one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent to improve vision (e.g., increasing visual acuity and / or visual field) in a patient having a vascular disorder of the eye associated with retinopathy.In some embodiments, provided is a method for using an ophthalmic composition comprising, consisting essentially of, or further comprising one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent to improve the vision (e.g., increase visual acuity and / or visual field) of a patient having an ocular vascular disorder associated with optic neuropathy. In some embodiments, provided is a method for using an ophthalmic composition comprising, consisting essentially of, or further comprising one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent to improve the vision (e.g., increase visual acuity and / or visual field) of a patient having ischemic retinopathy. In some embodiments, provided is a method for using an ophthalmic composition comprising, consisting essentially of, or further comprising one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent to improve the vision (e.g., increase visual acuity and / or visual field) of a patient having ischemic optic neuropathy. In some embodiments, provided is a method for using an ophthalmic composition comprising, consisting essentially of, or further comprising one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent to improve the vision (e.g., increase visual acuity and / or visual field) of a patient having retinopathy associated with microvascular insufficiency. In some embodiments, provided is a method for using an ophthalmic composition comprising, consisting essentially of, or further comprising one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent to improve the vision (e.g., increase visual acuity and / or visual field) of a patient having optic neuropathy associated with microvascular insufficiency.In particular, the present disclosure relates to one or more rifamycin compounds for improving vision and / or visual field in patients having one or more diseases selected from age-related macular degeneration (e.g., age-related macular degeneration, juvenile macular degeneration, dry macular degeneration, Stargardt's disease, and Best disease), retinal vein occlusion (e.g., central retinal vein occlusion, branch retinal vein occlusion, and ischemic retinal vein occlusion), retinal artery occlusion (e.g., central retinal artery occlusion, branch retinal artery occlusion, and ischemic retinal artery occlusion), retinopathy, ischemic optic neuropathy [e.g., anterior ischemic optic neuropathy (arteritic and non-arteritic) and posterior ischemic optic neuropathy], macular telangiectasia (type I or II), retinal ischemia (e.g., acute retinal ischemia or chronic retinal ischemia), ocular ischemia syndrome, retinal vasculitis, and retinopathy of prematurity. In some embodiments, the present disclosure provides a method for using an ophthalmic composition comprising, consisting essentially of, or further comprising one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent to improve the vision (e.g., increase vision and / or visual field) of patients having anemia. In some embodiments, the present disclosure provides a method for using an ophthalmic composition comprising, consisting essentially of, or further comprising one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent to improve the vision (e.g., increase vision and / or visual field) of patients having myelodysplastic syndrome. In some embodiments, the present disclosure provides a method for using an ophthalmic composition comprising, consisting essentially of, or further comprising one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent to improve the vision (e.g., increase vision and / or visual field) of patients having sideroblastic anemia. In some embodiments, the present disclosure provides a method for using an ophthalmic composition comprising, consisting essentially of, or further comprising one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent to improve the vision (e.g., increase vision and / or visual field) of patients having abnormal hemoglobinopathy.In some embodiments, provided is a method for using an ophthalmic composition comprising, consisting essentially of, or further comprising one or more rifamycin compounds, a buffering agent, and a viscosity-imparting agent to improve the vision (e.g., increase visual acuity and / or visual field) of patients with sarcoidosis. In some embodiments, provided is a method for using an ophthalmic composition comprising, consisting essentially of, or further comprising one or more rifamycin compounds, a buffering agent, and a viscosity-imparting agent to improve the vision (e.g., increase visual acuity and / or visual field) of patients with sickle cell disease. Optionally, the disclosed method for improving vision (e.g., increasing visual acuity and / or visual field) in a patient having an eye disease further comprises administering one or more supportive therapies for treating or preventing the eye disease in addition to administering an ophthalmic composition comprising, consisting essentially of, or further comprising one or more rifamycin compounds, a buffering agent, and a viscosity-imparting agent. In a preferred embodiment, the above methods and compositions for improving the vision of a patient in need thereof comprise, consist essentially of, or further comprise an ophthalmic composition having a viscosity of at least 50 mPaS at 25°C. In a more preferred embodiment, the one or more rifampicin compounds are rifampicin, the one or more viscosity-imparting agents are petrolatum or liquid paraffin, and the effective amount of rifampicin comprises a final concentration of at least about 0.001% w / w to at least about 1% w / w in the composition. 【0162】 Macular degeneration results in loss of vision in the center of the visual field (macula) and is generally caused by damage to the retina [de Jong P T (2006) N Engl J Med 255(14):1474-1485]. It is a major cause of blindness and visual impairment and typically occurs in the elderly, who are generally affected by approximately 20 to 50 million people worldwide. Macular degeneration mainly appears in older adults and is often called age-related macular degeneration (AMD). In younger patients, macular degeneration is often called juvenile macular degeneration, which is generally the result of an underlying genetic disorder (e.g., Stargardt disease or Best disease) [Dryja et al. (1998) Science 279(5354): 1107]. Generally, macular degeneration appears as either a "dry" (non-exudative) or "wet" (exudative) disease. In dry macular degeneration, yellow deposits (drusen) accumulate in the macula between the retinal pigment epithelium and the underlying choroid. Large and / or numerous drusen deposits destroy the submacular pigment epithelial cell layer, which causes loss of vision due to damaged photoreceptors (cones and rods). Generally, wet macular degeneration is caused by abnormal blood vessel growth (choroidal neovascularization) from the choroidal capillaries through the Bruch membrane. These new blood vessels are fragile and result in leakage of blood and protein under the macula. Bleeding and scarring from these blood vessels can damage photoreceptors and thus may promote loss of vision. 【0163】 Unfortunately, the treatment options for dry age-related macular degeneration are limited. However, a large-scale scientific study (Age-Related Eye Disease Study 2) has shown that among people at high risk of developing advanced age-related macular degeneration, taking nutritional supplements of vitamin C, vitamin E, lutein, and zeaxanthin in combination with zinc reduces the progression to the advanced stages of the disease by at least 25% [Chew et al. (2013) Ophthalmology 120(8): 1604-1611]. Another large-scale study in women has shown benefits from taking folic acid as well as vitamins B6 and B12 [Christen et al. (2009) Arch Intern Med 169(4): 335-341]. Other studies have shown that lutein and zeaxanthin reduce the risk of developing dry age-related macular degeneration [Chew et al. (2013) Ophthalmology 131(7): 843-850]. 【0164】 The most common treatments for wet age-related macular degeneration are the administration of one or more vascular endothelial growth factor (VEGF) antagonists (inhibitors), including, for example, bevacizumab, ranibizumab, and aflibercept. Bevacizumab (Avastin®) is a humanized monoclonal VEGF-A antibody. Similarly, ranibizumab (Lucentis®) is a monoclonal VEGF-A antibody fragment (Fab). Aflibercept (Eylea®) is an immunoglobulin Fc fusion protein containing portions derived from the extracellular domains of human VEGF receptors 1 and 2. Most cases are treated with drug therapy, but surgery or laser therapy can also be used to treat wet age-related macular degeneration. In laser therapy, a focused beam of light is used to destroy abnormal blood vessels in the retina and prevent further abnormal blood vessel growth and leakage. In some cases, wet age-related macular degeneration can be treated with photodynamic therapy using a combination of a photoactivatable drug (photosensitizer) and a low-power laser. The photosensitive drug is injected into the patient and travels throughout the body, including abnormal blood vessels behind the eye. The low-power laser activates the drug, thereby directly targeting the abnormal blood vessels to specifically damage the unwanted blood vessels. 【0165】 In certain embodiments, the present disclosure provides methods and compositions for treating or preventing macular degeneration in a patient in need thereof by administering an ophthalmic composition comprising, consisting essentially of, or further consisting of one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent. In some embodiments, an ophthalmic composition comprising, consisting essentially of, or further consisting of one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent can be used to treat or prevent one or more of age-related macular degeneration, juvenile macular degeneration, Stargardt disease, Best disease, dry macular degeneration, and wet macular degeneration. In some embodiments, an ophthalmic composition comprising, consisting essentially of, or further consisting of one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent can be used to treat or prevent one or more complications of macular degeneration, including, for example, drusen deposition / accumulation, macular edema, and neovascularization. In some embodiments, an ophthalmic composition comprising, consisting essentially of, or further consisting of one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent can be used to improve vision (e.g., increase visual acuity and / or increase visual field) in a patient having macular degeneration. Optionally, a patient suffering from macular degeneration should be treated with one or more supportive therapies for treating macular degeneration (e.g., VEGF antagonists (e.g., bevacizumab, ranibizumab, and aflibercept), surgery, laser therapy, photodynamic therapy, and / or dietary supplements (e.g., vitamin C, vitamin E, lutein, zeaxanthin, zinc, folic acid, vitamin B6, vitamin B12, and zeaxanthin)) in addition to an ophthalmic composition comprising, consisting essentially of, or further consisting of one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent. In a preferred embodiment, the above methods and compositions for treating or preventing macular degeneration in a patient in need thereof comprise, consist essentially of, or further consist of an ophthalmic composition having a viscosity of at least 1 mPaS at 25°C.In a further preferred embodiment, the one or more rifampicin compounds are rifampicin, the one or more viscosity-imparting agents are petrolatum or liquid paraffin, and the effective amount of rifampicin comprises a final concentration of at least about 0.001% w / w to 1% w / w in the composition. 【0166】 Subjects with diabetes suffer from life-limiting and life-threatening complications that are not limited to macrovascular-related stroke, ischemic heart disease, and peripheral arterial disease and / or microvascular-related retinopathy, neuropathy, and nephropathy. Diabetic retinopathy is the most common microvascular complication of diabetes and is a rapidly increasing global health problem (Antonetti DA, et al. N Engl J Med. 2012;366(13):1227-1239). Microvascular lesions are used as the main criteria for evaluating and classifying the retina in diabetic retinopathy. Diabetic retinopathy is classified into two broad categories: early non-proliferative diabetic retinopathy (NPDR) and advanced proliferative diabetic retinopathy (PDR) (Stitt AW, et al. Prog Retin Eye Res. 2016; 51:156-186). The classification of NPDR is based on clinical findings revealed by visible features including microaneurysms, retinal hemorrhages, intraretinal microvascular abnormalities (IRMA), and venous caliber changes. The classification of PDR is based on the presence of pathologic preretinal neovascularization. A further classification in diabetic retinopathy is diabetic macular edema (DME), which occurs across both the severity levels of NPDR and PDR and represents the most common cause of blindness in patients. DME results from the breakdown of the blood-retinal barrier (BRB) induced by diabetes, resulting in vascular leakage of body fluids and circulating proteins into the neural retina. The extravascular leakage of fluid into the neural retina leads to abnormal retinal thickening and often cystoid macular edema. Systemic features of diabetes such as hyperglycemia, dyslipidemia, and hypertension also affect the development of diabetic retinopathy. 【0167】 Intraocular treatment modalities for diabetic retinopathy include laser photocoagulation, intravitreal injection of anti-VEGF and steroid agents, and vitreoretinal surgery. The current treatment paradigm focuses on treating advanced disease when PDR or DME develops (Duh EJ et al., JCI Insight. July 20, 2017; 2(14): e93751), but these current treatment methods focus on treating advanced disease when PDR or DME develops (Duh EJ et al., JCI Insight. July 20, 2017; 2(14): e93751). 【0168】 In certain embodiments, methods and compositions are provided for treating or preventing diabetic retinopathy in a patient in need thereof by administering an ophthalmic composition comprising, consisting essentially of, or further consisting of one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent. In some embodiments, an ophthalmic composition comprising, consisting essentially of, or further consisting of one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent can be used to treat or prevent one or more of diabetic retinopathy, non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), and / or diabetic macular edema (DME). In some embodiments, an ophthalmic composition comprising, consisting essentially of, or further consisting of one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent can be used to treat or prevent one or more complications of diabetic retinopathy including, for example, vitreous hemorrhage, retinal detachment, glaucoma, blindness, blurred vision, fluctuating vision, and / or macular edema. In some embodiments, an ophthalmic composition comprising, consisting essentially of, or further consisting of one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent can be used to improve the vision (e.g., increase visual acuity and / or increase visual field) of a patient having diabetic retinopathy. Optionally, a patient suffering from diabetic retinopathy can, in addition to an ophthalmic composition comprising, consisting essentially of, or further consisting of one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent, receive one or more supportive therapies for diabetic retinopathy [e.g., VEGF antagonists (e.g., bevacizumab, ranibizumab, and aflibercept), surgery, laser therapy, photodynamic therapy, and / or dietary supplements (e.g., vitamin C, vitamin E, lutein, zeaxanthin, zinc, folic acid, vitamin B6, vitamin B12, and. An ophthalmic composition having a viscosity of at least 1 mPaS at 25° C. is included, consists essentially of, or further consists of, in the treatment of diabetic retinopathy in a patient in need thereof.In a more preferred embodiment, the rifampicin compound(s) is / are rifampicin, the viscosity modifier(s) is / are petrolatum, liquid paraffin, light liquid paraffin, or sesame oil, and the effective amount of rifampicin comprises a final concentration of at least about 0.001% w / w to 1% w / w in the composition. 【0169】 In some embodiments of the methods and compositions disclosed herein, the ophthalmic composition has a viscosity of at least 1 mPaS at 25 °C and comprises, consists essentially of, or consists of a) an effective amount of one or more rifamycin compounds or a pharmaceutically acceptable salt thereof, b) a buffer, and c) one or more viscosity - enhancing agents. In some preferred embodiments, the one or more rifamycin compounds are rifampicin and the one or more viscosity - enhancing agents are petrolatum. In some preferred embodiments, the one or more rifamycin compounds are rifampicin and the one or more viscosity - enhancing agents are liquid paraffin. In some embodiments, one or more rifampicin compounds are rifampicin, one or more viscosity - enhancing agents are petrolatum, and the effective amount of rifampicin comprises a final concentration of at least about 0.001% w / w in the composition. In some embodiments, one or more rifampicin compounds are rifampicin, one or more viscosity - enhancing agents are liquid paraffin, and the effective amount of rifampicin comprises a final concentration of at least about 0.001% w / w in the composition. In some embodiments, one or more rifampicin compounds are rifampicin, one or more viscosity - enhancing agents are petrolatum, and the effective amount of rifampicin comprises a final concentration of at least about 1% w / w in the composition. In some embodiments, one or more rifampicin compounds are rifampicin, one or more viscosity - enhancing agents are liquid paraffin, and the effective amount of rifampicin comprises a final concentration of at least about 1% w / w in the composition. In further embodiments, one or more rifamycin compounds are rifampicin, one or more viscosity - enhancing agents are petrolatum, the effective amount of rifampicin comprises a final concentration of at least about 0.001% w / w in the composition, and the composition has a final viscosity of at least about 1 mPaS, at least about 9 mPaS, at least about 55 mPaS, at least about 146 mPaS, about 161 mPaS, at least about 867 mPaS, at least about 2145 mPaS, or at least about 3815 mPaS at 25 °C.In a further embodiment, the one or more rifamycin compounds are rifampicin, the one or more viscosity modifiers are petrolatum, the effective amount of rifampicin comprises a final concentration of at least about 1% w / w in the composition, and the composition comprises a final viscosity of at least about 1 mPaS, at least about 9 mPaS, at least about 55 mPaS, at least about 146 mPaS, about 161 mPaS, at least about 867 mPaS, at least about 2145 mPaS, or at least about 3815 mPaS at 25°C. In a further embodiment, the one or more rifamycin compounds are rifampicin, the one or more viscosity modifiers are liquid paraffin, the effective amount of rifampicin comprises a final concentration of at least about 0.001% w / w in the composition, and the composition comprises a final viscosity of about 1 mPaS, at least about 9 mPaS, at least about 55 mPaS, at least about 146 mPaS, at least about 161 mPaS, at least about 867 mPaS, at least about 2145 mPaS, or at least about 3815 mPaS at 25°C. In a further embodiment, the one or more rifamycin compounds are rifampicin, the one or more viscosity modifiers are liquid paraffin, the effective amount of rifampicin comprises a final concentration of at least about 1% w / w in the composition, and the composition comprises a final viscosity of about 1 mPaS, at least about 9 mPaS, at least about 55 mPaS, at least about 146 mPaS, at least about 161 mPaS, at least about 867 mPaS, at least about 2145 mPaS, or at least about 3815 mPaS at 25°C. 【0170】 In certain embodiments, the present disclosure provides a method for delivering one or more rifamycin compounds to the eye. In some embodiments, the method comprises, consists essentially of, or further comprises topically administering to the eye an ophthalmic composition comprising one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent. In some embodiments, the present disclosure provides a method for delivering one or more rifamycin compounds to the subretinal, scleral, retinal, and / or vitreous tissues, the method comprising topically administering to the eye an ophthalmic composition comprising, consisting essentially of, or further comprising one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent. In some embodiments, the present disclosure provides a method for treating an angiogenesis eye disease, the method comprising topically administering to the eye an ophthalmic composition comprising, consisting essentially of, or further comprising one or more rifamycin compounds, a buffering agent, and a viscosity enhancing agent. In some embodiments, administration of the composition results in delivery of one or more rifamycin compounds to the subretinal, scleral, retinal, and / or vitreous tissues. In some embodiments, administration of the composition results in delivery of one or more rifamycin compounds to the subretinal and scleral tissues. In some embodiments, administration of the composition inhibits angiogenesis in the subretinal tissue. In some embodiments, topical administration of the composition results in at least about 5-fold, 10-fold, 50-fold, 100-fold, 500-fold, 1,000-fold, or 5,000-fold decrease in plasma exposure of one or more rifamycin compounds compared to oral administration at 300 mg. In some embodiments, topical administration of the composition results in at least about 100-fold decrease in plasma exposure of one or more rifamycin compounds compared to oral administration at 300 mg. In some embodiments, the composition is topically administered at a single dose per eye. In some further embodiments, the volume of the composition administered at a single dose per eye, referred to herein as the "target dose volume per eye" of the composition, ranges from about 2 μL to about 50 μL. In a more preferred embodiment, the target dose volume per eye ranges from about 5 μL to about 25 μL.In some further preferred embodiments, the target dosage volume per eye is in the range of about 5 μL to 15 μL. In some embodiments, the neovascular eye disease is macular degeneration, diabetic retinopathy, chronic glaucoma, retinal detachment, sickle cell retinopathy, age-related macular degeneration (AMD), retinal ganglion cell damage, iris neovascularization, inflammatory disease, chronic uveitis, neoplasm, Fuchs heterochromic iridocyclitis, neovascular glaucoma, corneal neovascularization, choroidal neovascularization, retinal neovascularization, retinal vascular tumor proliferation, glaucoma, glaucoma surgery. In some embodiments, the neovascular eye disease is AMD. In some embodiments, the neovascular eye disease is dry AMD. In some embodiments, the neovascular eye disease is wet AMD. In a preferred embodiment, the above method comprises, consists essentially of, or further consists of an ophthalmic composition having a viscosity of at least 1 mPaS at 25°C. In a further preferred embodiment, the one or more rifampicin compounds are rifampicin, the one or more viscosity modifiers are petrolatum or liquid paraffin, and the effective amount of rifampicin comprises a final concentration of at least about 0.001% w / w to at least about 1% w / w in the composition. 【0171】 Administration of the pharmaceutical compositions by the exemplary therapeutic uses described herein is effected by any method that enables delivery of the active ingredient (e.g., one or more rifamycin compounds) to the site of action. The compositions are administered ophthalmically, topically, orally, parenterally, enterally, intraperitoneally, transdermally, intranasally, topically, parenterally, via spray, subcutaneously, intravenously, intratonsillarly, intramuscularly, buccally, sublingually, rectally, intraarterially, by infusion, or intrathecally. In some embodiments, the composition is administered to the eye. In some embodiments, the composition is administered topically. In some embodiments, the composition is administered systemically. In some embodiments, the composition is administered via intravitreal injection. In some embodiments, the composition is administered orally. In some embodiments, the composition is administered subcutaneously. In some embodiments, oral administration comprises, consists essentially of, or consists of administration of any of the oral dosage forms described herein. The effective amount of the active ingredient (e.g., one or more rifamycin compounds) administered depends on the subject being treated, the severity of the disorder or condition, the rate of administration, the formulation of the active ingredient (e.g., one or more rifamycin compounds), and the discretion of the prescribing physician. 【0172】 In some embodiments, the method of the present disclosure includes administering to a subject an effective dose of one or more rifamycin compounds or compositions disclosed herein. As used herein, an effective dose of one or more rifamycin compounds or compositions disclosed herein is the dose required to produce a protective response in the subject to which it is administered. A defensive response in this context is a response that prevents or ameliorates a disease in the subject. The one or more rifamycin compounds or compositions disclosed herein can be administered one or more times. The pharmaceutically effective dose depends on the type of disease, the composition used, the route of administration, the subject being treated, the physical characteristics of the subject under consideration, concomitant medications, and other factors recognized by those skilled in the medical arts. Generally, an amount of the active ingredient of 0.1 mg / kg to 100 mg / kg body weight is administered depending on the potency of the formulated composition. In some embodiments, the one or more rifamycin compounds or compositions disclosed herein are administered at an effective dose of one or more rifamycin compounds of at least 0.01 mg / kg, at least 0.02 mg / kg, at least 0.07 mg / kg, at least 0.1 mg / kg, at least 0.2 mg / kg, at least 0.7 mg / kg, at least 2 mg / kg, at least 7 mg / kg, or at least 20 mg / kg. In some embodiments, the one or more rifamycin compounds or compositions disclosed herein are administered at an effective dose of one or more rifamycin compounds of at least 0.7 mg / kg. In some embodiments, the effective dose of the one or more rifamycin compounds or compositions disclosed herein is administered once a day, twice a day, three times a day, four times a day, five times a day, six times a day, seven times a day, or eight times a day. In some embodiments, the effective dose of the one or more rifamycin compounds or compositions disclosed herein is administered at intervals of at least 1 day, 2 days, 3 days, 4 days, 7 days, at least 14 days, at least 21 days, at least 28 days, at least 35 days, at least 42 days, at least 49 days, at least 56 days, or at least 64 days. 【0173】 Example The invention generally described herein will probably be more readily understood by reference to the following examples, which are included solely for the purpose of illustration of particular embodiments and examples of the invention and are not intended to limit the invention. 【0174】 Example 1: Ophthalmic preparation containing rifamycin compound The active ingredient, namely rifampicin, rifabutin, rifapentine, rifalazil or rifaximin, is dissolved in physiological saline or water, and a surfactant such as polysorbate 80, Tween 80 or Tween 20 is added and mixed with the solution. Further, various additives such as glycerin, xanthan gum, hydroxypropylmethylcellulose (HPMC), cyclodextrin derivatives such as hydroxypropyl-β-cyclodextrin, isotonic agents such as sodium chloride, potassium chloride or sodium bisulfate, preservatives such as disodium EDTA or methylparaben, and antioxidants such as ascorbic acid are optionally added to the solution and mixed with the solution to form a clear solution. After the solution thus obtained is filtered to remove particulate matter, an acid such as hydrochloric acid or a base such as sodium chloride is added to adjust the pH to obtain a desired pH value. 【0175】 Example 2: Preparation containing rifamycin compound As disclosed in Tables 1 to 3, 16 kinds of preparations were prepared for use as a topical ophthalmic agent containing rifampicin. Preparations Ex.1A (Table 1) and Ex.6A (Table 2) were used in the following tests. 【0176】 The following ophthalmic preparations were prepared at room temperature (Tables 1 and 2). Rifampicin was added to each ophthalmic preparation to obtain the final concentrations listed below. 【0177】 【Table 1】 【0178】 【Table 2】 【0179】 Rifampicin was completely dissolved at room temperature in the eye drop formulations of Example 1A and Examples 5A - 8A listed in Tables 1 and 2. Rifampicin did not precipitate in these formulations for several weeks. The rifampicin solution was stored at room temperature or in a refrigerator. 【0180】 The buffer solutions added to Examples 1A - 10A (including both ends) were 50 mM borate - borax or 100 mM boric acid - NaOH. The pH values of these added buffer solutions are listed in Tables 1 and 2. Liquid formulations were prepared by mixing the listed structural components with each other, then the powder of rifampicin was added to these formulations, and subsequently mixed for 2 - 3 hours. Rifampicin was mixed into the formulations, and then the pH values were measured. The obtained pH values are shown in Tables 1 - 3. 【0181】 【Table 3】 【0182】 The buffer solutions, NaCl, Tween 80, and EDTA listed in Table 3 were mixed with each other at room temperature in a beaker, and then rifampicin was added to the mixture and completely dissolved in these liquid formulations at room temperature. A stock solution of sodium formaldehyde sulfoxylate dihydrate or L - ascorbic acid was added to each formulation, and then the pH value of the formulation was measured (including Examples 11A - 16A). The formulations of Examples 11A and 12A were stable at room temperature for several days or more, and no precipitate formed therein. The formulations of Examples 13A - 16A were stable in a refrigerator or over a period of several days or more, and no precipitate formed therein. 【0183】 Example 3: Topical Application of Rifamycin Compounds to the Retina Rifampicin was delivered to the retina by application of a topical eye drop. In these tests, 0.25% rifampicin eye drops were used. The eye drops showed good delivery efficiency, and the retinal tissue obtained the microgram concentration of rifampicin per gram of tissue by application of the eye drops. 【0184】 Four male Sprague-Dawley rats (250 - 300 g) were used to measure the retinal exposure level of rifampicin after eye drop application. Two rats received three drops of the eye drop formulation (0.25% rifampicin) shown as Example 1A in Table 1 in each eye under isoflurane sedation. The remaining two rats received the same application in each eye under isoflurane sedation but received ten drops of the eye drop. One drop contained 5 μL of the above formulation, and the application of each drug drop was performed at 30-minute intervals. After eye drop application, the retina was excised from each rat under a dissecting microscope. In addition, a "non-treated" negative control was used, and the retina was excised from two rats without any treatment of the rats. The retina was placed in a 1.5 ml microcentrifuge tube (1 retina / tube) and washed thoroughly with DPBS. After completion of the washing procedure, the retinal tissue in the microcentrifuge tube was frozen in dry ice and then stored for quantification by LC / MS analysis. Table 4 shows the quantification of rifampicin extracted from the retinal tissue. Rifampicin was delivered to the retina by the eye drop formulation (0.25% rifampicin) in a dose-dependent manner. 【0185】 【Table 4】 【0186】 The retinal delivery of rifampicin by application of the topical eye drop formulation shown as Example 1A in Table 1 was more than 100 times more efficient than dexamethasone retinal delivery. As shown in Table 5, the topical eye drop formulations of the present disclosure, for example, the formulation shown as Example 1A in Table 1, surprisingly show increased effectiveness of retinal delivery of rifampicin compared to other drugs. 【0187】 【Table 5】 【0188】 Example 4: Local Application of Rifamycin Compounds to the Retina This example provides the experimental procedures and results of a PK study showing that rifampicin is delivered to the retina by subcutaneous (SC) injection. The detected amount of rifampicin delivered by SC was equivalent to that delivered by topical eye drops. 【0189】 Six male Sprague-Dawley rats (250 - 300 g) were used to measure the retinal exposure level of rifampicin after subcutaneous injection (20 mg / kg). The formulation shown in Example 6A of Table 2 was used, and rifampicin was administered to the rats by SC. At 1 hour, 3 hours, and 7 hours after SC injection, retinal tissue was excised from the rats under a dissecting microscope. In addition, a "non-treated" negative control was used, and retinas were excised from two rats without any treatment of the rats. The retinas were placed in 1.5 ml microcentrifuge tubes (1 retina / tube) and washed thoroughly with DPBS. After completion of the washing procedure, the retinal tissue in the microcentrifuge tubes was frozen in dry ice and then stored for quantification by LC / MS analysis. Table 6 shows the quantification results of rifampicin extracted from the retinal tissue. The amount of rifampicin detected in the retina delivered by SC was equivalent to the amount of rifampicin delivered by topical eye drops (see Table 3). 【0190】 [Table 6] 【0191】 Example 5: Pharmacokinetic Study Using 0.25% Rifampicin Eye Drops This example provides the experimental procedures and results of a PK test using a 0.25% rifampicin eye drop formulation. Six male Sprague-Dawley rats (250 - 300 g) were used to measure the retinal exposure level of rifampicin after application of the topical eye drops. The eye drop formulation (15 μL) shown as Example 1A in Table 1 was used, and the compound was administered to the right eye of each rat. The above formulation (15 μL) contained 37.5 μg of rifampicin. At 1 hour, 3 hours, and 7 hours after application of the eye drops, retinal tissue was excised from the rats under a dissecting microscope. Additionally, a "non-treated" negative control was used, and the retina was excised from one rat without any treatment. The retina was placed in a 1.5 mL microcentrifuge tube (1 retina / tube) and washed thoroughly with DPBS. After completion of the washing procedure, the retinal tissue in the microcentrifuge tube was frozen in dry ice and then stored for quantification by LC / MS analysis. Table 7 shows the quantification of rifampicin extracted from the retinal tissue. Rifampicin was delivered to the retina by the eye drop formulation (0.25% rifampicin). 【0192】 【Table 7】 【0193】 Example 6: Dose-Response Test Using 0.25% and 0.5% Rifampicin Eye Drops This example provides the experimental procedures and results of a dose-response test using 0.25% and 0.5% rifampicin eye drop formulations. 【0194】 Four male Sprague-Dawley rats (250 - 300 g) were used to measure the retinal exposure level of rifampicin after application of topical eye drops. The eye drop formulations (15 μL each) shown as Example 1A and Example 6A listed in Table 1 and Table 2 were used, and the compounds were applied to the right eye of each rat respectively. The above formulations (15 μL each) contained 37.5 μg and 75 μg of rifampicin respectively. One hour after the application of the eye drops, the retinal tissue was excised from the rats under a dissecting microscope. Further, a "non-treated" negative control was used, and the retina was excised from one rat without any treatment to the rat. The retina was placed in a 1.5 ml microcentrifuge tube (1 retina / tube) and washed thoroughly with DPBS. After completion of the washing procedure, the retinal tissue in the microcentrifuge tube was frozen in dry ice and then stored for quantification by LC / MS analysis. Table 8 shows the quantification of rifampicin extracted from the retinal tissue. Rifampicin was delivered to the retina by applying two eye drop formulations (0.25% and 0.5% rifampicin) in a dose-dependent manner. 【0195】 【Table 8】 【0196】 Example 7: Preclinical Efficacy This example provides the experimental procedures of a preclinical efficacy study conducted on a rat model of oxygen-induced retinopathy using a 0.25% rifampicin eye drop formulation. 【0197】 The oxygen-induced retinopathy rat model was created according to the protocols of Yanni et al. (2010) and Dorfmann et al. (2008). Sprague-Dawley rat pups (and their lactating mothers) were exposed to a cyclical oxygen environment (80% and 21% respectively, for approximately 1 day) starting from the day of birth (day 0) for 15 days. On day 15 (P15), the animals were moved to room air. Six pups, seven pups, and six pups were assigned to the treatment groups, namely, the vehicle-only control group, the rifampicin eye drop treatment group, and the SC injection treatment group, respectively. The eye drop formulation shown as Example 1A in Table 1, or vehicle only, was administered to the eyes of the baby rats every day for 5 days between P15 and P19, in the morning, around noon, and in the evening. Using the formulation shown as Example 6A in Table 2, rifampicin was administered to the baby rats by SC injection at a dose of 20 mg / kg once a day between P15 and P19. On P20, all the animals were euthanized and the retinas were visualized as tissue sections. In these tissue sections, the capillaries in the retinal tissue in three eyes (rifampicin topical application, rifampicin SC injection treatment group, and non-induction of retinopathy) or five eyes (vehicle-only control treatment group) were counted, and as a result, angiogenesis was quantified. These eyes were selected from different animals in the above treatment groups. Representative images of histological sections are shown (see Figures 1A - 1H). The retina treated with vehicle only showed an increase in the number of small new capillaries on the retinal surface (see Figures 1A and 1B). The retina treated with the AMD 101 topical eye drop formulation showed a slight focus of new capillary growth on the retinal surface, but the number of new capillaries was less than that in the control group (see Figures 1C and 1D). The retina treated with rifampicin SC injection showed a small focus of new capillary growth on the retinal surface, but the number of new capillaries was less than that in the control group (see Figures 1E and 1F). The retina in which retinopathy was not induced showed a few small vascular cross-sections but no new capillaries (see Figures 1G and 1H). Table 9 shows the quantification of capillaries detected in histological sections. 【0198】 【Table 9】 【0199】 Example 8: Delivery of an ophthalmic preparation containing a rifamycin compound via a device An ophthalmic preparation containing an active ingredient, namely rifampicin, rifabutin, rifapentine, rifalazil or rifaximin, and a pharmaceutically acceptable carrier, and optionally an additive disclosed herein, is incorporated into an ophthalmic solution used for soaking or washing contact lenses. A contact lens made of a hydrophilic gel is optionally dried at ambient temperature and then immersed in a solution of a soaking or swelling agent containing an effective amount of the ophthalmic preparation, thereby washing it or soaking it therein. 【0200】 Example 9: Oil- or water-based preparations Oily preparations (A-F; Table 10-1) containing petrolatum and liquid paraffin mixed in various ratios and including sesame oil and light liquid paraffin were prepared. Rifampicin was formulated at 1% (w / w). Table 10-1 shows the measured viscosities of oil-based and water-based formulations (A-F) measured at 25 °C at various shear rates measured using a modular compact rheometer (MCR302, Anton Paar). A temperature control unit (P-PTD200) and a shaft (CP25-2) were used for these measurements. The temperature of each measurement was controlled and maintained in the range of at least 25.0 ± 0.1 °C. 【0201】 【Table 10-1】 【0202】 Aqueous suspension formulations (G and H; Table 10-2) were prepared using NaCl in the presence or absence of a viscosity enhancer (cellulose polymer), respectively. An aqueous solubilized formulation (RK32) was prepared using polyoxyethylene castor oil, ethylene glycol monostearate, and a viscosity enhancer (cellulose polymer). Rifampicin was formulated at 1% (w / w). The pH of formulations H and RK32 was adjusted to a pH of approximately 7.0 and 8.4, respectively, by using phosphate buffer. The pH of formulation G was adjusted to a pH of approximately 7.0 by using phosphate buffer. Table 10-2 shows the measured viscosities of the aqueous formulations (G, H, and RK32) at 25 °C at various shear rates by using a modular compact rheometer (MCR302, Anton Paar). In these measurements, a temperature control unit (P-PTD200) and a shaft (CP25-2) were used. During the measurement, the temperature was controlled and maintained in the range of at least 25.0 ± 0.1 °C. 【0203】 【Table 10-2】 【0204】 The relationship between viscosity and shear rate was determined at 25 °C for the oily formulations (A - F) and the aqueous formulations (G, H, and RK32). Shear is the relative motion between adjacent layers of a fluid. Shear rate is the rate of change of the velocity at which a fluid layer passes through another adjacent fluid layer. The relationship between the viscosity (mPaS) and shear rate (s -1 ) for each formulation is shown in Figures 3A and 3B. 【0205】 An oily preparation (E; Table 10-3) containing petrolatum and liquid paraffin was prepared, and rifampicin was formulated at 0.01% (w / w) and 0.001% (w / w). Table 10-3 describes the measured viscosities of the oil-based formulations measured at 25 °C at various shear rates by using a modular compact rheometer (MCR302, Anton Paar). For these measurements, a temperature control unit (P-PTD200) and a shaft (CP25-2) were used. During the measurement, the temperature was controlled and maintained in the range of at least 25.0 ± 0.1 °C. 【0206】 【Table 10-3】 【0207】 Oil-based preparations (A - G; Table 10) containing petrolatum and liquid paraffin, sesame oil, dimethylpolysiloxane, and light liquid paraffin mixed in various ratios were prepared, and rifampicin was formulated at 1% (w / w), 0.01% (w / w), or 0.001% (w / w) at 37 °C. The viscosities of the oily preparations (A - G) were measured at 37 °C. 【0208】 Example 10: Determination of the effective dose of rifampicin in a mouse laser-induced CNV model. The eyes of C57BL / 6J mice were irradiated with a laser to induce CNV in the subretinal tissue of the eyes. A negative control of only the vehicle dissolved in an aqueous formulation or rifampicin at various concentrations was administered once daily by subcutaneous injection. Seven days after the laser irradiation, an FITC-dextran solution was administered via the tail vein. The eyeballs were removed under euthanasia, and the removed eyeballs were fixed with 4% paraformaldehyde phosphate buffer. The cornea, iris, and lens were excised, and the retinal tissue other than the retinal pigment epithelial cells was peeled off using a micropacer. The optic cup was divided into 4 - 6 sections using a corneal microtome and placed on a slide glass. These fluorescent images showing the angiogenesis induced subretinally were photographed using a confocal laser scanning microscope. The CNV area was quantified using ImageJ (Tables 11-1 and 11-2; publicly available image software by NIH). The pixels derived from the fluorescent CNV area in the eyes of the negative control with only the vehicle were evaluated as 100%, and the percentage of fluorescent pixels from the treatment groups administered with rifampicin at various concentrations was evaluated. The P-value for the negative control results obtained from the group administered only the vehicle was evaluated by the Williams multiple comparison test. 【0209】 【Table 11-1】 【0210】 【Table 11-2】 【0211】 These results suggest that SC injection at a dose of 0.7 mg / kg significantly inhibits angiogenesis in the mouse laser-induced CNV model. The effective systemic dose of rifampicin for inhibiting bacterial infection was previously evaluated at 20 mg / kg. Therefore, the effective dose for inhibiting subretinal angiogenesis in the CNV model was approximately 30-fold smaller than that for bacterial inhibition. The level of angiogenesis inhibition achieved by SC injection of rifampicin at a dose of 0.7 mg / Kg or higher was equivalent to that achieved by intravitreal injection of Eylea. 【0212】 To evaluate the area under the curve (AUC) of rifampicin delivered subretinally in mice, rifampicin was administered to C57BL / 6J mice by SC injection at 0.7 mg / kg. This effective dose and route of administration were evaluated in a dose escalation study using a mouse laser-induced CNV model. AUC reflects the exposure to the drug after administration of the drug dose and is expressed in hr·ng / mg tissue. AUC depends on the dose administered and the rate of drug disappearance from the tissue. AUC is directly proportional to the dose when the drug follows linear kinetics, and AUC is inversely proportional to the clearance of the drug. At 1 hour, 3 hours, 6 hours, and 18 hours after SC injection, the eyeballs were extracted. Tissues from the retina and tissues from the sclera + subretinal complex were isolated and extracted. These tissues were immediately frozen in liquid nitrogen. The tissues were subjected to LC / MS analysis for quantification. The limit of detection was 0.25 ng / g tissue. The mean rifampicin delivered to the sclera + subretinal complex (ng / mg tissue) is shown in Table 12. 【0213】 【Table 12】 【0214】 The effective AUC was estimated to be approximately 0.27 (hr·ng / mg tissue). Therefore, the effectiveness of rifampicin in inhibiting neovascularization is expected to be seen when at least an effective AUC is delivered to the subretinal tissue or more is delivered. In separate mouse pharmacokinetic studies with SC injection of rifampicin, the delivery ratio between the subretinal tissue and the scleral tissue was estimated to be approximately 7:3, respectively. Therefore, approximately 70% of the rifampicin delivered to the subretinal + scleral complex was estimated to be delivered subretinally. 【0215】 Example 11: Ocular Tissue Delivery of Rifampicin via Topical Application of Oily, Aqueous Suspension, and Water-Soluble Formulations Rabbits (Kbs:JW) were anesthetized by injecting a mixture of ketamine / xylazine. Both 20 μL of oil and aqueous formulations (A-H; Table 10-1) and 50 μL of aqueous formulation (RK32) contained 1% rifampicin. The formulations were topically administered to the eyes of the rabbits. One hour after topical application of the formulations (A-F, and H), blood samples were collected from the rabbits and the plasma fraction of the blood samples was stored in vials. One hour and 18 hours after topical application of the formulations (A-F), the rabbits were euthanized and the eyes to which the formulations were administered were excised. The eyes were incised and vitreous, retina, subretinal, and scleral tissues were prepared and immediately frozen in liquid nitrogen. At 0.5 hour, 1 hour, 3 hours, and 6 hours after topical application of the water-soluble formulation RK32, at 1 hour, 3 hours, 6 hours, and 18 hours after topical application of the oil and aqueous suspension formulations (B, C, F, and H), and at 1 hour and 6 hours after topical application of the aqueous suspension formulation (G), plasma fractions of blood samples and eye tissues (including retina and subretinal tissues) were collected and extracted. They were immediately frozen in liquid nitrogen. These eye tissues and plasma samples were subjected to LC / MS analysis for quantification. The detection limit was 0.25 ng / g tissue or 0.25 ng / mL plasma. 【0216】 The effective AUC was evaluated in a mouse study that showed the efficacy and pharmacokinetic profile of the CNV model in tissues including scleral and subretinal tissues. The mouse effective AUC was compared with the AUC values connecting the time points from 1 hour to 18 hours, and each average concentration was detected in the retina and subretina obtained from rabbit tests using oil formulations (A-F), aqueous suspension formulations (G and H), and water-soluble formulation (RK32). 【0217】 【Table 13-1】 【0218】 【Table 13-2】 【0219】 These data suggest that all of the oily formulations (A - F), aqueous suspension formulations (G and H), and the water - soluble formulation (RK32) delivered to the retina and sub - retinal tissue with rifampicin are in an amount equal to or greater than the effective AUC required for the inhibition of angiogenesis in the mouse CNV model by topical application. Thus, when these oil - or water - based formulations containing 1% rifampicin are applied to the eyes of animals or humans, neovascularization in the sub - retinal or retinal tissue is effectively inhibited. Accordingly, the formulations presented herein are utilized for treating posterior neovascular eye diseases including AMD and diabetic retinopathy. 【0220】 Example 12: Relationship between AUC value and viscosity of the formulation in the pharmacokinetic study The AUC values evaluated in the sub - retinal and retinal tissues in the pharmacokinetic study (Example 11, Tables 13 - 1 and 13 - 2) were analyzed to determine the AUC correlation with the viscosity of formulations A - F. The AUC (as X - fold AUC) was plotted against the viscosity (mPaS) for each dose administered (Figures 2A and 2B). A negative non - linear relationship was found in the range of approximately 100 mPaS to 4000 mPaS. 【0221】 Example 13: Ocular tissue delivery of rifampicin via an aqueous suspension formulation by topical application Rabbits (Kbs:JW) are placed under anesthesia by injecting a mixture of ketamine / xylazine. 20 μL of the aqueous suspension formulation (G; Table 10 - 2) contains 1% rifampicin. The formulation is topically administered to the eyes of the rabbits. One hour after topical application of the formulation, blood samples are collected from the rabbits and the plasma fraction of the blood samples is stored in vials. One hour, three hours, six hours, and 18 hours after topical application, the rabbits are euthanized and the administered eyeballs are extracted from the formulation. The eyeballs are incised and the vitreous, retinal, sub - retinal, and scleral tissues are prepared and immediately frozen in liquid nitrogen. These eye tissues are subjected to LC / MS analysis for quantification. The detection limit is 0.25 ng / g tissue or 0.25 ng / mL plasma. 【0222】 Rifampicin prepared in the aqueous formulation (G) can be detected in the subretinal and retinal tissues. The effective AUC was previously evaluated in a mouse study that demonstrated the efficacy and pharmacokinetic profile of the CNV model in tissues including the sclera and subretinal tissue. The mouse effective AUC is compared with the AUC values connecting the time points from 1 hour to 18 hours, and the average concentrations detected in the subretinal and retinal tissues obtained in the rabbit test using the aqueous suspension formulation (G) are used. 【0223】 Example 14: Plasma Exposure of Oil-Based Formulations In the pharmacokinetic test described in Example 11, oil and aqueous formulations (A - D, and RK32) containing 1% rifampicin were topically applied to the eyes of rabbits. One hour after topical application, blood samples were collected from the rabbits, and plasma fractions were prepared from the blood samples to evaluate the systemic exposure of rifampicin. Rifampicin in the plasma fraction was quantified by LC / MS (Table 14). 【0224】 [Table 14] 【0225】 The plasma exposure detected by administering the oil-based formulations (A - D) was significantly lower than the exposure detected by administering the aqueous formulation (RK32). The improvement by the oil formulation was evaluated in plasma exposure. 【0226】 Example 14: Plasma Exposure of Oil-Based Formulations In the pharmacokinetic test described in Example 11, oil-based formulations (E - H) containing 1% rifampicin were topically applied to the eyes of rabbits. To evaluate the systemic exposure of rifampicin, blood samples were collected from the rabbits 1 hour after topical application, and plasma fractions were prepared from the blood samples. The amount of rifampicin in the plasma fraction was quantified by LC / MS. 【0227】 Example 15: Subretinal and Retinal Delivery of Rifampicin via Oil-Based Formulations Rabbits (Kbs:JW) were anesthetized by injecting a mixture of ketamine / xylazine. Twenty microliters of an oil-based formulation (C; Table 10-3) contained 0.01% and 0.001% rifampicin. Twenty microliters of an oil-based formulation (E; Table 10-3) contained 0.1% and 0.01% rifampicin. The formulations were topically administered to the eyes of the rabbits. The rabbits were euthanized 1 hour, 3 hours, 6 hours, and 18 hours after topical application of the oil-based formulation C or E, and the eyeballs to which the formulations were administered were excised. The eyeballs were incised, and vitreous, retinal, subretinal, and scleral tissues were prepared and immediately frozen in liquid nitrogen. These eye tissues were subjected to LC / MS analysis for quantification using a detection limit of 0.25 ng / g tissue or 0.25 ng / mL plasma (Table 15). 【0228】 【Table 15】 【0229】 When topical application of a rifampicin formulation to the eyes of animals or humans is applied in a concentration range of at least 1% to 0.01%, angiogenesis in the subretinal or retinal tissue is effectively inhibited. Therefore, the oil-based formulations of the present disclosure are utilized for treating posterior angiogenic eye diseases including AMD and diabetic retinopathy. 【0230】 Equivalents The technology should not be limited to the specific embodiments described in this application, which are intended as a single illustration of individual aspects of the technology. As will be apparent to those skilled in the art, many modifications and variations of the technology can be made without departing from the spirit and scope of the technology. In addition to those listed herein, functionally equivalent methods and apparatuses within the scope of the technology will be apparent to those skilled in the art from the foregoing description. Such modifications and variations are intended to be within the scope of the technology. It should be understood that this technology is not limited to a particular method, reagent, compound composition, or biological system and can, of course, vary. Similarly, it should be understood that the terms used herein are for the purpose of describing particular aspects only and are not limiting. 【0231】 In addition, when a feature or aspect of the disclosure is described in terms of a Markush group, those skilled in the art will recognize that the disclosure is thereby also described in terms of any individual member or subgroup of members of the Markush group. 【0232】 As will be understood by those skilled in the art, for any and all purposes, particularly with respect to providing a written description, all ranges disclosed herein include any and all possible sub-ranges and combinations of those sub-ranges. Any recited range can be readily recognized as being fully described and enabled such that the same range is broken down into at least equal halves, thirds, quarters, fifths, etc. As a non-limiting example, each range discussed herein can be readily broken down into a lower third, middle third, and upper third, etc. Also, as will be understood by those skilled in the art, all language such as "up to," "at least," "greater than," "less than," etc. includes the recited number and refers to ranges that can be subsequently broken down into the sub-ranges discussed above. Finally, as will be understood by those skilled in the art, ranges include each individual member. Thus, for example, a group having 1 to 3 cells refers to a group having 1, 2, or 3 cells. Similarly, a group having 1 to 5 cells refers to a group having 1, 2, 3, 4, or 5 cells, etc. 【0233】 All patents, patent applications, provisional applications, and publications referred to or cited in this specification are hereby incorporated by reference in their entirety, including the drawings and tables thereof, to the extent that they are not inconsistent with the explicit disclosure of this specification.

Claims

[Claim 1] An ophthalmic composition having a viscosity of at least 1 mPaS at 25°C, comprising an effective amount of one or more rifamycin compounds or pharmaceutically acceptable salts thereof, a buffer, and optionally one or more viscosity imparters. [Claim 2] The composition according to claim 1, wherein the one or more rifamycin compounds are selected from the group consisting of rifamycin SV, 3-formylrifamycin SV, rifampicin, rifabutin, rifapentin, and rifaximin. [Claim 3] The composition according to claim 1, wherein one or more rifamycin compounds are rifampicin. [Claim 4] The composition according to claim 1, wherein the effective amount of one or more rifamycin compounds comprises a final concentration in the composition of at least 0.01% w / w, or at least 0.01 to 0.25% w / w, at least 0.25 to 0.5% w / w, at least 0.5 to 1.5% w / w, at least 0.75 to 1.5% w / w, at least 1 to 1.5% w / w, or at least 1 to 1.5% w / w. [Claim 5] The buffer solution contains acetic acid, boric acid, citric acid, phosphoric acid, hydrochloric acid, glycine, citrate phosphoric acid, succinic acid, phthalic acid, cacodylic acid, tris(trishydroxymethylaminomethane), barbituric acid, 2-amino-2-methyl-1,3-propanediol (anmedial), sodium bicarbonate, HEPES(4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), ACES(N-(2-acetamido)iminodiacetic acid), BES(N,N-bis(2-hydroxyethyl)sulfonic acid), bis(2-hydroxyethyl)imino RIS(hydroxymethyl)methane, CAPS(N-cyclohexyl-3-aminopropanesulfonic acid), CAPSO(N-cyclohexyl-2-aminopropanesulfonic acid), CHES(N-cyclohexyl-2-aminoethanesulfonic acid), DIPSO(3-[4-(2-hydroxyethyl)-1-piperazinyl]propanesulfonic acid), HEPES-Na(2-[4-(2-hydroxyethyl)-1-piperazinyl]ethanesulfonate sodium), HEPPSO(2-hydroxy-3-[4-(2-hydroxyethyl)-1-piperazinyl]propanesulfonic acid monohydrate), MES(2-morpholinoethanesulfonic acid), MOPSO(2-hydroxy-3-morpholinopropanesulfonic acid), PIPES(piperazine-1,4-bis(2-ethanesulfonic acid) The composition according to claim 1, comprising: glycine ()), POPSO (piperazine-1,4-bis(2-hydroxy-3-propanesulfonic acid), TAPSO (2-hydroxy-N-tris(hydroxymethyl)methyl-3-aminopropanesulfonic acid), TES (N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid), tricine (N-[tris(hydroxymethyl)methyl]glycine), hydrochloric acid, sodium hydroxide, sodium phosphate, sodium borate, sodium borate, sodium citrate, sodium acetate, and sodium lactate; and buffering agents, such as citrate / dextrose, sodium bicarbonate, and ammonium chloride, as well as selected from the group consisting of citric acid, phosphoric acid, boric acid, bicarbonate, sodium salts, and potassium. [Claim 6] The one or more viscosity-imparting agents mentioned above include petrolatum, liquid paraffin, light liquid paraffin, castor oil, mineral oil, cottonseed oil, soybean oil, sesame oil, cellulose polymer, corn oil, petroleum resin, macrogol, glycerol, polybutene, rosin, polyvinyl alcohol, polystyrene, polyacrylic acid, propylene glycol, piperonyl butoxide, hypromellose, talc, gelatin, hydrogenated rosin glycerol ester, aliphatic hydrocarbon resin, benzyl acetate, copal resin, silicic acid, silicone, dimethylpolysiloxane, aluminum magnesium silicate, xanthan gum, sodium chondroitin sulfate, cyclodextrin, carboxyvinyl polymer, sodium alginate, and alginate. The composition according to claim 1, selected from the group consisting of propylene glycol phosphate, carrageenan, carmellose sodium, gluconolactone, squalene, stearyl alcohol, aluminum stearate, lanolin, cetanol, gelatin, sorbitol, dextran, dextrin, tragacanth, palmitic acid, hyaluronic acid, hydroxyethylcellulose, hydroxyethylmethylcellulose, hydroxypropylcellulose, butylene glycol, polyoxyethylene polyoxypropylene glycol, polysorbate, sodium metaphosphate, methylcellulose, methyl vinyl ester maleic anhydride copolymer, locust bean gum, and cellulosic polymers. [Claim 7] The composition according to claim 6, wherein the one or more viscosity imparters are petrolatum, liquid paraffin, light liquid paraffin, sesame oil, or cellulose polymer. [Claim 8] The composition according to claim 7, comprising a final viscosity of at least about 0 mPaS to about 1 mPaS at 25°C, at least about 1 mPaS to about 5 mPaS at 25°C, at least about 5 mPaS to about 50 mPaS at 25°C, at least about 50 mPaS to about 100 mPaS at 25°C, at least about 100 mPaS to about 200 mPaS at 25°C, or optionally about 100 mPaS, about 150 mPaS, about 160 mPaS, about 170 mPaS, about 180 mPaS, about 190 mPaS, or about 200 mPaS. [Claim 9] The composition according to claim 8, wherein the composition has a final viscosity of at least about 161 mPaS at 25°C. [Claim 10] The composition according to claim 9, wherein the composition comprises a final viscosity at 25°C of at least about 500 mPaS to about 900 mPaS, or optionally about 500 mPaS, about 600 mPaS, about 700 mPaS, about 800 mPaS, about 850 mPaS, about 860 mPaS, about 870 mPaS, about 880 mPaS, about 890 mPaS, or about 900 mPaS at 25°C. [Claim 11] The composition according to claim 10, comprising a final viscosity of at least about 781 mPaS at 25°C, at least about 801 mPaS at 25°C, or at least about 867 mPaS at 25°C. [Claim 12] The composition according to claim 11, wherein the composition has a final viscosity at 25°C of at least about 1000 mPaS to about 2500 mPaS, or optionally comprises about 1000 mPaS, about 1500 mPaS, about 2000 mPaS, about 2100 mPaS, about 2200 mPaS, about 2300 mPaS, about 2400 mPaS, or about 2500 mPaS at 25°C. [Claim 13] The composition according to claim 12, wherein the composition has a final viscosity of at least about 2145 mPaS at 25°C. [Claim 14] The composition according to claim 13, wherein the composition contains a viscosity at 25°C of at least about 3,000 mPaS to at least about 4,000 mPaS, or optionally about 3,000 mPaS, about 3,500 mPaS, about 3,600 mPaS, about 3,700 mPaS, about 3,800 mPaS, about 3,900 mPaS, or about 4,000 mPaS. [Claim 15] The composition according to claim 14, wherein the composition comprises a viscosity of at least about 3815 mPaS at 25°C. [Claim 16] The composition according to claim 8, wherein the one or more rifampicin compounds are rifampicin, the one or more viscosity imparters are petrolatum, and the effective amount of rifampicin in the composition is at least about 0.5% w / w in final concentration. [Claim 17] The composition according to claim 8, wherein the one or more rifampicin compounds are rifampicin, the one or more viscosity modifiers are liquid paraffin, and the effective amount of rifampicin in the composition is at least about 0.001% w / w to about 1% w / w in a final concentration. [Claim 18] The composition according to claim 8, wherein the one or more rifamycin compounds are rifampicin, the one or more viscosity imparters are petrolatum, and the effective amount of rifampicin in the composition is at least about 0.001% w / w to about 1% w / w in a final concentration. [Claim 19] The composition according to claim 8, wherein the one or more rifampicin compounds are rifampicin, the one or more viscosity modifiers are liquid paraffin, and the effective amount of rifampicin in the composition is at least about 0.001% w / w to about 1% w / w in a final concentration. [Claim 20] The composition according to claim 1, wherein the one or more rifamycin compounds are rifampicin, the one or more viscosity imparters are petrolatum, the effective amount of rifampicin in the composition is at least about 0.001% w / w to about 1% w / w in a final concentration, and the composition has a viscosity of at least about 3815 mPaS at 25°C. [Claim 21] The composition according to claim 1, wherein the one or more rifamycin compounds are rifampicin, the one or more viscosity imparters comprise petrolatum and liquid paraffin, the effective amount of rifampicin in the composition is at least about 0.001% w / w to about 1% w / w in final concentration, and the composition has a viscosity of at least about 2145 mPaS at 25°C. [Claim 22] The composition according to claim 1, wherein the one or more rifamycin compounds are rifampicin, the one or more viscosity imparters comprise petrolatum and liquid paraffin, the effective amount of rifampicin comprises at least about 0.001% w / w to about 1% w / w in the composition at a final concentration, and the composition has a viscosity of at least about 867 mPaS at 25°C. [Claim 23] The composition according to claim 1, wherein the one or more rifamycin compounds are rifampicin, the one or more viscosity imparters comprise liquid paraffin, an effective amount of rifampicin is present in the composition at a final concentration of at least about 0.001% w / w to about 1% w / w, and the composition has a viscosity of at least about 161 mPaS at 25°C. [Claim 24] The composition according to claim 1, wherein the one or more rifamycin compounds are rifampicin, the one or more viscosity imparters include sesame oil, the effective amount of rifampicin in the composition is at least about 0.001% w / w to about 1% w / w in a final concentration, and the composition has a viscosity of at least about 59 mPaS at 25°C. [Claim 25] The composition according to claim 1, wherein the one or more rifamycin compounds are rifampicin, the one or more viscosity imparters comprise a light liquid paraffin, the effective amount of rifampicin in the composition is at least about 0.001% w / w to about 1% w / w in a final concentration, and the composition has a viscosity of at least about 5 mPaS at 25°C. [Claim 26] The composition according to claim 1, wherein the one or more rifamycin compounds are rifampicin, an effective amount of rifampicin is present in the composition at a final concentration of at least about 0.001% w / w to about 1% w / w, and the composition has a viscosity of at least about 1 mPaS at 25°C. [Claim 27] The composition according to claim 1, wherein the one or more rifamycin compounds are rifampicin, an effective amount of rifampicin is present in the composition at a final concentration of at least about 0.001% w / w to about 1% w / w, the composition has a viscosity of at least about 1 mPaS at 25°C, and the composition does not contain a viscosity imparter. [Claim 28] The composition according to claim 1, wherein the one or more rifamycin compounds are rifampicin, the one or more viscosity imparters comprise a cellulose polymer, an effective amount of rifampicin is present in the composition at a final concentration of at least about 0.001% w / w to about 1% w / w, and the composition has a viscosity of at least about 38 mPaS at 25°C. [Claim 29] The composition according to claim 1, wherein the one or more rifamycin compounds are rifampicin, the one or more viscosity imparters comprise a cellulose polymer, the effective amount of rifampicin in the composition comprises a final concentration of at least about 0.001% w / w to about 1% w / w, and the composition comprises a viscosity of at least about 290 mPaS at 25°C. [Claim 30] The composition according to claim 1, wherein the effective amount of one or more rifamycin compounds or pharmaceutically acceptable salts thereof is the sole therapeutically active compound in the composition. [Claim 31] The composition according to claim 1 for delivery to subretinal, scleral, retinal and / or vitreous tissue. [Claim 32] A pharmaceutical composition for treating neovascular eye disease, comprising the composition described in any one of claims 1 to 31. [Claim 33] The pharmaceutical composition according to claim 32, which is administered topically as a single dose per eye. [Claim 34] The pharmaceutical composition according to claim 33, wherein the volume of the composition administered as a single dose per eye is in the range of about 2 μL to about 60 μL. [Claim 35] The pharmaceutical composition according to claim 33, wherein the volume of the composition administered as a single dose per eye is in the range of about 10 μL to about 50 μL. [Claim 36] The pharmaceutical composition according to claim 33, wherein the volume of the composition administered as a single dose per eye is in the range of approximately 20 μL to 30 μL. [Claim 37] The pharmaceutical composition according to claim 32, which is administered systemically. [Claim 38] The pharmaceutical composition according to claim 32, which is administered parenterally. [Claim 39] The pharmaceutical composition according to claim 32, administered via intravitreous injection. [Claim 40] The pharmaceutical composition according to claim 32, which is administered by oral administration, infusion, transplantation, subcutaneous injection, intravenous injection, or intramuscular injection. [Claim 41] The pharmaceutical composition according to claim 32, wherein the composition is administered in an effective dose of one or more rifamycin compounds, at least 0.2 mg / kg, at least 0.7 mg / kg, at least 2 mg / kg, or at least 20 mg / kg. [Claim 42] The pharmaceutical composition according to claim 32, wherein the composition is administered at intervals of at least 1 day, at least 2 days, at least 7 days, at least 14 days, at least 21 days, at least 28 days, at least 35 days, at least 42 days, at least 49 days, at least 56 days, or at least 64 days. [Claim 43] The pharmaceutical composition according to claim 32, which inhibits angiogenesis in the subretinal tissue. [Claim 44] The pharmaceutical composition according to claim 32, wherein administration of the composition results in at least about 5 times, 10 times, 50 times, or 100 times reduction in plasma exposure of the one or more rifamycin compounds compared to oral administration of 300 mg. [Claim 45] The pharmaceutical composition according to claim 44, wherein administration of the composition results in at least about 100 times reduction in plasma exposure of the one or more rifamycin compounds compared to oral administration of 300 mg. [Claim 46] The pharmaceutical composition according to claim 32, wherein topical administration of the composition results in at least about 5 times, 10 times, 50 times, or 100 times reduction in plasma exposure of the one or more rifamycin compounds compared to oral administration at 300 mg. [Claim 47] The pharmaceutical composition according to claim 46, wherein topical administration of the composition results in at least about 100 times reduction in plasma exposure of the one or more rifamycin compounds compared to oral administration at 300 mg. [Claim 48] The pharmaceutical composition according to claim 32, wherein the neovascular eye disease is selected from the group consisting of macular degeneration, diabetic retinopathy, chronic glaucoma, retinal detachment, sickle cell retinopathy, age-related macular degeneration (AMD), retinal ganglion cell injury, iritis, inflammatory disease, chronic uveitis, neoplasm, Fuchs heterochromia iridocyclitis, neovascular glaucoma, corneal neovascularization, choroidal neovascularization, retinal neovascularization, retinal hemangioma proliferation, glaucoma surgery, glaucoma surgery, tissue adhesion, scarring, tissue fibrosis, and brain injury. [Claim 49] The pharmaceutical composition according to claim 48, wherein the neovascular eye disease is AMD. [Claim 50] The pharmaceutical composition according to claim 49, wherein the AMD is dry AMD or wet AMD. [Claim 51] The pharmaceutical composition according to claim 32, for treating or preventing one or more complications of macular degeneration, including drus deposition / accumulation, macular edema, and neovacuole formation. [Claim 52] The pharmaceutical composition according to claim 32, wherein the neovascular eye disease is diabetic retinopathy. [Claim 53] The pharmaceutical composition according to claim 52, wherein the diabetic retinopathy is non-proliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR). [Claim 54] The pharmaceutical composition according to claim 53, wherein the diabetic retinopathy includes diabetic macular edema (DME).

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