Ophthalmic platform for delivering active ingredients to the anterior and / or posterior chamber tissue of the eye, use of a delivery composition, a compound formulation containing the delivery composition, and use of the compound formulation.

Abstract

To provide a non-invasive drug delivery platform capable of effectively delivering drugs to the anterior and / or posterior chambers of the eye. [Solution] An eye drop platform for delivering an active ingredient to the anterior chamber and / or posterior chamber tissue of the eye is provided. The eye drop platform for delivering an active ingredient to the anterior chamber and / or posterior chamber tissue of the eye comprises a delivery composition and a pharmaceutically acceptable solvent for dissolving the delivery composition to form a solution as an eye drop platform for delivering an active ingredient to the anterior chamber and / or posterior chamber tissue of the eye. The delivery composition comprises cyclodextrin and / or its derivatives, and caffeine. The concentration of cyclodextrin and / or its derivatives in the solution is in the range of 5 to 500 mg / mL, and the concentration of caffeine in the solution is in the range of 0.5 to 50 mg / mL. The active ingredient is a hydrophilic compound, and the hydrophilic compound has water solubility greater than 1 mg / mL.

Description

Technical Field

[0001] The present disclosure relates to an ophthalmic drug delivery platform for delivering an active ingredient. In particular, the present disclosure relates to an ophthalmic drug delivery platform for delivering an active ingredient to the anterior chamber tissue and / or posterior chamber tissue of the eye, and to its use.

Background Art

[0002] The structure of the eye can be divided into the anterior chamber (including, for example, the tear film, cornea, pupil, lens, and ciliary body), and the posterior chamber (including, for example, the sclera, choroid, retina, vitreous humor, and optic nerve).

[0003] The eye has multiple natural barriers that limit its ability to penetrate drugs and reach the target lesion site. In particular, for drugs with high water solubility, only a very limited amount can be delivered to the lesion site in the posterior chamber of the eye.

[0004] As a result, the treatment of posterior chamber diseases often depends on intravitreal injection of drugs. However, invasive treatments are associated with a high risk of infection, and due to the fear associated with injections and the need for regular clinical visits, patient compliance is insufficient. On the other hand, conventional eye drops have limited applicability because it is difficult to deliver drugs to the posterior chamber tissue.

[0005] Therefore, there is still a need to develop a non-invasive drug delivery platform that can effectively deliver drugs to the anterior chamber tissue and / or posterior chamber tissue of the eye.

Summary of the Invention

Problems to be Solved by the Invention

[0006] Treatment of posterior chamber diseases often relies on intravitreal injection of medication. However, intravitreal injection is an invasive treatment, carrying a high risk of infection, and patient compliance is poor due to injection-related fears and the need for regular clinical visits. On the other hand, conventional eye drops have limited applicability because it is difficult to deliver the medication to the posterior chamber tissue. The primary objective of this disclosure is to provide a non-invasive drug delivery platform capable of effectively delivering medication to the anterior and / or posterior chambers of the eye. [Means for solving the problem]

[0007] This disclosure provides an eye drop platform for delivering an active ingredient to the anterior and / or posterior chamber tissue of the eye, as well as related uses thereof.

[0008] In other words, this disclosure may include, but is not limited to, the following:

[0009] [1] An eye drop platform for delivering an active ingredient to the anterior chamber and / or posterior chamber of the eye, wherein the eye drop platform is A delivery composition, Cyclodextrin and / or its derivatives, A delivery composition containing caffeine, and A pharmaceutically acceptable solvent for dissolving the delivery composition and forming a solution, the solution comprising a pharmaceutically acceptable solvent that functions as an eye drop platform for delivering the active ingredient to the anterior and / or posterior chamber tissue of the eye, The concentration of the cyclodextrin and / or its derivative in the aforementioned solution is in the range of 5 to 500 mg / mL. The concentration of caffeine in the aforementioned solution is in the range of 0.5 to 50 mg / mL. The aforementioned active ingredient is a hydrophilic compound having water solubility in a concentration of more than 1 mg / mL, comprising an eye drop platform.

[0010] [2] The cyclodextrin is α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, and An eye drop platform for delivering the active ingredient according to [1] to the anterior and / or posterior chamber tissue of the eye, comprising at least one of δ-cyclodextrins.

[0011] [3] The derivative of the cyclodextrin is Hydroxypropyl (hydroxypropyl) modified cyclodextrin, succinyl-modified cyclodextrins, and It contains at least one of the methyl-modified cyclodextrins, The hydroxypropyl-modified cyclodextrin is, (2-hydroxypropyl)-β-cyclodextrin; and / or An eye drop platform for delivering the active ingredient described in [1], comprising (2-hydroxypropyl)-γ-cyclodextrin, to the anterior and / or posterior chamber tissue of the eye.

[0012] [4] The delivery composition further comprises a water-soluble polymer, the concentration of the water-soluble polymer in the solution being in the range of 0.5 to 20 mg / mL. The aforementioned water-soluble polymer is Hydroxypropyl methylcellulose, Hydroxypropylcellulose, Carboxymethylcellulose, Polyvinylpyrrolidone, Polyvinyl alcohol, and An eye drop platform for delivering the active ingredient according to [1] to the anterior and / or posterior chamber tissue of the eye, comprising at least one of poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) triblock copolymer.

[0013] [5] An eye drop for improving the exposure of an active ingredient in the anterior chamber tissue and / or posterior chamber tissue of the eye, wherein the eye drop is a delivery composition, cyclodextrin and / or its derivative, caffeine, and a delivery composition containing the same, and a pharmaceutically acceptable solvent for dissolving the delivery composition to form a solution, wherein the solution functions as the eye drop for improving the exposure of the active ingredient in the anterior chamber tissue and / or posterior chamber tissue of the eye, and includes a pharmaceutically acceptable solvent. The concentration of the cyclodextrin and / or its derivative in the eye drop is in the range of 5 to 500 mg / mL. The concentration of the caffeine in the eye drop is in the range of 0.5 to 50 mg / mL. The active ingredient is a hydrophilic compound having a water solubility exceeding 1 mg / mL, and the eye drop.

[0014] [[ID=​​​​​​​​​​​​​​​​​​​​​​​​(2-Hydroxypropyl)-γ-cyclodextrin-containing eye drops for improving the exposure of an active ingredient in the anterior chamber tissue and / or posterior chamber tissue described in [5].

[0016] [8] The delivery composition further contains a water-soluble polymer, and the concentration of the water-soluble polymer in the solution is in the range of 0.5 to 20 mg / mL. The water-soluble polymer is hydroxypropylmethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, and at least one of poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) triblock copolymer, the eye drops for improving the exposure of an active ingredient in the anterior chamber tissue and / or posterior chamber tissue described in [5].

[0017] [9] A composite preparation, the composite preparation an active ingredient, the active ingredient is a hydrophilic compound having water solubility exceeding 1 mg / mL, the active ingredient, and a delivery composition, cyclodextrin and / or its derivative, and caffeine, a delivery composition containing, and a pharmaceutically acceptable solvent for dissolving the active ingredient and the delivery composition to form a solution, the solution functioning as the composite preparation, a pharmaceutically acceptable solvent, containing The concentration of the active ingredient in the solution is in the range of 0.05 to 500 mg / mL. The concentration of the cyclodextrin and / or its derivative in the solution is in the range of 5 to 500 mg / mL. The concentration of the caffeine in the solution is in the range of 0.5 to 50 mg / mL. The composite preparation is an eye drop.

[0018]

[10] The active ingredient is Drugs with neuroprotective properties, Complement inhibitors, AMP-activated protein kinase (AMPK) activator, and The combination formulation according to [9], comprising at least one Rho-associated coiled-coil kinase inhibitor.

[0019]

[11] The drug having neuroprotective function is Sodium phenylbutyrate (SPB), dexmedetomidine HCl, and A compound formulation according to

[10] , comprising tauro-ursodesoxycholic acid (TUDCA).

[0020]

[12] The complement inhibitor comprises iptacopan (LNP-023) and / or nafamostat mesylate (FUT-175) as described in

[10] .

[0021]

[13] The AMP-activated protein kinase activator comprises a biguanide agent, the biguanide agent comprises metformin HCl, and the compound formulation according to

[10] .

[0022]

[14] The Rho-related coiled-coil kinase inhibitor is a compound formulation according to

[10] , comprising (S)-N-(4-(1H-pyrazol-4-yl)phenyl)-3-amino-2-phenylpropanamide dihydrochloride (ITRI-E-(S)4046).

[0023]

[15] The cyclodextrin is α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, and The compound formulation according to [9], comprising at least one of δ-cyclodextrins.

[0024]

[16] The derivatives of the cyclodextrin are, Hydroxypropyl-modified cyclodextrin, succinyl-modified cyclodextrin, and It contains at least one of the methyl-modified cyclodextrins, The hydroxypropyl-modified cyclodextrin is, (2-hydroxypropyl)-β-cyclodextrin; and / or The compound formulation according to [9], comprising (2-hydroxypropyl)-γ-cyclodextrin.

[0025]

[17] The delivery composition further comprises a water-soluble polymer, the concentration of the water-soluble polymer in the solution being in the range of 0.5 to 20 mg / mL. The aforementioned water-soluble polymer is Hydroxypropyl methylcellulose, Hydroxypropylcellulose, Carboxymethylcellulose, Polyvinylpyrrolidone, Polyvinyl alcohol, and The composite formulation according to [9], comprising at least one of poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) triblock copolymer.

[0026]

[18] Eye drops for the treatment and / or prevention of anterior chamber and / or posterior chamber diseases of the eye, comprising the combination formulation described in [9].

[0027]

[19] The active ingredient is Drugs with neuroprotective properties, Complement inhibitors, AMP-activated protein kinase (AMPK) activator, and An eye drop for treating and / or preventing anterior chamber and / or posterior chamber disease of the eye, comprising at least one Rho-associated coiled-coil kinase inhibitor, as described in

[18] .

[0028]

[20] The drug having neuroprotective function is Sodium phenylbutyrate (SPB), dexmedetomidine HCl, and An eye drop comprising tauro-ursodesoxycholic acid (TUDCA) as described in

[19] for the treatment and / or prevention of anterior chamber and / or posterior chamber diseases of the eye.

[0029]

[21] The complement inhibitor comprises iptacopan (LNP-023) and / or nafamostat mesylate (FUT-175), as described in

[19] , an eye drop for treating and / or preventing anterior chamber and / or posterior chamber diseases of the eye.

[0030]

[22] The AMP-activated protein kinase activator comprises a biguanide agent, the biguanide agent comprising metformin HCl, the eye drop for treating and / or preventing anterior chamber and / or posterior chamber diseases of the eye according to

[19] .

[0031]

[23] The Rho-related coiled-coil kinase inhibitor comprises (S)-N-(4-(1H-pyrazole-4-yl)phenyl)-3-amino-2-phenylpropanamide dihydrochloride (ITRI-E-(S)4046) as described in

[19] , an eye drop for treating and / or preventing anterior chamber and / or posterior chamber diseases of the eye.

[0032]

[24] The cyclodextrin is α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, and An eye drop for treating and / or preventing anterior chamber and / or posterior chamber disease of the eye, comprising at least one δ-cyclodextrin, as described in

[18] .

[0033]

[25] The derivatives of the cyclodextrin are Hydroxypropyl-modified cyclodextrin, succinyl-modified cyclodextrin, and It contains at least one of the methyl-modified cyclodextrins, The hydroxypropyl-modified cyclodextrin is, (2-hydroxypropyl)-β-cyclodextrin; and / or An eye drop for treating and / or preventing anterior chamber and / or posterior chamber diseases of the eye, comprising (2-hydroxypropyl)-γ-cyclodextrin, as described in

[18] .

[0034]

[26] The delivery composition further comprises a water-soluble polymer, the concentration of the water-soluble polymer in the solution being in the range of 0.5 to 20 mg / mL, The aforementioned water-soluble polymer is Hydroxypropyl methylcellulose, Hydroxypropylcellulose, Carboxymethylcellulose, Polyvinylpyrrolidone, Polyvinyl alcohol, and An eye drop for treating and / or preventing anterior chamber disease and / or posterior chamber disease, according to

[18] , comprising at least one of poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) triblock copolymer.

[0035]

[27] The anterior chamber disease is, Glaucoma Anterior uveitis Cataracts, and An eye drop for treating and / or preventing anterior chamber and / or posterior chamber disease of the eye, as described in

[18] , comprising at least one of dry eye.

[0036]

[28] The aforementioned posterior chamber disease is Age-related macular degeneration (AMD), Diabetic macular edema, and An eye drop for treating and / or preventing anterior chamber and / or posterior chamber disease of the eye, as described in

[18] , comprising at least one of diabetic retinopathy.

[0037]

[29] An eye drop for the treatment and / or prevention of age-related macular degeneration, wherein the eye drop is It is a compound formulation, Sodium phenylbutyrate and A delivery composition, (2-hydroxypropyl)-β-cyclodextrin and / or (2-hydroxypropyl)-γ-cyclodextrin, A compound formulation comprising a caffeine-containing composition, a delivery composition comprising, and A pharmaceutically acceptable solvent for dissolving the sodium phenylbutyrate and the delivery composition to form a solution, wherein the solution functions as the compound formulation, comprising: The concentration of sodium phenylbutyrate in the aforementioned solution is in the range of 0.05 to 150 mg / mL. The concentration of (2-hydroxypropyl)-β-cyclodextrin and / or (2-hydroxypropyl)-γ-cyclodextrin in the aforementioned solution is in the range of 5 to 500 mg / mL. An eye drop in which the concentration of caffeine in the solution is in the range of 0.5 to 50 mg / mL.

[0038]

[30] The delivery composition further comprises hydroxypropyl methylcellulose, wherein the concentration of hydroxypropyl methylcellulose in the solution is in the range of 0.5 to 20 mg / mL, the eye drop for treating and / or preventing age-related macular degeneration according to

[29] .

[0039] Preferred embodiments are described below with reference to the accompanying drawings in order to facilitate understanding of the foregoing and other aspects, features, and advantages of this disclosure. [Brief explanation of the drawing]

[0040] [Figure 1A] The procedure for an animal disease model experiment induced by NaIO3, according to one embodiment of this disclosure, is shown. [Figure 1B] The results of staining the outer nuclear layer (ONL) of the rabbit retina with hematoxylin and eosin (H&E) in an animal disease model experiment induced by NaIO3 according to one embodiment of the present disclosure are shown. [Figure 1C] This shows the thickness of the outer granular layer of the rabbit retina in an animal disease model experiment induced by NaIO3 according to one embodiment of this disclosure. N≧6, and values ​​are expressed as Mean ± Standard Error of the Mean (SEM). *: Untreated group compared to untreated group. p<0.05. #: Sodium phenylbutyrate (SPB) administered group compared to untreated group. p<0.05. [Figure 2A]The procedure for an animal disease model experiment induced by hydroquinone (HQ) according to one embodiment of this disclosure is described below. [Figure 2B] The image shows the results of immunofluorescence staining of mouse specimens in an animal disease model experiment induced by hydroquinone (HQ) according to one embodiment of the present disclosure. Arrows indicate clusterin expression. ONL: outer nuclear layer. IS / OS: inner / outer segment junction of photoreceptors. RPE: retinal pigment epithelium. [Figure 2C] This shows the expression levels of clatherin in mouse samples in an animal disease model experiment induced by hydroquinone (HQ) according to one embodiment of the present disclosure. N≧6, and values ​​are expressed as Mean ± Standard Error of the Mean (SEM). *: Control group (untreated group) compared to the untreated group. p<0.05. #: Sodium phenylbutyrate (SPB) administered group compared to the control group (untreated group). p<0.05. [Figure 3A] The following shows the electroretinogram signals (wave a / wave b) of mice on day 0 in an animal disease model experiment induced by hydroquinone (HQ) according to one embodiment of this disclosure. N≧14, and the values ​​are expressed as Mean ± Standard Error of the Mean (SEM). Wave a: photoreceptors. Wave b: inner nuclear layer (INL). [Figure 3B] The electroretinogram signals (a-wave / b-wave) of mice at day 14 in an animal disease model experiment induced by hydroquinone (HQ) according to one embodiment of this disclosure are shown. N≧14, and values ​​are expressed as mean ± standard error of the mean. a-wave: photoreceptor. b-wave: inner granular layer. *: p<0.05, indicating a statistically significant difference. [Figure 3C]The electroretinogram signals (a-wave / b-wave) of mice at day 35 in an animal disease model experiment induced by hydroquinone (HQ) according to one embodiment of this disclosure are shown. N≧14, and values ​​are expressed as mean ± standard error of the mean; ANOVA. *: Untreated group compared to untreated group. p<0.05. #: Sodium phenylbutyrate (SPB) administered group compared to untreated group. p<0.05. a-wave: photoreceptor. b-wave: inner granular layer. [Modes for carrying out the invention]

[0041] This disclosure may provide an eye drop platform for delivering an active ingredient to the anterior and / or posterior chamber tissue of the eye.

[0042] The active ingredients described herein may include, but are not limited to, hydrophilic active ingredients. As used herein, the term "hydrophilic active ingredient" refers to any biologically active substance that has water solubility greater than approximately 1 mg / mL.

[0043] The hydrophilic active ingredients mentioned above may include, but are not limited to, drugs with neuroprotective properties, complement inhibitors, AMP-activated protein kinase (AMPK) activators, Rho-associated coiled-coil kinase inhibitors, or any combination thereof.

[0044] Examples of drugs having the neuroprotective function described above include, but are not limited to, sodium phenylbutyrate (SPB), dexmedetomidine HCl, and tauro-ursodesoxycholic acid (TUDCA), or any combination thereof.

[0045] Examples of complement inhibitors mentioned above include, but are not limited to, iptacopan (LNP-023) and nafamostat mesylate (FUT-175), or any combination thereof.

[0046] Furthermore, the AMP-activated protein kinase (AMPK) activators mentioned above may include, but are not limited to, biguanide drugs. An example of a biguanide drug mentioned above may include, but are not limited to, metformin HCl.

[0047] Furthermore, examples of the Rho-related coiled-coil kinase inhibitors mentioned above include, but are not limited to, (S)-N-(4-(1H-pyrazol-4-yl)phenyl)-3-amino-2-phenylpropanamide dihydrochloride (ITRI-E-(S)4046). The aforementioned (S)-N-(4-(1H-pyrazol-4-yl)phenyl)-3-amino-2-phenylpropanamide dihydrochloride is also a myosin light chain kinase 4 inhibitor. In other words, (S)-N-(4-(1H-pyrazole-4-yl)phenyl)-3-amino-2-phenylpropanamide dihydrochloride is a dual-target drug that targets both Rho-related coiled-coil kinase and myosin light chain kinase 4.

[0048] The above-mentioned eye drop platform for delivering active ingredients to the anterior and / or posterior chamber tissues of the eye can, in other cases, efficiently deliver hydrophilic drugs to the posterior chamber tissue and increase and / or improve drug exposure within the posterior chamber when administered as eye drops without requiring an invasive route of administration, even for hydrophilic drugs that are difficult to deliver to the posterior chamber or exhibit low exposure within the posterior chamber.

[0049] The eye drop platform described above for delivering the active ingredient to the anterior and / or posterior chamber tissue of the eye may, but is not limited to, a delivery composition and a pharmaceutically acceptable solvent for dissolving the delivery composition to form a solution. The solution described above functions as an eye drop platform for delivering the active ingredient to the anterior and / or posterior chamber tissue of the eye.

[0050] In the eye drop platform described above for delivering the active ingredient to the anterior and / or posterior chamber tissue of the eye, the delivery composition may, but is not limited to, cyclodextrin and / or its derivatives, and caffeine.

[0051] In one embodiment, the concentration of cyclodextrin and / or its derivatives in the above-mentioned solution is approximately 5 to 500 mg / mL, for example, approximately 10 to 475 mg / mL, approximately 15 to 450 mg / mL, approximately 20 to 425 mg / mL, approximately 25 to 400 mg / mL, approximately 5 mg / mL, approximately 10 mg / mL, approximately 15 mg / mL, approximately 20 mg / mL, approximately 25 mg / mL, approximately 30 mg / mL, approximately 35 mg / mL, approximately 40 mg / mL, approximately 45 mg / mL, approximately 50 mg / mL, approximately 55 mg / mL, approximately 60 mg / mL, approximately 65 mg / mL, approximately 70 mg / mL, approximately 75 mg / mL. The dosage may be in the range of g / mL, approximately 80 mg / mL, approximately 85 mg / mL, approximately 90 mg / mL, approximately 95 mg / mL, approximately 100 mg / mL, approximately 125 mg / mL, approximately 150 mg / mL, approximately 175 mg / mL, approximately 200 mg / mL, approximately 225 mg / mL, approximately 250 mg / mL, approximately 275 mg / mL, approximately 300 mg / mL, approximately 325 mg / mL, approximately 350 mg / mL, approximately 375 mg / mL, approximately 400 mg / mL, approximately 425 mg / mL, approximately 450 mg / mL, approximately 475 mg / mL, and approximately 500 mg / mL, but is not limited to these ranges.

[0052] The cyclodextrins mentioned above may include, but are not limited to, α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, and δ-cyclodextrin, or any combination thereof.

[0053] The above-mentioned derivatives of cyclodextrins may include, but are not limited to, hydroxypropyl-modified cyclodextrins, succinyl-modified cyclodextrins, and methyl-modified cyclodextrins, or any combination thereof. Examples of hydroxypropyl-modified cyclodextrins may include, but are not limited to, (2-hydroxypropyl)-β-cyclodextrin and (2-hydroxypropyl)-γ-cyclodextrin, or any combination thereof.

[0054] Furthermore, in one embodiment, the caffeine concentration in the above-mentioned solution is approximately 0.5 to 50 mg / mL, for example, approximately 1 to 45 mg / mL, approximately 5 to 40 mg / mL, approximately 0.5 mg / mL, approximately 0.75 mg / mL, approximately 1 mg / mL, approximately 1.25 mg / mL, approximately 1.5 mg / mL, approximately 2 mg / mL, approximately 2.2 mg / mL, approximately 2.5 mg / mL, approximately 2.75 mg / mL, approximately 3 mg / mL, approximately 3.5 mg / mL, and approximately 4 mg / mL. The levels may be in the range of approximately 4.5 mg / mL, approximately 5 mg / mL, approximately 5.5 mg / mL, approximately 6 mg / mL, approximately 7 mg / mL, approximately 8 mg / mL, approximately 9 mg / mL, approximately 10 mg / mL, approximately 12 mg / mL, approximately 15 mg / mL, approximately 20 mg / mL, approximately 25 mg / mL, approximately 30 mg / mL, approximately 35 mg / mL, approximately 40 mg / mL, approximately 45 mg / mL, and approximately 50 mg / mL, but are not limited to these ranges.

[0055] Furthermore, in one embodiment, the concentration of the above-mentioned delivery composition in the solution of the eye drop platform for delivering the active ingredient to the anterior and / or posterior chamber tissue of the eye is approximately 6 to 570 mg / mL, for example, approximately 10 to 565 mg / mL, approximately 15 to 560 mg / mL, approximately 20 to 555 mg / mL, approximately 25 to 550 mg / mL, approximately 30 to 545 mg / mL, approximately 40 to 540 mg / mL, approximately 45 to 535 mg / mL, approximately 50 to 530 mg / mL, approximately 55 to 525 mg / mL, and approximately 60 to 500 mg / mL. g / mL, approximately 65 to 450 mg / mL, approximately 70 to 400 mg / mL, approximately 6 mg / mL, approximately 7 mg / mL, approximately 8 mg / mL, approximately 9 mg / mL, approximately 10 mg / mL, approximately 11 mg / mL, approximately 12 mg / mL, approximately 13 mg / mL, approximately 15 mg / mL, Approximately 18mg / mL, approximately 20mg / mL, approximately 21mg / mL, approximately 24mg / mL, approximately 25mg / mL, approximately 27mg / mL, approximately 30mg / mL, approximately 31mg / mL, approximately 32mg / mL, approximately 33mg / mL, approximately 34mg / mL, approximately 35mg / mL, approximately 36mg / mL, about 37mg / mL, about 38mg / mL, about 39mg / mL, about 40mg / mL, about 41mg / mL, about 42mg / mL, about 45mg / mL, about 48mg / mL, about 50mg / mL, about 51mg / mL, about 52mg / mL, about 55mg / mL, approximately 60mg / mL, approximately 61mg / mL, approximately 62mg / mL, approximately 65mg / mL, approximately 70mg / mL, approximately 75mg / mL, approximately 80mg / mL, approximately 85mg / mL, approximately 90mg / mL, approximately 95mg / mL, approximately 100mg / mL, The dosage may be, but is not limited to, approximately 125 mg / mL, 150 mg / mL, 175 mg / mL, 200 mg / mL, 225 mg / mL, 250 mg / mL, 275 mg / mL, 300 mg / mL, 325 mg / mL, 350 mg / mL, 375 mg / mL, 400 mg / mL, 425 mg / mL, 450 mg / mL, 475 mg / mL, 500 mg / mL, 525 mg / mL, 550 mg / mL, and 570 mg / mL.

[0056] Furthermore, the pharmaceutically acceptable solvents in the eye drop platform for delivering the active ingredient to the anterior and / or posterior chamber tissues of the eye may include, but are not limited to, water, physiological saline, or any combination thereof.

[0057] In one embodiment, the delivery composition in the eye drop platform for delivering the active ingredient to the anterior and / or posterior chamber tissue of the eye may further include, but is not limited to, a water-soluble polymer in addition to cyclodextrin and / or its derivatives, and caffeine. The addition of a water-soluble polymer can provide more sustained delivery of the active ingredient to the anterior and / or posterior chamber tissue of the eye.

[0058] In one embodiment, the concentration of the water-soluble polymer in the above-mentioned solution is approximately 0.5 to 20 mg / mL, for example, approximately 1 to 15 mg / mL, approximately 2 to 10 mg / mL, approximately 0.5 mg / mL, approximately 0.75 mg / mL, approximately 1 mg / mL, approximately 1.25 mg / mL, approximately 1.5 mg / mL, approximately 2 mg / mL, approximately 2.25 mg / mL, approximately 2.75 mg / mL, approximately 3 mg / mL, approximately 3.25 mg / mL, approximately 3.5 mg / mL, approximately 3.75 mg / mL, approximately 4 mg / mL, approximately 4.25 mg / mL, approximately 4.5 mg / mL, approximately 4.75 mg / mL, approximately 5 mg / mL, and approximately 5.25 mg / mL. The levels may be in the range of approximately 5.5 mg / mL, approximately 5.75 mg / mL, approximately 6 mg / mL, approximately 6.25 mg / mL, approximately 6.5 mg / mL, approximately 6.75 mg / mL, approximately 7 mg / mL, approximately 7.25 mg / mL, approximately 7.5 mg / mL, approximately 7.75 mg / mL, approximately 8 mg / mL, approximately 8.25 mg / mL, approximately 8.5 mg / mL, approximately 8.75 mg / mL, approximately 9 mg / mL, approximately 9.25 mg / mL, approximately 9.5 mg / mL, approximately 9.75 mg / mL, approximately 10 mg / mL, approximately 12.5 mg / mL, approximately 15 mg / mL, and approximately 20 mg / mL, but are not limited to these ranges.

[0059] The water-soluble polymers mentioned above may include, but are not limited to, hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (hydroxypropyl cellulose), carboxymethyl cellulose (CMC), polyvinylpyrrolidone (PVP), polyvinyl alcohol, and poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) triblock copolymers (PEG-PPG-PEG(ABA) triblock copolymers), or any combination thereof.

[0060] Based on the foregoing, this disclosure further provides the use of a delivery composition in the preparation of eye drops for delivering an active ingredient to the anterior and / or posterior chamber tissue of the eye.

[0061] Similarly, based on the foregoing, the Disclosure further provides a method for delivering an active ingredient to the anterior and / or posterior chamber tissues of the eye. The method may include, but is not limited to, administering the active ingredient to a subject requiring the active ingredient via eye drops containing the delivery composition.

[0062] The use of a delivery composition in the preparation of an eye drop for delivering an active ingredient to the anterior and / or posterior chamber tissue of the eye, as described herein, and the delivery composition in the method for delivering an active ingredient to the anterior and / or posterior chamber tissue of the eye, as described herein, may be the same as the delivery composition in the eye drop platform for delivering an active ingredient to the anterior and / or posterior chamber tissue of the eye, as described herein. Accordingly, all relevant descriptions of the delivery composition and its components in use can be found in the preceding paragraphs relating to the delivery composition and its components in the eye drop platform for delivering an active ingredient to the anterior and / or posterior chamber tissue of the eye, as described herein, and will not be repeated herein.

[0063] Furthermore, the use of a delivery composition in the preparation of eye drops for delivering the active ingredient to the anterior and / or posterior chamber tissue of the eye, and the descriptions relating to the active ingredient in the above-mentioned methods for delivering the active ingredient to the anterior and / or posterior chamber tissue of the eye, can be referenced from all relevant descriptions relating to the active ingredient in the foregoing descriptions relating to the eye drop platform for delivering the active ingredient to the anterior and / or posterior chamber tissue of the eye, and these descriptions are not repeated herein.

[0064] Furthermore, based on the foregoing, this disclosure further provides the use of a delivery composition in the preparation of eye drops to improve exposure of the active ingredient in the anterior chamber and / or posterior chamber tissue of the eye.

[0065] Similarly, based on the foregoing, the present disclosure can further provide eye drops for improving exposure to an active ingredient in the anterior and / or posterior chamber tissues of the eye. These eye drops may, but are not limited to, a delivery composition and a pharmaceutically acceptable solvent for dissolving the delivery composition to form a solution. The above-described solution functions as an eye drop for improving exposure to an active ingredient in the anterior and / or posterior chamber tissues of the eye.

[0066] Similarly, based on the foregoing, the disclosure can further provide methods for improving exposure to the active ingredient in the anterior and / or posterior chamber tissues of the eye. The methods may include, but are not limited to, administering the active ingredient to a subject requiring the active ingredient via eye drops containing a delivery composition and a pharmaceutically acceptable solvent.

[0067] The delivery composition in the preparation of eye drops for improving exposure to the active ingredient in the anterior and / or posterior chamber tissue of the eye, the eye drops for improving exposure to the active ingredient in the anterior and / or posterior chamber tissue of the eye, and the method for improving exposure to the active ingredient in the anterior and / or posterior chamber tissue of the eye, as described above, may be the same as the delivery composition in the eye drop platform for delivering the active ingredient to the anterior and / or posterior chamber tissue of the eye, as described above. Accordingly, all relevant descriptions of the delivery composition, and all relevant descriptions of the components of the delivery composition in the use, eye drops, and method, can be found in the preceding paragraphs relating to the delivery composition and its components in the eye drop platform for delivering the active ingredient to the anterior and / or posterior chamber tissue of the eye, as described above, and will not be repeated herein.

[0068] Furthermore, with respect to the use of a delivery composition in the preparation of eye drops for improving exposure of the active ingredient in the anterior and / or posterior chamber tissue of the eye, the eye drops for improving exposure of the active ingredient in the anterior and / or posterior chamber tissue of the eye, and the descriptions relating to the active ingredient in the methods for improving exposure of the active ingredient in the anterior and / or posterior chamber tissue of the eye as described above, you can refer to all relevant descriptions of the active ingredient in the relevant descriptions of the eye drop platform of the disclosure for delivering the active ingredient to the anterior and / or posterior chamber tissue of the eye, as described herein, and these descriptions will not be repeated.

[0069] Examples of pharmaceutically acceptable solvents in the eye drops for improving exposure of the active ingredient in the anterior and / or posterior chamber tissues of the eye, as described above, and in the methods for improving exposure of the active ingredient in the anterior and / or posterior chamber tissues of the eye, as described above, include, but are not limited to, water, physiological saline, or any combination thereof.

[0070] Furthermore, based on the foregoing, the present disclosure further provides compound formulations. The above-described compound formulations may comprise an active ingredient, a delivery composition, and a pharmaceutically acceptable solvent for dissolving the active ingredient and the delivery composition to form a solution. The solution functions as a compound formulation, but is not limited thereto. In one embodiment, the above-described compound formulation of the present disclosure is an eye drop.

[0071] For relevant descriptions of the active ingredients in the compound formulations of this disclosure, you can refer to all relevant descriptions of the active ingredients in the preceding descriptions of this disclosure relating to the eye drop platform for delivering the active ingredients to the anterior and / or posterior chamber tissues of the eye, which will not be repeated herein.

[0072] In one embodiment, the concentration of the active ingredient in the solution of the composite formulation of the present disclosure described above is approximately 0.05 to 500 mg / mL, for example, approximately 0.1 to 450 mg / mL, approximately 0.25 to 400 mg / mL, approximately 0.5 to 350 mg / mL, approximately 1 to 300 mg / mL, approximately 5 to 250 mg / mL, approximately 10 to 200 mg / mL, approximately 15 to 150 mg / mL, approximately 20 to 100 mg / mL, approximately 0.05 mg / mL, approximately 0.1 mg / mL, approximately 0.25 mg / mL, approximately 0.5 mg / mL, approximately 0.75 mg / mL, approximately 1 mg / mL, approximately 2 mg / mL, approximately 3 mg / mL, approximately 4 mg / mL, approximately 5 mg / mL, approximately 6 mg / mL, approximately 7 mg / mL, and approximately 8 mg / mL. The dosage may be, but is not limited to, the range of approximately 9 mg / mL, approximately 10 mg / mL, approximately 11 mg / mL, approximately 12 mg / mL, approximately 13 mg / mL, approximately 14 mg / mL, approximately 15 mg / mL, approximately 17 mg / mL, approximately 18 mg / mL, approximately 19 mg / mL, approximately 20 mg / mL, approximately 30 mg / mL, approximately 40 mg / mL, approximately 50 mg / mL, approximately 60 mg / mL, approximately 70 mg / mL, approximately 80 mg / mL, approximately 90 mg / mL, approximately 100 mg / mL, approximately 150 mg / mL, approximately 200 mg / mL, approximately 250 mg / mL, approximately 300 mg / mL, approximately 350 mg / mL, approximately 400 mg / mL, approximately 450 mg / mL, and approximately 500 mg / mL.

[0073] In certain embodiments, the active ingredient in the compound formulation of the present disclosure is sodium phenylbutyrate, and the concentration of sodium phenylbutyrate in solution may be, but is not limited to, in the range of about 0.05 to 150 mg / mL.

[0074] In other specific embodiments, the active ingredient in the composite formulation of the present disclosure may be metformin HCl, and the concentration of metformin HCl in solution may be, but is not limited to, in the range of about 200 to 300 mg / mL.

[0075] In yet another specific embodiment, the active ingredient in the composite formulation of the present disclosure is dexmedetomidine HCl, and the concentration of dexmedetomidine HCl in solution may be, but is not limited to, in the range of about 0.5 to 20 mg / mL.

[0076] In certain embodiments, the active ingredient in the compound formulation of the present disclosure is iptacopan, and the concentration of iptacopan in solution may be in the range of about 1 to 25 mg / mL, but is not limited thereto.

[0077] In certain embodiments, the active ingredient in the compound formulation of the present disclosure is tauroursodeoxycholic acid (TUDCA), and the concentration of tauroursodeoxycholic acid (TUDCA) in solution may be in the range of about 5 to 50 mg / mL, but is not limited thereto.

[0078] Furthermore, in certain embodiments, the active ingredient in the compound formulation of the present disclosure is nafamostat mesilate, and the concentration of nafamostat mesilate in solution may be, but is not limited to, in the range of about 10 to 150 mg / mL.

[0079] Furthermore, in another specific embodiment, the active ingredient in the composite formulation of the present disclosure is (S)-N-(4-(1H-pyrazole-4-yl)phenyl)-3-amino-2-phenylpropanamide dihydrochloride (ITRI-E-(S)4046), and the concentration of (S)-N-(4-(1H-pyrazole-4-yl)phenyl)-3-amino-2-phenylpropanamide dihydrochloride (ITRI-E-(S)4046) in solution may be, but is not limited to, in the range of about 1 to 25 mg / mL.

[0080] The delivery composition in the compound formulation of the present disclosure described above may be the same as the delivery composition in the eye drop platform for delivering the active ingredient to the anterior and / or posterior chamber tissue of the eye described above. Accordingly, all relevant descriptions of the delivery composition in the compound formulation and all relevant descriptions of its components can be similarly referenced to the preceding paragraphs relating to the delivery composition and its components in the eye drop platform for delivering the active ingredient to the anterior and / or posterior chamber tissue of the eye described above, and will not be repeated herein.

[0081] Furthermore, the pharmaceutically acceptable solvents in the compound formulations of this disclosure may include, but are not limited to, water, physiological saline, or any combination thereof.

[0082] Furthermore, based on the foregoing, this disclosure further provides the use of any of the above-described combination formulations in the preparation of eye drops for treating and / or preventing anterior chamber and / or posterior chamber diseases of the eye.

[0083] Similarly, based on the foregoing, this disclosure further provides eye drops for treating and / or preventing anterior chamber and / or posterior chamber diseases of the eye. The eye drops may include, but are not limited to, any of the combination formulations described above.

[0084] Similarly, based on the foregoing, the Disclosure further provides methods for the treatment and / or prevention of anterior chamber and / or posterior chamber diseases of the eye. The methods may include, but are not limited to, administering any of the above-described combination formulations of the Disclosure, or any eye drops for the treatment and / or prevention of anterior chamber and / or posterior chamber diseases of the eye of the Disclosure, to a subject in need of treatment and / or prevention.

[0085] Anterior chamber diseases include, but are not limited to, glaucoma, anterior uveitis, cataracts, dry eye, or any combination thereof.

[0086] Posterior chamber diseases may include, but are not limited to, retinopathy. Retinopathy may include, but is not limited to, macular degeneration, macular edema, diabetic retinopathy, or any combination thereof. Macular degeneration may include, but is not limited to, age-related macular degeneration (AMD), pathological myopia-related macular degeneration, or any combination thereof. Macular edema may include, but is not limited to, diabetic macular edema.

[0087] Furthermore, this disclosure further provides the use of compound formulations in the preparation of eye drops for the treatment and / or prevention of age-related macular degeneration. The compound formulations described herein may be any of the compound formulations described herein above.

[0088] Similarly, based on the foregoing, the Disclosure further provides eye drops for the treatment and / or prevention of age-related macular degeneration. The eye drops of the Disclosure may include, but are not limited to, any combination formulations of the Disclosure as described above.

[0089] Similarly, based on the foregoing, the Disclosure further provides methods for the treatment and / or prevention of age-related macular degeneration. The methods may include, but are not limited to, administering any of the above-described combination formulations of the Disclosure, or any of the above-described eye drops for the treatment and / or prevention of anterior chamber and / or posterior chamber diseases of the eye, to a subject in need of treatment and / or prevention.

[0090] In certain embodiments, for the use of a compound formulation in the preparation of the eye drops for treating and / or preventing age-related macular degeneration of the present disclosure, the eye drops for treating and / or preventing age-related macular degeneration of the present disclosure, and the method for treating and / or preventing age-related macular degeneration of the present disclosure, the active ingredient in the compound formulation of the present disclosure is sodium phenylbutyrate, and the cyclodextrin and / or derivative of the delivery composition in the compound formulation of the present disclosure is (2-hydroxypropyl)-β-cyclodextrin and / or (2-hydroxypropyl)-γ-cyclodextrin. The concentration of sodium phenylbutyrate in solution may range from approximately 0.05 to 150 mg / mL, the concentration of (2-hydroxypropyl)-β-cyclodextrin and / or (2-hydroxypropyl)-γ-cyclodextrin in solution may range from approximately 5 to 500 mg / mL, and the concentration of caffeine in solution may range from approximately 0.5 to 50 mg / mL. Furthermore, the delivery composition in the compound formulation may further contain a water-soluble polymer. The water-soluble polymer is hydroxypropyl methylcellulose, and the concentration of hydroxypropyl methylcellulose in solution may range from approximately 0.5 to 20 mg / mL.

[0091] As used herein, the term “subject” may include, but is not limited to, vertebrates. Vertebrates may include, but are not limited to, fish, amphibians, reptiles, birds, or mammals. Examples of mammals may include, but are not limited to, humans, apes, monkeys, horses, donkeys, llamas, dogs, cats, rabbits, guinea pigs, rats, and mice. In one embodiment, the subject is a human.

[0092] Examples A. Drugs for testing the delivery efficiency of eye drop platforms

[0093] Table 1 lists the various drugs used in the experiments of the following examples, and their corresponding functions. All drugs listed in Table 1 are hydrophilic drugs with water solubility exceeding 1 mg / mL. [Table 1]

[0094] B. Experiment 1. Example 1 The effect of eye drops containing varying amounts of hydroxypropylmethylcellulose (HPMC) upon exposure to sodium phenylbutyrate (SPB) delivered to the retinal tissue of the posterior chamber.

[0095] 1-1. Experimental Method 1-1-1. Preparation of eye drops containing sodium phenylbutyrate 2-hydroxypropyl-β-cyclodextrin (HPβCD), caffeine, hydroxypropyl methylcellulose (HPMC), and sodium phenylbutyrate (SPB) were mixed at room temperature according to the concentrations shown in Table 2 below to prepare eye drops containing sodium phenylbutyrate (SPB). The detailed procedure is described below. [Table 2]

[0096] 2-Hydroxypropyl-β-cyclodextrin (HPβCD), caffeine, and hydroxypropyl methylcellulose (HPMC) were dissolved in deionized water at room temperature to form a clear aqueous solution.

[0097] Subsequently, sodium phenylbutyrate (SPB) was added to the aforementioned clear aqueous solution and stirred until the sodium phenylbutyrate (SPB) was completely dissolved. Then, deionized water was added to adjust the solution to a predetermined volume, and the solution was filtered through a filter with a pore size of 0.22 μm to obtain eye drops containing sodium phenylbutyrate (SPB).

[0098] Finally, the concentration of sodium phenylbutyrate (SPB) in the obtained ophthalmic solutions containing sodium phenylbutyrate (SPB) was analyzed by high-performance liquid chromatography (HPLC).

[0099] 1-1-2. Method for exposure analysis of posterior chamber tissue Pigmented rabbits purchased from a rabbit farm were weighed and then restrained with a restraint device. 35 μL of test eye drops were administered into the conjunctival sac of both the left and right eyes of each rabbit. The eyelids were then closed, and the eyes were gently massaged to ensure the eye drops were evenly distributed across the entire ocular surface.

[0100] At 1, 3, and 6 hours after administration, the animals were sacrificed using CO2. Subsequently, the eyeballs were collected, and the visual tissue was dissected to obtain retinal and choroidal tissue belonging to the posterior chamber. Then, the retinal and choroidal tissues were individually mixed with phosphate-buffered saline (PBS) and homogenized to obtain test retinal homogenates and test choroidal homogenates.

[0101] Finally, the drug content of the aforementioned test retinal homogenates and test choroidal homogenates was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS / MS). The procedure for processing and analyzing the retinal and choroidal samples is described below.

[0102] (a) Preparation of standard solutions First, a standard mixture solution was prepared by mixing the drug reference standard with dimethyl sulfoxide (DMSO), and a working solution for calibration standards and quality control samples were prepared. Subsequently, each working solution was mixed with blank (untreated) rabbit retinal homogenate or choroidal homogenate in predetermined ratios to obtain calibration standards and quality control samples at various concentrations.

[0103] (b) Extraction of retinal and choroidal samples Calibration standards, quality control samples, and analytical retinal homogenete samples or analytical choroidal homogenete samples were added to separate 1.5 mL centrifuge tubes. Then, an acetonitrile solution containing the internal standard was added to the centrifuge tubes and mixed uniformly using a shaker. The mixtures were then centrifuged, and the supernatant (over 90 μL) was collected. The supernatant was transferred to an HPLC vial and analyzed by LC / MS / MS.

[0104] 1-2. Experimental Results The experimental results are shown in Table 3. [Table 3]

[0105] According to Tables 2 and 3, the eye drops from Group 2 and Group 3 achieved significantly higher exposure concentrations of sodium phenylbutyrate (SPB) to retinal tissue than those achieved by the eye drops from Group 1. In other words, when the eye drops contained 2-hydroxypropyl-β-cyclodextrin (HPβCD) and caffeine, they were able to effectively increase exposure to sodium phenylbutyrate (SPB) in retinal tissue.

[0106] Furthermore, as shown in Tables 2 and 3, the eye drops in Group 3 were able to continuously increase exposure to sodium phenylbutyrate (SPB) in retinal tissue 3 hours after administration. In other words, when the eye drops further contained hydroxypropyl methylcellulose (HPMC) in addition to 2-hydroxypropyl-β-cyclodextrin (HPβCD) and caffeine, the sustained exposure to sodium phenylbutyrate (SPB) in retinal tissue was effectively enhanced.

[0107] 2. Example 2 The effects of eye drops containing various amounts of caffeine upon exposure to sodium phenylbutyrate (SPB) delivered to the retinal tissue of the posterior chamber.

[0108] 2-1. Experimental Method 2-1-1. Preparation of eye drops containing sodium phenylbutyrate According to the respective concentrations of each component shown in Table 4 below, 2-hydroxypropyl-β-cyclodextrin (HPβCD), caffeine, hydroxypropyl methylcellulose (HPMC), and sodium phenylbutyrate were combined at room temperature to prepare eye drops containing sodium phenylbutyrate. The preparation method for the eye drops was carried out by referring to the method described in Example 1 above. [Table 4]

[0109] 2-1-2. Method for exposure analysis of posterior chamber tissue Similarly, the method for the exposure analysis test of posterior chamber tissue can also be carried out by referring to the method described in Example 1 above.

[0110] 2-2. Experimental Results The experimental results are shown in Table 5 below. [Table 5]

[0111] According to Tables 4 and 5, the eye drops in Group 1 achieved a maximum exposure concentration of less than 10 ng / g of sodium phenylbutyrate (SPB) in retinal tissue after administration. In other words, solutions containing only sodium phenylbutyrate (SPB) showed limited exposure to sodium phenylbutyrate in retinal tissue.

[0112] In contrast, the eye drops in Group 2 achieved a maximum exposure concentration of less than 69.6 ng / g of sodium phenylbutyrate (SPB) in retinal tissue after administration. In other words, when the eye drops contained 2-hydroxypropyl-β-cyclodextrin, exposure to sodium phenylbutyrate (SPB) in retinal tissue was improved.

[0113] Furthermore, groups 3-5 showed that when the eye drops contained caffeine at concentrations of 5-40 mg / mL in addition to 2-hydroxypropyl-β-cyclodextrin, the exposure concentration of sodium phenylbutyrate (SPB) in retinal tissue significantly increased (904.8-3908.5 ng / g). Moreover, the caffeine concentration showed a positive correlation with the exposure concentration of sodium phenylbutyrate (SPB) in retinal tissue.

[0114] The above experimental data demonstrates that eye drops containing 2-hydroxypropyl-β-cyclodextrin and caffeine can increase exposure to sodium phenylbutyrate (SPB) in retinal tissue.

[0115] 3. Example 3 The effect of eye drops containing varying concentrations of 2-hydroxypropyl-β-cyclodextrin (HPβCD) upon exposure to sodium phenylbutyrate (SPB) delivered to the retinal tissue of the posterior chamber.

[0116] 3-1. Experimental Method 3-1-1. Preparation of eye drops containing sodium phenylbutyrate According to the respective concentrations of each component shown in Table 6 below, 2-hydroxypropyl-β-cyclodextrin (HPβCD), caffeine, hydroxypropyl methylcellulose (HPMC), and sodium phenylbutyrate were combined at room temperature to prepare eye drops containing sodium phenylbutyrate. The method for preparing the eye drops and the method for the posterior chamber tissue exposure analysis test can be carried out by referring to the method described in Example 1 above. [Table 6]

[0117] 3-1-2. Method for exposure analysis of posterior chamber tissue Similarly, the method for the exposure analysis test of posterior chamber tissue can also be carried out by referring to the method described in Example 1 above.

[0118] 3-2. Experimental Results The experimental results are shown in Table 7 below. [Table 7]

[0119] According to Tables 6 and 7, the eye drops from groups 2-4 achieved significantly higher maximum exposure concentrations of sodium phenylbutyrate (SPB) in retinal tissue after administration than those achieved by the eye drops from group 1. Specifically, when the concentration of sodium phenylbutyrate (SPB) in the eye drops was fixed at 30 mg / mL, the concentration of caffeine was fixed at 20 mg / mL, and the concentration of 2-hydroxypropyl-β-cyclodextrin was adjusted to 60-400 mg / mL, the maximum concentration of sodium phenylbutyrate (SPB) in retinal tissue after administration reached 3441.0-4385.0 ng / g. All of these concentrations are significantly higher than the exposure concentrations of sodium phenylbutyrate (SPB) in retinal tissue achieved by solutions containing only sodium phenylbutyrate (SPB).

[0120] Furthermore, the results of administering eye drops in groups 5 and 6 showed that when the concentration of sodium phenylbutyrate (SPB) in the eye drops was fixed at 40 mg / mL, the concentration of caffeine was fixed at 20 mg / mL, and the concentration of 2-hydroxypropyl-β-cyclodextrin was adjusted to 30-60 mg / mL, the maximum concentration of sodium phenylbutyrate (SPB) in the retinal tissue after administration reached 5349.5-5486.5 ng / g.

[0121] 4. Example 4 The effects of eye drops containing various types of cyclodextrins upon exposure to sodium phenylbutyrate (SPB) delivered to the retinal tissue of the posterior chamber.

[0122] 4-1. Experimental Method 4-1-1. Preparation of eye drops containing sodium phenylbutyrate As shown in Table 8 below, various types of cyclodextrin, caffeine, hydroxypropyl methylcellulose (HPMC), and sodium phenylbutyrate were combined at room temperature according to the respective concentrations of each compound to prepare eye drops containing sodium phenylbutyrate. The preparation method for the eye drops was carried out by referring to the method described in Example 1 above. [Table 8]

[0123] 4-1-2. Method for exposure analysis of posterior chamber tissue Similarly, the method for the exposure analysis test of posterior chamber tissue can also be carried out by referring to the method described in Example 1 above.

[0124] 4-2. Experimental Results The experimental results are shown in Table 9 below. [Table 9]

[0125] According to Tables 8 and 9, the eye drops from groups 2 and 3 achieved significantly higher maximum exposure concentrations of sodium phenylbutyrate (SPB) in retinal tissue after administration than those achieved by the eye drops from group 1. Specifically, when the concentration of sodium phenylbutyrate (SPB) in the eye drops was fixed at 30 mg / mL and the concentration of caffeine was fixed at 20 mg / mL, the maximum concentration of sodium phenylbutyrate (SPB) in retinal tissue after administration reached 3441.0–3447.5 ng / g, regardless of whether 2-hydroxypropyl-β-cyclodextrin or 2-hydroxypropyl-γ-cyclodextrin was used. All of these concentrations are significantly higher than the exposure concentrations of sodium phenylbutyrate (SPB) in retinal tissue achieved by solutions containing only sodium phenylbutyrate (SPB).

[0126] The above data demonstrate that eye drops formulated with 2-hydroxypropyl-β-cyclodextrin or 2-hydroxypropyl-γ-cyclodextrin in combination with caffeine can improve exposure to sodium phenylbutyrate (SPB) in retinal tissue.

[0127] 5. Example 5 The effect of eye drops containing specific amounts of cyclodextrin and caffeine upon exposure to metformin HCl delivered to the choroidal tissue of the posterior chamber.

[0128] 5-1. Experimental Method 5-1-1. Preparation of eye drops containing metformin HCl According to the respective concentrations of each component shown in Table 10 below, 2-hydroxypropyl-β-cyclodextrin (HPβCD), caffeine, hydroxypropyl methylcellulose (HPMC), and metformin HCl were combined at room temperature to prepare eye drops containing metformin HCl. The preparation method for the eye drops was the same as that described in Example 1 above, except that sodium phenylbutyrate was replaced with metformin HCl. [Table 10]

[0129] 5-1-2. Method for exposure analysis of posterior chamber tissue Regarding the method for the exposure analysis test of posterior chamber tissue, all other procedures may be the same as those described in Example 1 above, except that the timing of animal administration was adjusted to 0.5, 1, and 3 hours.

[0130] 5-2. Experimental Results The experimental results are shown in Table 11 below. [Table 11]

[0131] According to Tables 10 and 11, when eye drops containing metformin HCl were further containing 400 mg / mL of 2-hydroxypropyl-β-cyclodextrin (HPβCD) and 20 mg / mL of caffeine, the maximum concentration of metformin HCl in choroidal tissue after administration reached 26,437.5 ng / g, which was significantly higher than the maximum concentration achieved by eye drops consisting of metformin HCl solution alone.

[0132] The above experimental data demonstrates that eye drops containing 2-hydroxypropyl-β-cyclodextrin (HPβCD) and caffeine can increase the exposure of choroidal tissue to metformin HCl.

[0133] 6. Example 6 The effect of eye drops containing specific amounts of cyclodextrin and caffeine upon exposure to dexmedetomidine HCl delivered to the retinal and choroidal tissues of the posterior chamber.

[0134] 6-1. Experimental Method 6-1-1. Preparation of eye drops containing dexmedetomidine HCl According to the respective concentrations of each component shown in Table 10 below, 2-hydroxypropyl-β-cyclodextrin (HPβCD), caffeine, hydroxypropyl methylcellulose (HPMC), and dexmedetomidine HCl were combined at room temperature to prepare eye drops containing dexmedetomidine HCl. The preparation method for the eye drops was the same as that described in Example 1 above, except that sodium phenylbutyrate was replaced with dexmedetomidine HCl. [Table 12]

[0135] 6-1-2. Method for exposure analysis of posterior chamber tissue Regarding the method for the posterior chamber tissue exposure analysis test, all other procedures can be carried out by referring to those described in Example 1 above, except that the timing of animal administration was adjusted to 0.5 and 3 hours.

[0136] 6-2. Experimental Results The experimental results are shown in Table 13 below. [Table 13]

[0137] According to Tables 12 and 13, when eye drops containing dexmedetomidine HCl were further containing 400 mg / mL of 2-hydroxypropyl-β-cyclodextrin and 20 mg / mL of caffeine, the maximum concentration of dexmedetomidine HCl in retinal tissue after administration reached 290.5 ng / g, and the maximum concentration of dexmedetomidine HCl in choroidal tissue after administration reached 2711.7 ng / g.

[0138] The above experimental data demonstrates that eye drops containing 2-hydroxypropyl-β-cyclodextrin and caffeine can effectively deliver dexmedetomidine HCl to the posterior chamber tissue.

[0139] 7. Example 7 The effect of eye drops containing specific amounts of cyclodextrin and caffeine upon exposure of iptacopan to retinal and choroidal tissues of the posterior chamber.

[0140] 7-1. Experimental Method 7-1-1. Preparation of eye drop formulations containing iptacopan According to the respective concentrations of each component shown in Table 14 below, 2-hydroxypropyl-β-cyclodextrin (HPβCD), caffeine, hydroxypropyl methylcellulose (HPMC), and iptacopan were combined at room temperature to prepare eye drops containing iptacopan. The preparation method for the eye drops was the same as that described in Example 1 above, except that sodium phenylbutyrate was replaced with iptacopan. [Table 14]

[0141] 7-1-2. Method for exposure analysis of posterior chamber tissue Regarding the analysis method for exposure of posterior chamber tissue, all other procedures were the same as those described in Example 1 above, except that the timing of animal administration was adjusted to 0.5 and 3 hours.

[0142] 7-2. Experimental Results The experimental results are shown in Table 15 below. [Table 15]

[0143] According to Tables 14 and 15, when eye drops containing iptacopan contained 400 mg / mL of 2-hydroxypropyl-β-cyclodextrin and 20 mg / mL of caffeine, the maximum concentration of iptacopan in retinal tissue after administration reached 86.6 ng / g, and the maximum concentration in choroidal tissue reached 268.0 ng / g.

[0144] The above experimental data demonstrates that eye drops containing 2-hydroxypropyl-β-cyclodextrin and caffeine can effectively deliver iptacopan to the posterior chamber tissue.

[0145] 8. Example 8 The effect of eye drops containing specific amounts of cyclodextrin and caffeine upon exposure to tauro-ursodesoxycholic acid (TUDCA) delivered to the retinal and choroidal tissues of the posterior chamber.

[0146] 8-1. Experimental Method 8-1-1. Preparation of eye drops containing sodium phenylbutyrate According to the respective concentrations of each compound shown in Table 18 below, 2-hydroxypropyl-β-cyclodextrin (HPβCD), caffeine, hydroxypropyl methylcellulose (HPMC), and tauroursodeoxycholic acid (TUDCA) were combined at room temperature to prepare eye drops containing tauroursodeoxycholic acid (TUDCA). The preparation method for the eye drops was the same as that described in Example 1 above, except that sodium phenylbutyrate was replaced with tauroursodeoxycholic acid (TUDCA). [Table 16]

[0147] 8-1-2. Method for exposure analysis of posterior chamber tissue Regarding the analysis method for exposure of posterior chamber tissue, all other procedures were the same as those described in Example 1 above, except that the timing of animal administration was adjusted to 0.5 and 3 hours.

[0148] 8-2. Experimental Results The experimental results are shown in Table 17 below. [Table 17]

[0149] According to Tables 16 and 17, when an eye drop containing tauroursodeoxycholic acid (TUDCA) also contained 400 mg / mL of 2-hydroxypropyl-β-cyclodextrin and 20 mg / mL of caffeine, the maximum concentration of tauroursodeoxycholic acid (TUDCA) in retinal tissue after administration reached 73.0 ng / g, and the maximum concentration in choroidal tissue reached 38.7 ng / g.

[0150] The above experimental data demonstrates that eye drops containing 2-hydroxypropyl-β-cyclodextrin and caffeine can effectively deliver tauroursodeoxycholic acid (TUDCA) to the posterior chamber tissue.

[0151] 9. Example 9 The effect of eye drops containing specific amounts of cyclodextrin and caffeine upon exposure to nafamostat mesylate (FUT-175) delivered to the retinal and choroidal tissues of the posterior chamber.

[0152] 9-1. Experimental Method 9-1-1. Preparation of eye drops containing nafamostat mesylate (FUT-175) According to the respective concentrations of each component shown in Table 18 below, 2-hydroxypropyl-β-cyclodextrin (HPβCD), caffeine, hydroxypropyl methylcellulose (HPMC), and nafamostat mesilate were combined at room temperature to prepare eye drops containing nafamostat mesilate. The preparation method for the eye drops was the same as that described in Example 1 above, except that sodium phenylbutyrate was replaced with nafamostat mesilate. [Table 18]

[0153] 9-1-2. Methods for exposure analysis of posterior chamber tissue: Regarding the analysis method for exposure of posterior chamber tissue, all other procedures were the same as those described in Example 1 above, except that the timing of animal administration was adjusted to 0.5, 1, and 3 hours.

[0154] 9-2. Experimental Results The experimental results are shown in Table 19 below. [Table 19]

[0155] According to Tables 18 and 19, when eye drops containing 30 mg / mL of nafamostat mesilate also contained 400 mg / mL of 2-hydroxypropyl-β-cyclodextrin and 20 mg / mL of caffeine, the maximum concentration of nafamostat mesilate in retinal tissue after administration reached 60.0 ng / g, and the maximum concentration in choroidal tissue reached 418.5 ng / g.

[0156] When eye drops containing 100 mg / mL of nafamostat mesilate also contained 400 mg / mL of 2-hydroxypropyl-β-cyclodextrin and 20 mg / mL of caffeine, the maximum concentration of nafamostat mesilate in retinal tissue after administration reached 261.9 ng / g, and the maximum concentration in choroidal tissue reached 1165.0 ng / g.

[0157] The above experimental data demonstrates that eye drops containing 2-hydroxypropyl-β-cyclodextrin and caffeine can effectively deliver nafamostat mesylate to the posterior chamber tissue.

[0158] 10. Example 10 The effect of eye drops containing specific amounts of cyclodextrin and caffeine upon exposure to (S)-N-(4-(1H-pyrazole-4-yl)phenyl)-3-amino-2-phenylpropanamide dihydrochloride (ITRI-E-(S)4046) delivered to the retinal and choroidal tissues of the posterior chamber.

[0159] 10-1. Experimental Method 10-1-1. Preparation of eye drops containing (S)-N-(4-(1H-pyrazol-4-yl)phenyl)-3-amino-2-phenylpropanamide dihydrochloride (ITRI-E-(S)4046)

[0160] According to the respective concentrations of each compound shown in Table 20 below, 2-hydroxypropyl-β-cyclodextrin (HPβCD), caffeine, hydroxypropyl methylcellulose (HPMC), and (S)-N-(4-(1H-pyrazole-4-yl)phenyl)-3-amino-2-phenylpropanamide dihydrochloride were combined at room temperature to prepare eye drops containing (S)-N-(4-(1H-pyrazole-4-yl)phenyl)-3-amino-2-phenylpropanamide dihydrochloride. The procedure for preparing the eye drops was the same as that described in Example 1 above, except that sodium phenylbutyrate was replaced with (S)-N-(4-(1H-pyrazole-4-yl)phenyl)-3-amino-2-phenylpropanamide dihydrochloride. [Table 20]

[0161] 10-1-2. Method for exposure analysis of posterior chamber tissue Regarding the method for the exposure analysis test of posterior chamber tissue, all other procedures were the same as those described in Example 1 above, except that the timing of animal administration was adjusted to 0.5 and 3 hours.

[0162] 10-2. Experimental Results The experimental results are shown in Table 21 below. [Table 21]

[0163] According to Tables 20 and 21, when an eye drop containing (S)-N-(4-(1H-pyrazole-4-yl)phenyl)-3-amino-2-phenylpropanamide dihydrochloride also contained 400 mg / mL of 2-hydroxypropyl-β-cyclodextrin and 20 mg / mL of caffeine, the maximum concentration of (S)-N-(4-(1H-pyrazole-4-yl)phenyl)-3-amino-2-phenylpropanamide dihydrochloride in retinal tissue after administration reached 71.5 ng / g, and the maximum concentration in choroidal tissue reached 78.3 ng / g.

[0164] The above experimental data demonstrates that eye drops containing 2-hydroxypropyl-β-cyclodextrin and caffeine can effectively deliver (S)-N-(4-(1H-pyrazole-4-yl)phenyl)-3-amino-2-phenylpropanamide dihydrochloride to the posterior chamber tissue.

[0165] 11. Example 11 Verification of the therapeutic effect of eye drops containing sodium phenylbutyrate (SPB) in animal disease models induced by sodium iodate (NaIO3).

[0166] 11-1. Experimental Method 11-1-1. Preparation of eye drops containing sodium phenylbutyrate An eye drop containing sodium phenylbutyrate was prepared by compounding 2-hydroxypropyl-β-cyclodextrin (HPβCD), caffeine, hydroxypropyl methylcellulose (HPMC), and sodium phenylbutyrate at room temperature, according to the respective concentrations of each compound shown in Table 22 below. The procedure for preparing the eye drop can be carried out by referring to the procedure described in Example 1 above. [Table 22]

[0167] 11-1-2. Structure and analysis of animal disease models induced by NaIO3 Animal disease models induced by sodium iodate (NaIO3) were found to be suitable as models for age-related macular degeneration (AMD).

[0168] Pigmented rabbits were sedated and anesthetized by intramuscular injection of a mixed solution of Rompun and Zoletil 50, followed by topical anesthesia and pupil dilation using 0.5% Alcaine and Mydrin-P eye drops.

[0169] Next, please refer to Figure 1A. Figure 1A shows the experimental procedure for an animal disease model induced by NaIO3. First, colored rabbits were administered 8 mg / mL of NaIO3 (50 μL) as a single intravitreal injection using a 29G needle to induce retinal degeneration. Simultaneously, an antibiotic ointment was applied to reduce the risk of infection associated with the intravitreal injection. During the NaIO3-induced retinal degeneration period, previously prepared eye drops containing sodium phenylbutyrate (SPB) were administered four times a day. Seven days after administration, the experimental animals were sacrificed and eye samples were collected.

[0170] Subsequently, visual tissue was embedded in paraffin and sectioned, and the sections were subjected to hematoxylin and eosin staining (H&E). Finally, based on the results of H&E staining, the change in the thickness of the outer nuclear layer (ONL) of the retina, which contains the nuclei of retinal photoreceptor cells consisting of rod cells and cone cells, in rabbit retinal tissue sections was evaluated as an indicator of therapeutic effect.

[0171] 11-2. Experimental Results The experimental results are shown in Figures 1B and 1C.

[0172] As shown in Figures 1B and 1C, the prepared eye drops containing sodium phenylbutyrate (SPB) effectively delivered sodium phenylbutyrate (SPB) to the retinal tissue.

[0173] Furthermore, compared to the untreated group, the prepared eye drops containing sodium phenylbutyrate (SPB) effectively protected the thickness of the outer granular layer (ONL) of the retina under NaIO3-induced retinal degeneration. In other words, the prepared eye drops containing sodium phenylbutyrate (SPB) showed a protective effect in the outer granular layer of the retina.

[0174] Furthermore, eye drops prepared with low, medium, and high doses of sodium phenylbutyrate (SPB) achieved improvement efficiencies of 8.92%, 42.84%, and 75.53% for retinal degeneration, respectively, demonstrating dose-dependent therapeutic effects.

[0175] 12. Example 12 Verification of the therapeutic effect of eye drops containing sodium phenylbutyrate (SPB) in an animal disease model induced by hydroquinone (HQ).

[0176] 12-1. Experimental Method 12-1-1. Preparation of eye drops containing sodium phenylbutyrate As shown in Table 23 below, 2-hydroxypropyl-β-cyclodextrin (HPβCD), caffeine, hydroxypropyl methylcellulose (HPMC), and sodium phenylbutyrate were combined at room temperature according to their respective concentrations to prepare an eye drop containing sodium phenylbutyrate. The procedure for preparing the eye drop can be carried out by referring to the procedure described in Example 1 above. [Table 23]

[0177] 12-1-2. Structure and Analysis of Hydroquinone (HQ)-Induced Animal Disease Models The hydroquinone (HQ)-induced animal disease model was found to be suitable as a model for age-related macular degeneration (AMD).

[0178] C57BL / 6 mice were anesthetized by intraperitoneal injection of a mixture of Zoletil 50 and xylazine, followed by topical anesthesia by dropping 5 μL of Alicaine into both eyes of each mouse.

[0179] Next, please refer to Figure 2A. Figure 2A shows the experimental procedure for an animal disease model induced by hydroquinone (HQ).

[0180] First, a disease animal model was established by administering 75 mM hydroquinone (HQ) (10 μL) per eye subconjunctivally three times a week using a needle of 30G or larger to C57BL / 6 mice. After observing the induction of hydroquinone (HQ) and lesion formation, a previously prepared eye drop containing sodium phenylbutyrate (SPB) was administered as a single dose of 5 μL per eye for a period of three weeks, at a frequency of four or eight times a day.

[0181] On days 0, 14, and 35, electroretinogram signals (wave a and wave b) were measured in the experimental animals. In addition, eye samples were collected after sacrificing the animals at the end of the experiment. Finally, the expression of clusterin, a biomarker for drusen, was evaluated and quantitatively analyzed based on the results of immunofluorescence staining (IF).

[0182] The results are shown in Figures 2B and 2C (administration of 5 μL per eye of a previously prepared eye drop containing sodium phenylbutyrate (SPB) four times a day), and Figures 3A to 3C (administration of 5 μL per eye of a previously prepared eye drop containing sodium phenylbutyrate (SPB) eight times a day).

[0183] Figure 2B shows the results of immunofluorescence staining of mouse samples in an animal disease model experiment induced by hydroquinone (HQ), with arrows indicating the expression regions of clatherin. Figure 2C shows the quantified expression levels of clatherin in mouse samples in an animal disease model experiment induced by hydroquinone (HQ).

[0184] As shown in Figures 2B and 2C, compared to the untreated group, the prepared eye drops containing sodium phenylbutyrate (SPB) at concentrations exceeding 30 mg / mL effectively reduced clathelin expression under the subretinal pigment epithelium (RPE) in a hydroquinone (HQ)-induced retinal degeneration, demonstrating a dose-dependent inhibitory effect.

[0185] Figures 3A to 3C show the electroretinogram signals (wave a and wave b) of experimental animals on day 0, day 14, and day 35, respectively.

[0186] As shown in the electroretinograms in Figures 3A-3C, compared to the untreated group, the prepared eye drops containing sodium phenylbutyrate (SPB) at a concentration of 60 mg / mL or higher effectively restored hydroquinone (HQ)-induced retinal dysfunction, and the therapeutic effect showed a dose-dependent tendency.

[0187] While the disclosure has been described above with reference to preferred embodiments, it is not intended to be limited thereto. Those skilled in the art can make various modifications and refinements without departing from the spirit and scope of the disclosure. Therefore, the scope of protection of the disclosure should be defined by the appended claims. [Explanation of symbols]

[0188] none

[0189] [Deposit of biomaterials] none

Claims

1. An eye drop platform for delivering an active ingredient to the anterior chamber tissue and / or posterior chamber tissue of the eye, wherein the eye drop platform is A delivery composition, Cyclodextrin and / or its derivatives, A delivery composition containing caffeine, and A pharmaceutically acceptable solvent for dissolving the delivery composition and forming a solution, the solution comprising a pharmaceutically acceptable solvent that functions as an eye drop platform for delivering the active ingredient to the anterior and / or posterior chamber tissue of the eye, The concentration of the cyclodextrin and / or its derivative in the aforementioned solution is in the range of 5 to 500 mg / mL. The concentration of caffeine in the aforementioned solution is in the range of 0.5 to 50 mg / mL. The aforementioned active ingredient is a hydrophilic compound having water solubility in a concentration of more than 1 mg / mL, comprising an eye drop platform.

2. The cyclodextrin mentioned above is α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, and An eye drop platform for delivering the active ingredient according to claim 1, comprising at least one δ-cyclodextrin, to the anterior and / or posterior chamber tissue of the eye.

3. The aforementioned derivatives of cyclodextrin are Hydroxypropyl (hydroxypropyl) modified cyclodextrin, succinyl-modified cyclodextrins, and It contains at least one of the methyl-modified cyclodextrins, The hydroxypropyl-modified cyclodextrin is, (2-hydroxypropyl)-β-cyclodextrin; and / or An eye drop platform for delivery to the anterior and / or posterior chamber tissue of the eye, comprising the active ingredient according to claim 1, wherein the active ingredient comprises (2-hydroxypropyl)-γ-cyclodextrin.

4. The delivery composition further comprises a water-soluble polymer, the concentration of the water-soluble polymer in the solution being in the range of 0.5 to 20 mg / mL. The aforementioned water-soluble polymer is Hydroxypropyl methylcellulose, Hydroxypropylcellulose, Carboxymethylcellulose, Polyvinylpyrrolidone, Polyvinyl alcohol, and An eye drop platform for delivering the active ingredient according to claim 1 to the anterior and / or posterior chamber tissue of the eye, comprising at least one of poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) triblock copolymer.

5. An eye drop for improving exposure of the active ingredient in the anterior chamber tissue and / or posterior chamber tissue of the eye, wherein the eye drop is A delivery composition, Cyclodextrin and / or its derivatives, A delivery composition containing caffeine, and A pharmaceutically acceptable solvent for dissolving the delivery composition and forming a solution, the solution comprising a pharmaceutically acceptable solvent that functions as an eye drop for improving exposure of the active ingredient to the anterior and / or posterior chamber tissue of the eye, The concentration of the cyclodextrin and / or its derivative in the eye drops is in the range of 5 to 500 mg / mL. The concentration of caffeine in the eye drops is in the range of 0.5 to 50 mg / mL. The aforementioned active ingredient is a hydrophilic compound having water solubility in a concentration of more than 1 mg / mL, in an eye drop preparation.

6. The cyclodextrin mentioned above is α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, and An eye drop for improving exposure of the active ingredient in the anterior chamber and / or posterior chamber tissue of the eye, according to claim 5, comprising at least one of δ-cyclodextrins.

7. The aforementioned derivatives of cyclodextrin are Hydroxypropyl-modified cyclodextrin, succinyl-modified cyclodextrin, and It contains at least one of the methyl-modified cyclodextrins, The hydroxypropyl-modified cyclodextrin is, (2-hydroxypropyl)-β-cyclodextrin; and / or An eye drop for improving exposure of the active ingredient in the anterior chamber and / or posterior chamber tissue of the eye, according to claim 5, comprising (2-hydroxypropyl)-γ-cyclodextrin.

8. The delivery composition further comprises a water-soluble polymer, the concentration of the water-soluble polymer in the solution being in the range of 0.5 to 20 mg / mL. The aforementioned water-soluble polymer is Hydroxypropyl methylcellulose, Hydroxypropylcellulose, Carboxymethylcellulose, Polyvinylpyrrolidone, Polyvinyl alcohol, and An eye drop for improving exposure of the active ingredient in the anterior chamber and / or posterior chamber tissue of the eye, according to claim 5, comprising at least one of poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) triblock copolymer.

9. A compound formulation, wherein the compound formulation is An active ingredient, wherein the active ingredient is a hydrophilic compound having water solubility in a concentration of more than 1 mg / mL; A delivery composition, Cyclodextrin and / or its derivatives, A delivery composition containing caffeine; and A pharmaceutically acceptable solvent for dissolving the active ingredient and the delivery composition to form a solution, wherein the solution functions as the compound formulation, comprising: The concentration of the active ingredient in the solution is in the range of 0.05 to 500 mg / mL. The concentration of the cyclodextrin and / or its derivative in the aforementioned solution is in the range of 5 to 500 mg / mL. The concentration of caffeine in the aforementioned solution is in the range of 0.5 to 50 mg / mL. The aforementioned compound formulation is an eye drop formulation.

10. The aforementioned active ingredient is Drugs with neuroprotective properties, Complement inhibitors, AMP-activated protein kinase (AMPK) activator, and The compound formulation according to claim 9, comprising at least one Rho-associated coiled-coil kinase inhibitor.

11. The drug having the neuroprotective function is Sodium phenylbutyrate (SPB), dexmedetomidine HCl, and The compound formulation according to claim 10, comprising tauro-ursodesoxycholic acid (TUDCA).

12. The composite formulation according to claim 10, wherein the complement inhibitor comprises iptacopan (LNP-023) and / or nafamostat mesylate (FUT-175).

13. The compound formulation according to claim 10, wherein the AMP-activated protein kinase activator comprises a biguanide agent, and the biguanide agent comprises metformin HCl.

14. The composite formulation according to claim 10, wherein the Rho-related coiled-coil kinase inhibitor comprises (S)-N-(4-(1H-pyrazol-4-yl)phenyl)-3-amino-2-phenylpropanamide dihydrochloride (ITRI-E-(S)4046).

15. The cyclodextrin mentioned above is α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, and The compound formulation according to claim 9, comprising at least one of δ-cyclodextrins.

16. The aforementioned derivatives of cyclodextrin are Hydroxypropyl-modified cyclodextrin, succinyl-modified cyclodextrin, and It contains at least one of the methyl-modified cyclodextrins, The hydroxypropyl-modified cyclodextrin is, (2-hydroxypropyl)-β-cyclodextrin; and / or The compound formulation according to claim 9, comprising (2-hydroxypropyl)-γ-cyclodextrin.

17. The delivery composition further comprises a water-soluble polymer, the concentration of the water-soluble polymer in the solution being in the range of 0.5 to 20 mg / mL. The aforementioned water-soluble polymer is Hydroxypropyl methylcellulose, Hydroxypropylcellulose, Carboxymethylcellulose, Polyvinylpyrrolidone, Polyvinyl alcohol, and The composite formulation according to claim 9, comprising at least one of poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) triblock copolymer.

18. An eye drop for treating and / or preventing anterior chamber disease and / or posterior chamber disease of the eye, comprising the compound formulation described in claim 9.

19. The aforementioned active ingredient is Drugs with neuroprotective properties, Complement inhibitors, AMP-activated protein kinase (AMPK) activator, and An eye drop for treating and / or preventing anterior chamber and / or posterior chamber disease of the eye, according to claim 18, comprising at least one Rho-associated coiled-coil kinase inhibitor.

20. The drug having the neuroprotective function is Sodium phenylbutyrate (SPB), dexmedetomidine HCl, and An eye drop for treating and / or preventing anterior chamber and / or posterior chamber diseases of the eye, according to claim 19, comprising tauro-ursodesoxycholic acid (TUDCA).

21. The complement inhibitor comprises iptacopan (LNP-023) and / or nafamostat mesylate (FUT-175), as described in claim 19, for the treatment and / or prevention of anterior chamber and / or posterior chamber diseases of the eye.

22. An eye drop for treating and / or preventing anterior chamber and / or posterior chamber diseases of the eye, according to claim 19, wherein the AMP-activated protein kinase activator comprises a biguanide agent, and the biguanide agent comprises metformin HCl.

23. The Rho-related coiled-coil kinase inhibitor comprises (S)-N-(4-(1H-pyrazole-4-yl)phenyl)-3-amino-2-phenylpropanamide dihydrochloride (ITRI-E-(S)4046), as described in claim 19, for the treatment and / or prevention of anterior chamber and / or posterior chamber diseases of the eye.

24. The cyclodextrin mentioned above is α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, and An eye drop for treating and / or preventing anterior chamber and / or posterior chamber diseases of the eye, according to claim 18, comprising at least one of δ-cyclodextrins.

25. The aforementioned derivatives of cyclodextrin are Hydroxypropyl-modified cyclodextrin, succinyl-modified cyclodextrin, and It contains at least one of the methyl-modified cyclodextrins, The hydroxypropyl-modified cyclodextrin is, (2-hydroxypropyl)-β-cyclodextrin; and / or An eye drop for treating and / or preventing anterior chamber and / or posterior chamber diseases of the eye, according to claim 18, comprising (2-hydroxypropyl)-γ-cyclodextrin.

26. The delivery composition further comprises a water-soluble polymer, the concentration of the water-soluble polymer in the solution being in the range of 0.5 to 20 mg / mL. The aforementioned water-soluble polymer is Hydroxypropyl methylcellulose, Hydroxypropylcellulose, Carboxymethylcellulose, Polyvinylpyrrolidone, Polyvinyl alcohol, and An eye drop for treating and / or preventing anterior chamber and / or posterior chamber diseases of the eye, according to claim 18, comprising at least one of poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) triblock copolymer.

27. The aforementioned anterior chamber disease is, Glaucoma Anterior uveitis Cataracts, and An eye drop for treating and / or preventing anterior chamber and / or posterior chamber diseases of the eye, according to claim 18, comprising at least one of dry eye.

28. The aforementioned posterior chamber disease is, Age-related macular degeneration (AMD), Diabetic macular edema, and An eye drop for treating and / or preventing anterior chamber and / or posterior chamber disease of the eye, according to claim 18, comprising at least one of diabetic retinopathy.

29. An eye drop for treating and / or preventing age-related macular degeneration, wherein the eye drop is It is a compound formulation, Sodium phenylbutyrate and A delivery composition, (2-hydroxypropyl)-β-cyclodextrin and / or (2-hydroxypropyl)-γ-cyclodextrin, A delivery composition containing caffeine, and A compound formulation comprising a pharmaceutically acceptable solvent for dissolving the sodium phenylbutyrate and the delivery composition to form a solution, wherein the solution functions as the compound formulation, The concentration of sodium phenylbutyrate in the aforementioned solution is in the range of 0.05 to 150 mg / mL. The concentration of the (2-hydroxypropyl)-β-cyclodextrin and / or the (2-hydroxypropyl)-γ-cyclodextrin in the aforementioned solution is in the range of 5 to 500 mg / mL. An eye drop in which the concentration of caffeine in the solution is in the range of 0.5 to 50 mg / mL.

30. The delivery composition further comprises hydroxypropyl methylcellulose, the concentration of the hydroxypropyl methylcellulose in the solution being in the range of 0.5 to 20 mg / mL, as described in claim 29, for the treatment and / or prevention of age-related macular degeneration.

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