Application of steroid compound in preparation of medicine for preventing and / or treating presbyopia

Abstract

The invention provides an application of a steroid compound in preparation of a medicine for preventing and / or treating presbyopia. The steroid compound provided by the invention is shown as a formula (I), has treatment, alleviation and prevention effects on presbyopia, and can greatly relieve and / or cure presbyopia and improve vision definition. # imgabs0 #

Description

Application of steroid compounds in the preparation of drugs for preventing and / or treating presbyopia Technical Field

[0001] The present invention belongs to the technical field of chemical medicine and relates to the use of a steroid compound in preparing a medicine for preventing and / or treating presbyopia. Background Art

[0002] Presbyopia, also known as old eyesight, is a physiological condition that occurs with aging, resulting in a hardening of the lens and a decline in the eye's ability to accommodate vision. Initial symptoms include the need to maintain a certain distance to see clearly, and difficulty reading at close range in low light. These symptoms worsen with age. Besides age, the development of presbyopia is also associated with factors such as refractive error, physical fitness, and medications.

[0003] Currently, the main means of treating presbyopia include wearing frame reading glasses, wearing contact lenses, corneal refractive surgery, scleral refractive surgery, and lens refractive surgery. In October 2021, the U.S. Food and Drug Administration (FDA) approved Allergan's ophthalmic drug Vuity (pilocarpine, 1.25% eye drops), a subsidiary of AbbVie, to treat presbyopia. Vuity is a topical medication that is dropped into both eyes once a day. It takes effect 15 minutes after being dropped into the eyes, and the effect is long-lasting. Patients can read without wearing glasses. It is the first eye drop specifically used to treat presbyopia, but it can only relieve its symptoms but cannot completely cure presbyopia. Therefore, there is an urgent need for other drugs that can prevent, relieve or treat presbyopia in clinical practice.

[0004] Summary of the Invention

[0005] In view of the shortcomings of the existing technology, the purpose of the present invention is to provide a steroid compound for use in the preparation of a drug for preventing and / or treating presbyopia. The steroid compound provided by the present invention can have a good therapeutic, alleviating and preventive effect on presbyopia, can greatly reduce and / or cure presbyopia, and improve visual clarity.

[0006] To achieve this object, the present invention adopts the following technical solutions:

[0007] In a first aspect, the present invention provides a use of a steroidal compound in the preparation of a medicament for preventing and / or treating presbyopia, wherein the steroidal compound is a compound having a structure as shown in Formula I, or a stereoisomer, tautomer, nitrogen oxide, solvate, metabolite, pharmaceutically acceptable salt, or prodrug of the compound having a structure as shown in Formula I;

[0008] wherein R is H, D (deuterium), alkyl, sulfate, phosphate, alkylsilyl, benzyl, or -C(O)-X;

[0009] X is selected from aryl, heteroaryl, cycloalkyl, heterocyclyl, heteroalkyl or alkyl;

[0010] The aryl, heteroaryl, cycloalkyl, heterocyclyl, heteroalkyl, alkylsilyl and alkyl groups in R and X are optionally substituted with 1, 2, 3 or 4 substituents which are the same or different;

[0011] The substituent is selected from D, halogen, hydroxyl, thiol, amino, cyano, nitro, carboxyl, alkylcarbonyl, alkyl, haloalkyl, cycloalkyl, heterocyclic, aryl, arylalkyl, heteroaryl, carboxyl, R 1 R 2 NC(=O)- or R 1 R 2 NC(=NH)-NR 3 -;

[0012] R 1 、R 2 and R 3 Each is independently selected from -H, -D or alkyl.

[0013] In some embodiments, the steroidal compound is a compound having a structure as shown in Formula II, or a stereoisomer, tautomer, nitrogen oxide, solvate, metabolite, pharmaceutically acceptable salt or prodrug of a compound having a structure as shown in Formula II;

[0014] wherein R is defined as in formula (I).

[0015] In some embodiments, R is H, D, C 1-6 Alkyl, sulfate, phosphate, C 1-6 Alkylsilyl, benzyl or -C(O)-X.

[0016] In some embodiments, X is selected from C 6-10 Aryl, C 2-9 Heteroaryl, C 3-8 Cycloalkyl, C 2-10 Heterocyclic group, C 1-6 Heteroalkyl or C 1-6 alkyl.

[0017] In some embodiments, the C 6-10 Aryl, C 2-9 Heteroaryl, C 3-8 Cycloalkyl, C 2-10 Heterocyclic group, C 1-6 Heteroalkyl, C 1-6 Alkylsilyl or C1-6 The alkyl group is optionally substituted with 1, 2, 3 or 4 substituents which may be the same or different.

[0018] In some embodiments, the substituent is selected from D, halogen, hydroxyl, thiol, amino, cyano, nitro, carboxyl, C 1-6 Alkylcarbonyl, C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 3-8 Cycloalkyl, C 2-10 Heterocyclic group, C 6-10 Aryl, C 6-10 Aryl C 1-6 Alkyl, C 2-9 Heteroaryl, carboxyl (e.g. -COOH), R 1 R 2 NC(=O)- or R 1 R 2 NC(=NH)-NR 3 -.

[0019] In some embodiments, R 1 、R 2 and R 3 Each independently selected from -H, -D or C 1-6 alkyl.

[0020] In some embodiments, X is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, hydroxymethyl, hydroxyethyl, mercaptomethyl, mercaptoethyl, aminomethyl, aminoethyl, aminopropyl, phenylmethyl, phenylethyl, imidazolylmethyl, carboxymethyl, carboxyethyl, methylthiomethyl, methylthioethyl, phenyl, naphthyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl, dihydrothiophenyl, 1,3-dioxolane, dithiocyclopentyl, tetrahydropyranyl, dihydropyranyl, 2H-pyranyl, 4H-pyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, dioxanyl, dithianyl, thioxanyl, homopiperazinyl, homopiperidinyl, oxepanyl, thiepanyl, oxazepinyl, diazepinyl, thiazepinyl, indolyl, 1,2,3,4-tetrahydroquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl, furanyl, imidazolyl, 3-isoxazolyl, isoxazolyl, oxazolyl, pyrrolyl, pyridinyl, pyrimidinyl, pyridazinyl, thiazolyl, tetrazolyl, triazolyl, 2-thienyl, 3-thienyl, pyrazolyl, isothiazolyl, 1,2,3-oxadiazolyl, 1,2,5-oxadiazolyl, 1,2,4-oxadiazolyl, 1 ,2,3-triazolyl, 1,2,3-thiodiazolyl, 1,3,4-thiodiazolyl, 1,2,5-thiodiazolyl, pyrazinyl, 1,3,5-triazinyl, benzimidazolyl, benzofuranyl, benzothiophenyl, indolyl, purinyl, quinolyl, isoquinolyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-b]pyridazinyl, [1,2,4]triazolo[4,3-b]pyridazinyl, [1,2,4]triazolo[1,5-a]pyrimidinyl, [1,2,4]triazolo[1,5-a]pyridinyl, C with H2NC(=O)-substituent 1-3 Alkyl or C with H2NC(=NH)-NH-substituent 1-3 alkyl.

[0021] In some embodiments, the substituents in R and X are selected from -H, -D, halogen, hydroxy, amino, cyano, nitro, carboxyl, C 1-6 Alkylcarbonyl, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-8 Cycloalkyl, C 2-9 Heterocyclic group, C 6-10 Aryl or C 2-9 Heteroaryl.

[0022] In other embodiments, the substituents in R and X are selected from -H, -D, -F, -Cl, -Br, hydroxyl, amino, cyano, carboxyl, formyl, acetyl, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl, trifluoromethyl, difluoromethyl, phenyl, naphthyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl, dihydrothiophenyl, 1,3-dioxolane, disulfide pentyl, tetrahydropyranyl, dihydropyranyl, 2H-pyranyl, 4H-pyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, dioxanyl, dithianyl, thioxanyl, homopiperazinyl, homopiperidinyl, oxepanyl, thiepanyl, oxazepinyl, diazepinyl, thiazepinyl, indolinyl, 1,2,3,4-tetrahydroquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl, furanyl, imidazolyl, 3-isoxazole yl, isoxazolyl, oxazolyl, pyrrolyl, pyridyl, pyrimidinyl, pyridazinyl, thiazolyl, tetrazolyl, triazolyl, 2-thienyl, 3-thienyl, pyrazolyl, isothiazolyl, 1,2,3-oxadiazolyl, 1,2,5-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,3-triazolyl, 1,2,3-thiodiazolyl, 1,3,4-thiodiazolyl, 1,2,5-thiodiazolyl, pyrazinyl, 1,3,5-triazinyl, benzimidazolyl, benzofuranyl, benzothiophenyl, indolyl, purinyl, quinolinyl, isoquinolinyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-b]pyridazinyl, [1,2,4]triazolo[4,3-b]pyridazinyl, [1,2,4]triazolo[1,5-a]pyrimidinyl or [1,2,4]triazolo[1,5-a]pyridinyl.

[0023] As a specific embodiment of the present invention, X is selected from any of the following groups:

[0024] As a specific embodiment of the present invention, the compound represented by the structure of Formula I or II is selected from any one of the following compounds:

[0025] The steroid compound provided by the present invention can be used as an unprocessed chemical drug for treatment, or can be provided as an active ingredient of a pharmaceutical composition.

[0026] In a second aspect, the present invention provides the use of a composition in the preparation of a medicament for preventing and / or treating presbyopia, wherein the composition comprises the steroid compound described in the first aspect, and one or more pharmaceutically acceptable carriers, excipients, diluents, adjuvants or vehicles.

[0027] Examples of pharmaceutically acceptable carriers include, but are not limited to, ion exchangers; aluminum; aluminum stearate; lecithin; serum proteins, such as human serum albumin; buffer substances, such as phosphates; glycine; sorbic acid; potassium sorbate; partial glyceride mixtures of saturated vegetable fatty acids; water; salts; electrolytes, such as protamine sulfate; disodium hydrogen phosphate; potassium hydrogen phosphate; sodium chloride; zinc salts; colloidal silicon; magnesium trisilicate; polyvinyl pyrrolidone; polyacrylates; waxes; polyethylene-polyoxypropylene-blocked polymers; lanolin; sugars, such as lactose, glucose, and sucrose; starches, such as corn starch and potato starch; and cellulose and its derivatives, such as carboxymethyl cellulose. sodium cellulose, ethylcellulose and cellulose acetate; gum powder; malt; gelatin; talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; glycol compounds such as propylene glycol and polyethylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffers such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethanol, phosphate buffered solution, and other non-toxic suitable lubricants such as sodium lauryl sulfate and magnesium stearate, colorants, release agents, coatings, sweeteners, flavorings and fragrances, preservatives and antioxidants.

[0028] In some embodiments, the composition comprises: a steroidal compound according to the present invention, hypromellose, poloxamer 407, poloxamer 188, and water.

[0029] In some embodiments, the composition comprises: 10-40 parts by mass of the steroid compound of the present invention, 110-120 parts by mass of hypromellose, 2050-2060 parts by mass of poloxamer 407, 160-170 parts by mass of poloxamer 188 and 10,000 parts by mass of water.

[0030] In some embodiments, the composition may be eye drops. The eye drops may be suspension eye drops. In some embodiments of the present invention, the eye drops may have a volume of 10 mL.

[0031] In a third aspect, the present invention provides a method for preventing and / or treating presbyopia, comprising administering the steroid compound of the first aspect or the composition of the second aspect to a subject in need thereof.

[0032] Compared with the prior art, the present invention has the following beneficial effects:

[0033] The present invention has found that the steroid compound provided by the present invention can improve the elasticity of the lens and enhance the patient's near vision, and can be used to prevent, treat, cure or alleviate the patient's presbyopia, with minimal or no side effects. DETAILED DESCRIPTION

[0034] The technical solution of the present invention is further described below by way of specific embodiments. It should be understood by those skilled in the art that the specific embodiments are merely to help understand the present invention and should not be regarded as specific limitations of the present invention.

[0035] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0036] As used herein, "stereoisomers" refer to compounds that have the same chemical structure but differ in the spatial arrangement of atoms or groups. Stereoisomers include enantiomers, diastereomers, conformers (rotamers), geometric isomers (cis / trans) isomers, atropisomers, and the like.

[0037] Depending on the choice of starting materials and process, the compounds of the present invention may exist as one of the possible isomers or as a mixture thereof, such as a racemate or a mixture of diastereoisomers (depending on the number of asymmetric carbon atoms). Optically active (R)- or (S)-isomers can be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques. If the compound contains a double bond, the substituents may be in the E or Z configuration; if the compound contains a disubstituted cycloalkyl group, the cycloalkyl substituents may be in the cis or trans configuration.

[0038] Any resulting mixture of stereoisomers can be separated into the pure or substantially pure geometric isomers, enantiomers, and diastereomers on the basis of the differences in the constituent physicochemical properties, for example, by chromatography and / or fractional crystallization.

[0039] Unless otherwise indicated, the structural formulae described herein include all isomeric forms (e.g., enantiomers, diastereomers, and geometric isomers (or conformers): for example, R and S configurations containing asymmetric centers, (Z) and (E) isomers of double bonds, and (Z) and (E) conformers. Therefore, single stereochemical isomers of the compounds of the present invention or mixtures of their enantiomers, diastereomers, or geometric isomers (or conformers) are within the scope of the present invention.

[0040] The term "prodrug" as used herein refers to a compound that is converted in vivo into a compound represented by Formula I. Such conversion is affected by hydrolysis of the prodrug in the blood or by enzymatic conversion to the parent structure in the blood or tissues. The prodrug compounds of the present invention may be esters. In the prior art, esters that can be used as prodrugs include phenyl esters, aliphatic (C 1-24 ) esters, acyloxymethyl esters, carbonates, carbamates, and amino acid esters. For example, a compound of the present invention containing a hydroxyl group can be acylated to produce a prodrug form of the compound. Other prodrug forms include phosphate esters, such as these phosphate ester compounds, which are obtained by phosphorylating a hydroxyl group on the parent compound. For a complete discussion of prodrugs, see T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems, Vol. 14 of the ACSSymposium Series, Edward B. Roche, ed., Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press, 1987, J. Rautio et al, Prodrugs: Design and Clinical Applications, Nature Review Drug Discovery, 2008, 7, 255-270, and SJ Hecker et al, Prodrugs of Phosphates and Phosphonates, Journal of Medicinal Chemistry, 2008, 51, 2328-2345.

[0041] Any racemate of the resulting final product or intermediate can be resolved into its optical antipodes by methods familiar to those skilled in the art using known methods, such as by separation of its diastereomeric salts obtained. Racemic products can also be separated by chiral chromatography, such as high performance liquid chromatography (HPLC) using a chiral adsorbent. In particular, enantiomers can be prepared by asymmetric synthesis, for example, see Jacques, et al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981); Principles of Asymmetric Synthesis (2nd Ed. Robert E. Gawley, Jeffrey Aubé, Elsevier, Oxford, UK, 2012); Eliel, EL Stereochemistry of Carbon Compounds (McGraw-Hill, NY, 1962); Wilen, SH Tables of Resolving Agents and Optical Resolutions p. 268 (EL Eliel, Ed., Univ. of Notre Dame Press, Notre Dame, IN 1972); Chiral Separation Techniques: A Practical Approach (Subramanian, G. Ed., Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany, 2007).

[0042] The term "tautomer" or "tautomeric form" refers to structural isomers with different energies that are interconvertible via a low energy barrier. If tautomerism is possible (such as in solution), a chemical equilibrium of the tautomers can be achieved. For example, proton tautomers (also known as prototropic tautomers) include interconversions via migration of a proton, such as keto-enol isomerizations and imine-enamine isomerizations. Valence tautomers include interconversions via reorganization of some of the bonding electrons. A specific example of keto-enol tautomerism is the interconversion of pentane-2,4-dione and 4-hydroxypent-3-en-2-one tautomers. Another example of tautomerism is phenol-keto tautomerism. A specific example of phenol-keto tautomerism is the interconversion of pyridin-4-ol and pyridin-4(1H)-one tautomers. Unless otherwise indicated, all tautomeric forms of the compounds of the present invention are within the scope of the present invention.

[0043] The salts mentioned in the present invention are pharmaceutically acceptable salts, wherein "pharmaceutically acceptable salts" are well known in the art, as described in the literature: Berge et al., describe pharmaceutically acceptable salts in detail in J. Pharmacol Sci, 1997, 66, 1-19. Non-limiting examples of pharmaceutically acceptable salts include inorganic acid salts formed by reaction with an amino group, such as hydrochlorides, hydrobromides, phosphates, metaphosphates, sulfates, sulfites, nitrates, and perchlorates, and organic acid salts, such as carboxylates, sulfonates, sulfinates, and thiocarboxylates, specifically, but not limited to, methanesulfonates, ethanesulfonates, formates, acetates, succinates, benzoates, succinates, pamoates, salicylates, galactarates, glucoheptanoates, mandelates, 1,2-ethanedisulfonates, 2-naphthalenesulfonates, carbonates, trifluoroacetates, glycolates, isethionates, oxalates, maleates, tartrates, citrates, succinates, malonates, benzenesulfonates, p-toluenesulfonates, malates, fumarates, lactates, lactobionates, or oxalates, or such salts may be obtained by other methods described in the literature, such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, cyclopentylpropionate, digluconate, dodecylsulfate, ethanesulfonate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, laurate, lauryl sulfate, nicotinate, nitrate, oleate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, picrate, pivalate, propionate, stearate, thiocyanate, undecanoate, valerate, etc. In addition, pharmaceutically acceptable salts also include salts obtained with appropriate bases, such as alkali metal, alkaline earth metal, ammonium and N + (C 1-4 The present invention also contemplates quaternary ammonium salts formed by any compound containing a N group. Water-soluble or oil-soluble or dispersible products can be obtained by quaternization. Alkali metal or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Pharmaceutically acceptable salts further include appropriate, non-toxic ammonium, quaternary ammonium salts and amine cations formed by counter ions, such as halides, carboxylates, sulfates, phosphates, nitrates, C 1-8 Sulfonates and aromatic sulfonates.

[0044] Pharmaceutically acceptable salts can be formed with inorganic and organic acids, for example, acetate, aspartate, benzoate, benzenesulfonate, bromide / hydrobromide, bicarbonate / carbonate, bisulfate / sulfate, camphorsulfonate, chloride / hydrochloride, chlorophylline, citrate, edisylate, fumarate, glucoheptonate, gluconate, glucuronate, hippurate, hydroiodide / iodide, isethionate, lactate, lactobionate, lauryl sulfate, malate, maleate, malonate, mandelate, methanesulfonate, methylsulfate, naphthoate, naphthylate, nicotinate, nitrate, octadecanoate, oleate, oxalate, palmitate, pamoate, phosphate / hydrogenphosphate / dihydrogenphosphate, polygalactonate, propionate, stearate, succinate, sulfosalicylate, tartrate, toluenesulfonate, and trifluoroacetate.

[0045] Inorganic acids from which salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like.

[0046] Organic acids from which salts can be derived include, for example, acetic acid, propionic acid, glycolic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, sulfosalicylic acid, and the like.

[0047] As used herein, a "solvate" refers to an association formed between one or more solvent molecules and a compound of the present invention. Solvents that form solvates include, but are not limited to, water, isopropanol, ethanol, methanol, dimethyl sulfoxide, ethyl acetate, acetic acid, and aminoethanol. The term "hydrate" refers to an association formed when the solvent molecule is water.

[0048] A "pharmaceutical composition" refers to a mixture of one or more compounds, salts, or physiologically / pharmaceutically acceptable salts or prodrugs thereof described herein with other chemical components, such as physiologically / pharmaceutically acceptable carriers or excipients. The purpose of a pharmaceutical composition is to facilitate administration of the compound to an organism.

[0049] As used herein, the term "treating" any disease or condition, in some embodiments, refers to ameliorating the disease or condition (i.e., slowing or arresting or alleviating the development of the disease or at least one clinical symptom thereof). In other embodiments, "treating" refers to alleviating or improving at least one physical parameter, including physical parameters that may not be perceived by the patient. In other embodiments, "treating" refers to regulating the disease or condition physically (e.g., stabilizing a perceptible symptom) or physiologically (e.g., stabilizing a physical parameter), or both. In other embodiments, "treating" refers to preventing or delaying the onset, occurrence, or worsening of a disease or condition.

[0050] As used herein, the term "alkyl" refers to a saturated, linear or branched, monovalent hydrocarbon radical of 1 to 20 carbon atoms, or 1 to 10 carbon atoms, or 1 to 8 carbon atoms, or 1 to 6 carbon atoms, or 1 to 4 carbon atoms, or 1 to 3 carbon atoms, wherein the alkyl radical may be independently and optionally substituted with one or more substituents described herein. Examples of alkyl radicals include, but are not limited to, methyl (Me, -CH3), ethyl (Et, -CH2CH3), n-propyl (n-Pr, -CH2CH2CH3), isopropyl (i-Pr, -CH(CH3)2), n-butyl (n-Bu, -CH2CH2CH2CH3), isobutyl (i-Bu, -CH2CH(CH3)2), sec-butyl (s-Bu, -CH(CH3)CH2CH3), tert-butyl (t-Bu, -CH(CH3)CH2CH3), ... -C(CH3)3), n-pentyl (-CH2CH2CH2CH2CH3), 2-pentyl (-CH(CH3)CH2CH2CH3), 3-pentyl (-CH(CH2CH3)2), 2-methyl-2-butyl (-C(CH3)2CH2CH3), 3-methyl-2-butyl (-CH(CH3)CH(CH3)2), 3-methyl-1-butyl (-CH2CH2CH(CH3)2), 2-methyl-1- Butyl (-CH2CH(CH3)CH2CH3), n-hexyl (-CH2CH2CH2CH2CH2CH3), 2-hexyl (-CH(CH3)CH2CH2CH2CH3), 3-hexyl (-CH(CH2CH3)(CH2CH2CH3)), 2-methyl-2-pentyl (-C(CH3)2CH2CH2CH3), 3-methyl-2-pentyl (-CH(CH3)CH(CH3)CH2CH3 ), 4-methyl-2-pentyl (-CH(CH3)CH2CH(CH3)2), 3-methyl-3-pentyl (-C(CH3)(CH2CH3)2), 2-methyl-3-pentyl (-CH(CH2CH3)CH(CH3)2), 2,3-dimethyl-2-butyl (-C(CH3)2CH(CH3)2), 3,3-dimethyl-2-butyl (-CH(CH3)C(CH3)3), n-heptyl, n-octyl, and the like. The term "alkyl" and its prefix "alkane" as used herein include both straight and branched saturated carbon chains. The term "alkylene" as used herein refers to a saturated divalent hydrocarbon radical derived from a straight or branched saturated hydrocarbon by eliminating two hydrogen atoms, examples of which include, but are not limited to, methylene, ethylene, isopropylidene, and the like.

[0051] The term "cycloalkyl" refers to a monovalent or polyvalent, non-aromatic, saturated or partially unsaturated ring containing no heteroatoms, including monocyclic rings of 3-12 carbon atoms or bicyclic rings of 7-12 carbon atoms. Bicyclic carbocycles of 7-12 atoms may be bicyclic [4,5], [5,5], [5,6], or [6,6] systems, while bicyclic carbocycles of 9 or 10 atoms may be bicyclic [5,6] or [6,6] systems. Suitable cyclic aliphatic groups include, but are not limited to, cycloalkyl, cycloalkenyl, and cycloalkynyl groups. Examples of cyclic aliphatic groups include, but are in no way limited to, cyclopropyl, cyclobutyl, cyclopentyl, 1-cyclopentyl-1-enyl, 1-cyclopentyl-2-enyl, 1-cyclopentyl-3-enyl, cyclohexyl, 1-cyclohexyl-1-enyl, 1-cyclohexyl-2-enyl, 1-cyclohexyl-3-enyl, cyclohexadienyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl, and the like. And the "cyclic aliphatic group" or "carbocycle", "carbocyclyl", "cycloalkyl" may be substituted or unsubstituted, wherein the substituents may be, but are not limited to, hydroxy, amino, halogen, cyano, aryl, heteroaryl, alkoxy, alkylamino, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, thiol, nitro, aryloxy, hydroxy-substituted alkoxy, hydroxy-substituted alkyl-C(=O), alkyl-C(=O), alkyl-S(=O), alkyl-S(=O)2-, hydroxy-substituted alkyl-S(=O), hydroxy-substituted alkyl-S(=O)2, carboxyalkoxy, etc.

[0052] The terms "heterocycle," "heterocyclyl," "heteroalicyclic," or "heterocyclic" are used interchangeably herein and refer to a monocyclic, bicyclic, or tricyclic ring system in which one or more carbon atoms in the ring(s) are independently and optionally replaced by heteroatoms, wherein the heteroatoms have the meanings herein, the ring(s) may be fully saturated or contain one or more degrees of unsaturation, but are never aromatic, and have only one point of attachment to another molecule. One or more hydrogen atoms in the ring(s) are independently and optionally replaced by one or more substituents as described herein. In some embodiments, the "heterocycle", "heterocyclyl", "heteroalicyclic" or "heterocyclic" group is a 3-7 membered monocyclic ring (1-6 carbon atoms and 1-3 heteroatoms selected from N, O, P, S, wherein S or P is optionally replaced by one or more oxygen atoms to give groups such as SO, SO2, PO, PO2, and when the ring is a three-membered ring, there is only one heteroatom therein), or a 7-10 membered bicyclic ring (4-9 carbon atoms and 1-3 heteroatoms selected from N, O, P, S, wherein S or P is optionally replaced by one or more oxygen atoms to give groups such as SO, SO2, PO, PO2).

[0053] Heterocyclic groups can be carbon groups or heteroatom groups. "Heterocyclic group" also includes groups formed by the combination of a heterocyclic group with a saturated or partially unsaturated ring or heterocyclic ring. Examples of heterocyclic rings include, but are not limited to, pyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, thiomorpholinyl, thioxanyl, thiazolidinyl, oxazolidinyl, piperazinyl, homopiperazinyl, azetidinyl, oxetanyl, thietanyl, piperidinyl, homopiperidinyl, glycidyl, azepanyl, oxetanyl, thiepanyl, 4-methoxy-piperidin-1-yl, 1,2,3,6-tetrahydropyridin-1-yl, oxazepine Base, diazepine Base, thiazolin yl, pyrrolin-1-yl, 2-pyrrolin-1-yl, 3-pyrrolin-1-yl, indolinyl, 2H-pyranyl, 4H-pyranyl, dioxane, 1,3-dioxolane, pyrazolinyl, dithianyl, dithiolanyl, dihydrothienyl, pyrazolidinylimidazolinyl, imidazolidinyl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2,6-thiadiazinane 1,1-dioxol-2-yl, 4-hydroxy-1,4-azaphosphane 4-oxide-1-yl, 2-hydroxy-1-(piperazin-1-yl)ethanone-4-yl, 2-hydroxy-1-(5,6-dihydro-1,2,4-triazin-1(4H)-yl)ethanone-4-yl, 5,6-dihydro-4 H-1,2,4-oxadiazin-4-yl, 2-hydroxy-1-(5,6-dihydropyridin-1(2H)-yl)ethan-4-yl, 3-azabicyclo[3.1.0]hexyl, 3-azabicyclo[4.1.0]heptyl, azabicyclo[2.2.2]hexyl, 2-methyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-c]pyrimidin-6-yl, 4,5,6,7-tetrahydroisoxazolo[4,3-c]pyridin-5-yl, 3H-indolyl, 2-oxo-5-azabicyclo[2.2.1]heptan-5-yl, 2-oxo-5-azabicyclo[2.2.2]octan-5-yl, quinolizinyl and N-pyridylurea. Examples of heterocyclic groups also include 1,1-dioxothiomorpholinyl, and pyrimidinedione in which two carbon atoms in the ring are replaced by oxygen atoms. The heterocyclic group may be substituted or unsubstituted, and the substituents may be, but are not limited to, oxo (=O), hydroxy, amino, halogen, cyano, heteroaryl, alkoxy, alkylamino, alkyl, alkenyl, alkynyl, heterocyclic group, mercapto, nitro, aryloxy, hydroxy-substituted alkoxy, hydroxy-substituted alkyl-C (=O), alkyl-C (=O), alkyl-S (=O), alkyl-S (=O) 2-, hydroxy-substituted alkyl-S (=O), hydroxy-substituted alkyl-S (=O) 2, carboxyalkoxy, and the like.

[0054] The term "aryl" can be used alone or as part of "aralkyl," "aralkoxy," or "aryloxyalkyl" to refer to monocyclic, bicyclic, and tricyclic carbocyclic ring systems containing a total of 6-14 ring members, wherein at least one ring system is aromatic, wherein each ring system contains 3-7 ring members, and has only one point of attachment to the rest of the molecule. The term "aryl" can be used interchangeably with the term "aromatic ring," and aromatic rings can include, for example, phenyl, naphthyl, and anthracenyl. And the aryl group may be substituted or unsubstituted, wherein the substituents may be, but are not limited to, hydroxy, amino, halogen, cyano, aryl, heteroaryl, alkoxy, alkylamino, alkyl, alkenyl, alkynyl, heterocyclyl, thiol, nitro, aryloxy, hydroxy-substituted alkoxy, hydroxy-substituted alkyl-C(=O), alkyl-C(=O), alkyl-S(=O), alkyl-S(=O)2-, hydroxy-substituted alkyl-S(=O), hydroxy-substituted alkyl-S(=O)2, carboxyalkoxy, and the like.

[0055] The term "heteroaryl" refers to monocyclic, bicyclic, and tricyclic ring systems containing a total of 5-14 ring members, wherein at least one ring system is aromatic and at least one ring system contains one or more heteroatoms, wherein the heteroatoms have the meanings herein, and wherein each ring system contains 3-7 ring members and has only one point of attachment to the rest of the molecule. The term "heteroaryl" may be used interchangeably with the terms "heteroaromatic" or "heteroaromatic compound." And the heteroaryl group may be substituted or unsubstituted, wherein the substituents may be, but are not limited to, hydroxy, amino, halogen, cyano, aryl, heteroaryl, alkoxy, alkylamino, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, thiol, nitro, aryloxy, hydroxy-substituted alkoxy, hydroxy-substituted alkyl-C(=O)-, alkyl-C(=O)-, alkyl-S(=O)-, alkyl-S(=O)2-, hydroxy-substituted alkyl-S(=O)-, hydroxy-substituted alkyl-S(=O)2-, carboxyalkoxy and the like.

[0056] In other embodiments, heteroaryl includes, but is not limited to, the following monocyclic rings: 2-furyl, 3-furyl, N-imidazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 4-methylisoxazol-5-yl, N-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, 4-pyrimidinyl, pyrimidin-5-yl, pyridazinyl (such as 3-pyridazinyl), 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, tetrazolyl (such as 5-tetrazolyl), triazolyl (such as 2-triazolyl and 5-triazolyl), 2-thienyl, 3-thienyl, pyrazolyl (such as 2-pyrazolyl), ), isothiazolyl, 1,2,3-oxadiazolyl, 1,2,5-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,3-triazolyl, 1,2,3-thiodiazolyl, 1,3,4-thiodiazolyl, 1,2,5-thiodiazolyl, 1,3,4-thiadiazol-2-yl, pyrazinyl, pyrazin-2-yl, 1,3,5-triazinyl; also includes the following dioxadiazolyl ring, but is in no way limited to these bicyclic rings: benzimidazolyl, benzofuranyl, benzothiophenyl, indolyl (such as 2-indolyl), purinyl, quinolyl (such as 2-quinolyl, 3-quinolyl, 4-quinolyl), and isoquinolyl (such as 1-isoquinolyl, 3-isoquinolyl or 4-isoquinolyl), benzo[d]thiazol-2-yl, imidazo[1,5-a]pyridin-6-yl.

[0057] The term "heteroatom" means one or more O, S, N, P and Si atoms, including N, S and P in any oxidation state; in the form of primary, secondary, tertiary amines and quaternary ammonium salts; or in the form of a nitrogen atom in a heterocyclic ring in which the hydrogen is substituted, for example, N (e.g., N in 3,4-dihydro-2H-pyrrolyl), NH (e.g., NH in pyrrolidinyl) or NR (e.g., NR in N-substituted pyrrolidinyl).

[0058] The term "heteroalkyl" means that one or more heteroatoms may be inserted into the middle of the alkyl chain, wherein the alkyl group and heteroatom have the meanings as described herein. Unless otherwise specified, the heteroalkyl group contains 1-10 carbon atoms, in other embodiments, the heteroalkyl group contains 1-8 carbon atoms, in other embodiments, the heteroalkyl group contains 1-6 carbon atoms, in other embodiments, the heteroalkyl group contains 1-4 carbon atoms, and in other embodiments, the heteroalkyl group contains 1-3 carbon atoms. Such examples include, but are not limited to, CH3OCH2-, CH3CH2OCH2-, CH3SCH2-, CH3SCH2CH2-, (CH3)2NCH2-, (CH3)2CH2OCH2-, CH3OCH2CH2-, CH3CH2OCH2CH2-, etc.

[0059] The term "halogen" refers to F, Cl, Br or I.

[0060] The term "halogenated" used in the present invention means that the group following it is substituted with halogen, and the number of substitutions can be one or more.

[0061] The term "hydroxy-substituted" used in the present invention means that the group following it is substituted with a hydroxyl group, and the number of substitutions may be one or more.

[0062] When "substituted" in the present invention is used between two groups, it is preceded by a substituent, such as "aryl-substituted alkyl" means that the alkyl group has an aryl substituent, and "alkoxycarbonyl-substituted alkyl" means that the alkyl group has an alkoxycarbonyl substituent.

[0063] When multiple groups of the present invention are used in combination, they are in a substitution relationship from left to right, such as "arylalkyl" represents an alkyl substituted by an aryl group, and "alkoxyalkoxy" represents an alkoxy substituted by an alkoxy group.

[0064] Example 1

[0065] The present invention provides an eye drop, the composition of which is shown in Table 1.

[0066] Table 1

[0067] The preparation method is as follows:

[0068] Under aseptic operation, the above ingredients were mixed, stirred at 2-8°C overnight to obtain a homogeneous mixed solution, and then stored in an eye dropper bottle.

[0069] Example 2 Presbyopia Effect Testing Method

[0070] Patients with presbyopia were recruited and, after signing an informed consent form, were administered the eye drops prepared according to Example 1 daily, four times a day, with one drop in each eye each time, for 8 consecutive weeks. Visual acuity was examined before administration (V1, baseline), and 2 weeks (V2), 4 weeks (V3), and 8 weeks (V4) after administration to monitor the improvement / treatment of the patients' presbyopia.

[0071] The visual acuity test used the ETDR near visual acuity chart to test the improvement of the patient's uncorrected near visual acuity (UCNVA).

[0072] The test results are listed in Table 2 below.

[0073] Table 2

[0074] As shown in Table 2, after 8 weeks of continuous use of the eye drops, patients with varying degrees of presbyopia experienced significant improvement in their presbyopia symptoms, with their uncorrected near vision improving by an average of approximately 13 letters. These results demonstrate that the eye drops of the present invention have a favorable therapeutic effect on patients with presbyopia and are safe and convenient.

[0075] Example 3 Mouse lens elasticity test

[0076] 1. Animals and Instruments

[0077] 1) Experimental animals

[0078] C57BL / 6J male mice were purchased from Zhejiang Weitonglihua Experimental Animal Technology Co., Ltd., 40 of which were 8 months old and 10 were 8 weeks old.

[0079] 2) Experimental equipment and instruments

[0080] Table 3. Main instruments of the experiment

[0081] 2. Experimental Methods and Procedures

[0082] 1) Administration: The drug was administered by eye drops with a pipette, with a volume of 5 μL, and only the left eye was dropped. The administration frequency was once a day (QD) or three times a day (TID) according to the group. The elasticity of the mouse lens was tested after 28 days of administration.

[0083] 2) Lens elasticity test

[0084] Lens collection: Mice were sacrificed by overdose of carbon dioxide. The eyeball on the instilled side was removed using ophthalmic forceps and quickly placed in HBSS solution containing 95% O2 and 5% CO2. After three rinses, the optic nerve, sclera, cornea, and retina were removed in sequence using Venus scissors and microtweezers under a stereomicroscope to obtain the lens, which was then immersed in HBSS.

[0085] Preparation for shooting: prepare a slide and a cover glass (weigh the weight, both are about 0.24 g), place the slide under the stereoscope, and select a fixed position to place the lens and then the cover glass.

[0086] Image acquisition: Use a disposable pipette to aspirate the lens from the HBSS solution and place it on a glass slide. After quickly absorbing excess liquid, use the camera provided with the stereoscope to acquire the lens image (uncompressed lens image 1). Quickly place the glass slide on the lens from a fixed position and acquire the lens image again (use the image after 2 minutes as lens image 2).

[0087] Data analysis: Data were collected using Excel and analyzed using Prism (Graph Pad Software, Inc.). Lens elasticity values ​​between groups were compared using one-way analysis of variance with the Sidak test. P < 0.05 was considered significant.

[0088] Calculation formula: Lens elasticity value = lens perimeter in image 2 - lens perimeter in image 1.

[0089] 3. Experimental Results

[0090] In this experiment, we evaluated the efficacy of Formulation 2 in Example 1 in the spontaneous lens elasticity reduction model of aged C57BL / 6 mice.

[0091] The statistical values ​​of lens elasticity after 28 days of administration are shown in Table 4. From the statistical data, the lens elasticity of 8-month-old mice was significantly lower than that of 8-week-old mice. In addition, compared with the vehicle control group 3, prescription 2 once a day or three times a day showed a strong improvement in lens elasticity.

[0092] Table 4: Changes in lens elasticity after four weeks of administration

[0093] 4. Conclusion

[0094] Overall, the lens elasticity of 8-month-old mice was significantly weaker than that of 8-week-old mice, making them suitable as a model for reduced lens elasticity. Once-daily and three-times-daily administration of Prescription 2 eye drops significantly improved the lens elasticity of 8-month-old mice, making them potentially useful for the prevention or treatment of presbyopia and ophthalmic diseases caused by reduced lens elasticity.

[0095] Although the present invention has been described in detail above using general explanations, specific embodiments, and experiments, it will be apparent to those skilled in the art that modifications and improvements may be made based on the present invention. Therefore, such modifications and improvements, which do not depart from the spirit of the present invention, are intended to be within the scope of protection claimed herein.

Claims

1. Use of a steroid compound in the preparation of a medicament for preventing and / or treating presbyopia, characterized in that: The steroidal compound is a compound having a structure as represented by formula (I), or a stereoisomer, tautomer, nitrogen oxide, solvate, metabolite, pharmaceutically acceptable salt or prodrug of the compound having a structure as represented by formula (I); wherein R is H, D, alkyl, sulfate, phosphate, alkylsilyl, benzyl, or -C(O)-X; X is selected from aryl, heteroaryl, cycloalkyl, heterocyclyl, heteroalkyl or alkyl; The aryl, heteroaryl, cycloalkyl, heterocyclyl, heteroalkyl, alkylsilyl and alkyl groups in R and X are optionally substituted with 1, 2, 3 or 4 substituents which are the same or different; The substituent is selected from D, halogen, hydroxyl, thiol, amino, cyano, nitro, carboxyl, alkylcarbonyl, alkyl, haloalkyl, cycloalkyl, heterocyclic, aryl, arylalkyl, heteroaryl, carboxyl, R 1 R 2 NC(=O)- or R 1 R 2 NC(=NH)-NR 3 -; R 1 、R 2 and R 3 Each is independently selected from H, D or alkyl.

2. The use according to claim 1, wherein The steroid compound is a compound having a structure as represented by formula (II) or a stereoisomer, tautomer, nitrogen oxide, solvate, metabolite, pharmaceutically acceptable salt or prodrug of the compound having a structure as represented by formula (II), wherein R is defined as in formula (I).

3. The use according to claim 1, wherein: R is H, D, C 1-6 Alkyl, sulfate, phosphate, C 1-6 Alkylsilyl, benzyl or -C(O)-X; X is selected from C 6-10 Aryl, C 2-9 Heteroaryl, C 3-8 Cycloalkyl, C 2-10 Heterocyclic group, C 1-6 Heteroalkyl or C 1-6 alkyl; R and X are described in C 6-10 Aryl, C 2-9 Heteroaryl, C 3-8 Cycloalkyl, C 2-10 Heterocyclic group, C 1-6 Heteroalkyl, C 1-6 Alkylsilyl or C 1-6 The alkyl group is optionally substituted with 1, 2, 3 or 4 substituents which may be the same or different; The substituent is selected from D, halogen, hydroxyl, thiol, amino, cyano, nitro, carboxyl, C 1-6 Alkylcarbonyl, C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 3-8 Cycloalkyl, C 2-10 Heterocyclic group, C 6-10 Aryl, C 6-10 Aryl C 1-6 Alkyl, C 2-9 Heteroaryl, carboxyl, R 1 R 2 NC(=O)- or R 1 R 2 NC(=NH)-NR 3 -; R 1 、R 2 and R 3 Each independently selected from H, D or C 1-6 alkyl.

4. The use according to any one of claims 1 to 3, characterized in that X is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, hydroxymethyl, hydroxyethyl, mercaptomethyl, mercaptoethyl, aminomethyl, aminoethyl, aminopropyl, phenylmethyl, phenylethyl, imidazolylmethyl, carboxymethyl, carboxyethyl, methylthiomethyl, methylthioethyl, phenyl, naphthyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl, dihydrothiophenyl, 1,3-dioxocyclopentyl, cyclohexyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl, dihydrothiophenyl, 1,3-dioxocyclopentyl, cyclohexyl, tetrahydrofuranyl, dihydrofuranyl, cyclohex ... pentyl, dithiolanyl, tetrahydropyranyl, dihydropyranyl, 2H-pyranyl, 4H-pyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, dioxanyl, dithianyl, thioxanyl, homopiperazinyl, homopiperidinyl, oxepanyl, thiepanyl, oxazepinyl, diazepinyl, thiazepinyl, indolinyl, 1,2,3,4-tetrahydroquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl, furanyl, imidazolyl, 3-[4-(2-methyl-2-oxo-4-yl)-1-oxo-4-oxo-3 ... -isoxazolyl, isoxazolyl, oxazolyl, pyrrolyl, pyridyl, pyrimidinyl, pyridazinyl, thiazolyl, tetrazolyl, triazolyl, 2-thienyl, 3-thienyl, pyrazolyl, isothiazolyl, 1,2,3-oxadiazolyl, 1,2,5-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,3-triazolyl, 1,2,3-thiodiazolyl, 1,3,4-thiodiazolyl, 1,2,5-thiodiazolyl, pyrazinyl, 1,3,5-triazine yl, benzimidazolyl, benzofuranyl, benzothiophenyl, indolyl, purinyl, quinolinyl, isoquinolinyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-b]pyridazinyl, [1,2,4]triazolo[4,3-b]pyridazinyl, [1,2,4]triazolo[1,5-a]pyrimidinyl, [1,2,4]triazolo[1,5-a]pyridinyl, C with H2NC(=O)-substituent 1-3 Alkyl or C with H2NC(=NH)-NH-substituent 1-3 alkyl.

5. The use according to any one of claims 1 to 4, characterized in that The substituent is selected from -D, halogen, hydroxy, amino, cyano, nitro, carboxyl, C 1-6 Alkylcarbonyl, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 3-8 Cycloalkyl, C 2-9 Heterocyclic group, C 6-10 Aryl or C 2-9 Heteroaryl.

6. The use according to any one of claims 1 to 5, characterized in that The substituents are selected from -D, -F, -Cl, -Br, hydroxyl, amino, cyano, carboxyl, formyl, acetyl, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl, trifluoromethyl, difluoromethyl, phenyl, naphthyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl, dihydrothiophenyl, 1,3-dioxolane, dithiocyclopentyl, tetrahydropyranyl, dihydropyranyl , 2H-pyranyl, 4H-pyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, dioxanyl, dithianyl, thioxanyl, homopiperazinyl, homopiperidinyl, oxepanyl, thiepanyl, oxazepinyl, diazepinyl, thiazepinyl, indolinyl, 1,2,3,4-tetrahydroquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl, furanyl, imidazolyl, 3-isoxazolyl, isoxazolyl, oxazole yl, pyrrolyl, pyridyl, pyrimidinyl, pyridazinyl, thiazolyl, tetrazolyl, triazolyl, 2-thienyl, 3-thienyl, pyrazolyl, isothiazolyl, 1,2,3-oxadiazolyl, 1,2,5-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,3-triazolyl, 1,2,3-thiodiazolyl, 1,3,4-thiodiazolyl, 1,2,5-thiodiazolyl, pyrazinyl, 1,3,5-triazinyl, benzimidazolyl , benzofuranyl, benzothiophenyl, indolyl, purinyl, quinolinyl, isoquinolinyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-b]pyridazinyl, [1,2,4]triazolo[4,3-b]pyridazinyl, [1,2,4]triazolo[1,5-a]pyrimidinyl or [1,2,4]triazolo[1,5-a]pyridinyl.

7. The use according to any one of claims 1 to 6, characterized in that X is selected from any of the following groups:

8. The use according to claim 1, characterized in that The compound represented by the formula I is selected from any one of the following compounds:

9. Use of the composition in preparing a medicament for preventing and / or treating presbyopia, characterized in that: The composition comprises the steroid compound according to any one of claims 1 to 8, and one or more pharmaceutically acceptable carriers, excipients, diluents, adjuvants or vehicles.

10. The use according to claim 9, characterized in that The composition comprises: a steroid compound, hypromellose, poloxamer 407, poloxamer 188 and water; Optionally, the composition comprises: 10-40 parts by mass of a steroid compound, 110-120 parts by mass of hypromellose, 2050-2060 parts by mass of poloxamer 407, 160-170 parts by mass of poloxamer 188 and 10,000 parts by mass of water.

11. A method for preventing and / or treating presbyopia, comprising administering the steroid compound or composition defined in any one of claims 1 to 10 to a subject in need thereof.

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