Use of a steroidal compound for the preparation of a medicament for the prevention and / or treatment of floaters

Abstract

The application of a steroid compound in the preparation of a medicine for preventing and / or treating floaters. The steroid compound can have a good treatment, alleviation and prevention effect on floaters, can greatly alleviate and / or cure floaters, and improve visual clarity.

Description

Technical Field

[0001] This invention belongs to the field of chemical and pharmaceutical technology, and relates to the application of a steroid compound in the preparation of drugs for the prevention and / or treatment of floaters. Background Technology

[0002] Floaters are generally caused by vitreous degeneration, a natural aging phenomenon. As we age, the vitreous humor liquefies, producing opacities. Therefore, the formal name for floaters is "vitreous opacities" or "vitreous floaters." They appear as black dots floating in front of the eyes, resembling flying mosquitoes, hence the name. Floaters are caused by opaque objects within the vitreous humor projecting onto the retina. They are more noticeable in bright light or against a white background; sensitive individuals can even depict their various shapes. Many floaters persist for a long time, remain unchanged year after year, do not affect vision, and show no abnormalities in the eye organs upon examination. They often do not require treatment, and there are no effective treatments available.

[0003] Some elderly people may suddenly experience one or two dark spots in their field of vision without other symptoms. This is often due to posterior vitreous detachment and is generally not very harmful. However, if a large number of dark spots suddenly appear, retinal vascular rupture and hemorrhage or retinal tear formation should be considered, as it may be a precursor to retinal detachment, and a more detailed fundus examination is necessary. In choroiditis, many inflammatory cells or exudates can enter the vitreous body, which is also a common cause of pathological floaters, but it is often difficult to detect because of the coexisting visual impairment. Floaters experienced by nearsighted patients are often related to vitreous liquefaction and degeneration.

[0004] Floaters are a unique yet quite common eye condition. A small percentage of floaters pose a serious threat to the eyeball, while the majority are benign, or "physiological floaters," and generally require no treatment. However, even these can significantly impact a patient's physical and mental health. While some over-the-counter medications can alleviate symptoms, they often have significant side effects. Currently, there is no definitively effective treatment for floaters; therefore, finding a clinically effective medication with minimal side effects is a pressing need. Summary of the Invention

[0005] In view of the shortcomings of the existing technology, the purpose of this invention is to provide an application of steroidal compounds in the preparation of drugs for the prevention and / or treatment of floaters. The steroidal compounds provided by this invention can have good therapeutic, alleviating and preventive effects on floaters, can greatly reduce and / or cure floaters, and improve visual clarity.

[0006] To achieve this objective, the present invention adopts the following technical solution:

[0007] In a first aspect, the present invention provides the use of a steroidal compound in the preparation of a medicament for the prevention and / or treatment of floaters, said steroidal compound having a structure as shown in Formula I, or being a stereoisomer, tautomer, nitrogen oxide, solvate, metabolite, pharmaceutically acceptable salt or prodrug of a compound having a structure as shown in Formula I.

[0008]

[0009] Wherein, X is selected from aryl, heteroaryl, cycloalkyl, heterocycloalkyl, heteroalkyl, substituted or unsubstituted alkyl groups, and the substituted group is selected from hydroxyl, mercapto, amino, aryl, heteroaryl, carboxyl, R 1 R 2 NC (=O) or R 1 R 2 NC(=NH)-NR 3 -;

[0010] The R described in this invention 1 R 2 NC (=O) or R 1 R 2 NC(=NH)-NR 3 - Includes R 1 R 2 Both are two groups attached to N.

[0011] Each of the n Qs is independently selected from -H, -D, halogen, hydroxyl, amino, cyano, nitro, carboxyl, alkyl carbonyl, alkyl, haloalkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl.

[0012] The alkyl carbonyl group mentioned in this invention refers to RC (=O)-, where R is an alkyl group and the carbonyl carbon bonded to X is a carbonyl carbon.

[0013] n can be 0, 1, 2, or 3.

[0014] R 1 R 2 and R 3 Each is independently selected from -H, -D, or alkyl groups.

[0015] As a preferred embodiment of the present invention, X is selected from C. 6-10 Aryl, C 2-9 heteroaryl, C 3-8 cycloalkyl, C 2-10 Heterocyclic alkyl, C 1-6 Heteroalkyl, substituted or unsubstituted C 1-6 Alkyl, the C 1-6 If the alkyl group has a substituent, the substituent is selected from hydroxyl, mercapto, amino, C 6-10 Aryl, C 2-9heteroaryl, carboxyl, R 1 R 2 NC (=O) or R 1 R 2 NC(=NH)-NR 3 -;

[0016] R 1 R 2 and R 3 Each can be independently selected from -H, -D, or -C. 1-6 alkyl.

[0017] The C 6-10 It can be C6, C7, C8, C9, or C10. The C... 2-9 It can be C3, C4, C5, C6, C7, or C8. The C... 3-8 It can be C4, C5, C6, or C7. The C... 2-10 It can be C3, C4, C5, C6, C7, C8, or C9. The C... 1-6 It can be C2, C3, C4, or C5.

[0018] As a preferred embodiment of the present invention, X is selected from methyl, ethyl, 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, tetrahydrothiopheneyl, di... Hydrothiopheneyl, 1,3-dioxocyclopentyl, dithiocyclopentyl, tetrahydropyranyl, dihydropyranyl, 2H-pyranyl, 4H-pyranyl, tetrahydrothiopheneyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazine, dioxane, dithiaalkyl, thiaoxane, homopiperazine, homopiperidinyl, oxetaneheptane, thioheptanyl, oxazetane, diazayl, thioazetane, indololinyl, 1,2,3,4-tetrahydroquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl, furfural nylonyl, imidazolyl, 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-Triazinyl, Benzimidazolyl, Benzifuranyl, Benzithiophenyl, Indoleyl, Purylyl, Quinolinyl, Isoquinolinyl, Imidazolo[1,2-a]pyridyl, Pyrazolo[1,5-a]pyridyl, Pyrazolo[1,5-a]pyrimidinyl, Imidazolo[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]pyridyl, C with H2NC(=O)- substituent 1-3 Alkyl groups or C groups with H2NC(=NH)-NH- substituents 1-3 alkyl.

[0019] In a preferred embodiment of the present invention, each of the n Q groups is independently selected from -H, -D, halogen, hydroxyl, amino, cyano, nitro, carboxyl, and C. 1-6 alkyl carbonyl, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-8 cycloalkyl, C 2-9 Heterocyclic group, C 6-10 Aryl or C 2-9 Mixed aromatic compounds.

[0020] The C 1-6 It can be C2, C3, C4, or C5. The C...3-8 It can be C4, C5, C6, or C7. The C... 2-9 It can be C3, C4, C5, C6, C7, or C8. The C... 6-10 It can be C6, C7, C8, C9, or C10.

[0021] In a preferred embodiment of the present invention, each of the n Q groups is independently 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, tetrahydrothiophene, dihydrothiophene, 1,3-dioxocyclopentyl, di... Thiocyclopentyl, tetrahydropyranyl, dihydropyranyl, 2H-pyranyl, 4H-pyranyl, tetrahydrothiaranyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazine, dioxane, dithiaranyl, thiaranyl, homopiperazine, homopiperidinyl, oxetaneheptane, thioheptanyl, oxazine, diazayl, thiazolyl, indololinyl, 1,2,3,4-tetrahydroquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl, furanyl, imidazolyl, 3-isoquinolinyl Oxazolyl, Isoxazolyl, Oxazolyl, Pyrroleyl, Pyridyl, Pyrimidinyl, Pyridazinyl, Thiazolyl, Tetrazolyl, Triazolyl, 2-Thiophenyl, 3-Thiophenyl, 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]pyridyl, pyrazolo[1,5-a]pyridyl, 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]pyridyl.

[0022] As a specific embodiment of the present invention, the compound with the structure shown in Formula I is selected from any one of the following compounds:

[0023]

[0024]

[0025]

[0026]

[0027]

[0028] The steroidal compounds provided by this invention can be used as unprocessed chemical drugs for treatment, or as active ingredients in pharmaceutical compositions.

[0029] In a second aspect, the present invention provides the use of the composition in the preparation of a medicament for the prevention and / or treatment of floaters, said composition comprising the steroidal compound described in the first aspect, and one or more of a pharmaceutically acceptable carrier, excipient, diluent, adjuvant, or medium.

[0030] Substances that can serve as pharmaceutically acceptable carriers include, but are not limited to, ion exchangers; aluminum; aluminum stearate; lecithin; serum proteins, such as human serum albumin; buffering substances such as phosphates; glycine; sorbic acid; potassium sorbate; mixtures of partial glycerides of saturated vegetable fatty acids; water; salts; electrolytes, such as protamine sulfate; disodium hydrogen phosphate; potassium hydrogen phosphate; sodium chloride; zinc salts; colloidal silica; magnesium trisilicate; polyvinylpyrrolidone; polyacrylates; waxes; polyethylene-polyoxypropylene-blocking polymers; lanolin; sugars, such as lactose, glucose, and sucrose; starches, such as corn starch and potato starch; cellulose and its derivatives, such as carboxymethyl cellulose. Sodium thiosulfate, ethyl cellulose 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; glycols 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 salts; Ringer's solution; ethanol, phosphate buffer solution, and other non-toxic and suitable lubricants such as sodium lauryl sulfate and magnesium stearate, colorants, release agents, coatings, sweeteners, flavorings and spices, preservatives and antioxidants.

[0031] Compared with the prior art, the present invention has the following beneficial effects:

[0032] The present invention has found that the steroidal compounds provided by the present invention can be used to prevent, treat, cure or alleviate floaters in patients, and have very few, if any, side effects. Detailed Implementation

[0033] The technical solution of the present invention will be further illustrated below through specific embodiments. Those skilled in the art should understand that the specific embodiments described are merely illustrative of the present invention and should not be construed as limiting the invention.

[0034] Unless otherwise stated, all technical terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0035] The "stereoisomers" described in this invention refer to compounds that have the same chemical structure but whose atoms or groups are arranged differently in space. Stereoisomers include enantiomers, diastereomers, conformational isomers (rotational isomers), geometrical isomers (cis / trans) isomers, and hindered isomers, etc.

[0036] Depending on the choice of starting materials and methods, the compounds of this invention can exist as one or a mixture of possible isomers, such as racemic mixtures and diastereomeric mixtures (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 E or Z configurations; if the compound contains a disubstituted cycloalkyl group, the cycloalkyl substituents may be cis or trans configurations.

[0037] Any mixture of stereoisomers obtained can be separated into pure or substantially pure geometric isomers, enantiomers, and diastereomers based on differences in the physicochemical properties of the components, for example, by chromatography and / or fractional crystallization.

[0038] Unless otherwise indicated, the structural formulas described in this invention include all isomers (e.g., enantiomers, diastereomers, and geometric isomers (or conformational isomers): for example, R and S configurations containing an asymmetric center, (Z) and (E) isomers of double bonds, and (Z) and (E) conformational isomers. Therefore, any single stereochemical isomer of the compounds of this invention, or a mixture of its enantiomers, diastereomers, or geometric isomers (or conformational isomers), is within the scope of this invention.

[0039] The term "prodrug" as used in this invention refers to the conversion of a compound into a compound represented by Formula I in vivo. Such conversion is influenced by the hydrolysis of the prodrug in the blood or its enzymatic conversion into the parent structure in the blood or tissues. The prodrug compounds of this invention can be esters; among existing inventions, esters that can serve as prodrugs include phenyl esters and aliphatic (C14) esters. 1-24Esters, acyloxymethyl esters, carbonates, carbamates, and amino acid esters. For example, one compound in this invention contains a hydroxyl group, meaning it can be acylated to yield a prodrug form. Other prodrug forms include phosphate esters, such as those obtained by phosphorylation of a parent compound with a hydroxyl group. For a complete discussion of prodrugs, please refer to the following literature: T. Higuchi and V. Stella, Prodrugs 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.

[0040] Racemic mixtures of any resulting end product or intermediate can be separated into optical enantiomers using known methods, such as by separating their diastereomeric salts. Racemic products can also be separated by chiral chromatography, such as high-performance liquid chromatography (HPLC) using chiral adsorbents. 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, ELStereochemistry of Carbon Compounds (McGraw-Hill, NY, 1962); Wilen, SH Tables of Resolving Agents and Optical Resolutions p. 268 (ELEliel, 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).

[0041] The terms "tautomer" or "tautomer form" refer to structural isomers with different energies that can interconvert through a low energy barrier. If tautomerism is possible (e.g., in solution), chemical equilibrium of the tautomers can be achieved. For example, proton tautomers (also known as prototropic tautomers) include interconversions via proton transfer, such as keto-enol isomerization and imine-enamine isomerization. Valence tautomers include interconversions via the rearrangement of some bonding electrons. Specific examples of keto-enol tautomers are the interconversion between pentane-2,4-dione and 4-hydroxypent-3-en-2-one tautomers. Another example of tautomers is phenol-keto tautomers. A specific example of phenol-keto tautomers is the interconversion between pyridine-4-ol and pyridine-4(1H)-keto tautomers. Unless otherwise indicated, all tautomer forms of the compounds of this invention are within the scope of this invention.

[0042] The salts mentioned in this invention are pharmaceutically acceptable salts, and the term "pharmaceutically acceptable salts" is well known in the field, as described in the literature: Berge et al., describe pharmaceutically acceptable salts in detail in J. Pharmacol Sci, 1997, 66, 1-19. Pharmaceutically acceptable, non-limiting examples of salts include inorganic acid salts formed by reactions with amino groups, such as hydrochlorides, hydrobroms, 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, bis(hydroxynaphthyl) salts, salicylates, galactobionates, gluconates, mandelates, 1,2-ethanedisulfonates, 2-naphthalenesulfonates, carbonates, trifluoroacetates, glycolates, hydroxyethylsulfonates, oxalates, maleates, tartrates, citrates, succinates, malonates, benzenesulfonates, p-toluenesulfonates, malates, fumarates, lactates, lactobionates, or oxalic acid, or 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, dodecyl sulfate, ethanesulfonate, glucono-heptahydrate, glycerophosphate, gluconate, hemisulfate, heptahydrate, hexanoate, hydroiodate, 2-hydroxy-ethanesulfonate, lacturonate, laurate, lauryl sulfate, nicotinate, nitrate, oleate, palmitate, pyruvate, pectinate, persulfate, 3-phenylpropionate, picrate, pentanoate, propionate, stearate, thiocyanate, undecanoate, valerate, etc. Furthermore, pharmaceutically acceptable salts also include those obtained by means of appropriate bases, such as alkali metals, alkaline earth metals, ammonium, and nitrogen. + (C 1-4 Salts of alkyl groups (4). This invention also contemplates quaternary ammonium salts formed from any compound containing an N group. Water-soluble or oil-soluble or dispersed products can be obtained by quaternization. Alkali metal or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, etc. Pharmaceutically acceptable salts further include suitable, non-toxic ammonium, quaternary ammonium salts, and amine cations resistant to the formation of equilibrium ions, such as halides, carboxylates, sulfates, phosphates, nitrates, C 1-8 Sulfonates and aromatic sulfonates.

[0043] Medicinal salts can form with inorganic and organic acids, such as acetates, aspartates, benzoates, benzenesulfonates, bromides / hydrobromoates, bicarbonates / carbonates, hydrogen sulfates / sulfates, camphor sulfonates, chlorides / hydrochlorides, theophylline salts, citrates, ethanedisulfonates, fumarates, gluconate, glucuronide, gluconate, glucuronide, hippurate, hydroiodide / iodide, hydroxyethyl sulfonate, lactate, lacturonide, lauryl sulfate, malate, maleate, malonate, mandelate, methanesulfonate, methyl sulfate, naphthate, naphthalenesulfonate, nicotinate, nitrates, stearate, oleate, oxalate, palmitate, pyrate, phosphates / hydrogen phosphates / dihydrogen phosphates, polygalactonates, propionates, stearates, succinates, sulfosalicylate, tartrates, toluenesulfonates, and trifluoroacetates.

[0044] Inorganic acids from which salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid.

[0045] 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, etc.

[0046] In this invention, "solvent" refers to an association formed by one or more solvent molecules and the compound of this invention. Solvents forming 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 molecules are water.

[0047] "Pharmaceutical composition" means a mixture of one or more compounds, salts, or physiologically / pharmaceutically acceptable salts or prodrugs described herein with other chemical components, such as physiologically / pharmaceutical acceptable carriers or excipients. The purpose of a pharmaceutical composition is to facilitate the administration of the compound to a living organism.

[0048] As used in this invention, the term "treatment" refers to any disease or condition, and in some embodiments, it means improving the disease or condition (i.e., slowing down or stopping or alleviating the development of the disease or at least one of its clinical symptoms). In other embodiments, "treatment" means alleviating or improving at least one bodily parameter, including bodily parameters that may not be perceived by the patient. In still other embodiments, "treatment" means regulating the disease or condition physically (e.g., stabilizing perceptible symptoms) or physiologically (e.g., stabilizing bodily parameters) or both. In still other embodiments, "treatment" means preventing or delaying the onset, occurrence, or worsening of the disease or condition.

[0049] As used in this invention, the term "alkyl" refers to a saturated straight-chain or branched monovalent hydrocarbon group having 1-20 carbon atoms, or 1-10 carbon atoms, or 1-8 carbon atoms, or 1-6 carbon atoms, or 1-4 carbon atoms, or 1-3 carbon atoms, wherein the alkyl group may be independently and optionally substituted by one or more substituents described in this invention. Examples of alkyl groups 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, -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, etc. The term "alkyl" and its prefix "alkane" are used herein to refer to both straight-chain and branched saturated carbon chains. The term "alkane" is used herein to refer to a saturated divalent hydrocarbon group obtained by eliminating two hydrogen atoms from a straight-chain or branched saturated hydrocarbon; examples of such groups include, but are not limited to, methylene, methine, methinepropyl, etc.

[0050] The term "cycloalkyl" refers to a monovalent or polyvalent, non-aromatic, saturated or partially unsaturated ring that does not contain heteroatoms, including monocyclic rings of 3-12 carbon atoms or bicyclic rings of 7-12 carbon atoms. Bicyclic carbocyclic rings with 7-12 atoms can be bicyclic [4,5], [5,5], [5,6], or [6,6] systems, while bicyclic carbocyclic rings with 9 or 10 atoms can be bicyclic [5,6] or [6,6] systems. Suitable cyclic aliphatic groups include, but are not limited to, cycloalkyl, cycloalkenyl, and cycloynyl groups. Examples of cyclic aliphatic groups include, but are by no means 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, etc. Furthermore, the "cyclic aliphatic group" or "carbocyclic", "carbocyclic group", and "cycloalkyl" may be substituted or unsubstituted, wherein the substituent may be, but is not limited to, hydroxyl, amino, halogen, cyano, aryl, heteroaryl, alkoxy, alkylamino, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, 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, etc.

[0051] The terms “heterocyclic,” “heterocyclic group,” “heterocyclic alicyclic group,” or “heterocyclic” are used interchangeably herein to refer to monocyclic, bicyclic, or tricyclic systems in which one or more carbon atoms on the ring are independently and optionally substituted with heteroatoms, which have the meaning as described herein. The ring may be fully saturated or contain one or more unsaturations, but is by no means aromatic, and has only one connection point to another molecule. One or more hydrogen atoms on the ring are independently and optionally substituted with one or more substituents described herein. Some of these embodiments are that the "heterocycle", "heterocyclic group", "heterocyclic alicyclic group" 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 obtain a group such as SO, SO2, PO, PO2, and when the ring is a three membered ring, there is only one heteroatom), 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 obtain a group such as SO, SO2, PO, PO2).

[0052] Heterocyclic groups can be carbonyl or heteroatomyl. "Heterocyclic group" also includes groups formed by the fusion of a heterocyclic group with a saturated or partially unsaturated ring or heterocycle. Examples of heterocycles include, but are not limited to, pyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothiophenyl, piperidinyl, morpholinyl, thiomorpholinyl, thiazolyl, thiazolyl, oxazolyl, piperazine, homopiperazine, aziridine, oxacyclobutyl, thiohexacyclobutyl, piperidinyl, homopiperidinyl, glycidyl, aziridineheptyl, oxacycloheptyl, thiohexacycloheptyl, 4-methoxy-piperidin-1-yl, 1,2,3,6-tetrahydropyridin-1-yl, oxacyclobutyl... 2-diaza Base, sulfur nitrogen 1-pyrrololin-1-yl, 2-pyrrololin-3-pyrrololin-1-yl, dihydroindolyl, 2H-pyranyl, 4H-pyranyl, dioxacyclohexyl, 1,3-dioxopentyl, pyrazolinyl, dithiaalkyl, dithiamonyl, dihydrothiophenyl, pyrazolinyl imidazolinyl, imidazolinyl, 1,2,3,4-tetrahydroisoquinolinyl, 1,2,6-thiadiazinane 1,1-dioxo-2-yl, 4-hydroxy-1,4-azaphosphane 4-oxide-1-yl, 2-hydroxy-1-(piperazin-1-yl)acetone-4-yl, 2-hydroxy-1-(5,6-dihydro-1,2,4-triazin-1(4H)-yl)acetone-4-yl, 5,6-dihydro-4 H-1,2,4-oxadiazine-4-yl, 2-hydroxy-1-(5,6-dihydropyridin-1(2H)-yl) acetone-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]triazol[1,5-c]pyrimidin-6-yl, 4,5,6,7-tetrahydroisoxazol[4,3-c]pyridin-5-yl, 3H-indolyl-2-oxo-5-azabicyclo[2.2.1]heptane-5-yl, 2-oxo-5-azabicyclo[2.2.2]octane-5-yl, quinazinyl and N-pyridinyl urea. Examples of heterocyclic groups also include 1,1-dioxothiomorpholino, and those in which two carbon atoms on the ring are replaced by oxygen atoms, such as pyrimidinide groups. Furthermore, the heterocyclic group can be substituted or unsubstituted, wherein the substituent can be, but is not limited to, oxo(=O), hydroxyl, amino, halogen, cyano, heteroaryl, alkoxy, alkylamino, alkyl, alkenyl, alkynyl, heterocyclic, 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, etc.

[0053] The term "aryl" can be used alone or as a part of "aranyl," "aranalkoxy," or "aranoxyalkyl," referring to a monocyclic, bicyclic, or tricyclic carbocyclic system containing 6-14 membered rings, wherein at least one ring system is aromatic, and each ring system contains 3-7 membered rings with only one attachment point connected to the rest of the molecule. The term "aryl" can be used interchangeably with the term "aromatic ring," as aromatic rings can include phenyl, naphthyl, and anthracene. Furthermore, the aryl group may be substituted or unsubstituted, wherein the substituent may be, but is not limited to, hydroxyl, amino, halogen, cyano, aryl, heteroaryl, alkoxy, alkylamino, alkyl, alkenyl, alkynyl, heterocyclic, 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, etc.

[0054] The term "heteroaryl" refers to monocyclic, bicyclic, and tricyclic systems containing 5-14 membered rings, wherein at least one ring system is aromatic, and at least one ring system contains one or more heteroatoms, wherein the heteroatoms have the meaning as described in this invention, wherein each ring system contains 3-7 membered rings and has only one attachment site connected to the rest of the molecule. The term "heteroaryl" may be used interchangeably with the terms "aromatic heterocyclic" or "heteroaromatic compound". Furthermore, the heteroaryl group can be substituted or unsubstituted, wherein the substituent can be, but is not limited to, hydroxyl, amino, halogen, cyano, aryl, heteroaryl, alkoxy, alkylamino, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, mercapto, nitro, aryloxy, hydroxy-substituted alkoxy, hydroxy-substituted alkyl-C(=O)-, alkyl-C(=O)-, alkyl-S(=O)2-, hydroxy-substituted alkyl-S(=O)-, hydroxy-substituted alkyl-S(=O)2-, carboxyalkoxy, etc.

[0055] Other embodiments include, but are not limited to, the following monocyclic compounds: 2-furanyl, 3-furanyl, 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, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, 4-pyrimidinyl, pyrimidin-5-yl, pyridazinyl (e.g., 3-pyridazinyl), 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, tetrazolyl (e.g., 5-tetrazolyl), triazolyl (e.g., 2-triazolyl and 5-triazolyl), 2-thienyl, 3-thienyl, pyrazolyl (e.g., 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 bis Cyclic, but not limited to these bicyclic rings: benzimidazolyl, benzofuranyl, benzothiophenyl, indolyl (e.g., 2-indolyl), purinyl, quinolinyl (e.g., 2-quinolinyl, 3-quinolinyl, 4-quinolinyl), and isoquinolinyl (e.g., 1-isoquinolinyl, 3-isoquinolinyl, or 4-isoquinolinyl), benzo[d]thiazolyl-2-yl, imidazo[1,5-a]pyridin-6-yl.

[0056] The term “heteroatom” refers to one or more O, S, N, P, and Si atoms, including N, S, and P in any oxidation state; primary, secondary, tertiary amines, and quaternary ammonium salts; or in the form where the hydrogen atom on the nitrogen atom in the heterocycle is substituted, for example, N (e.g., N in 3,4-dihydro-2H-pyrrole), NH (e.g., NH in pyrroleyl), or NR (e.g., NR in N-substituted pyrroleyl).

[0057] The term "heteroalkyl" indicates that one or more heteroatoms may be inserted in the middle of an alkyl chain, wherein the alkyl group and the heteroatom have the meanings as described in this invention. 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.

[0058] The term "halogen" refers to F, Cl, Br, or I.

[0059] In this invention, "halogenated" means replacing the following group with a halogen, and the number of substitutions can be one or more.

[0060] In this invention, "hydroxyl-substituted" means that the group following it is replaced by a hydroxyl group, and the number of substitutions can be one or more.

[0061] When the term "substituted" is used between two groups in this invention, it is preceded by a substituent, such as "aryl-substituted alkyl" indicating that the alkyl group has an aryl substituent, and "alkoxycarbonyl-substituted alkyl" indicating that the alkyl group has an alkoxycarbonyl substituent.

[0062] When multiple groups of the present invention are used in combination, from left to right, they are in a substitution relationship, such as "arylalkyl", which means aryl-substituted alkyl, and "alkoxyalkoxy", which means alkoxy-substituted alkoxy.

[0063] Example 1

[0064] This invention provides an eye drop solution composed of the following components:

[0065]

[0066] The preparation method is as follows:

[0067] Under aseptic conditions, the above ingredients are mixed and stirred overnight at 2-8°C to obtain a homogeneous mixture, which is then stored in an eye drop bottle.

[0068] Example 2

[0069] This embodiment provides a method for using the eye drops provided in Embodiment 1.

[0070] Use the eye drops provided in Example 1 daily, four times a day, 1 to 2 drops each time.

[0071] Effect test

[0072] Ten patients with floaters were selected for clinical efficacy evaluation. From the date of diagnosis, the patients used the eye drops provided in Example 1 four times a day, 1-2 drops each time, and returned for follow-up visits on the 15th and 30th days. The treatment effects are shown in Table 1 below:

[0073] Table 1:

[0074]

[0075]

[0076] As shown in Table 1, in clinical use, after about 15 days of medication, the black spots or stripes in front of the eyes can be significantly lightened and the contrast sensitivity can be improved, reducing visual disturbance when observing white backgrounds such as ceilings and walls; after about 30 days of medication, floaters can be basically cured, the floating black spots or stripes almost disappear, there is no visual disturbance when observing white backgrounds such as ceilings and walls, the visual quality such as contrast sensitivity is significantly improved, and there are no other side effects.

[0077] Although the present invention has been described in detail above with general descriptions, specific embodiments, and experiments, modifications or improvements can be made to it, which will be obvious to those skilled in the art. Therefore, all such modifications or improvements made without departing from the spirit of the present invention fall within the scope of protection claimed by the present invention.

Claims

1. The use of steroidal compounds in the preparation of medicaments for the prevention and / or treatment of floaters, characterized in that, The steroidal compound has the following structure, or is a pharmaceutically acceptable salt thereof; 2. The use of the composition in the preparation of a medicament for the prevention and / or treatment of floaters, characterized in that, The composition comprises a steroid compound having the following formula or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

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